Pharmaceutical packaging coated with atomic layer deposition, as well as improved syringes and vials for, for example, lyophilized / cold chain drugs / vaccines.

Abstract

This disclosure also relates to improved methods for handling pharmaceutical packaging or other containers used for the storage and transport of formulations, venipuncture and other medical sample collection, and other purposes, such as multiple identical pharmaceutical packaging or other containers. [Solution] This disclosure relates to pharmaceutical packaging such as syringes, vials, and blood collection tubes having thermoplastic walls coated with a gas barrier coating applied by atomic layer deposition, at least one of which is a layer of gas barrier coating. The gas barrier coating may include, for example, one or more layers of SiO2, one or more layers of Al2O3, or a combination thereof, and may function as a barrier to a variety of gases, including oxygen, water vapor, and nitrogen. This disclosure also relates to syringes and vials configured to store lyophilized or cold-chain drugs and, in particular, to maintain container closure integrity throughout the supply and storage conditions associated with such drugs. This disclosure also relates to vacuum blood collection tubes having a long shelf life.

Description

[Technical Field]

[0001] This application claims priority to U.S. Provisional Patent Application No. 63 / 042,545 filed on 22 June 2020; U.S. Provisional Patent Application No. 63 / 080,675 filed on 18 September 2020; U.S. Provisional Patent Application No. 63 / 109,232 filed on 3 November 2020; U.S. Provisional Patent Application No. 63 / 113,808 filed on 13 November 2020; and U.S. Provisional Patent Application No. 63 / 168,580 filed on 31 March 2021, all of which are incorporated herein by reference.

[0002] The present invention relates to the technical field of barrier coatings, such as the inner surface, of pharmaceutical packaging or other containers that store or come into contact with fluids. Examples of suitable fluids include food, nutritional supplements, drugs, inhalation anesthetics, diagnostic test materials, bioactive compounds, or body fluids, such as blood. The present invention also relates to methods for creating pharmaceutical packaging or other containers and pharmaceutical packaging having a pH-protective coating or layer between the contents and the barrier coating or layer. More generally, the present invention also relates to articles other than packaging or containers, such as medical products including catheters.

[0003] This disclosure also relates to improved methods for handling pharmaceutical packaging or other containers used for the storage and transport of formulations, venipuncture and other medical sample collection, and other purposes, such as multiple identical pharmaceutical packaging or other containers.

[0004] The packaging to be produced is also described in the claims. Such pharmaceutical packaging or other containers must be used in large quantities for these purposes, be relatively economical to manufacture, and still be highly reliable for storage and use. [Background technology]

[0005] One important consideration when manufacturing pharmaceutical packaging or other containers that store or come into contact with fluids, such as vials and pre-filled syringes, is that the contents of the pharmaceutical packaging or other containers should preferably have a reasonable shelf life. During this shelf life, it is important to separate the material filling the pharmaceutical packaging or other containers from the container walls containing the material, or from the barrier layer or other functional layer applied to the walls of the pharmaceutical packaging or other containers, thereby preventing the material from reaching the pre-filled contents from the walls, barrier layer, or other functional layer of the pharmaceutical packaging or other containers, or vice versa.

[0006] Conventional glass pharmaceutical packaging or other containers are prone to breakage or deterioration during manufacturing, filling, transport, and use, meaning that glass particles may enter the medication. The presence of glass particles has led to numerous FDA warnings and product recalls.

[0007] As a result, some companies have switched to plastic pharmaceutical packaging or other containers, which offer higher dimensional tolerances and lower breakage than glass. However, its use in primary pharmaceutical packaging remains limited due to gas permeability: plastics allow small molecular gases such as oxygen to permeate into (outside) the article. In addition to oxygen, many plastic materials also allow moisture, i.e., water vapor, to permeate into (outside) the article. The permeability of plastics to gases such as oxygen and water vapor is far higher than that of glass, and in many cases (such as for oxygen-sensitive drugs like epinephrine), plastics were unacceptable for this reason.

[0008] The problem of gas permeability has been addressed by using special resins (e.g., cyclic olefin polymers ("COP") or cyclic olefin copolymers ("COC")) to add an oxygen barrier coating or layer to the part of the plastic pharmaceutical packaging that comes into contact with the fluid contents. One such oxygen barrier layer is coated by plasma chemical vapor deposition, SiO2 as defined below. xThis is an extremely thin coating. COP and COC special resins have been used due to their water vapor barrier properties. This is because, in contrast to the oxygen barrier properties that can be provided by PECVD of a thin SiOx coating, there is no known method for applying a suitable, thin, yet effective and safe water vapor barrier coating by PECVD, for example, for use in pharmaceutical packaging. The inability to provide a suitable water vapor barrier coating by PECVD necessitates the use of special resins such as COP and COC.

[0009] Containers made from specialty resins such as COP and COC have been shown to offer properties suitable for several applications. These properties include, among others, gas barrier properties that protect against dissolution by aqueous contents of the packaging, water vapor barrier properties (a property of COP and COC resins), low levels of organic and inorganic extractability, and low levels of visible and invisible particles (meeting USP789 - ophthalmic requirements). It would be desirable to obtain similar or identical properties using general-purpose resins, which are much cheaper to produce. However, in contrast to COP and COC specialty resins, which can be successfully coated by the PECVD process to produce the desired attributes, general-purpose resins have several drawbacks.

[0010] Most notably, containers made from general-purpose resins allow for a much higher degree of water vapor permeability than COP and COC specialty resins.

[0011] Furthermore, in at least some cases, containers produced from general-purpose resins have a much higher surface roughness. Because coatings are deposited relatively quickly using the PECVD process, the surface roughness of the plastic surface to which the coating is deposited can cause defects in the coating and render it unsuitable. Therefore, the PECVD coating process described above may not be suitable for obtaining containers made from general-purpose resins that have the desired properties (including protection from dissolution by aqueous contents of the packaging, and barrier properties against gases such as oxygen and water vapor).

[0012] The storage of lyophilized or cold-chain drugs typically involves temperature changes, such as use at very low temperatures and / or when the primary drug packaging is returned to room temperature before administration. Glass vials and syringes can crack or break under such thermal stress. Even conventional plastic vials and syringes can suffer loss of container closure integrity (CCI) under high thermal stress. Furthermore, conventional plastic vials and syringes do not provide the barrier properties required by many lyophilized or cold-chain drugs. [Overview of the Initiative] [Means for solving the problem]

[0013] One aspect of the present invention is a container having a lumen at least partially defined by a wall, the wall having an inner surface and an outer surface facing the lumen, and a set of coatings on the inner surface including a barrier coating or layer such as an optional tie coating or layer, an oxygen barrier layer and / or a water vapor barrier layer, a pH protective coating or layer, wherein optionally, one or more layers of the barrier coating consist of multiple atomic monolayers of pure elements or compounds, such as those that can be applied by atomic layer deposition (ALD).

[0014] If a tie coating or layer is present, SiO x C y or Si(NH) x C y It may include. In any chemical formula, x is about 0.5 to about 2.4 and y is about 0.6 to about 3. The tie coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the wall.

[0015] The barrier coating or layer is SiO xcan include, and x is from 1.5 to 2.9. Alternatively or additionally, the barrier coating or layer can include one or more metals or metal oxides such as Al2O3 or combinations thereof. The barrier layer can be 2 to 1000 nm thick. The barrier coating or layer can have an inner surface facing the lumen and an outer surface facing the inner surface of the tie coating or layer. The barrier coating or layer can optionally be effective in reducing the ingress of atmospheric gases into the lumen as compared to a container without the barrier coating or layer. In some embodiments, the barrier coating or layer is SiO where x is from 1.5 to 2.9 x can include one or more layers of and one or more layers of a metal or metal oxide such as Al2O3. The SiO x coating or layer can be effective in reducing the ingress of oxygen into the lumen as compared to a container without the barrier coating or layer, and the Al2O3 layer can be effective in reducing the ingress of water vapor (i.e., moisture) into the lumen as compared to a container without the barrier coating or layer. A portion of the barrier coating or barrier layer coating can include or consist of multiple monolayers of SiOx and / or multiple monolayers of aluminum oxide, each of which can be prepared by atomic layer deposition.

[0016] In any embodiment, the barrier coating can include at least one atomic monolayer of Al2O3, Al x Ti y O z , HfO2, In2O3, MgO, SiO2, SrTiO x , Ta2O5, TiO2, Y2O3, ZnO, ZnO:Al, ZrO2, La2O3, CeO2, AlN, TiAlCN, TiN, TaN x , Ir, Pd, Pt, Si, Al or Ru. In any embodiment, the barrier coating can include at least one atomic monolayer of Al2O3 or ZnO. In any embodiment, the barrier coating can include at least one atomic monolayer of SiO2.

[0017] In any embodiment, an oxygen barrier coating or layer may be effective in reducing the intrusion of oxygen into the lumen to less than 0.0005 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0004 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0003 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.0001 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar.

[0018] In any embodiment, a water vapor barrier coating or layer may be effective in reducing the intrusion of water vapor into the lumen to less than 0.05 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / package / day at 60°C and 40% relative humidity, and optionally less than 0.01 mg / package / day at 60°C and 40% relative humidity.

[0019] In any embodiment, one or more layers of the barrier coating may be supported on the inner surface of the wall. In some embodiments, a water vapor barrier coating or layer may be positioned between the inner surface of the wall and the oxygen barrier coating or layer, and the oxygen barrier coating or layer may be positioned between the water vapor barrier coating or layer and the lumen. In other embodiments, an oxygen barrier coating or layer may be positioned between the inner surface of the wall and the water vapor barrier coating or layer, and the water vapor barrier coating or layer may be positioned between the oxygen barrier coating or layer and the lumen.

[0020] pH protective coating or layer is basically SiO x C y or Si(NH) x C y It may contain or SiO x C y or Si(NH) x C yIt can consist of the following: x is approximately 0.5 to approximately 2.4, and y is approximately 0.6 to approximately 3. The pH protective coating or layer may have an inner surface facing the lumen and an outer surface facing the inner surface of the barrier coating or layer.

[0021] When a fluid composition having a pH of 5 to 9 is present in the lumen, a pH protective coating or layer, or a combination of a pH protective coating or layer and a tie coating or layer, may be effective in providing packaging with a calculated shelf life of more than 6 months at a storage temperature of 4°C.

[0022] In any embodiment, the above-described container is intended to include, or basically consist of, or consist of, a thermoplastic material such as a cyclic olefin polymer (e.g., COP or COC) or a low-cost general-purpose resin such as PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN® (a product of Eastman Chemical Company), or a thermoplastic olefin polymer, in at least a portion of the container wall. In some embodiments, the container, the container wall, or at least a portion of the container wall may include or be made of a cyclic block copolymer (CBC). Cyclic block copolymers are styrene-based fully hydrogenated polymers and dienes conjugated via anionic polymerization. Examples of cyclic block copolymers include, for example, the VIVION® family, such as VIVION® 0510, VIVION® 0510HF, or VIVION® 1325, manufactured by USI Corporation (Taiwan). Cyclic block copolymers are less expensive than COP and COC resins, at least in part due to their low-cost raw materials (styrene, butadiene, hydrogen, and cyclohexane solvents) and the low-cost color plates used in the polymerization and finishing processes.

[0023] The above-described containers, including syringe barrels, vials, or blister packaging, are intended in any embodiment. In some embodiments, the lumen may have a volume of 10 mL or less, optionally 5 mL or less, and optionally 2 mL or less.

[0024] The barrier coating or layer, or at least a portion of the barrier coating or layer, is coated by ALD and may be 1-50 nm thick, alternatively 1-20 nm thick, alternatively 2-15 nm thick, alternatively 2-10 nm thick, alternatively 3-9 nm thick, alternatively 4-8 nm thick, or alternatively 5-7 nm thick. In some embodiments, the water vapor barrier coating or layer may be 1-15 nm thick, alternatively 2-12 nm thick, alternatively 3-10 nm thick, alternatively 4-8 nm thick, or alternatively 5-7 nm thick, as described above for any embodiment. In some embodiments, the oxygen barrier coating or layer may be 1-15 nm thick, alternatively 2-12 nm thick, alternatively 3-10 nm thick, alternatively 4-8 nm thick, or alternatively 5-7 nm thick.

[0025] The pH protective coating or layer is SiO x C y The above-described container, including the above, is intended in any embodiment.

[0026] The above-described container is intended in any embodiment to be coated by PECVD of a precursor feed comprising acyclic siloxane, monocyclic siloxane, polycyclic siloxane, polysilsesquioxane, monocyclic silazane, polycyclic silazane, polysilsesquiazane, silatoran, silk acilatran, silproatoran, azasilatoran, azasilacilatran, azasilproatoran, or any two or more combinations thereof.

[0027] The above-described container is intended in any embodiment, in which the pH protective coating or layer is applied by PECVD of a precursor feed containing octamethylcyclotetrasiloxane (OMCTS).

[0028] The pH protective coating or layer to be applied is 10 to 1000 nm thick, and the above-described container is intended in any embodiment.

[0029] In any embodiment, the above-described container is intended such that the evaporative rate of the pH protective coating or layer is less than 20% of the evaporative rate of the barrier coating or layer when in direct contact with a fluid composition having pH 8, or when in direct contact with the same fluid composition under the same conditions.

[0030] In any embodiment, the above-described container is intended to have a pH protective coating or layer having at least the same extent as the barrier coating or layer.

[0031] In any embodiment, the above-described container is intended to remove the pH protective coating or layer at a rate of 1 nm or less per 44 hours of contact with the fluid composition.

[0032] In any embodiment, the above-described container is intended to further include a lubricating coating or layer applied between the pH protective coating or layer and the lumen. The lubricating coating or layer can basically contain or consist of SiOxCy, where x is about 0.5 to about 2.4 and y is about 0.6 to about 3. In some embodiments, the lubricating coating or layer may be applied by PECVD, e.g., PECVD of linear siloxanes, monocyclic siloxanes, polycyclic siloxanes, polysilsesquioxanes or any combination thereof, optionally PECVD of monocyclic siloxanes, optionally PECVD of octamethylcyclotetrasiloxane (OMCTS).

[0033] The container described above is intended in any embodiment, wherein the container is a syringe barrel, and the lubricating coating or layer provides (i) lower plunger sliding force, (ii) lower plunger sliding yield stress, or (iii) both (i) and (ii) compared to the same syringe barrel without a lubricating coating or layer. For example, the container described above is intended in any embodiment, wherein the container is a syringe barrel, and the lubricating coating or layer provides (i) a plunger sliding force, (ii) a plunger sliding yield stress, or (iii) both (i) and (ii) that are reduced by at least 45%, optionally at least 60%, compared to the same syringe barrel without a lubricating coating or layer.

[0034] In some embodiments, the lubricating coating or layer may be placed between the pH protective coating or layer and the lumen.

[0035] The FTIR absorbance spectrum of the pH protective coating or layer is • The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, • The maximum amplitude of the Si-O-Si asymmetric stretching peak is approximately 1060 to 1100 cm⁻¹. The above-described container is intended in any embodiment to have a ratio greater than 0.75, optionally greater than 0.8, and optionally greater than 0.9 between these values.

[0036] The FTIR absorbance spectrum of the lubricating coating or layer is: • The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, • The maximum amplitude of the Si-O-Si asymmetric stretching peak is approximately 1060 to 1100 cm⁻¹. In any embodiment, the above-described container is intended to have a ratio of at most 0.75 between the two.

[0037] The silicon dissolution rate from the container is less than 170 ppb / day, using a 50 mM potassium phosphate buffer diluted with water for injection, adjusted to pH 8 with concentrated nitric acid and containing 0.2 wt.% polysorbate 80 surfactant, as intended in any embodiment.

[0038] The above-described container is intended in any embodiment, wherein, when dissolved from the container in a 0.1N potassium hydroxide aqueous solution at 40°C, the total silicon content of the pH protective coating or layer and the barrier coating or layer is less than 66 ppm.

[0039] The calculated storage life (total Si / Si dissolution rate) is more than 2 years, and the above-described container is intended for any embodiment.

[0040] The pH protective coating or layer is

number

[0041] The pH protective coating or layer is

number

[0042] The above-described container is intended in any embodiment to be coated by PECVD of a precursor feed containing octamethylcyclotetrasiloxane (OMCTS), tetramethyldisiloxane (TMDSO), or hexamethyldisiloxane (HMDSO) as the tie coating or layer.

[0043] In any embodiment, the above-described container is intended to have a tie coating or layer, if present, with an average thickness of 5 to 200 nm. In some embodiments, the tie coating or layer is 1 to 15 nm thick, alternatively 2 to 12 nm thick, alternatively 3 to 10 nm thick, alternatively 4 to 8 nm thick, or alternatively 5 to 7 nm thick.

[0044] In any embodiment, the above-described container is intended to have a tie coating or layer having at least the same extent as the barrier coating or layer.

[0045] The tie coating or layer is applied by atomic layer deposition (ALD) as described above in any embodiment.

[0046] The above-described container is intended in any embodiment, wherein the barrier coating or layer is 1 to 50 nm thick, alternatively 1 to 20 nm thick, alternatively 2 to 15 nm thick, alternatively 2 to 10 nm thick, alternatively 3 to 9 nm thick, alternatively 4 to 8 nm thick, or alternatively 5 to 7 nm thick.

[0047] The barrier coating or layer is applied by atomic layer deposition (ALD), as intended in any embodiment of the above-described container.

[0048] One aspect of the present invention is a container comprising a container having a lumen at least partially defined by a wall, the wall having an inner surface and an outer surface facing the lumen, and the wall being made mainly of a general-purpose resin. The container is provided with a water vapor barrier coating or layer which is effective in reducing the intrusion of water vapor into the lumen, thereby the container having a water vapor transmission rate that is at least equal to that of the same container made of COP resin but without the water vapor barrier coating or layer, optionally lower than the water vapor transmission rate of the same container made of COP resin but without the water vapor barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, and optionally at least 90% lower.

[0049] In the absence of a water vapor barrier coating or layer, the container is made of COP resin, but has a water vapor transmission rate at least twice, optionally at least three times, optionally at least four times, or optionally at least five times that of a container without a water vapor barrier coating or layer, as described above, in any embodiment.

[0050] One aspect of the present invention is a container comprising a container having a lumen at least partially defined by a wall, the wall having an inner surface and an outer surface facing the lumen, and the wall being made mainly of a general-purpose resin. The container is provided with a water vapor barrier coating or layer which is effective in reducing the intrusion of water vapor into the lumen compared to a container without a water vapor barrier coating or layer, thereby the container having a water vapor transmission rate of less than 0.05 mg / container / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / container / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / container / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / container / day at 60°C and 40% relative humidity, and optionally less than 0.01 mg / container / day at 60°C and 40% relative humidity.

[0051] In the absence of a water vapor barrier coating or layer, the container is intended in any embodiment to have a water vapor transmission rate of more than 1.0 g / container / day, optionally more than 2.0 g / container / day, and optionally more than 3.0 g / container / day.

[0052] The above-mentioned containers are intended in any embodiment, and the general-purpose resins include PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN® (product of Eastman Chemical Company), thermoplastic olefin polymers, cyclic block copolymers (CBCs), etc. In some embodiments, the container, the container wall, or at least a portion of the container wall can be made of a cyclic block copolymer (CBC) or CBC. Cyclic block copolymers are fully hydrogenated polymers based on styrene and dienes conjugated via anionic polymerization. Examples of cyclic block copolymers include, for example, the VIVION® family, such as VIVION® 0510, VIVION® 0510HF, or VIVION® 1325, manufactured by USI Corporation (Taiwan).

[0053] One aspect of the present invention is a container comprising a container having a lumen at least partially defined by a wall, the wall having an inner surface and an outer surface facing the lumen, and the wall being mainly made of COP resin. The container is provided with a water vapor barrier coating or layer which is effective in reducing the intrusion of water vapor into the lumen, thereby the container having a water vapor transmission rate that is at least 5% lower, at least 10% lower, at least 20% lower, at least 30% lower, at least 40% lower, at least 50% lower, at least 60% lower, at least 70% lower, at least 80% lower, and at least 90% lower than that of the same container made of COP resin but without the water vapor barrier coating or layer.

[0054] One aspect of the present invention is a container comprising a container having a lumen at least partially defined by a wall, the wall having an inner surface and an outer surface facing the lumen, and the wall being mainly made of COC resin. The container is provided with a water vapor barrier coating or layer which is effective in reducing the intrusion of water vapor into the lumen, thereby the container having a water vapor transmission rate that is, optionally at least 5%, optionally at least 10%, optionally at least 20%, optionally at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 80%, and optionally at least 90% lower than that of the same container made of COC resin.

[0055] In some embodiments, the container may have a lumen volume of 10 mL or less, optionally 5 mL or less, or optionally 2 mL or less. In some embodiments, the container may be a syringe or a vial.

[0056] In some embodiments, the water vapor barrier coating or layer may include or consist of multiple atomic monolayers, and optionally the water vapor barrier coating or layer is applied by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

[0057] In some embodiments, the water vapor barrier coating or layer includes a metal oxide coating, such as aluminum oxide, or is basically composed of a metal oxide coating, such as aluminum oxide.

[0058] In some embodiments, the water vapor barrier coating or layer may be supported by the inner surface of the container wall such that the water vapor barrier coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the wall. In other embodiments, the water vapor barrier coating or layer may be supported by the outer surface of the container wall such that the water vapor barrier coating or layer has an inner surface facing the outer surface of the wall. In other embodiments, the water vapor barrier coating or layer may be sandwiched between thermoplastic layers of the container wall and thus applied during the molding of the container such that it has an inner surface facing the inner surface of the wall and an outer surface facing the outer surface of the wall.

[0059] In some embodiments, the water vapor barrier coating or layer may be 1 to 50 nm thick, alternatively 5 to 50 nm thick, alternatively 10 to 50 nm thick, alternatively 1 to 40 nm thick, alternatively 5 to 40 nm thick, alternatively 10 to 40 nm thick, alternatively 1 to 30 nm thick, alternatively 5 to 30 nm thick, or alternatively 10 to 30 nm thick.

[0060] In any embodiment, the above-described container is intended to be further provided with an oxygen barrier coating or layer, which is effective in reducing the intrusion of atmospheric gases into the lumen compared to a container without an oxygen barrier coating or layer.

[0061] In some embodiments, the oxygen barrier coating or layer comprises or consists essentially of multiple atomic monolayers, and optionally, the oxygen barrier coating or layer is applied by atomic layer deposition, optionally, by plasma-assisted atomic layer deposition. In other embodiments, the oxygen barrier coating or layer may be applied by PECVD.

[0062] In some embodiments, the oxygen barrier coating or layer may contain SiOx, where x is 1.5 to 2.9 and optionally SiO2.

[0063] In some embodiments, the oxygen barrier coating or layer may be supported by the inner surface of the container wall, thereby having an inner surface facing the lumen and an outer surface facing the inner surface of the wall. In some embodiments, the water vapor barrier coating or layer may be located between the oxygen barrier coating or layer and the inner surface of the wall.

[0064] In some embodiments, the container may further include a pH protective coating or layer and / or a lubricating coating or layer, as described herein.

[0065] One aspect of the present invention is a container having a lumen at least partially defined by a wall, the wall being mainly made of a general-purpose resin and having an inner surface facing the lumen and an outer surface. The wall is provided with both (a) an oxygen barrier coating or layer which is effective in reducing the intrusion of atmospheric gases into the lumen compared to a container without an oxygen barrier coating or layer, and (b) a water vapor barrier coating or layer which is effective in reducing the intrusion of water vapor into the lumen. In some embodiments, the wall may also be provided with a pH protective coating or layer which is effective in extending the calculated storage life of the container.

[0066] One aspect of the present invention is a container containing a lumen, at least partially defined by a wall, the wall being mainly made of COP or COC resin and having an inner surface and an outer surface facing the lumen. The wall is provided with both (a) an oxygen barrier coating or layer which is effective in reducing the intrusion of atmospheric gases into the lumen compared to a container without an oxygen barrier coating or layer, and (b) a water vapor barrier coating or layer which is effective in reducing the intrusion of water vapor into the lumen. In some embodiments, the wall may also be provided with a pH protective coating or layer which is effective in extending the calculated storage life of the container.

[0067] Another aspect of the present invention is a container having an oxygen barrier coating or layer that represents an improvement over SiOx oxygen barriers applied by PECVD, in that a relatively thin coating or layer applied by atomic layer deposition can provide much higher barrier properties than those obtained by PECVD-coated oxygen barriers of the same thickness. One aspect of the present invention is a container comprising a lumen at least partially defined by a wall, the wall having an inner surface and an outer surface facing the lumen, and a coating set on the inner or outer surface, the coating set comprising an oxygen barrier coating or layer, the oxygen barrier coating or layer having a thickness of 1 nm to 15 nm, optionally 1 nm to 10 nm, and effective in providing a container wall having an oxygen permeability constant of less than 0.0003 d-1, optionally less than 0.0002 d-1, and optionally less than 0.0001 d-1.

[0068] In some embodiments, the container may have an oxygen permeability constant lower than that of an otherwise uniform container, which is coated by PECVD with an oxygen barrier coating or layer having substantially the same composition and thickness, optionally at least 10%, optionally at least 20%, optionally at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 80%, or optionally at least 90% lower.

[0069] One aspect of the present invention is a method for preparing a container having barrier properties suitable for storing liquid pharmaceutical formulations over a period of time, by providing a container having a lumen at least partially defined by a wall, the wall being mainly made of either COP or COC resin or a general-purpose resin, and having an inner surface facing the lumen and an outer surface; and applying a water vapor barrier coating by atomic layer deposition, the water vapor barrier coating being effective in reducing the intrusion of water vapor into the lumen.

[0070] In any embodiment, the above method is intended to provide a water vapor barrier coating, which includes a metal oxide coating, optionally aluminum oxide, and optionally an aluminum oxide coating deposited using a trimethylaluminum precursor.

[0071] In any embodiment, the water vapor barrier coating is intended to be applied by plasma-assisted atomic layer deposition as described above. In any embodiment, the wall is maintained at a temperature of less than 100°C, optionally less than 80°C, during the deposition of the coating as described above.

[0072] In any embodiment, the above method is intended to mask the outer surface of the wall during deposition so that the coating is deposited only on the inner surface of the wall.

[0073] The method is intended in any embodiment to further include providing at least 20 containers, optionally at least 50 containers, optionally at least 100 containers, optionally at least 150 containers, optionally at least 200 containers, optionally at least 500 containers, optionally at least 800 containers, optionally at least 1000 containers within a reactor, optionally at least PICOSUN® P-1000B PRO, and providing a substantially uniform flow of a precursor gas to each of the containers under conditions sufficient to construct a layer of water vapor barrier coating substantially uniformly across the containers, optionally at least 95% uniformity, optionally at least 96% uniformity, optionally at least 97% uniformity.

[0074] In some embodiments, the above method is intended to apply an oxygen barrier coating to the container wall. In some embodiments, the oxygen barrier coating is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition. In some embodiments, the oxygen barrier coating contains SiOx. 、x is between 1.5 and 2.9. In some embodiments, the SiOx barrier coating or layer may be deposited using a silicon-containing precursor selected from the group consisting of aminosilanes, alkylaminosilanes, 1,2-bis(diisopropylamino)disilane, diisopropylaminosilane, tris(dimethylamino)silane, bis(ethyl-methyl-amino)silane, and any combination thereof. In some embodiments, the oxygen barrier coating is applied in the same reactor as the water vapor barrier coating.

[0075] One aspect of the present invention is a method for preparing a container having barrier properties suitable for storing liquid pharmaceutical formulations over a period of time, by providing a container having a lumen at least partially defined by a wall, the wall being mainly made of either COP or COC resin or a general-purpose resin, and having an inner surface facing the lumen and an outer surface; and applying an oxygen barrier coating by atomic layer deposition, the oxygen barrier coating being effective in reducing the penetration of oxygen into the lumen.

[0076] The oxygen barrier coating comprises SiOx, where x is 1.5 to 2.9, and optionally x is 2, as described above in any embodiment. In some embodiments, the SiOx barrier coating or layer may be deposited using a silicon-containing precursor selected from the group consisting of aminosilanes, alkylaminosilanes, 1,2-bis(diisopropylamino)disilane, diisopropylaminosilane, tris(dimethylamino)silane, bis(ethyl-methyl-amino)silane, and any combination thereof.

[0077] The oxygen barrier coating is deposited by plasma-assisted atomic layer deposition, as intended in any embodiment of the above method. The wall is maintained at a temperature of less than 100°C, optionally less than 80°C, during the deposition of the coating, as intended in any embodiment of the above method.

[0078] In any embodiment, the above method is intended to mask the outer surface of the wall during deposition so that the coating is deposited only on the inner surface of the wall.

[0079] The method is intended in any embodiment to further include providing at least 20 containers, optionally at least 50 containers, optionally at least 100 containers, optionally at least 150 containers, optionally at least 200 containers, optionally at least 500 containers, optionally at least 800 containers, optionally at least 1000 containers within a reactor, optionally at least PICOSUN® P-1000B PRO, and providing a substantially uniform flow of a precursor gas to each of the containers under conditions sufficient to construct a substantially uniform layer of oxygen barrier coating across the containers, optionally at least 95% uniformity, optionally at least 96% uniformity, optionally at least 97% uniformity.

[0080] In any embodiment, the above method is intended to include the application of a water vapor barrier coating to the container wall.

[0081] One aspect of the present invention is a thermoplastic vial comprising a lumen at least partially defined by side walls and a bottom wall, the side walls having inner and outer surfaces facing the lumen, and the bottom wall having upper and lower surfaces facing the lumen, and a gas barrier coating supported by at least one of the inner and outer surfaces of the walls, the gas barrier coating comprising at least a portion of which basically consists of an atomic monolayer of a pure element or compound. The thermoplastic vial may further include a stopper seated at the opening (the combination may sometimes be called packaging). Another aspect of the present invention is a primary drug packaging comprising the thermoplastic vial described above, a stopper, and a liquid formulation of a drug stored in the lumen of the vial. In some embodiments, the drug may include a cold chain drug, optionally a DNA-type or mRNA-type vaccine.

[0082] In any embodiment, the thermoplastic vial or primary drug packaging described above is intended to produce an ink blot that covers at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 75%, optionally at least 80%, optionally at least 85%, or optionally at least 90% of the surface area corresponding to the vial footprint.

[0083] During freeze-drying, the vial's heat transfer coefficient (Kv × 10 4 ) At least 3.3 cal / s / cm 2 / ℃, or alternatively, at least 3.4 cal / s / cm 2 / ℃, or alternatively, at least 3.5 cal / s / cm 2 In any embodiment, the above-described thermoplastic vial or primary drug packaging is intended to have a temperature of / ℃.

[0084] In some embodiments, the primary drug packaging or thermoplastic vials are further subjected to lyophilization at 0.15 cal / s / cm². 2 Below / ℃, alternatively 0.12 cal / s / cm 2 Below / ℃, alternatively 0.10 cal / s / cm 2 Below / ℃, alternatively 0.08 cal / s / cm 2 The heat transfer coefficient has a standard deviation of less than / ℃, for example, the standard deviation is calculated over a sample of at least 20 units, optionally at least 50 units, optionally at least 100 units, optionally at least 200 units, and optionally at least 300 units.

[0085] In any embodiment, the thermoplastic vial or primary drug packaging described above is intended to maintain container closure integrity for at least 3 months, optionally at least 6 months, optionally at least 9 months, or optionally at least 12 months when stored at -80°C.

[0086] The packaging is stored at -80°C for at least 3 months, optionally at least 6 months, optionally at least 9 months, and optionally at least 12 months, after which it is 0.005d -1 Less than 0.004d (optionally). -1 Less than 0.003d (optionally). -1 Less than 0.002d (optionally). -1 Less than 0.001d (optionally). -1 Less than 0.0005d (optionally). -1 In any embodiment, the above-mentioned thermoplastic vial or primary drug packaging having an oxygen permeability constant of less than is intended.

[0087] In any embodiment, the gas barrier coating is intended for the thermoplastic vial or primary drug packaging described above, which is supported by the inner surface of the wall.

[0088] In any embodiment, the thermoplastic vial or primary drug packaging described above is intended to include a pH protective coating between the lumen and the gas barrier coating, the pH protective coating being effective in extending the calculated shelf life of the container.

[0089] In some embodiments, at least the surface of the pH protective coating facing the lumen may have a surface energy that is customized for the fluid pharmaceutical product stored in the lumen.

[0090] In some embodiments, for example, at least the surface of the pH protective coating facing the lumen may be hydrophilic and have a water contact angle of 25° to 60°, alternatively 25° to 50°, alternatively 30° to 60°, alternatively 30° to 50°, alternatively 40° to 60°, and alternatively 40° to 50°. In other embodiments, for example, at least the surface of the pH protective coating facing the lumen may be hydrophobic and have a water contact angle of 70° to 105°, alternatively 75° to 105°, alternatively 80° to 105°, alternatively 85° to 105°, alternatively 90° to 105°, and alternatively 95° to 105°. In yet another embodiment, at least the surface of the pH protective coating facing the lumen may have a water contact angle of 50° to 80°, alternatively 55° to 75°, and alternatively 60° to 70°.

[0091] In some embodiments, for example, at least the surface of the pH protective coating facing the lumen has a surface free energy of 20 mJ / m², measured using the Kitazaki-Hata method. 2 ~50mJ / m 2 Alternatively, 25 mJ / m 2 ~50 mJ / m 2 , alternatively 20mJ / m 2 ~45mJ / m 2 Alternatively, 25 mJ / m 2 ~45mJ / m 2 , alternatively 20mJ / m 2 ~40mJ / m 2 Alternatively, 25 mJ / m 2 ~40mJ / m 2 In other embodiments, at least the surface of the pH protective coating facing the lumen has a surface free energy of 60 mJ / m², measured using the Kitazaki-Hata method. 2 ~100mJ / m 2 Alternatively, 60 mJ / m 2 ~90mJ / m 2 Alternatively, 65 mJ / m 2 ~100mJ / m 2 Alternatively, 65 mJ / m 2 ~90mJ / m 2 , alternatively 70mJ / m 2 ~100mJ / m 2 , alternatively 70mJ / m 2~90mJ / m 2 It may have.

[0092] In any embodiment, the thermoplastic vial or primary drug packaging described above is intended to contain fewer than 50 particles per mL that are 2 μm or larger in size, optionally fewer than 40 particles per mL that are 2 μm or larger in size, optionally fewer than 30 particles per mL that are 2 μm or larger in size, optionally fewer than 25 particles per mL that are 2 μm or larger in size, optionally fewer than 20 particles per mL that are 2 μm or larger in size, optionally fewer than 15 particles per mL that are 2 μm or larger in size, optionally fewer than 12 particles per mL that are 2 μm or larger in size, and optionally fewer than 10 particles per mL that are 2 μm or larger in size.

[0093] The above-described thermoplastic vial or drug primary packaging is intended in any embodiment, wherein the gas barrier coating includes an oxygen barrier coating or layer, which is effective in reducing the intrusion of oxygen into the lumen to less than 0.0005 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0004 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0003 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar.

[0094] The gas barrier coating includes an oxygen barrier coating or layer, and the oxygen barrier coating or layer is 0.0010d -1 Less than 0.0008d (optionally). -1 Less than 0.0006d (optionally). -1 Less than 0.0004d (optionally). -1 Less than 0.0003d (optionally). -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1In any embodiment, the above-described thermoplastic vial or primary drug packaging is intended to be effective in providing packaging or vials having an oxygen permeability constant of less than .

[0095] In any embodiment, the thermoplastic vial or primary drug packaging described above is intended to include a gas barrier coating, an oxygen barrier coating or layer, which basically consists of multiple atomic monolayers, and optionally the oxygen barrier coating or layer is deposited by atomic layer deposition, or optionally by plasma-assisted atomic layer deposition.

[0096] In any embodiment, the above-described thermoplastic vial or primary pharmaceutical packaging is intended to include or consist of a metal oxide, optionally Al2O3, as an oxygen barrier coating or layer. x In any embodiment, the above-described thermoplastic vial or primary drug packaging is intended to include or essentially consist of, where x is 1.5 to 2.9, and optionally x is 2.

[0097] The above-described thermoplastic vial or drug primary packaging is intended in any embodiment, wherein the gas barrier coating includes a water vapor barrier coating or layer, which is effective in reducing the intrusion of water vapor into the lumen to less than 0.05 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / package / day at 60°C and 40% relative humidity, and optionally less than 0.01 mg / package / day.

[0098] In any embodiment, the above-described thermoplastic vial or drug primary packaging is intended to include a gas barrier coating, a water vapor barrier coating or layer, which basically consists of multiple atomic monolayers, and optionally the water vapor barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

[0099] The water vapor barrier coating or layer comprises or is essentially composed of a metal oxide, optionally Al2O3, as intended in any embodiment for the thermoplastic vial or primary pharmaceutical packaging described above. x It includes or basically consists of, where x is between 1.5 and 2.9, and optionally x is 2.

[0100] The headspace of the lumen further contains nitrogen gas, and the gas barrier coating includes a nitrogen barrier coating or layer, which limits nitrogen gas leakage from the lumen to less than 0.0002 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally 0.0001 cc / The above-described thermoplastic vials or primary drug packaging are intended in any embodiment to be effective in reducing the amount to less than packaging / day, optionally less than 0.00005 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.00001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar.

[0101] The gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer has a nitrogen permeability constant (NTR) of 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 Less than 0.00008d (optionally). -1 Less than 0.00006d (optionally). -1 Less than 0.00004d (optionally) -1 Less than 0.00003d (optionally). -1 Less than 0.00002d (optionally) -1 Less than 0.00001d (optionally). -1 In any embodiment, the above-described thermoplastic vial or primary drug packaging is intended to be effective in providing packaging or vials having less than .

[0102] In any embodiment, the above-described thermoplastic vial or drug primary packaging is intended to include a gas barrier coating, a nitrogen barrier coating or layer, which basically consists of multiple atomic monolayers, and optionally the nitrogen barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

[0103] In any embodiment, the above-described thermoplastic vial or primary pharmaceutical packaging is intended to include or consist of a nitrogen barrier coating or layer containing a metal oxide, optionally Al2O3. The nitrogen barrier coating or layer is SiO2O3. x In any embodiment, the above-described thermoplastic vial or primary drug packaging is intended to include or essentially consist of, where x is 1.5 to 2.9 and x is 2.

[0104] The lumen further contains carbon monoxide, and the gas barrier coating includes a carbon monoxide barrier coating or layer, which limits carbon monoxide leakage from the lumen to less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally 0.0001 cc / The above-described thermoplastic vials or primary drug packaging are intended in any embodiment to be effective in reducing the amount to less than packaging / day, optionally less than 0.00005 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.00001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar.

[0105] The gas barrier coating includes a carbon monoxide barrier coating or layer, and the carbon monoxide barrier coating or layer has a carbon monoxide transmission rate (COTR) of 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 Less than 0.00008d (optionally).-1 less than, optionally 0.00006d -1 less than, optionally 0.00004d -1 less than, optionally 0.00003d -1 less than, optionally 0.00002d -1 less than, optionally 0.00001d -1 The above thermoplastic vial or primary drug packaging that is effective for providing a package or vial having less than is contemplated in any embodiment.

[0106] The gas barrier coating includes a carbon monoxide barrier coating or layer, and the carbon monoxide barrier coating or layer basically consists of a plurality of atomic monolayers. Optionally, the carbon monoxide barrier coating or layer is deposited by atomic layer deposition, optionally plasma-assisted atomic layer deposition. The above thermoplastic vial or primary drug packaging is contemplated in any embodiment.

[0107] The carbon monoxide barrier coating or layer includes or basically consists of a metal oxide, optionally Al2O3. The above thermoplastic vial or primary drug packaging is contemplated in any embodiment. The carbon monoxide barrier coating or layer includes SiO x including or basically consisting of it, where x is 1.5 to 2.9, and optionally x is 2. The above thermoplastic vial or primary drug packaging is contemplated in any embodiment.

[0108] The lumen further contains carbon dioxide, and the gas barrier coating includes a carbon dioxide barrier coating or layer, which limits carbon dioxide leakage from the lumen to less than 0.005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.004 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.003 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally 25°C, relative humidity The thermoplastic vials or primary drug packaging described above are intended in any embodiment to be effective in reducing the amount to less than 0.002 cc / package / day at 60% and 0.21 bar, optionally less than 0.001 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0008 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, and optionally less than 0.0005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar.

[0109] The above-described thermoplastic vial or primary drug packaging is intended in any embodiment, wherein the gas barrier coating includes a carbon dioxide barrier coating or layer, and the carbon dioxide barrier coating or layer is effective in providing packaging or vials having a carbon dioxide transmission rate (CO2TR) of less than 0.005d-1, optionally less than 0.004d-1, optionally less than 0.002d-1, optionally less than 0.001d-1, optionally less than 0.0008d-1, optionally less than 0.0006d-1, optionally less than 0.0005d-1, optionally less than 0.0004d-1, optionally less than 0.0003d-1, optionally less than 0.0002d-1, and optionally less than 0.0001d-1.

[0110] In any embodiment, the above-described thermoplastic vial or drug primary packaging is intended to include a gas barrier coating, which comprises a carbon dioxide barrier coating or layer, which basically consists of multiple atomic monolayers, and optionally the carbon dioxide barrier coating or layer is deposited by atomic layer deposition, or optionally by plasma-assisted atomic layer deposition.

[0111] In any embodiment, the above-described thermoplastic vial or primary pharmaceutical packaging is intended to include or consist of a carbon dioxide barrier coating or layer containing a metal oxide, optionally Al2O3. The carbon dioxide barrier coating or layer is SiO2O3. x In any embodiment, the above-described thermoplastic vial or primary drug packaging is intended to include or essentially consist of, where x is 1.5 to 2.9, and optionally x is 2.

[0112] In any embodiment, the thermoplastic vial or primary drug packaging described above is intended to include a gas barrier coating, which is an ethylene oxide barrier coating or layer. In any embodiment, the thermoplastic vial or primary drug packaging described above is intended to be sterilized in a final step using optionally selected ethylene oxide.

[0113] In any embodiment, the above-mentioned thermoplastic vials or primary drug packaging are intended to consist mainly of thermoplastic materials selected from PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN®, cyclic block copolymer (CBC) resin, thermoplastic olefin polymers, COP, COC, or any combination thereof.

[0114] In any embodiment, a thermoplastic vial or primary drug packaging or a plurality of thermoplastic vials or primary drug packaging is intended, configured to maintain container closure integrity (CCI) when the packaging or vial cycles through -20°C to 10°C, optionally -20°C to 20°C, optionally -20°C to 30°C, optionally -40°C to 10°C, optionally -40°C to 20°C, optionally -40°C to 30°C, optionally -40°C to 40°C, optionally -20°C to 40°C, optionally -70°C to 10°C, optionally -70°C to 20°C, optionally -70°C to 30°C, and optionally -70°C to 40°C. In some embodiments, the packaging or vial undergoes at least 3 cycles, optionally, the packaging or vial undergoes 3 cycles. During each cycle, the packaging or vial may be kept at both low temperatures for 24 hours or more and high temperatures for 24 hours or more; optionally, during each cycle, the packaging or vial may be kept at both low temperatures for approximately 24 hours and high temperatures for approximately 24 hours.

[0115] In any embodiment, a thermoplastic vial or primary drug packaging, or a plurality of thermoplastic vials or primary drug packaging, is intended such that the filling volume of the vial is at least 20% of the nominal capacity of the vial, optionally, the filling volume of the vial is at least 10% of the nominal capacity of the vial, optionally, the filling volume of the vial is at least 5% of the nominal capacity of the vial. In some embodiments, the vial may have a nominal capacity of either 10 mL or 2 mL, optionally, the vial may have a nominal capacity of 10 mL, optionally, the vial may have a nominal capacity of 2 mL.

[0116] In any embodiment, the above-described thermoplastic vials or primary drug packaging are intended to include a plurality of vials or packaging comprising at least 50 untested packages, optionally comprising a plurality of packages consisting of samples of 50 untested packages, optionally comprising a plurality of packages comprising at least 100 untested packages, optionally comprising a plurality of packages consisting of samples of 100 untested packages, optionally comprising a plurality of packages comprising at least 500 untested packages, optionally comprising a plurality of packages consisting of samples of 500 untested packages, optionally comprising a plurality of packages comprising at least 1000 untested packages, optionally comprising a plurality of packages consisting of samples of 1000 untested packages.

[0117] One aspect of the present invention is a thermoplastic syringe barrel comprising a lumen at least partially defined by a side wall, the side wall having an inner surface and an outer surface facing the lumen, a front partial injection opening and a rear opening, and a gas barrier coating supported by at least one of the inner surface and the outer surface of the side wall, wherein at least a portion of the gas barrier coating basically consists of a plurality of atomic monolayers of pure elements or compounds. Another aspect of the present invention is a syringe comprising the thermoplastic syringe barrel described above and a plunger seated in the rear opening. Another aspect of the present invention is a primary drug packaging comprising the thermoplastic syringe barrel described above, a liquid formulation of a drug in the lumen, and a plunger seated in the syringe barrel and having a front surface facing the liquid formulation. In some embodiments, the liquid formulation of a drug may optionally include a cold chain drug, and optionally include a DNA-type or mRNA-type vaccine.

[0118] In any embodiment, the thermoplastic syringe barrel, syringe, or primary drug packaging described above is intended to include a steakd needle or Luer lock at the front injection opening.

[0119] In any embodiment, the lumen is intended to be the thermoplastic syringe barrel, syringe, or primary drug packaging described above, having a nominal filling capacity of 0.25 to 10 mL, and optionally 0.5 to 5 mL.

[0120] In any embodiment, the above-described thermoplastic syringe barrel, syringe, or primary drug packaging is intended to be configured such that, when the syringe barrel is filled with MilliQ water and subjected to one or more of the following: inversion for 2 hours at 50 rpm, incubation for 2 weeks at 4°C, and freeze-thaw cycles of 20°C to -40°C for 5 cycles, the contents of the syringe have fewer than 500,000 particles of size 300 nm or larger, alternatively fewer than 400,000 particles of size 300 nm or larger, or alternatively fewer than 300,000 particles of size 300 nm or larger, according to resonant mass metric.

[0121] In some embodiments, for example, a syringe barrel or syringe is filled with MilliQ water and inverted at 50 rpm for 2 hours, such that the contents of the syringe have fewer than 500 particles of size 2 μm or larger, alternatively fewer than 400 particles of size 2 μm or larger, alternatively fewer than 300 particles of size 2 μm or larger, and alternatively fewer than 200 particles of size 2 μm or larger, according to FlowCAM® microflow digital imaging, a light shielding test, or both. In some embodiments, for example, a syringe barrel or syringe is configured such that, when filled with MilliQ water and incubated at 4°C for two weeks, the contents of the syringe contain fewer than 2,000 particles of size 2 μm or larger, alternatively fewer than 1,000 particles of size 2 μm or larger, alternatively fewer than 900 particles of size 2 μm or larger, alternatively fewer than 800 particles of size 2 μm or larger, alternatively fewer than 700 particles of size 2 μm or larger, alternatively fewer than 600 particles of size 2 μm or larger, and alternatively fewer than 500 particles of size 2 μm or larger, according to FlowCAM® microflow digital imaging, a light shielding test, or both. In some embodiments, for example, a syringe barrel is configured such that, when filled with MilliQ water and subjected to 5 cycles of freeze-thaw at 20°C to -40°C, the contents of the syringe have fewer than 20,000 particles of size 2 μm or larger, alternatively fewer than 10,000 particles of size 2 μm or larger, alternatively fewer than 5,000 particles of size 2 μm or larger, alternatively fewer than 2,000 particles of size 2 μm or larger, alternatively fewer than 1,000 particles of size 2 μm or larger, alternatively fewer than 500 particles of size 2 μm or larger, and alternatively fewer than 300 particles of size 2 μm or larger, according to FlowCAM® microflow digital imaging, a light shielding test, or both.

[0122] In any embodiment, the above-described syringe barrel, syringe, or primary drug packaging is intended to contain fewer than 50 particles having a size greater than 10 μm after the liquid formulation has been rotated at 40°C for 5 minutes, followed by three freeze-thaw cycles from +5°C to -20°C at 1°C per minute for 2 or 4 weeks, or after the container has been stored at 5°C, 25°C and 60% relative humidity or 40°C and 75% relative humidity for 3 months.

[0123] In any embodiment, the thermoplastic syringe barrel, syringe, or primary drug packaging described above is intended to contain fewer than five particles having a size greater than 25 μm after the liquid formulation has been rotated at 40°C for 5 minutes, followed by 2 or 4 weeks, or three freeze-thaw cycles from +5°C to -20°C at 1°C per minute, or after the container has been stored at 5°C, 25°C / 60% relative humidity, or 40°C / 75% relative humidity for 3 months.

[0124] In any embodiment, a thermoplastic syringe barrel, syringe, or primary drug packaging described above is intended, which does not have silicone oil or silicone coating on the syringe barrel and plunger.

[0125] In any embodiment, a thermoplastic syringe barrel, syringe, or primary drug packaging described herein is intended in which the lubricating coating or layer described herein is supported by the inner surface of the wall.

[0126] In any embodiment, a thermoplastic syringe barrel, syringe, or primary drug packaging described above is intended, in which the gas barrier coating is supported by the inner surface of the wall.

[0127] In any embodiment, the thermoplastic syringe barrel, syringe, or primary drug packaging described herein is intended to further include a pH protective coating between the lumen and the gas barrier coating, the pH protective coating being effective in extending the calculated storage life of the container.

[0128] In some embodiments, at least the surface of the pH protection coating facing the lumen may have a surface energy customized for the fluid pharmaceutical product stored within the lumen.

[0129] In some embodiments, for example, at least the surface of the pH protection coating facing the lumen may be hydrophilic, for example, having a water contact angle of 25° to 60°, alternatively 25° to 50°, alternatively 30° to 60°, alternatively 30° to 50°, alternatively 40° to 60°, alternatively 40° to 50°. In other embodiments, at least the surface of the pH protection coating facing the lumen may be hydrophobic, for example, having a water contact angle of 70° to 105°, alternatively 75° to 105°, alternatively 80° to 105°, alternatively 85° to 105°, alternatively 90° to 105°, alternatively 95° to 105°. In still other embodiments, at least the surface of the pH protection coating facing the lumen may have a water contact angle of 50° to 80°, alternatively 55° to 75°, alternatively 60° to 70°.

[0130] In some embodiments, for example, at least the surface of the pH protection coating facing the lumen has a surface free energy of 20 mJ / m 2 ~50 mJ / m 2 , alternatively 25 mJ / m 2 ~50 mJ / m 2 , alternatively 20 mJ / m 2 ~45 mJ / m 2 , alternatively 25 mJ / m 2 ~45 mJ / m 2 , alternatively 20 mJ / m 2 ~40 mJ / m 2 , alternatively 25 mJ / m 2 ~40 mJ / m 2 measured using the Kitazaki-Hata method. In other embodiments, at least the surface of the pH protection coating facing the lumen has a surface free energy of 60 mJ / m 2 ~100 mJ / m 2 , alternatively 60 mJ / m 2 ~90 mJ / m 2 , alternatively 65 mJ / m 2 ~100 mJ / m2 Alternatively, 65 mJ / m 2 ~90mJ / m 2 , alternatively 70mJ / m 2 ~100mJ / m 2 , alternatively 70mJ / m 2 ~90mJ / m 2 It may have.

[0131] Multiple thermoplastic syringe barrels, syringes, or drug primary packaging are envisioned in any embodiment, having a consistent inner diameter of syringe barrels with a standard deviation of less than 0.03 mm, optionally less than 0.02 mm, optionally less than 0.01 mm, optionally less than 0.008 mm, optionally less than 0.006 mm, optionally less than 0.005 mm, and optionally less than 0.004 mm. Multiple thermoplastic syringe barrels, syringes, or drug primary packaging are envisioned in any embodiment, having a consistent needle hub outer diameter of syringe barrels with a standard deviation of less than 0.15 mm, optionally less than 0.10 mm, optionally less than 0.08 mm, optionally less than 0.05 mm, optionally less than 0.02 mm, optionally less than 0.008 mm, and optionally less than 0.005 mm. Multiple thermoplastic syringe barrels, syringes, or drug primary packaging described above are intended in any embodiment, having a consistent length of syringe barrels with a standard deviation of less than 0.06 mm, optionally less than 0.05 mm, optionally less than 0.04 mm, optionally less than 0.03 mm, optionally less than 0.02 mm, and optionally less than 0.01 mm. Multiple thermoplastic syringe barrels, syringes, or drug primary packaging described above are intended in any embodiment, having a consistent weight of syringe barrels with a standard deviation of less than 0.025 g, optionally less than 0.020 g, optionally less than 0.015 g, optionally less than 0.010 g, optionally less than 0.0075 g, and optionally less than 0.005 g. The standard deviation is calculated over samples of at least 20 units, optionally at least 50 units, optionally at least 100 units, optionally at least 200 units, and optionally at least 300 units, as described above for any multiple thermoplastic syringe barrels, syringes, or primary drug packaging.

[0132] The above-described thermoplastic syringe barrel, syringe, or drug primary packaging is intended in any embodiment, wherein the gas barrier coating includes an oxygen barrier coating or layer, which is effective in reducing the intrusion of oxygen into the lumen to less than 0.0005 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0004 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0003 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar.

[0133] The gas barrier coating includes an oxygen barrier coating or layer, and the oxygen barrier coating or layer is 0.0010d -1 Less than 0.0008d (optionally). -1 Less than 0.0006d (optionally). -1 Less than 0.0004d (optionally). -1 Less than 0.0003d (optionally). -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 In any embodiment, the above-described thermoplastic syringe barrel, syringe, or drug primary packaging is intended to be effective in providing a syringe barrel, syringe, or drug primary packaging having an oxygen permeability constant of less than .

[0134] In any embodiment, the above-described thermoplastic syringe barrel, syringe, or drug primary packaging is intended to include an oxygen barrier coating or layer, the oxygen barrier coating or layer basically consisting of multiple atomic monolayers, and optionally the oxygen barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

[0135] In any embodiment, thermoplastic syringe barrels, syringes, or primary drug packaging are intended to have an oxygen barrier coating or layer containing or essentially consisting of a metal oxide, optionally Al2O3. The oxygen barrier coating or layer is SiO2O3.x In any embodiment, the above-described thermoplastic syringe barrel, syringe, or primary drug packaging is intended to include or essentially consist of, where x is 1.5 to 2.9, and optionally x is 2.

[0136] The above-described thermoplastic syringe barrel, syringe, or drug primary packaging is intended in any embodiment, wherein the gas barrier coating includes a water vapor barrier coating or layer, which is effective in reducing the intrusion of water vapor into the lumen to less than 0.05 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / package / day at 60°C and 40% relative humidity, and optionally less than 0.01 mg / package / day.

[0137] In any embodiment, the above-described thermoplastic syringe barrel, syringe, or primary drug packaging is intended to include a gas barrier coating, a water vapor barrier coating or layer, the water vapor barrier coating or layer basically consisting of multiple atomic monolayers, and optionally the water vapor barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

[0138] In any embodiment, a thermoplastic syringe barrel, syringe, or primary drug packaging is intended to have a water vapor barrier coating or layer containing or essentially consisting of a metal oxide, optionally Al2O3. The water vapor barrier coating or layer is SiO2O3. x In any embodiment, the above-described thermoplastic syringe barrel, syringe, or primary drug packaging is intended to include or essentially consist of, where x is 1.5 to 2.9, and optionally x is 2.

[0139] The inner cavity headspace further contains nitrogen gas, and the gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer reduces the leakage of nitrogen gas from the inner cavity to less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0001 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00005 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00001 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar. The above-mentioned thermoplastic syringe barrel, syringe, or primary drug packaging is contemplated in any embodiment.

[0140] The gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer has a nitrogen transmission rate constant (NTR) of less than 0.0003 d -1 optionally less than 0.0002 d -1 optionally less than 0.0001 d -1 optionally less than 0.00008 d -1 optionally less than 0.00006 d -1 optionally less than 0.00004 d -1 optionally less than 0.00003 d -1 optionally less than 0.00002 d -1 optionally less than 0.00001 d -1 The above-mentioned thermoplastic syringe barrel, syringe, or primary drug packaging is contemplated in any embodiment and is effective in providing a package or vial having such a nitrogen transmission rate constant (NTR) less than.

[0141] The gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer consists essentially of a plurality of atomic monolayers, and optionally, the nitrogen barrier coating or layer is deposited by atomic layer deposition, optionally plasma-assisted atomic layer deposition. The above-mentioned thermoplastic syringe barrel, syringe, or primary drug packaging is contemplated in any embodiment.

[0142] A nitrogen barrier coating or layer is contemplated in any embodiment for a thermoplastic syringe barrel, syringe or primary pharmaceutical packaging, which comprises a metal oxide, optionally containing or consisting essentially of Al2O3. The nitrogen barrier coating or layer comprises SiO x and consists essentially of it, where x is from 1.5 to 2.9, and optionally x is 2. A thermoplastic syringe barrel, syringe or primary pharmaceutical packaging as described above is contemplated in any embodiment.

[0143] Further comprising carbon monoxide in the lumen, the gas barrier coating comprises a carbon monoxide barrier coating or layer, and the carbon monoxide barrier coating or layer reduces the leakage of carbon monoxide from the lumen to less than 0.0002 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0001 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.00005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.00002 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.00001 cc / package / day at 25°C, 60% relative humidity and 0.21 bar. A thermoplastic syringe barrel, syringe or primary pharmaceutical packaging as described above is contemplated in any embodiment.

[0144] The gas barrier coating comprises a carbon monoxide barrier coating or layer, and the carbon monoxide barrier coating or layer has a carbon monoxide transmission rate (COTR) of less than 0.0003 d -1 , optionally less than 0.0002 d -1 , optionally less than 0.0001 d -1 , optionally less than 0.00008 d -1 , optionally less than 0.00006 d -1 , optionally less than 0.00004 d -1 , optionally less than 0.00003 d -1 , optionally less than 0.00002 d -1 , optionally less than 0.00001 d -1In any embodiment, the above-described thermoplastic syringe barrel, syringe, or primary drug packaging is intended to be effective in providing packaging or vials having less than [a certain value].

[0145] In any embodiment, the above-described thermoplastic syringe barrel, syringe, or drug primary packaging is intended to include a gas barrier coating, a carbon monoxide barrier coating or layer, the carbon monoxide barrier coating or layer basically consists of multiple atomic monolayers, and optionally the carbon monoxide barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

[0146] In any embodiment, a thermoplastic syringe barrel, syringe, or primary drug packaging is intended to have a carbon monoxide barrier coating or layer containing or essentially consisting of a metal oxide, optionally Al2O3. The carbon monoxide barrier coating or layer is SiO2O3. x In any embodiment, the above-described thermoplastic syringe barrel, syringe, or primary drug packaging is intended to include or essentially consist of, where x is 1.5 to 2.9, and optionally x is 2.

[0147] The lumen further contains carbon dioxide, and the gas barrier coating includes a carbon dioxide barrier coating or layer, which limits carbon dioxide leakage from the lumen to less than 0.005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.004 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.003 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally and The above-described thermoplastic syringe barrel, syringe, or drug primary packaging is intended in any embodiment to be effective in reducing the amount to less than 0.002 cc / package / day at 0.21 bar, optionally less than 0.001 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0008 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, and optionally less than 0.0005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar.

[0148] The above-described thermoplastic syringe barrel, syringe, or drug primary packaging is intended in any embodiment to provide packaging or vials having a carbon dioxide barrier coating or layer, wherein the gas barrier coating includes a carbon dioxide barrier coating or layer, and the carbon dioxide barrier coating or layer is effective in providing packaging or vials having a carbon dioxide transmission rate (CO2TR) of less than 0.005d-1, optionally less than 0.004d-1, optionally less than 0.002d-1, optionally less than 0.001d-1, optionally less than 0.0008d-1, optionally less than 0.0006d-1, optionally less than 0.0005d-1, optionally less than 0.0004d-1, optionally less than 0.0003d-1, optionally less than 0.0002d-1, and optionally less than 0.0001d-1.

[0149] In any embodiment, the above-described thermoplastic syringe barrel, syringe, or primary drug packaging is intended to include a gas barrier coating, a carbon dioxide barrier coating or layer, the carbon dioxide barrier coating or layer basically consists of multiple atomic monolayers, and optionally the carbon dioxide barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

[0150] In any embodiment, a thermoplastic syringe barrel, syringe, or primary drug packaging is intended to have a carbon dioxide barrier coating or layer containing or essentially consisting of a metal oxide, optionally Al2O3. The carbon dioxide barrier coating or layer is SiO2O3. x In any embodiment, the above-described thermoplastic syringe barrel, syringe, or primary drug packaging is intended to include or essentially consist of, where x is 1.5 to 2.9, and optionally x is 2.

[0151] In any embodiment, a thermoplastic syringe barrel, syringe, or primary drug packaging is intended to include an ethylene oxide barrier coating or layer as the gas barrier coating. In any embodiment, a thermoplastic syringe barrel, syringe, or primary drug packaging is intended to be optionally sterilized in the final step using ethylene oxide as the primary drug packaging.

[0152] In any embodiment, the above-mentioned thermoplastic syringe barrel, syringe, or primary drug packaging is intended to be made of a thermoplastic material selected mainly from PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN®, cyclic block copolymer (CBC) resin, thermoplastic olefin polymer, COP, COC, or any combination thereof.

[0153] In any embodiment, the above-described thermoplastic syringe barrel, syringe, or primary drug packaging is intended to further include a rigid needle shield.

[0154] In any embodiment, a thermoplastic syringe barrel, syringe, or primary drug packaging, or a plurality of thermoplastic syringe barrels, syringes, or primary drug packaging, is intended to be configured to maintain container closure integrity (CCI) when the packaging or syringe is circulated at -20°C to 10°C, optionally at -20°C to 20°C, optionally at -20°C to 30°C, optionally at -20°C to 40°C, optionally at -40°C to 10°C, optionally at -40°C to 20°C, optionally at -40°C to 30°C, optionally at -40°C to 40°C, optionally at -70°C to 10°C, optionally at -70°C to 20°C, optionally at -70°C to 30°C, or optionally at -70°C to 40°C. In some embodiments, the packaging or syringe may undergo at least three cycles, and optionally, the packaging or syringe may undergo three cycles. During each cycle, the packaging or syringe may be held at both low temperatures for 24 hours or more and at high temperatures for 24 hours or more, and optionally, during each cycle, the packaging or syringe may be held at both low temperatures for about 24 hours and at high temperatures for about 24 hours.

[0155] In any embodiment, a thermoplastic syringe barrel, syringe, or primary drug packaging or a plurality of thermoplastic syringe barrels, syringes, or primary drug packaging is intended, wherein the filling capacity of the syringe is at least 20% of the nominal capacity of the syringe, optionally at least 10% of the nominal capacity of the syringe, and optionally at least 5% of the nominal capacity of the syringe. In some embodiments, the syringe may have a nominal filling capacity of 0.25 to 10 mL, optionally 0.5 to 5 mL, optionally 0.5 to 1 mL, optionally 0.5 mL, optionally 1 mL, or optionally 2.25 mL.

[0156] Multiple drug primary packaging, syringes, or syringe barrels include at least 50 untested packaging, syringes, or syringe barrels, optionally consisting of samples of 50 untested packaging, syringes, or syringe barrels, optionally consisting of at least 100 untested packaging, syringes, or syringe barrels, optionally consisting of samples of 100 untested packaging, syringes, or syringe barrels, optionally consisting of multiple drug primary packaging, syringes, or syringe barrels In any embodiment, a plurality of thermoplastic syringe barrels, syringes, or primary drug packaging are intended to include at least 500 untested packages, syringes, or syringe barrels, and optionally, a plurality of primary drug packaging, syringes, or syringe barrels may include samples of 500 untested packages, syringes, or syringe barrels, and optionally, a plurality of primary drug packaging, syringes, or syringe barrels may include at least 1000 untested packages, syringes, or syringe barrels, and optionally, a plurality of primary drug packaging, syringes, or syringe barrels may include samples of 1000 untested packages, syringes, or syringe barrels.

[0157] The plunger includes a gasket attached to the distal end of the plunger, and optionally the gasket includes an elastic material, as intended in any embodiment of the syringe or primary drug packaging described above. In some embodiments, the gasket may include a film, optionally a fluoropolymer film, present on at least the circumferential outer surface portion. In some embodiments, the gasket may have one or more channels on at least the circumferential outer surface portion. In some embodiments, at least one of the one or more channels, optionally each, is discontinuous and includes a non-channel interruption portion. In some embodiments, the gasket may include a plurality of channels on the circumferential outer surface portion, each of the plurality of channels being substantially parallel to one another and spaced apart in the axial direction. In some embodiments, the non-channel interruption portion of each of the plurality of channels is not aligned with the non-channel interruption portion of one or more adjacent channels.

[0158] The plunger and attached gasket have a sliding yield stress of 4 to 20 Newtons (N), as intended in any embodiment of the syringe or primary drug packaging described above. The plunger and attached gasket have a sliding equilibrium stress of 4 to 20 Newtons (N), as intended in any embodiment of the syringe or primary drug packaging described above.

[0159] In any embodiment, the syringe or primary drug packaging described above is intended to be such that, when assembled, the syringe barrel and gasket are sized to provide a gap between the minimum syringe barrel inner diameter and the maximum gasket outer diameter such that the deviation from the nominal gap is ±100 microns or less, ±50 microns or less, ±35 microns or less, ±25 microns or less, ±20 microns or less, ±15 microns or less, ±10 microns or less, ±5 microns or less, or ±2 microns or less.

[0160] In any embodiment, the above-described syringe or primary drug packaging is intended to be configured such that the plunger does not move axially when the packaging or syringe is circulated at -20°C to 10°C, optionally at -20°C to 20°C, optionally at -20°C to 30°C, optionally at -20°C to 40°C, optionally at -40°C to 10°C, optionally at -40°C to 20°C, optionally at -40°C to 30°C, optionally at -40°C to 40°C, optionally at -70°C to 10°C, optionally at -70°C to 20°C, optionally at -70°C to 30°C, or optionally at -70°C to 40°C.

[0161] In any embodiment, the above-described syringe or primary drug packaging is intended to include a plunger rod and a backstop element that prevent axial backward movement of the plunger.

[0162] The plunger rod and the backstop element together prevent axial rearward movement of the plunger when the packaged or filled syringe is subjected to a temperature of -20°C or lower, optionally -30°C or lower, optionally -40°C or lower, optionally -50°C or lower, optionally -60°C or lower, optionally -70°C or lower, as contemplated in any embodiment of the syringe or primary drug package described above. In some embodiments, the plunger rod and the backstop element can prevent axial rearward movement of the plunger when the packaged or filled syringe is cycled between -20°C and 10°C, optionally between -20°C and 20°C, optionally between -20°C and 30°C, optionally between -20°C and 40°C, optionally between -40°C and 10°C, optionally between -40°C and 20°C, optionally between -40°C and 30°C, optionally between -40°C and 40°C, optionally between -70°C and 10°C, optionally between -70°C and 20°C, optionally between -70°C and 30°C, optionally between -70°C and 40°C.

[0163] The backstop element is attached to the syringe barrel and extends over the upper portion of the rear opening, as contemplated in any embodiment of the syringe or primary drug package described above. The backstop element includes an extended finger flange, as contemplated in any embodiment of the syringe or primary drug package described above.

[0164] The backstop engagement feature is a radially protruding portion, optionally a radially protruding continuous ring or a radially protruding discontinuous ring, as contemplated in any embodiment of the syringe or primary drug package described above. In some embodiments, the backstop engagement feature can be wedge-shaped.

[0165] The backstop element includes an aperture, which is aligned with the rear opening of the syringe barrel, as intended in any embodiment for the syringe or primary drug packaging described above. In some embodiments, the aperture may be defined by an inner wall, optionally having at least a portion of the inner wall move toward the rear opening of the syringe barrel and inclined inward.

[0166] When the plunger rod is inserted into the syringe barrel to its stopping position, the backward force on the plunger rod causes the backstop engagement feature to abut against the contact surface of the backstop element, thereby preventing further backward movement of the plunger rod, and optionally the contact surface of the backstop element includes the lower edge of the inner wall of the aperture, as intended in any embodiment of the syringe or primary drug packaging described above.

[0167] In any embodiment, the syringe or drug primary packaging described above is intended such that, when the plunger is in its resting position within the syringe barrel, the two are optionally located within approximately 1.5 mm, optionally within approximately 1.0 mm, optionally within approximately 0.75 mm, optionally within approximately 0.5 mm, and optionally within approximately 0.25 mm, adjacent to the contact surface of the backstop.

[0168] In any embodiment, the syringe or primary drug packaging described above is intended to be such that the position of the backstop engagement feature on the plunger rod is coordinated with the plunger insertion depth in the syringe barrel corresponding to the filling volume of the filled and fully assembled primary drug packaging.

[0169] In any embodiment, the syringe or primary drug packaging described above is intended to include a backstop element comprising a locking collet, a threaded housing, and a twist-lock thumb nut, and the plunger rod not having a backstop engagement feature.

[0170] In some embodiments, the backstop element includes an aperture aligned with the rear opening of the syringe barrel, and at least a portion of the aperture is defined by a flexible lock collet. The flexible lock collet may be configured such that its inner surface compresses a portion of the plunger rod that does not extend into the aperture. The lower part of a twist-lock thumb nut may interface with the upper part of the lock collet to compress the lock collet. A threaded housing, such as a housing with a threaded inner wall, may at least partially enclose the lock collet and may be configured to engage with the threaded portion of the twist-lock thumb nut. The threaded housing may engage with a portion of the backstop element to secure the threaded housing in place, for example, by a snap-fit ​​connection.

[0171] In some embodiments, the upper part of the lock collet may be varied such that the upper part of the lock collet has a diameter that increases as it moves downward. In some embodiments, the lock collet may be divided into multiple sections by a circumferential gap. In some embodiments, the lower wall portion of the twist lock thumb nut may be varied such that the aperture defined by the lower wall portion of the thumb nut has a diameter that increases as it moves downward.

[0172] In any embodiment, the syringe or primary drug packaging described above is intended to include a backstop element comprising a lock block cavity and a lock block slidable within the lock block cavity.

[0173] In some embodiments, the backstop element may include a central aperture aligned with the rear opening of the syringe barrel, and the lock block cavity may traverse the central aperture. The lock block may include an aperture having a large cross-sectional portion and a small cross-sectional portion, the effective diameter of which is greater than the diameter of the backstop engagement feature on the plunger rod, and the effective diameter of which is smaller than the diameter of the backstop engagement feature on the plunger rod. Sliding the lock block to the locked position may align the small cross-sectional portion of the aperture with the rear opening of the syringe barrel, and sliding the lock block to the unlocked position may align the large cross-sectional portion of the aperture with the rear opening of the syringe barrel. When the lock block is in the locked position, a rearward force on the plunger rod may cause the backstop engagement feature of the plunger rod to abut against the lower contact surface of the lock block, thereby preventing further rearward movement of the plunger rod.

[0174] In some embodiments, the inner wall defining at least partially the small cross-sectional portion may have a radius of curvature substantially corresponding to the radius of curvature of the plunger rod.

[0175] In some embodiments, the large and small sections are separated by one or more ribs, optionally pairs of opposing ribs located on the sidewalls. Each of the one or more ribs may include an inclined or curved surface facing the large section of the aperture, and the inclined or curved surface may be configured to facilitate the movement of the rib surface across the plunger rod when the lock block is moved from the unlocked position to the locked position. Each of the one or more ribs may include an inclined or curved surface facing the small section of the aperture, and the inclined or curved surface may be configured to facilitate the movement of the rib surface across the plunger rod when the lock block is moved from the locked position to the unlocked position.

[0176] In some embodiments, the lock block may include a first end and a second end, and the lock block is configured such that (i) a user can slide the lock block to the unlocked position by pressing the first end, and (ii) a user can slide the lock block to the locked position by pressing the second end. The first end may include a mark indicating that pressing the first end brings the lock block to the unlocked position, and / or the second end may include a mark indicating that pressing the second end brings the lock block to the locked position.

[0177] In some embodiments, the plunger rod may have one or more backstop engagement features, optionally two or more backstop engagement features. In some embodiments, one of the one or more backstop engagement features is located adjacent to the lower contact surface of the lock block when the plunger is in its stop position within the syringe barrel, optionally two of which are located within about 1.5 mm, optionally about 1.0 mm, optionally about 0.75 mm, optionally about 0.5 mm, and optionally about 0.25 mm.

[0178] In some embodiments, when the lock block is in the locked position, a forward force on the plunger rod may cause one or more second backstop engagement features to abut against the upper contact surface of the lock block, thereby preventing further forward movement of the plunger rod. In some embodiments, when the plunger is in its resting position within the syringe barrel, one or more second backstop engagement features are located adjacent to the upper contact surface of the lock block, optionally within about 1.5 mm, optionally within about 1.0 mm, optionally within about 0.75 mm, optionally within about 0.5 mm, and optionally within about 0.25 mm.

[0179] In some embodiments, the plunger rod may instead not include any backstop engagement features, and the small cross-sectional portion of the aperture may instead be configured to create an interference fit with the plunger rod.

[0180] In some embodiments, the backstop element may further include (i) one or more retaining elements that require the application of a threshold force to slide the lock block from the locked position, (ii) one or more retaining elements that require the application of a threshold force to slide the lock block from the unlocked position, or (iii) both of (i) and (ii). For example, at least one of the inner surface defining the lock block cavity and the outer surface of the lock block may include one or more retaining ribs, and the other of the inner surface defining the lock block cavity and the outer surface of the lock block may include one or more recesses, at least one of which is configured to receive at least one of the retaining ribs when the lock block is in the locked position. Similarly, at least one of the inner surface defining the lock block cavity and the outer surface of the lock block may include one or more retaining ribs, and the other of the inner surface defining the lock block cavity and the outer surface of the lock block may include one or more recesses, at least one of which is configured to receive at least one of the retaining ribs when the lock block is in the unlocked position.

[0181] In any embodiment, the syringe or drug primary packaging described above is intended to be configured such that the backstop element prevents the plunger from moving both axially backward and axially forward.

[0182] In any embodiment, the syringe or drug primary packaging described above is intended to be configured such that the backstop element allows the user to set the packaging or syringe into a locked configuration in which the plunger rod is prevented from moving within the syringe barrel, and an unlocked configuration in which the plunger rod moves within the syringe barrel. In some embodiments, for example, the backstop element may be configured so that the user can move between the locked and unlocked configurations by rotating a rotatable component of the backstop element, optionally a twist-lock thumb nut. In other embodiments, for example, the backstop element may be configured so that the user can move between the locked and unlocked configurations by pressing a movable component of the backstop element, optionally a lock block, in a direction traversing the longitudinal axis of the syringe barrel.

[0183] In any embodiment, the syringe or drug primary packaging described above is intended to be configured such that, when the backstop element is in an unlock configuration, the plunger rod moves within the syringe barrel without or substantially without resistance from the backstop element. In some embodiments, for example, when the unlock configuration is in an unlock configuration, the sliding force of the plunger may be the same as or substantially the same as the sliding force of the plunger in the same packaging or syringe but without a backstop element, and optionally the sliding force of the plunger may be within 10%, optionally within 5%, optionally within 3%, or optionally within 1% of the sliding force of the plunger in the same packaging or syringe but without a backstop element. In some embodiments, for example, in an unlocked configuration, the plunger sliding yield stress may be the same as or substantially the same as the plunger sliding yield stress of the same packaging or syringe but without a backstop element, and optionally the plunger sliding yield stress may be within 10%, optionally within 5%, optionally within 3%, or optionally within 1% of the plunger sliding yield stress of the same packaging or syringe but without a backstop element.

[0184] One aspect of the present invention is a lumen at least partially defined by a thermoplastic sidewall, wherein the thermoplastic sidewall has an inner surface and an outer surface facing the lumen, A vacuum blood collection tube comprising a gas barrier coating supported by at least one of the inner and outer surfaces of its side wall, wherein at least a portion of the gas barrier coating is basically composed of multiple atomic monolayers of a pure element or compound, an upper part defining an opening, and a stopper seated within the opening and sealing the lumen.

[0185] The vacuum blood collection tube described above is intended in any embodiment, wherein the gas barrier coating includes an oxygen barrier coating or layer, which is effective in reducing the intrusion of oxygen into the lumen to less than 0.0005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0004 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0003 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0002 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, and optionally less than 0.0001 cc / package / day.

[0186] The gas barrier coating includes an oxygen barrier coating or layer, and the oxygen barrier coating or layer is 0.0010d -1 Less than, alternatively 0.0008d -1 Less than, alternatively 0.0006d -1 Less than, alternatively 0.0004d -1 Less than, alternatively 0.0003d -1 Less than, alternatively 0.0002d -1 Less than, alternatively 0.0001d -1 The above-described vacuum blood collection tube is intended in any embodiment to be effective in providing a vacuum blood collection tube having an oxygen permeability constant of less than .

[0187] In any embodiment, the vacuum blood collection tube described above is intended to include a gas barrier coating, an oxygen barrier coating or layer, which basically consists of multiple atomic monolayers, and optionally the oxygen barrier coating or layer is deposited by atomic layer deposition, or optionally by plasma-assisted atomic layer deposition.

[0188] The oxygen barrier coating or layer comprises or is essentially composed of a metal oxide, optionally Al2O3, as intended in any embodiment of the vacuum blood collection tube described above. x The vacuum blood collection tube described above is intended in any embodiment, which includes or basically consists of, where x is between 1.5 and 2.9. Optionally, x is 2.

[0189] The vacuum blood collection tube described above is intended in any embodiment, wherein the gas barrier coating includes a water vapor barrier coating or layer, which is effective in reducing the intrusion of water vapor into the lumen to less than 0.05 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / package / day at 60°C and 40% relative humidity, and optionally less than 0.01 mg / package / day at 60°C and 40% relative humidity.

[0190] In any embodiment, the vacuum blood collection tube described above is intended to include a gas barrier coating, a water vapor barrier coating or layer, which basically consists of multiple atomic monolayers, and optionally the water vapor barrier coating or layer is deposited by atomic layer deposition, or optionally by plasma-assisted atomic layer deposition.

[0191] The water vapor barrier coating or layer contains or is essentially composed of a metal oxide, optionally Al2O3, as intended in any embodiment of the vacuum blood collection tube described above. The water vapor barrier coating or layer is SiO2O3. xThe vacuum blood collection tube described above is intended in any embodiment to include or basically consist of, where x is 1.5 to 2.9, and optionally x is 2.

[0192] The headspace of the lumen further contains nitrogen gas, and the gas barrier coating includes a nitrogen barrier coating or layer, which limits nitrogen gas leakage from the lumen to less than 0.0002 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally 0.00 The vacuum blood collection tube described above is intended in any embodiment to be effective in reducing the amount to less than 0.01 cc / package / day, optionally less than 0.00005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.00002 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, and optionally less than 0.00001 cc / package / day at 25°C, 60% relative humidity and 0.21 bar.

[0193] The gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer has a nitrogen permeability constant (NTR) of 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 Less than 0.00008d (optionally). -1 Less than 0.00006d (optionally). -1 Less than 0.00004d (optionally) -1 Less than 0.00003d (optionally). -1 Less than 0.00002d (optionally) -1 Less than 0.00001d (optionally). -1 The above-described vacuum blood collection tube is intended in any embodiment to be effective in providing a vacuum blood collection tube having less than .

[0194] In any embodiment, the vacuum blood collection tube described above is intended to include a gas barrier coating, a nitrogen barrier coating or layer, which basically consists of multiple atomic monolayers, and optionally the nitrogen barrier coating or layer is deposited by atomic layer deposition, or optionally by plasma-assisted atomic layer deposition.

[0195] In any embodiment, the above-described vacuum blood collection tube is intended to have a nitrogen barrier coating or layer containing or essentially consisting of a metal oxide, optionally Al2O3. The nitrogen barrier coating or layer is SiO2O3. x The vacuum blood collection tube described above is intended in any embodiment to include or basically consist of, where x is 1.5 to 2.9, and optionally x is 2.

[0196] The lumen further contains carbon dioxide, and the gas barrier coating includes a carbon dioxide barrier coating or layer, which prevents carbon dioxide from entering from the lumen at less than 0.005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.004 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.003 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally at 25°C The vacuum blood collection tube described above is intended in any embodiment to be effective in reducing the amount to less than 0.002 cc / package / day at a relative humidity of 60% and 0.21 bar, optionally less than 0.001 cc / package / day at 25°C, a relative humidity of 60% and 0.21 bar, optionally less than 0.0008 cc / package / day at 25°C, a relative humidity of 60% and 0.21 bar, and optionally less than 0.0005 cc / package / day at 25°C, a relative humidity of 60% and 0.21 bar.

[0197] The gas barrier coating includes a carbon dioxide barrier coating or layer, and the carbon dioxide barrier coating or layer is effective in providing a vacuum blood collection tube having a carbon dioxide transmission rate (CO2TR) of less than 0.005d-1, optionally less than 0.004d-1, optionally less than 0.002d-1, optionally less than 0.001d-1, optionally less than 0.0008d-1, optionally less than 0.0006d-1, optionally less than 0.0005d-1, optionally less than 0.0004d-1, optionally less than 0.0003d-1, optionally less than 0.0002d-1, and optionally less than 0.0001d-1. The above-described vacuum blood collection tube is intended in any embodiment.

[0198] In any embodiment, the vacuum blood collection tube described above is intended to include a gas barrier coating, a carbon dioxide barrier coating or layer, which basically consists of multiple atomic monolayers, and optionally the carbon dioxide barrier coating or layer is deposited by atomic layer deposition, or optionally by plasma-assisted atomic layer deposition.

[0199] In any embodiment, the vacuum blood collection tube described above is intended to have a carbon dioxide barrier coating or layer containing or essentially consisting of a metal oxide, optionally Al2O3. The carbon dioxide barrier coating or layer is SiO2O3. x The vacuum blood collection tube described above is intended in any embodiment to include or basically consist of, where x is 1.5 to 2.9, and optionally x is 2.

[0200] In any embodiment, the vacuum blood collection tube described above is intended to maintain a sufficient intraluminal vacuum level to draw blood from the patient's vein into the lumen against sea level ambient pressure for at least 28 months, optionally at least 30 months, optionally at least 32 months, optionally at least 34 months, or optionally at least 36 months.

[0201] The gas barrier coating is effective in extending the storage life of the vacuum blood collection tube to at least 28 months, optionally at least 30 months, optionally at least 32 months, optionally at least 34 months, and optionally at least 36 months, and the storage life, defined by the amount of time since the tube was vacuumed, is intended in any embodiment to maintain an intake capacity of at least 90% of the intake capacity of a newly vacuumed container of the same type.

[0202] In any embodiment, the vacuum blood collection tube described above is intended to further contain a blood preservative in its lumen, and the gas barrier coating is effective in reducing solvent loss of the blood preservative over the storage life of the blood collection tube.

[0203] In any embodiment, the vacuum blood collection tube described above is intended to include, optionally, a pH protective coating between the lumen and the gas barrier coating, with the gas barrier coating supported by the inner surface of the wall.

[0204] In any embodiment, the above-described container, vial, syringe, or primary drug packaging is intended to contain a fluid within the lumen, comprising a member selected from the group consisting of:

[0205] Biologics: Abatacept; Absiximab; Avobotulinum toxin A; Adalimumab; Adalimumab-adaz; Adalimumab-adbm; Adalimumab-afzb; Adalimumab-atto; Adalimumab-bwwd; Ado-trastuzumab emtansine; Aflibercept; Agalsidase beta; Albiglutide; Chromated CR-51 serum albumin; Aldesleukin; Alphacept; Alemtuzumab; Alglucosidase alfa; Alirocumab; Alteplase; Anakinra; Aprotinin; Asfotase alfa; Asparaginase; Asparagus Ginaze erwinia chrysanthemum; atezolizumab; avelumab; basiliximab; becaprelmin; beratacept; belimumab; benralizumab; belacant; bevacizumab; bevacizumab-awwb; bevacizumab-bvzr; bezlotoxumab; blinatumomab; brentuximab vedotin; brodalumab; brolucizumab-dbll; brosumab-twza; caraspargaze pegol-mknl; calfactant; canakinumab; capracizumab-yhdp; capromab pendetide; semiprimab-rwlc; senegermin-bkbj; se Luliponase alfa; certolizumab pegol; cetuximab; choriogonadotropin alfa; chorionic gonadotropin; chymopapain; collagenase; collagenase Clostridium histolyticum; corticolellin overvine triflutate; chryzanlizumab-tmca; dacrizumab; daratumumab; daratumumab and hyaluronidase-fihj; darbepoetin alfa; denileukin difutitox; denosumab; decilidine; dinutuximab; dorunase alfa; dorotrecogin alfa; dulaglutide; dupilumab; durvalumab Ecalantid; Eculizumab; Ephalizumab; Elapegademase-lvlr; Elosulfase alfa; Elotuzumab; Emapalmab-lzsg; Emicizumab-kxwh; Enfortumab vedotin-ejfv; Epoetin alfa; Epoetin alfa-epbx; Erenumab-aooe; Etanercept; Etanercept-szzs; Etanercept-ykro; Evolocumab; Fam-trastuzumab deruxtecan-nxki; Fibrinolysin and deoxyribonuclease mixture with chloramphenicol [bovine]; Filgrastim;Filgrastim-aafi; Filgrastim-sndz; Follitropin alfa; Follitropin beta; Fremanezumab-vfrm; Galcanezumab-gnlm; Galsulfase; Gemtuzumab ozogamicin; Glucarpidase; Golimumab; Guselkumab; Hyaluronidase; Human hyaluronidase; Ibalizumab-uiyk; Ibritumomab tiuxetan; Idarucizumab; Idursulfase; Imiglucerase; Incobotulinum toxin A; Innebilizumab-cdon; Infliximab; Infliximab-abda; Inf Liximab-AXXQ; Infliximab-DYYB; Infliximab-QBTX; Inotuzumab Ozogamicin; Insulin Aspart; Insulin Aspart Protamine and Insulin Aspart; Insulin Degludec; Insulin Degludec and Insulin Aspart; Insulin Degludec and Liraglutide; Insulin Detemir; Insulin Glargine; Insulin Glargine and Lixisenatide; Insulin Glurisine; Human Insulin; Human Isofen Insulin; Human Isofen Insulin and Human Insulin; Insulin Lispro; Insulin lisproprotamine and insulin lispro; insulin lispro-aabc; interferon alfa-2a; interferon alfa-2b; interferon alfacon-1; interferon alfa-n3 (derived from human leukocytes); interferon beta-1a; interferon beta-1b; interferon gamma-1b; ipilimumab; isatuximab-irfc; ixekizumab; lanadermab-flyo; laronidase; lixisenatide; ruspatercept-aamt; mecasermin; mecasermin linfavert Menotropins; Mepolizumab; Methoxypolyethylene glycol-epoetin beta; Metreleptin; Mogamulizumab-kpkc; Moxetumomab-pasudotox-tdfk; Muromanab-CD3; Natalizumab; Necitumumab; Nivolumab; Nofetumomab; Oviltoxaximab; Obinutuzumab; Ocrelizumab; Ocreplasmin; Ofatumumab; Oralatumab; Omalizumab; Onabotulinum toxin A; Oprelbequin; Palifermin; Palivizumab; Pancrelipase; Panitumumab; Parathyroid hormone;Bovine pegademase; pegaspargase; pegfilgrastim; pegfilgrastim-apgf; pegfilgrastim-bmez; pegfilgrastim-cbqv; pegfilgrastim-jmdb; pegyinterferon alfa-2a; pegyinterferon alfa-2a and ribavirin; pegyinterferon alfa-2b; pegyinterferon alfa-2b and ribavirin; pegyinterferon beta-1a; pegroticase; pegvariase-pqpz; pegvisomant; pembrolizumab; pertuzumab; polatuzumab vedotin-piiq; polactant alfa; prabotulinum toxin A-xvfs; radiolabeled albumin techne Tc-99m albumin colloid kit; ramucirumab; ranibizumab; rasburicase; ravulizumab-cwvz; laxibakumab; reslizumab; leteplase; lilonacept; botulinum toxin type B; risankizumab-rzaa; rituximab; rituximab and human hyaluronidase; rituximab-abbs; rituximab-pvvr; romiplostim; romosozumab-aqqg; sacituzumab govitecan-hziy; sacrosidase; salglamostim; sarilumab; seberipase alfa; secukinumab; siltuximab; somatropin; tagraxofusp-erzs; taliglucerase alfa; tbo-filgrastim; technetium-99m tcphanoresomab; tenecteplase; teprotumumab-trbw; tesamorelin acetate; human thyrotropin alpha; tildrakizumab-asmn; tocilizumab; tocitumomab and iodine I-131 tocitumomab; trastuzumab; trastuzumab and hyaluronidase-oysk; trastuzumab-anns; trastuzumab-dkst; trastuzumab-dttb; trastuzumab-pkrb; trastuzumab-qyyp; urof Folitropin; Urokinase; Ustekinumab; Vedolizumab; Veraglycerase alfa; Bestronidase alfa-vjbk; Ziv-Aflibercept; Amjevita (adalimumab-atto); Dupixent (dupilumab); Fulphila (pegfilgrastim-jmdb); Ilaris (canakinumab); Ixifi (infliximab-qbtx); Lyumjev (insulin lispro-aabc);Nyvepria (pegfilgrastim-apgf); Ogivri (trastuzumab-dkst); Semglee (insulin glargine); Uplizna (inebilizumab-cdon); APL (human chorionic gonadotropin); Abrillada (adalimumab-afzb); Accretropin (somatropin); Actemra (tocilizumab); Acthrel (corticolin overtriflutate); Actimmune (interferon gamma-1b) );Activase(Alteplase);Adagen(Cowpeguademase);Adakveo(Cryzanlizumab-tmca);Adcetris(Brentuximab Vedotin);Adlyxin(Lixisenatide);Admelog(Insulin Lispro);Afrezza(Human Insulin);Aimovig(Erenumab-aooe);Ajovy(Fremanezumab-vfrm);Aldurazyme(Laronidase);AlferonN Injectable Drug (Interferon) Alpha-n3 (derived from human leukocytes); Amevive (alefacept); Amphadase (hyaluronidase); Anthim (obiltoxaximab); Apidra (insulin glulisine); Aranesp (darbepoetin alfa); Arcalyst (lilonacept); Arzerra (ofatumumab); Asparlas (caraspargase pegol-mknl); Avastin (bevacizumab); Avonex (interferon beta-1a); Av sola (infliximab-axxq); Basaglar (insulin glargine); Bavencio (avelumab); Benlysta (belimumab); Beovu (brolucizumab-dbll); Besponsa (inotuzumab ozogamicin); Betaseron (interferon beta-1b); Bexxar (tositumomab and iodine I-131 tositumomab); Blincyto (blinatumomab); Botox (onabotulinum toxin A); Botox Cosmetic (onabotulinum toxin A); Bravelle (urofolitropin); Brineura (cerliponase alfa); Cablivi (caplacizumab-yhdp); Campath (aremutuzumab); Cathflo Activase (alteplase);Cerezyme (imiglucerase); Chorionic Gonadotropin; Chromalbin (chromium-oxidized CR-51 serum albumin); Chymodiactin (chymopapain); Cimzia (certolizumab pegol); Cinqair (resulizumab); Cosentyx (secukinumab); Cotazym (pancrelipase); Creon (pancrelipase); Crysvita (brosumab-twza); Curosurf (polactant alfa); Cyltez (adalimumab-adbm); Cyramza (ramucirumab); Darzalex (daratumumab); Darzalex Faspro (daratumumab and hyaluronider-fihj); Draximage MAA (Kit for preparing technetium Tc-99m albumin aggregation); Dysport (Avobotulinum toxin A); Egrifta (Tesamorelin acetate); Egrifta SV (Tesamorelin acetate); Elaprase (Idursulfase); Elase-chloromycetin (Mix of fibrinolysin and deoxyribonuclease with chloramphenicol [bovine]); Elelyso (Taliglucerase alpha); Elitek (Rasburicase); Elspar (Asparaginase); Elzonris (Taglaxofusp-erzs); Emgality (Galcanezumab-gnlm); Empliciti (Elotuzumab); Enbrel (Etanercept); Enbrel Mini (etanercept); Enhertu (fam-trastuzumab deruxtecan-nxki); Entyvio (vedolizumab); Epogen / Procrit (epoetin alfa); Erbitux (cetuximab); Erelzi (etanercept-szzs); Erelzi Sensoready (etanercept-szzs); Erwinaze (asparaginase erwinia chrysanthemum); Eticovo (etanercept-ykro); Evenity (romosozumab-aqqg); Extavia (interferon beta-1b); Eylea (aflibercept); Fabrazyme (agalsidase beta); Fasenra (benralizumab); Fiasp (insulin aspart);Follistim (Follitropin beta); Follistim AQ (Follitropin beta); Follistim AQ Cartridge (Follitropin beta); Gamifant (Emapalmab-lzsg); Gazyva (Obinutuzumab); Genotropin (Somatropin); ;Gonal-f (Follitropin alpha);Gonal-f RFF (Follitropin alpha);Gonal-f RFF RediJect (Follitropin alpha);Granix (tbo-filgrastim);Hadlima (adalimumab-bwwd);Hemlibra (emisizumab-kxwh);Herceptin (trastuzumab);Herceptin Hylecta (trastuzumab and hyaluronidase-oysk);Herzuma (trastuzumab-pkrb);Humalog (insulin lispro);Humalog Mix 50 / 50 (insulin lispro, protamine and insulin lispro);Humalog Mix 75 / 25 (insulin lispro, protamine and insulin lispro);Humatrope (somatropin);Humegon (menotropins);Humira (adalimumab);Humulin 70 / 30 (human isophene insulin and human insulin);Humulin N (Human Isophen Insulin); Humulin RU-100 (Human Insulin); Humulin RU-500 (Human Insulin); Hydase (Hyaluronidase); Hylenex Recombinant (Human Hyaluronidase); Hyrimoz (Adalimumab); Ilumya (Childrakizumab-asmn); Imfinzi (Durvalumab); Increlex (Mecasermin); Infasurf (Calfactant); Infergen (Interferon Alphacon-1); Inflectra (Infliximab-dyyb); Intron A (Interferon Alpha-2b); Iplex (Mecasermin Lymphobert); Iprivask (Desilidine); Jeanatope (Iodide Albumin I-125 Kit); Jetrea (Ocliplasmin); Jeuveau (Prabotulinum Toxin A-xvfs); Kadcyla (Ado-Trastuzumab Emtansine); Kalbitor (Ecalantide); Kanjinti (Trastuzumab-ANNS); Kanuma (Seberipase Alpha); Kepivance (Parifermin); Kevzara (Sarilumab); Keytruda (Pembrolizumab); Kineret (Anakinra); Kinlytic (Urokinase);Krystexxa (pegroticase); Lantus (insulin glargine); Lartruvo (olaratumab); Lemtrada (alemtuzumab); Leukine (salglamostim); Levemir (insulin detemir); Libtayo (semiprimab-rwlc); Lucentis (ranibizumab); Lumizyme (alglucosidase alfa); Lumoxiti (moxetumomab pasudotox-tdfk); Macrotec (kit for preparing technetium Tc-99m albumin agglutination); Megatope (kit for iodide albumin I131); Menopur (menotropins); Mepsevii (be Stronidase alfa-vjbk); Microlite (Radiolabeled albumin technetium Tc-99m albumin colloid kit); Mircera (Methoxypolyethylene glycol-epoetin beta); Mvasi (Bevacizumab-awwb); Myalept (Metreleptin); Mylotarg (Gemtuzumab ozogamicin); Myobloc (Botulinum toxin type B); Myozyme (Alglucosidase alfa); Myxredlin (Human insulin); N / A (Laxibacumab); Naglazyme (Galsulfase); Natpara (Parathyroid hormone); Neulasta (Pegfilgrastim); Neulasta Onpro (pegfilgrastim); Neumega (oprelbequine); Neupogen (filgrastim); NeutroSpec (technetium-99m tc-phanoresomab); Nivestym (filgrastim-aafi); Norditropin (somatropin); Novarel (human chorionic gonadotropin); Novolin 70 / 30 (human isophene insulin and human insulin); Novolin N (human isophene insulin); Novolin R (human insulin); Novolog (insulin aspart); Novolog Mix 50 / 50 (insulin aspart protamine and insulin aspart); Novolog Mix 70 / 30 (insulin aspart protamine and insulin aspart); Nplate (romiprostim); Nucala (mepolizumab); Nulojix (veratacept);Nutropin (Somatropin); Nutropin AQ (Somatropin); Ocrevus (Ocrelizumab); Omnitrope (Somatropin); Oncaspar (Pegaspar gauze); Ontak (Deniroikin difutitox); Ontruzant (Trastuzumab-dttb); Opdivo (Nivolumab); Orencia (Abatacept); Orthoclone OKT3 (Muromanab-CD3); Ovidrel (Coriogonadotropin alfa); Oxervate (Senegermin-bkbj); Padcev (Enfortumab vedotin-ejfv); Palynziq (Pegvariase-pqpz); Pancreaze (Pancrelipase); Pegasys (Peginterferon alfa-2a); Pegasys Copegus Combination Pack (Peginterferon alpha-2a and ribavirin); Pegintron (Peginterferon alpha-2b); PegIntron / Rebetol Combo Pack (Peginterferon alfa-2b and ribavirin); Pergonal (Menotropins); Perjeta (Pertuzumab); Pertzye (Pancrelipase); Plegridy (Peginterferon beta-1a); Polivy (Polatuzumab vedotin-piiq); Portrazza (Necitumumab); Poteligeo (Mogamulizumab-kpkc); Praluent (Alirocumab); Praxbind (Idarucizumab); Pregnyl (Cholegenic gonadotropin); Procrit (Epoetin alfa); Proleukin (Aldesleukin); Prolia (Denosumab); ProstaScint (Capromab pendetide); Pulmolite (Kit for preparing technetium Tc-99m albumin agglutination); Pulmotech MAA (Kit for preparing technetium Tc-99m albumin aggregation); Pulmozyme (Dolnaze Alpha); Raptiva (Ephalizumab); Rebif (Interferon Beta-1a); Reblozyl (Ruspatercept-aamt); Regranex (Becaprelmin); Remicade (Infliximab); Renflexis (Infliximab-abda);Reopro (absiximab); Repatha (evolocumab); Repronex (menotropins); Retacrit (epoetin alfa-epbx); Retavase (reteplase); Revcovi (erapegademase-lvlr); Rituxan (rituximab); Rituxan Hycela (rituximab and human hyaluronidase); Roferon-A (interferon alfa-2a); Ruxience (rituximab-pvvr); Ryzodeg 70 / 30 (insulin degludec and insulin aspart); Saizen (somatropin); Santyl (collagenase); Sarclisa (isatuximab-irfc); Serostim (somatropin); Siliq (brodalumab); Simponi (golimumab); Simponi Aria (golimumab); Simulect (basiliximab); Skyrizi (risankizumab-rzaa); Soliqua 100 / 33 (insulin glargine and lixisenatide); Soliris (eculizumab); Somavert (pegvisomant); Stellara (ustekinumab); Strensiq (asfotase alfa); Sucraid (sacrosidase); Survanta (bellactant); Sylvant (siltuximab); Synagis (palivizumab); Takhzyro (lanadermab-flyo); Taltz (ixekizumab); Tanzeum (albiglutide); Tecentriq (atezolizumab); Tepezza (teprotumumab-trbw); Thyrogen (human thyrotropin alfa) ;TNKase (Tenecteplase);Toujeo (Insulin Glargine);Trasylol (Aprotinin);Trazimera (Trastuzumab-qyyp);Tremfya (Guselkumab);Tresiba (Insulin Degludec);Trodelvy (Sacituzumab Govitecan-hziy);Trogarzo (Ivalizumab-uiyk);Trulicity (Dulaglutide);Truxima (Rituximab-abbs);Tysabri (Natalizumab);Udenyca (Pegfilgrastim-cbqv);Ultomiris (Labrizumab-cwvz);Unituxin (Dinutuximab);Vectibix (panitumumab); Verluma (nofetumomab); Vimizim (erosulfase alfa); Viokace (pancrelipase); Vitrase (hyaluronidase); Voraxaze (glucarpidase); VPRIV (veraglucerase alfa); Xeomin (incobotulinum toxin A); Xgeva (denosumab); Xiaflex (collagenase Clostridium histolyticum); Xigris (drotolecogin alfa); Xolair (omalizumab); Xultophy 100 / 3.6 (insulin degludec and liraglutide); Yervoy (ipilimumab); Zaltrap (Ziv-aflibercept); Zarxio (filgrastim-sndz); Zenapax (daclizumab); Zenpep (pancrelipase); Zevalin (ibritumomab tiuxetan); Ziextenzo (pegfilgrastim-bmez); Zinbryta (daclizumab); Zinplava (bezlotoxumab); Zirabev (bevacizumab-bvzr); Zomacton (somatropin); Zorbtive / Serostim (somatropin);

[0206] Inhaled anesthetics: Aliflurane; chloroform; cyclopropane; desflurane (Suprane); diethyl ether; enflurane (Ethrane); ethyl chloride; ethylene; halothane; isoflurane (Forane, Isoflo); isopropenyl vinyl ether; methoxyflurane; methoxyflurane; methoxypropane; nitrous oxide; loflurane; sevoflurane (Sevorane, Ultane, Sevoflo); teflurane; trichloroethylene; vinyl ether; xenon;

[0207] Injectable drugs: Ablavar (Gadophosbecet trisodium injection); Abarelix Depot; Avobotulinum toxin A injection (Dysport); ABT-263; ABT-869; ABX-EFG; Accretropin (Somatropin injection); Acetadote (Acetylcysteine ​​injection); Acetazolamide injection (Acetazolamide injection); Acetazolamide injection (Acetadote); Actemra (Tocilizumab injection); Acthrel (Corticoleline overtriflutate for injection); Actumune; Activase; Acyclovir for injection (Zovirax injection); Adacel; Adalimumab; Adenoscan (Adenosine injection) ); Adenosine injection (Adenoscan); Adrenaclick; AdreView (Iobenguan I123 injection for intravenous use); Afluria; Ak-Fluor (Fluorescein injection); Audrazyme (Laronidase); Alglucerase injection (Ceredes); Alkeran injection (Melphalan HCl injection); Allopurinol sodium for injection (Aloprim); Aloprim (Allopurinol sodium for injection); Alprostadil; Alsuma (Sumatriptan injection); ALTU-238; Amino acid injection; Aminosyn; Apidra; Apremilast; Alprostadil dual chamber system for injection (Caverject) Impulse);AMG009;AMG076;AMG102;AMG108;AMG114;AMG162;AMG220;AMG221;AMG222;AMG223;AMG317;AMG379;AMG386 ;AMG403;AMG477;AMG479;AMG517;AMG531;AMG557;AMG623;AMG655;AMG706;AMG714;AMG745;AMG785;AMG811;AMG827; AMG837; AMG853; AMG951; Amiodarone HCl injection (Amiodarone HCl injection); Amobarbital sodium injection (Amytal sodium); Amytal sodium (Amobarbital sodium injection); Anakinra; Anti-Abeta; Anti-Beta7; Anti-Beta20; Anti-CD4; Anti-CD20; Anti-CD40; Anti-IFNalpha; Anti-IL13;Anti-OX40L; Anti-oxLDS; Anti-NGF; Anti-NRP1; Arixtra; Amphadase (Hyaluronidase Injection); Ammonul (Sodium Phenylacetate and Sodium Benzoate Injection); Anaprox; Anzemet Injection (Dracetron Mesylate Injection); Apidra (Insulin Glucisine [rDNA Derived] Injection); Apomab; Aranesp (Darbepoetin Alfa); Argatroban (Argatroban Injection); Arginine Hydrochloride Injection (R-Gene 10; Aristocort; Aristospan; Arsenic trioxide injection (Trisenox); Alticane HCl and epinephrine injection (Septocaine); Arzera (ofatumumab injection); Asclera (polidocanol injection); Atallen; Atallen-DMD; Atenolol injection (Tenormin IV injection); Atracurium besylate injection (Atracurium besylate injection); Avastin; Azactam injection (Aztreonam injection); Azithromycin (Zithromax injection); Aztreonam injection (Azactam injection); Baclofen injection (Lioresal intrathecal injection); Bacteriostatic water (Bacteriostatic water for injection); Baclofen injection (Lioresal intrathecal injection); Bal in Oil Ampules (Dimercarprol injection); BayHepB; BayTet; Benadryl; Bendamustine hydrochloride injection (Treanda); Benztropine mesylate injection (Cogentin); Betamethasone suspension injection (Celestone Soluspan); Bexal; Bicillin C-R900 / 300 (Penicillin G benzathine and Penicillin G procaine injection); Blenoxan (Bleomycin sulfate injection); Blenoxan (Bleomycin sulfate injection); Boniva injection (Ibandronate sodium injection); Botox Cosmetic (Onabotulinum Toxin A for injection); BR3-FC; Bravelle (Urofolitropin injection); Bretilium (Bretillium tosylate injection); Brevital sodium (Methhexital sodium injection); Brethine; Briobacept; BTT-1023; Bupivacaine HCl; Byetta; Ca-DTPA (Calcium trisodium pentetate injection);Cabazitaxel injection (Jevtana); Caffeine alkaloids (caffeine and sodium benzoate injection); Calcigex injection (calcitriol); Calcitriol (calcigex injection); Calcium chloride (calcium chloride injection 10%); Calcium disodium bersenate (calcium disodium edetate injection); Campus (artemtuzumab); Camptosar injection (irinotecan hydrochloride); Canakinumab injection (iraris); Capastat sulfate (capreomycin for injection); Capreomycin for injection (capastat sulfate); Cardiolite (technetium Tc99 cestamivi preparation kit for injection); Carticel; Cathflo; Cefazolin and glucose for injection (cefazolin injection); Cefepime hydrochloride; Cefotaxime; Ceftriaxone; Cerezyme; Carnitor injection; Caverject; Celestone Soluspan; Celsior; Cerebyx (fosphenytoin sodium injection); Ceredese (alglucerase injection); Ceretec (technetium Tc99m examethadium injection); certolizumab; CF-101; chloramphenicol sodium succinate (chloramphenicol sodium succinate injection); chloramphenicol sodium succinate injection (chloramphenicol sodium succinate); Cholestagel (coloseveram HCl); chorionic gonadotropin alpha injection (Ovidrel); Cimzia; cisplatin (cisplatin injection); chloral (clofarabine injection); clomiphine citrate (Clomiphine Citrate); clonidine injection (Duraclon); cogentin (benztropine mesylate injection); colistimethate injection (Coly-Mycin M); Coly-Mycin M (Colistimate injection); Compath; Conivaptan HCl injection (Vaprisol); Conjugated estrogen for injection (Premarin injection); Copaxone; Corticoline overtriflutate injection (Acthrel); Colbert (Ibutylide fumarate injection); Cubicin (Daptomycin injection); CF-101; Cyanokit (Hydroxocobalamin injection);Cytarabine liposomal injection (Deposite); cyanocobalamin; Cytoben (ganciclovir); DHE45; dasetuzumab; Dacogen (decitabine injection); dalteparin; Dantrium IV (dantrolene sodium for injection); dantrolene sodium for injection (Danttrium IV); daptomycin injection (Cubicin); darbepoetin alfa; DDAVP injection (desmopressin acetate injection); Decavax; decitabine injection (Dacogen); anhydrous alcohol (anhydrous alcohol injection); denosumab injection (Prolia); delatestril; delestrone; delteparin sodium; Depacon (sodium valproate injection); Depo-Medrol (Methylprednisolone acetate suspension injection); Depotite (Cytarabine liposomal injection); Depodul (Morphine sulfate XR liposomal injection); Desmopressin acetate injection (DDAVP injection); Depo-estradiol; Depo-Provera 104 mg / ml; Depo-Provera 150 mg / ml; Depo-testosterone; Dexrazoxane for injection, intravenous only (Totect); Glucose / electrolytes; Glucose and sodium chloride injection (5% glucose in 0.9% sodium chloride); Glucose; Diazepam injection (Diazepam injection); Digoxin injection (Lanoxine injection); Dilaudide-HP (Hydromorphone hydrochloride injection); Dimercarprole injection (Bal in Oil Ampules); Diphenhydramine Injection (Benadryl Injection); Dipyridamole Injection (Dipyridamole Injection); DMOAD; Docetaxel Injection (Taxotere); Dracetron Mesylate Injection (Anzemet Injection); Doribax (Doripenem Injection); Doripenem Injection (Doribax); Doxelcalciferol Injection (Hectorol Injection); Doxil (Doxorubicin HCl Liposome Injection); Doxorubicin HCl Liposome Injection (Doxil); Duraclon (Clonidine Injection); Duramorph (Morphine Injection); Dysport (Avobotulinum Toxin A Injection); Ecalantide Injection (Kalbitor); EC-Naprosin (Naproxen); Calcium Disodium Edetate Injection (Calcium Disodium Versenate); Edex (Alprostadil Injection); Engerix;Edrophonium injection (Enlon); Eliglustat Tartate); Eloxatin (Oxaliplatin injection); Emend injection (Fosaprepitant dimeglumine injection); Enalaprilat injection (Enalaprilat injection); Enlon (Edrophonium injection); Enoxaparin sodium injection (Labnox); Eovist (Gadoxetate disodium injection); Enbrel (Etanercept); Enoxaparin; Epicel; Epinepherine; EpiPen; EpiPen Jr.; Epratuzumab; Erbitux; Ertapenem injection (Invanz); Erythropoieten; Essential amino acid injection (Nephramine); Estradiol cypionate; Estradiol valerate; Etanercept; Exenatide injection (Byetta); Evlotra; Fabrazyme (Adalsidase beta) (beta)); Famotidine injection; FDG (fludeoxyglucose F18 injection); Ferrahem (fermoxytol injection); Feridex IV (fermoxides injection solution); Fertinex; Fermoxides injection solution (Feridex IV); Fermoxytol injection (ferahem); Flagyl injection (metronidazole injection); Fluarix; Fludara (fludarabine phosphate); Fludeoxyglucose F18 injection (FDG); Fluorescein injection (Ak-Fluor); Follistim AQ cartridge (follitropin beta injection); follitropin alpha injection (Gonal-f RFF); Follitropin beta injection (Follistim AQ cartridge); Forotin (pralatrexate solution for intravenous injection); Fondaparinux; Forteo (teriparatide (rDNA-derived) injection); Fostamatinib; Fosaprepitant dimeglumine injection (Emend injection); Foscarnet sodium injection (Foscavir); Foscarnet sodium injection; Fosphenytoin sodium injection (Cerebyx); Fospropofol disodium injection (Lusedra); Fragmin; Fuzeon (Enfuvirtide); GA101; Gadopentate meglumine injection (Multihance);Gadphosbecet trisodium injection (Ablavar); Gadoteridol injection solution (Prohans); Cadvercetamide injection (OptiMARK); Gadoxetate disodium injection (Eovist); Ganirelix (Ganirelix acetate injection); Gardasil; GC1008; GDFD; Gemtuzumab ozogamicin for injection (Mylotarg); Genotropin; Gentamicin injection; GENZ-112638; Golimumab injection (Simponi injection); Gonal-f RFF (Follitropin alpha injection); Granisetron hydrochloride (Kytril injection); Gentamicin sulfate; Glatiramer acetate; Glucagen; Glucagon; HAE1; Haldol (Haloperidol injection); Havrix; Hectorol injection (Doxelcalciferol injection); Hedgehog pathway inhibitors; Heparin; Herceptin; hG-CSF; Humalog; Human growth hormone; Humatrope; HuMax; Humegon; Humira; Humulin; Ibandronate sodium injection (Boniva injection); Ibuprofen lysin injection (NeoProfen); Ibutylide fumarate injection (Colbert); Idarubicin PFS (Idarubicin hydrochloride injection); Idarubicin hydrochloride injection (Idarubicin PFS); Ilaris (Canakinumab injection); Imipenem and cilastatin for injection (Primaxin IV); Imitrex; Incobotulinum toxin A for injection (Xeomin); Increlex (Mecasermin [rDNA derived] injection); Indomethacin IV (Indomethacin injection); Indomethacin injection (Indomethacin IV); Infanrix; Inohep; Insulin; Insulin aspart [rDNA derived] injection (NovoLog); Insulin glargine [rDNA derived] injection (Lantus); Insulin glulisine [rDNA derived] injection (Apidra); Interferon alfa-2b for injection, recombinant (Intron A); Intron A for injection (Interferon alfa-2b, recombinant); Invanz (Ertapene injection); Invega Sustenna (paliperidone palmitate sustained-release suspension injection); Invirase (saquinavir mesylate); Iobenguan I123 intravenous injection (AdreView); Iopromide injection (Ultravist); Ioversol injection (Optiray injection); Iplex (mecasermin linfaber [rDNA derived] injection); Iprivask; Irinotecan hydrochloride (Camptosar injection); Iron sucrose injection (Venofar); Istodax (romidepsin for injection); Itraconazole injection (Sporanox injection);Jevtana (cabazitaxel injection); Jonexa; Kalbitor (ecalantide injection); KCL in D5NS (potassium chloride injection in 5% glucose and sodium chloride); KCL in D5W; KCL in NS; Kenalog 10 injection (triamcinolone acetonide suspension injection); Kepivans (palifermin); Kepra injection (levetiracetam); Keratinocyte; KFG; kinase inhibitors; Kineret (anakinra); Kinlytic (urokinase injection); Kinrix; Clonopin (clonazepam); Kytril injection (granisetron hydrochloride); Lacosamide tablets and injection (Vinpat); Ringer's lactate solution; Lanoxine injection (digoxin injection); Lansoprazole for injection (pre Bacid IV); Lantus; Leucovorin calcium (Leucovorin calcium injection); Lente (L); Leptin; Levemir; Leukain salglamostim; Leuprolide acetate; Levothyroxine; Levetiracetam (Keppra injection); Labnox; Levocarnitine injection (Carnitor injection); Lexcan (Legadenosone injection); Lioresal intrathecal injection (Baclofen injection); Liraglutide [rDNA] injection (Victoza); Labnox (Enoxaparin sodium injection); Lucentis (ranibizumab injection); Lumizyme; Lupron (leuprolide acetate injection); Lusedra (fospropofol disodium injection); Maci; Magnesium sulfate (magnesium sulfate injection); Mannitol injection (mannitol IV); Marcaine (bupivacaine hydrochloride and epinephrine injection); Maxipime (cefepime hydrochloride for injection); Technetium injection MDP multidose kit (technetium Tc99m medrone injection) ); Mecasermin [rDNA-derived] injection (Increlex); Mecasermin linfaber [rDNA-derived] injection (Iplex); Melphalan HCl injection (Alkeran injection); Methotrexate; Menactra; Menopur (Menotropins injection); Menotropins for injection (Repronex); Metohexital sodium for injection (Brevital sodium); Methyldopert hydrochloride injection, solution (Methyldopert HCl); Methylene blue (Methylene blue injection);Methylprednisolone acetate suspension injection (Depo-Medrol); MetMab; Metoclopramide injection (Reglan injection); Metrodin (urofolitropin for injection); Metronidazole injection (Flagyl injection); Miacalcin; Midazolam (Midazolam injection); Minpara (Cinacalet); Minosin injection (Minocycline injection); Minosin injection (Minosin injection); Mipomersen; Mitoxanthrone concentrate for injection (Novantrone); Morphine injection (Duramorph); Morphine sulfate XR liposome injection (Depodul); Sodium molinate (sodium molinate injection); motesanib; mozovir (plelixafor injection); Multihance (meglumine gadoventate injection); polyelectrolyte and glucose injection; polyelectrolyte injection; Mylotarg (gemtuzumab ozogamicin for injection); Myozyme (alglucosidase alfa); nafcillin injection (nafcillin sodium); nafcillin sodium (nafcillin injection); naltrexone XR injection (vivitrol); naprosin (naproxen); NeoProfen (ibuprofen lysine injection); nandroldecanoate (Nandrol Decanoate); Neostigmine methylsulfate (Neostigmine methylsulfate injection); NEO-GAA; NeoTect (Technetium Tc99m depreotide injection); Nephramine (Essential amino acid injection); Neulasta (Pegfilgrastim); Neupogen (Filgrastim); Novolin; Novolog; NeoRecormon; Neutrexin (Trimethrexate gluconate injection); NPH(N); Nexterone (Amiodarone HCl injection); Norde Nutropin (somatropin injection); physiological saline (sodium chloride injection); Novantrone (mitoxantrone concentrate for injection); Novolin 70 / 30 Inolet (70% NPH, human insulin isophene suspension and 30% regular, human insulin injection); NovoLog (insulin aspart [rDNA derived] injection); Nplate (romiplostim); Nutropin (somatropin for injection (rDNA derived)); Nutropin AQ; Nutropin Depot (somatropin for injection (rDNA derived));Octreotide acetate injection (Sandostatin LAR); Ocrelizumab; Ofatumumab injection (Arzera); Sustained-release olanzapine suspension injection (Zyprexa) Relprevv); Omnitarg; Omnitrope (Somatropin [rDNA-derived] injection); Ondansetron hydrochloride injection (Zofran injection); OptiMARK (Cadvercetamide injection); Optiray injection (Ioversol injection); Orencia; Osmitrol injection in Aviva (Mannitol injection in Aviva plastic container); Osmitrol injection in Viaflex (Mannitol injection in Viaflex plastic container); Osteoprotegrin; Ovidrel (Human chorionic gonadotropin alpha injection); Oxacillin (Oxacillin for injection); Oxaliplatin injection (Eloxatin); Oxytocin injection (Pitocin); Paliperidone palmitate sustained-release suspension injection (Invega Sustenna; Pamidronate disodium injection; Panitumumab injection for intravenous injection (Vectibix); Papaverine hydrochloride injection (Papaverine injection); Papaverine injection (Papaverine hydrochloride injection); Parathyroid hormone; Palicalcitol injection flip-top vial (Zemplar injection); PARP inhibitors; Pediarix; PegIntron; Peginterferon; Pegfilgrastim; Penicillin G benzathine and Penicillin G procaine; Pentetic acid Calcium trisodium injection (Ca-DTPA); zinc trisodium pentetate injection (Zn-DTPA); pepsid injection (famotidine injection); Pergonal; pertuzumab; phentolamine mesylate (phentolamine mesylate for injection); physostigmine salicylate (physostigmine salicylate (injectable)); physostigmine salicylate (injectable) (physostigmine salicylate); piperacillin and tazobactam injection (zosyn); pitosin (oxytocin injection); Plasma-Lyte 148 (polyelectrolyte injection); Plasma-Lyte 56 and glucose (polyelectrolyte and glucose injection, Viaflex plastic drug packaging); PlasmaLyte; prelixafor injection (mozovir);Polidocanol injection (Asclera); potassium chloride; pralatrexate solution for intravenous injection (Forotin); pramulintide acetate injection (Symlin); Premarin injection (conjugated estrogen for injection); Technetium Tc99 cesamivi preparation kit for injection (cardiolite); Prevacid IV (lansoprazole for injection); Primaxin IV (imipenem and cilastatin for injection); Prochymal; Procrit; progestin; Prohans (gadoteridol injection solution); Prolia (denosumab injection); promethazine HCl injection (promethazine hydrochloride injection); propranolol hydrochloride injection (propranolol hydrochloride injection); quinidine gluconate injection (quinidine injection); quinidine injection (quinidine gluconate injection); R-Gene 10 (Arginine hydrochloride injection); Ranibizumab injection (Lucentis); Ranitidine hydrochloride injection (Zantac injection); Raptiva; Reclast (Zoledronic acid injection); Recombivarix HB; Legadenoson injection (Lexcan); Reglan injection (Metoclopramide injection); Remicade; Renagel; Renvela (Sevelamer carbonate); Repronex (Menotropins for injection); Retrovir IV (Zidovudine injection); rhApo2L / TRAIL; Ringer's solution and 5% glucose injection (Ringer's solution with glucose); Ringer's injection (Ringer's injection); Rituxan; Rituximab; Rocephin (Ceftriaxone); Rocuronium bromide injection Drugs (Zemuron); Roferon-A (Interferon alpha-2a); Romazicon (Flumazenil); Romidepsin for injection (Istodax); Saizen (Somatropin injection); Sandostatin LAR (Octreotide acetate injection); Sclerostin Ab; Sensipar (Cinacalcet); Sensorcaine (Bupivacaine HCl injection); Septocaine (Alticane HCl and Epinephrine injection); Serostim LQ (Somatropin (rDNA-derived) injection); Simponi injection (Golimumab injection); Sodium acetate (Sodium acetate injection); Sodium bicarbonate (5% sodium bicarbonate injection); Sodium lactate (AVIVA sodium lactate injection);Sodium phenylacetate and sodium benzoate injection (Ammonul); somatropin for injection (rDNA-derived) (Neutropin); sporanox injection (itraconazole injection); stelara injection (ustekinumab); Stemgen; Sufenta (sufentanyl citrate injection); sufentanyl citrate injection (Sufenta); Sumavel; sumatriptan injection (Alsu; ma); Symlin; Symlin Pen; Systemic Hedgehog Antagonist; Synvisc-One (Hylan G-F20 Single Intra-articular Injection); Tarceva; Taxotere (Docetaxel for Injection); Technetium Tc99m; Teravancin for Injection (Vivative); Temsirolimus Injection (Torisel); Tenormin IV Injection (Atenolol Injection); Teriparatide (rDNA-derived) Injection (Forteo); Testosterone Cypionate; Testosterone Enanthate; Testosterone Propionate; Tev-Tropin (Somatropin for Injection, r DNA-derived); tgAAC94; thallium chloride; theophylline; thiotepa (thiotepa injection); thymoglobulin (anti-thymocyte globulin (rabbit)); thyrotropin (thyrotropin alfa for injection); ticarcillin sodium and potassium clavulanate Galaxy (timentin injection); Tigan injection (trimethobenzamide hydrochloride injectable); timentin injection (ticarcillin sodium and potassium clavulanate Galaxy); TNKase; tobramycin injection (tobramycin injection); Tocilizumab injection (Actemra); Torisel (Temsirolimus injection); Totect (Dexrazoxane for injection, intravenous only); Trastuzumab-DM1; Travasol (amino acid (injectable)); Treanda (Bendamustine hydrochloride injection); Torelstar (Triptrelymphamoate suspension injection); Triamcinolone acetonide; Triamcinolone acetate; Triamcinolone hexaacetonide suspension injection (Aristospan injection 20 mg); Triesence (Triamcinolone acetonide suspension injection); Trimethobene hydrochloride Zuamide injection (Tigan injection); Trimethrexate gluconate injection (Neutrexin); Triptrelympamoate suspension injection (Torelstar); Twinject; Trivaris (Triamcinolone acetonide suspension injection); Trisenox (Arsenic trioxide injection); Twinrix; Typhoid Vi; Ultravist (Iopromide injection); Urofolitropin for injection (Metrodin); Urokinase injection (Kinlytic); Ustekinumab (Stelara injection); Ultralente (U);Barium (diazepam); sodium valproate injection (Depacon); Valtropin (somatropin injection); vancomycin hydrochloride (vancomycin hydrochloride injection); vancomycin hydrochloride injection (vancomycin hydrochloride); vaprizol (conivaptan HCl injection); VAQTA; vasovist (gadophosbecet trisodium injection for intravenous injection); vectibix (panitumumab injection for intravenous injection); venofar (ferric glucose injection); verteporfin injection (visudine); vivative (teravancin for injection); victoza (liraglutide [rDNA] injection); vinpat (lacosamide tablets and injection); vinblastine sulfate (vinblastine sulfate injection); Vincasar PFS (Vincristine Sulfate Injection); Victoza; Vincristine Sulfate (Vincristine Sulfate Injection); Visudyne (Verteporfin Injection); Vitamin B-12; Vivitrol (Naltrexone XR Injection); Voluben (Hydroxyethyl Starch in Sodium Chloride Injection); Xeloda; Xenical (Orlistat); Xeomin (Incobotulinum Toxin A for Injection); Xolair; Zantac Injection (Ranitidine Hydrochloride Injection); Zemplar Injection (Paricalcitol Injection) (P-top type vial); Zemuron (Rocuronium bromide injection); Zenapax (Daclizumab); Zevalin; Zidovudine injection (Retrovir IV); Zithromax injection (Azithromycin); Zn-DTPA (Zinc trisodium pentetate injection); Zofran injection (Ondansetron hydrochloride injection); Zingo; Zoledronic acid for injection (Zometa); Zoledronic acid injection (Reclast); Zometa (Zoledronic acid for injection); Zosyn (Piperacillin and tazobactam injection); Zyprexa Relprevv (Sustained-release olanzapine suspension injection);

[0208] Liquid formulation (non-injectable): Abilify; AccuNeb (albuterol sulfate inhalation solution); Actidose Aqua (activated carbon suspension); Activated carbon suspension (Actidose Aqua); Advea; Agenerase oral solution (amprenavir oral solution); Akten (lidocaine hydrochloride ophthalmic gel); Alamast (pemilorast potassium eye drops); Albumin (human) 5% solution (Buminate 5%); Albuterol sulfate inhalation solution; Alinia; Alocril; Alphagan; Alrex; Alvesco; Amprenavir oral solution; Analpram-HC; Alformoterol tartrate inhalation solution (Brovana); Aristospan injection 20 mg (triamcinolone hexaacetonide suspension injection solution) ); Asacol; Azmanex; Astepro; Astepro (azelastine hydrochloride nasal spray); Atrovent nasal spray (ipratropium bromide nasal spray); Atrovent nasal spray .06; Augmentin ES-600; Azasite (azithromycin eye drops); Azelaic acid (Finacea gel); Azelastine hydrochloride nasal spray (Astepro); Azelex (azelaic acid cream); Azopt (brinzolamide suspension eye drops); Bacteriostatic saline; Balanced salt; Bepotastine; Bactroban nasal; Bactroban; Beclovent; Benzac W; Betimol; Betoptic S; Bepreve; Bimatoprost eye drops; Bleph 10 (Sulfacetamide sodium ophthalmic solution 10%); Brinzolamide suspension ophthalmic solution (Azopt); Bromfenac ophthalmic solution (Xibrom); Bromhist; Brovana (Alformoterol tartrate inhalation solution); Budesonide inhalation suspension (Pulmicort inhalation solution); Cambia (Diclofenac potassium for oral use); Capex; Carac; Carboxine-PSE; Carnitor; Cayston (Aztreonam for inhalation solution); CellCept; Centany; Cerumenex; Ciprodex ophthalmic solution (Ciprofloxacin HCl ophthalmic solution); Ciprodex; Ciprofloxacin HCl ophthalmic solution (Ciloxan ophthalmic solution); Clemastine fumarate syrup (Clemastine fumarate syrup); CoLyte (PEG electrolyte solution);Combiven; Comtan; Condylox; Cordran; Cortisporin suspension eye drops; Cortisporin ear suspension; Cromolyn sodium inhalation solution (Intal Nebulizer solution); Cromolyn sodium eye drops (Opticrom); Electrolyte-added crystalline amino acid solution (Aminosyn electrolyte); Cutivate; Cuvposa (glycopyrrolate oral solution); Cyanocobalamin (CaloMist nasal spray); Cyclosporine oral solution (Gengraf oral solution); Cyclozil; Cysview (hexaminolevulinate hydrochloride intravesical solution); DermOtic oil (fluocinolone acetonide oil ear drops); Desmopressin acetate nasal spray; DDAVP; Derma-Smoothe / FS; Dexamethasone Intensol; Dianil Hypocalcium; Dianil PD; Diclofenac Potassium Oral Solution (Cambia); Didanosine Powder for Children Oral Solution (Videx); Differin; Dirantin 125 (Phenytoin Oral Suspension); Ditropan; Dorzolamide Hydrochloride Eye Drops (Trusopt); Dorzolamide Hydrochloride-Timolol Maleate Eye Drops (Cosopt); Dovonex Scalp (Calcipotriene Solution) ;Doxycycline calcium oral suspension (Vibramycin for oral use);Efudex;Elaprace (Idursulfase solution);Elestat (Epinastine HCl eye drops);Elocon;Epinastine HCl eye drops (Elestat);Epivir HBV;Epogen (Epoetin alfa);Erythromycin topical solution 1.5% (Staticin);Ethiodol (Ethiodized oil);Ethosuximide oral solution (Zarontin oral solution);Eurax;Extraneal (Icodextri Peritoneal dialysis solution); Felbatol; Feridex IV (Fermoxides injection solution); Flovent; Floxin ear medicine (Ofloxacin ear solution); Flo-Pred (Prednisolone acetate oral suspension); Fluoroplex; Flunisolid nasal spray (Flunisolid nasal spray 0.025%); Fluorometholone suspension eye drops (FML); Flurbiprofen sodium eye drops (Ocufen); FML; Foradil; Formoterol fumarate inhalation solution (Perforomist);Fosamax; Fladantin (nitrofurantoin oral suspension); Floxone; Gammaguard solution (10% human immunoglobulin for intravenous injection); Gantrisin (acetylsulfisoxazole suspension for children); Gatifloxacin eye drops (Zymar); Gengraf oral solution (cyclosporine oral solution); Glycopyrrolate oral solution (Cuvposa); Halog solution (halcinonide topical solution); Halog solution (halcinonide topical solution); HEP-LOCK U / P (preservative-free heparin lock flush solution); Heparin lock flush solution (Hepflush 10); Hexaminolevulinate hydrochloride intravesical solution (Cysview); Hydrocodone bitartrate and acetaminophen oral solution (Lortab) Elixir; Hydroquinone 3% topical solution (Melquin-3 topical solution); IAP antagonist; Isopto; Ipratropium bromide nasal spray (Atrovent nasal spray); Itraconazole oral solution (Sporanox oral solution); Ketrolactromethamine eye drops (Acular LS); Kaletra; Lanoxin; Lexiva; Leupron Depot 11.25 mg leuprolide acetate for depot suspension; Levobetaxolol hydrochloride suspension eye drops (Betaxone); Levocarnitine tablets, oral solution, sugar-free (Carnitor); Levofloxacin eye drops 0.5% (Quixin); Lidocaine HCl sterile solution (Xylocaine MPF sterile solution); Lok Pak (Flush solution for heparin lock); Lorazepam Intensol; Lortab Elixir (hydrocodone hydrogen tartrate and acetaminophen oral solution); Lotemax (loteprednol ethanoate suspension eye drops); loteprednol ethanoate suspension eye drops (Alrex); hypocalcium peritoneal dialysis solution (Dianyl hypocalcium); Lumigan (bimatoprost eye drops for glaucoma 0.03%); Lupron Depot 11.25 mg (leuprolide acetate for depot suspension); megestrol acetate oral suspension (megestrol acetate oral suspension); MEK inhibitors; Mepron; Mesnex; Mestinon; mesalamine suspension enema (Rowasa); Melquin-3 topical solution (hydroquinone 3% topical solution); MetMab; methyldopert HCl (methyldopert hydrochloride injection, solution);Methylin oral solution (methylphenidate HCl oral solution 5 mg / 5 mL and 10 mg / 5 mL); methylprednisolone acetate suspension injection (Depo-Medrol); methylphenidate HCl oral solution 5 mg / 5 mL and 10 mg / 5 mL (Methylin oral solution); methylprednisolone sodium succinate (Solu-Medrol); metipranolol eye drops (Optipranolol); Migranal; Myochol-E (acetylcholine chloride intraocular solution); Micro-K for liquid suspension (potassium chloride sustained-release suspension) Drugs); Minosin (Minocycline Hydrochloride Oral Suspension); Nasacort; Neomycin Sulfate, and Polymyxin B Sulfate, and Hydrocortisone; Nepafenac Suspension Eye Drops (Nevanac); Nevanac (Nepafenac Suspension Eye Drops); Nitrofurantoin Oral Suspension (Fludantin); Noxafil (Posaconazole Oral Suspension); Nistatin (Oral) (Nistatin Oral Suspension); Nistatin Oral Suspension (Nistatin (Oral)); Ocufen (Flurbiprofen Sodium Eye Drops); Ofloxacin Eye Drops (Ofloxacin Syn eye drops; Ofloxacin otological solution (Floxin ear medicine); Olopatadine hydrochloride eye drops (Pataday); Opticrom (Cromolin sodium eye drops); Optipranolol (Metipranolol eye drops); Patanol; Pediapred; PerioGard; Phenytoin oral suspension (Dirantin 125); Phisohex; Posaconazole oral suspension (Noxafil); Potassium chloride sustained-release preparation for liquid suspension (Micro-K liquid for suspension); Pataday (Olopatadine hydrochloride eye drops); Patanase nasal spray (olopatadine hydrochloride nasal spray); PEG electrolyte solution (CoLyte); pemirolast potassium eye drops (Alamast); Penlac (cyclopirox topical solution); PENNSAID (diclofenac sodium topical solution); Perforomist (formoterol fumarate inhalation solution); peritoneal dialysis solution; phenylephrine hydrochloride eye drops (neo-synephrine); phospholine iodide (ecothiopart iodide for eye drops); podophyllox (podophyllox topical solution); Pred Forte (prednisolone acetate suspension eye drops); pralatrexate solution for intravenous injection (Forotin);Pred Mild; Prednisone Intensol; Prednisolone acetate suspension eye drops (Pred Forte); Prevacid; PrismaSol solution (Sterile hemofiltration hemodiafiltration solution); Proair; Proglycem; ProHance (Gadoteridol injection solution); Proparacaine hydrochloride eye drops (Alcaine); Propine; Pulmicort; Pulmozyme; Quixin (Levofloxacin eye drops 0.5%); QVAR; Rapammune; Rebetol; Relacon-HC; Rotarix (Oral live rotavirus vaccine suspension); Oral live rotavirus vaccine suspension (Rotarix); Rowasa (Mesalamine suspension enema); Sabril (Vigabatrin oral solution); Sacrosidase oral solution (Sucraid); Sandimmun; Sepra; Serevent Diskus; Solu-Cortef (hydrocortisone sodium succinate); Solu-Medrol (methylprednisolone sodium succinate); Spiriva; Sporanox oral solution (itraconazole oral solution); Staticin (erythromycin topical solution 1.5%); Starlix; Sterile hemofiltration; Hemodiafiltration solution (PrismaSol solution); Stimate; Sucralfate (Calafate suspension); Sulfacetamide sodium eye drops 10% (Bleph 10); Synarel nasal spray (nafarelin acetate nasal spray for endometriosis); Taclonex Scalp (calcipotriene and betamethasone dipropionate topical suspension); Tamiflu; TobraDex; Tobradex ST (Tobramycin / Dexamethasone Suspension Eye Drops 0.3% / 0.05%); Tobramycin / Dexamethasone Suspension Eye Drops 0.3% / 0.05% (Tobradex ST); Timolol; Timoptic; Travatans; Treprostinil Inhalation Solution (Tyvaso); Trusopt (Dorzolamide Hydrochloride Eye Drops); Tyvaso (Treprostinil Inhalation Solution); Ventolin; Vfend;Vibramycin for oral use (doxycycline calcium oral suspension); Videx (didanosine powder for oral use for children); Vigabatrin oral solution (Sabril); Viokase; Viracept; Viramune; Vitamin K1 (fluid colloidal solution of vitamin K1); Voltaren ophthalmic medicine (diclofenac sodium eye drops); Zarontin oral solution (ethosuximide oral solution); Ziagen; Zyvox; Zym; ar (Gatifloxacin eye drops); Zymaxid (Gatifloxacin eye drops);

[0209] Drugs: 5α-reductase inhibitors; 5-aminosalicylates; 5HT3 receptor antagonists; adamantane antiviral drugs; corticosteroids; corticosteroid inhibitors; adrenergic bronchodilators; drugs for hypertensive emergencies; drugs for pulmonary hypertension; aldosterone receptor antagonists; alkylating agents; α-adrenergic receptor antagonists; α-glucosidase inhibitors; alternative drugs; amoebicides; aminoglycosides; aminopenicillins; aminosalicylates; amylin analogs; analgesic combinations; analgesics; androgens and anabolic compounds Steroids; angiotensin-converting enzyme inhibitors; angiotensin II inhibitors; anorectal preparations; appetite suppressants; antacids; anthelmintics; antivascular ophthalmic drugs; anti-CTLA-4 monoclonal antibodies; antiinfective drugs; centrally acting antiadrenergic agonists; peripherally acting antiadrenergic agonists; antiandrogens; antianginal drugs; antiarrhythmic drugs; antiasthmatic combination drugs; antibiotics / antineoplastic drugs; anticholinergic antiemetics; anticholinergic antiparkinsonian drugs; anticholinergic bronchodilators; anticholinergic chronotropic drugs agents); anticholinergics / antispasmodics; anticoagulants; anticonvulsants; antidepressants; antidiabetic drugs; antidiabetic combination drugs; antidiarrheals; antidiuretic hormones; detoxifiers; antiemetics / anti-vertigo drugs; antifungal drugs; antigonadotropins; gout treatment drugs; antihistamines; drugs for hyperlipidemia; combination drugs for hyperlipidemia; antihypertensive combination drugs; uric acid lowering drugs; antimalarial drugs; antimalarial combination drugs; antimalarial quinolines; antimetabolites; antimigraine drugs; antitumor detoxifiers; antitumor interferons; antitumor monoclonal antibodies; antitumor drugs; antiparkinson's drugs; antiplatelet drugs; anti-Pseudomonas penicillin drugs; antipsoriasis drugs; antipsychotics; antirheumatic drugs; antiseptics and Antibacterial agents; antithyroid drugs; antitoxin and antisnake venom drugs; antituberculosis drugs; antituberculosis drug combinations; antitussives; antiviral drugs; antiviral drug combinations; antiviral interferons; anxiolytics, sedatives and hypnotics; aromatase inhibitors; atypical antipsychotics; azol antifungal drugs; bacterial vaccines; barbiturate anticonvulsants; barbiturates; BCR-ABL tyrosine kinase inhibitors; benzodiazepine anticonvulsants; benzodiazepines; β-adrenergic blockers; β-lactamase inhibitors; bile acid metal ion chelating agents; biological agents; bisphosphonate preparations; bone resorption inhibitors; bronchodilator combinations; bronchodilators; calcitonin;Calcium channel blockers; carbamate anticonvulsants; carbapenems; carbonic anhydrase inhibitors; carbonic anhydrase inhibitors; cardiac stressing agents; cardiac-selective beta-blockers; cardiovascular agents; catecholamines; CD20 monoclonal antibodies; CD33 monoclonal antibodies; CD52 monoclonal antibodies; central nervous system drugs; cephalosporins; earwax solution; chelating agents; chemokine receptor antagonists; chloride channel activators; cholesterol absorption inhibitors; cholinergic agonists; cholinergic muscle stimulants; cholinesterase inhibitors; central nervous system stimulants; coagulation regulators; colony-stimulating factors; contraceptives; adrenocorticotropic hormone; coumarins and indanediones Classes; Cox-2 inhibitors; decongestants; topical medications; diagnostic radiopharmaceuticals; dibenzazepine anticonvulsants; digestive enzymes; dipeptidyl peptidase-4 inhibitors; diuretics; dopaminergic antiparkinsonian drugs; drugs used for alcohol dependence; echinocandin; EGFR inhibitors; estrogen receptor antagonists; estrogen; expectorants; factor Xa inhibitors; fatty acid derivative anticonvulsants; fibrinate derivatives; first-generation cephalosporins; fourth-generation cephalosporins; functional bowel disease drugs; gallstone solubilizers. Solubilizing agent; gamma-aminobutyric acid analog; gamma-aminobutyric acid reuptake inhibitor; gamma-aminobutyric acid transaminase inhibitor; gastrointestinal drugs; general anesthetics; genitourinary tract agents; gastrointestinal stimulants; glucocorticoids; glucose elevating agents; glycopeptide antibiotics; glycoprotein platelet inhibitors Inhibitors; Glycylcyclines; Gonadotropin-releasing hormone; Gonadotropin-releasing hormone antagonists; Gonadotropins; Class I antiarrhythmic drugs; Class II antiarrhythmic drugs; Class III antiarrhythmic drugs; Class IV antiarrhythmic drugs; Class V antiarrhythmic drugs; Growth hormone receptor blockers; Growth hormone; H. pylori eradication drugs; H2 antagonists; Hematopoietic stem cell mobilizers; Heparin antagonists; Heparin; HER2 inhibitors; Plant products; Histone deacetylase inhibitors; Hormone replacement therapy; Hormones; Hormones / antinomatal drugs; Hydantoin anticonvulsants; Illegal (street) drugs;Immunoglobulins; immunotherapy drugs; immunosuppressants; impotence drugs; in vivo diagnostic biological agents; incretin mimetics; inhaled anti-infectives; inhaled corticosteroids; cardiac stimulants; insulin; insulin-like growth factor; integrase chain transfer inhibitors; interferon; intravenous nutritional products; iodine contrast agents; ionized iodine contrast agents; iron products; ketolides; laxatives; antileprosy agents; leukotriene regulators; lincomycin derivatives; lipid-containing glycopeptides; local injection anesthetics; loop diuretics; pulmonary surfactants; lymphatic staining agents; lysosomal enzymes; macrolide derivatives; macrolides; magnetic resonance imaging contrast agents; mast cell stabilizers; medical gases; meglitinides; metabolites; methylxanthines; mineralocorticoids; minerals and electrolytes; other drugs; other analgesics; other antibiotics; other anticonvulsants; other antidepressants; other antidiabetic drugs; other antiemetics Drugs; other antifungal drugs; other drugs for hyperlipidemia; other antimalarial drugs; other antitumor drugs; other antiparkinsonian drugs; other antipsychotic drugs; other antituberculosis drugs; other antiviral drugs; other anxiolytics, sedatives and hypnotics; other biological agents; other bone resorption inhibitors; other cardiovascular drugs; other central nervous system drugs; other coagulation regulators; other diuretics; other urogenital drugs; other gastrointestinal drugs; other hormones; other metabolites; other ophthalmic drugs; other otorhinols; other respiratory drugs; other sex hormones; other topical drugs; other unclassified drugs; other vaginal drugs. agents; mitotic inhibitors; monoamine oxidase inhibitors; monoclonal antibodies; mouth and throat products; mTOR inhibitors; mTOR kinase inhibitors; mucolytics; multikinase inhibitors; muscle relaxants; mydriatics; narcotic analgesic combinations; narcotic analgesics; nasal anticonjunctival agents; nasal antihistamines and decongestants; nasal lubricants and irrigants; nasal preparations; nasal steroids; natural penicillin derivatives; neuraminidase inhibitors; neuromuscular blockers; next-generation cephalosporins; nicotinic acid derivatives; nitrates; NNRTIs; non-cardiac selective beta-blockers; non-iodine contrast agents; non-ionic iodine contrast agents; nonsulfonylurea; nonsteroidal anti-inflammatory drugs;Norepinephrine reuptake inhibitors; norepinephrine-dopamine reuptake inhibitors; nucleoside reverse transcriptase inhibitors (NRTIs); nutritional supplements; nutritional products; ophthalmic anesthetics; ophthalmic infection drugs; ophthalmic anti-inflammatory drugs; ophthalmic antihistamines and decongestants; ophthalmic diagnostic agents; ophthalmic glaucoma drugs; ophthalmic lubricants and irrigants; ophthalmic preparations; ophthalmic steroids; infection drugs; additional ophthalmic steroids; ophthalmic surgical drugs agents); oral nutritional supplements; ear anesthetics; ear infection medications; ear preparations; ear steroids; ear steroids for infections; oxazolidinedione anticonvulsants; parathyroid hormones and analogues; penicillinase-resistant penicillin; penicillin-based drugs; peripheral opioid receptor antagonists; peripheral vasodilators; peripheral-acting anti-obesity drugs; phenothiazine antiemetics; phenothiazine antipsychotics; phenylpiperazine antidepressants; plasma expanders; platelet aggregation inhibitors; platelet stimulants; polyenes; potassium-sparing diuretics; probiotics; progestins; prolactin inhibitors; prostaglandin D2 antagonists; protease inhibitors; proton pump inhibitors; psoralens; psychotropic drugs; psychotherapeutic combination preparations. Combinations; purine nucleosides; pyrrolidine anticonvulsants; quinolones; contrast agents; radiologic adjuncts; radiologic agents; radiologic conjugating agents; radiopharmaceuticals; RANK ligand inhibitors; recombinant human erythropoietin; renin inhibitors; respiratory drugs; inhaled respiratory drugs; rifamycin derivatives; salicylates; sclerosing agents; second-generation cephalosporins; selective estrogen receptor modulators; selective serotonin reuptake inhibitors; serotonin-norepinephrine reuptake inhibitors; serotonergic neurolubricating modulators; sex hormone combinations; sex hormones; skeletal muscle relaxant combinations; skeletal muscle relaxants; smoking cessation drugs; somatostatin and somatostatin analogs; spermicides; statins; sterile irrigating solutions Solutions; Streptomyces derivatives; Succinimide anticonvulsants; Sulfonamides; Sulfonylureas; Synthetic ovulation inducers; Tetracyclic antidepressants; Tetracyclines; Therapeutic radiopharmaceuticals; Thiazide diuretics;Thiazolidinediones; Thioxanthenes; Third-generation cephalosporins; Thrombin inhibitors; Thrombolytic agents; Thyroid agents; Labor suppressants; Topical acne medications; Topical drugs; Local anesthetics; Topical infection medications; Topical antibiotics; Topical antifungal drugs; Topical antihistamines; Topical antipsoriasis drugs; Topical antiviral drugs; Topical astringents; Topical pus-draining agents; Topical depigments; Topical emollients; Topical keratolytic agents; Topical steroids; Additional topical steroids for infections; Toxoids; Triazine anticonvulsants; Tricyclic antidepressants; Trifunctional monoclonal antibodies; Tumor necrosis factor (TNF) inhibitors; Tyrosine kinase inhibitors; Ultrasonography contrast agents; Upper respiratory combinations; Urea anticonvulsants anticonvulsants; urinary tract infection drugs; urinary tract antispasmodics; urine pH adjusters; uterine contraction drugs; vaccines; combination vaccines; vaginal antiinfectives; vaginal suppositories; vasodilators; vasopressin antagonists; vasopressors; VEGF / VEGFR inhibitors; viral vaccines; intra-articular replacement drugs; vitamin and mineral complexes; vitamins; protein-based vaccines; DNA vaccines; mRNA vaccines;

[0210] Diagnostic test: 17-Hydroxyprogesterone; ACE (Angiotensin I-converting enzyme); Acetaminophen; Acid phosphatase; ACTH; Active clotting time; Activated protein C resistance; Adrenocorticotropic hormone (ACTH); Alanine aminotransferase (ALT); Albumin; Aldolase; Aldosterone; Alkaline phosphatase; Alkaline phosphatase (ALP); α1-Antitrypsin; α-Fetoprotein; α-Fetoprotein (fetoprotien); Ammonia level; Amylase; ANA (Antinuclear antibody); ANA (Antinuclear antibody) Angiotensin-converting enzyme (ACE); anion gap; anti-cardiolipin antibody; anti-cardiolipin antibodies (ACA); anti-centromere antibody; antidiuretic hormone; anti-DNA; anti-DNase-B; anti-gliadin antibody; anti-glomerular basement membrane antibody; anti-HBc (hepatitis B core antibody); anti-HBs (hepatitis B surface antibody); antiphospholipid antibody; anti-RNA polymerase; anti-Smith (Sm) antibody; anti-smooth muscle antibody; anti-streptolysin O value (ASO); anti-thrombin III; anti-Xa activity; anti-Xa assay; apolipoprotein; arsenic; asparagine Acid aminotransferase (AST); B12; basophilic leukocytes; β2-microglobulin; β-hydroxybutyrate; B-HCG; bilirubin; direct bilirubin; indirect bilirubin; total bilirubin; bleeding time; blood gas (arterial); blood urea nitrogen (BUN); BUN; BUN (blood urea nitrogen); CA125; CA15-3; CA19-9; calcitonin; calcium; calcium (ionized); carbon monoxide (CO); carcinoembryonic antigen (CEA); CBC; CEA; CEA (carcinoembryonic antigen); ceruloplasmin; CH50 chloride (CH50Chlor ide); cholesterol; cholesterol, HDL; thrombolysis time; clot regression time; CMP; CO2; cold agglutinin; complement component 3; copper; corticotropin-releasing hormone (CRH) stimulation test; cortisol; cortrosine stimulation test; C peptide; CPK (total); CPK-MB; C-reactive protein; creatinine; creatinine kinase (CK); cryoglobulin; DAT (direct antiglobulin test); D-dimer; dextamethasone suppression test; DHEA-S; diluted Russell's chain snake venom; oval erythrocytes; eosinophils; erythrocyte sedimentation rate (ESR); estradiol;Estriol; Ethanol; Ethylene glycol; Euglobulin solubilizer; Factor V Leiden; Factor VIII inhibitor; Factor VIII level; Ferritin; Fibrin degradation products; Fibrinogen; Folate; Folate (serum); Sodium fractional excretion rate (FENA); FSH (Follicle-stimulating factor); FTA-ABS; Gamma-glutamyltransferase (GGT); Gastrin; GGTP (Gamma-glutamyltransferase); Glucose; Growth hormone; Haptoglobin; HBeAg (Hepatitis B e antigen); HBs-Ag (Hepatitis B surface antigen); Helicobacter pylori pylori); hematocrit; hematocrit (HCT); hemoglobin; hemoglobin A1C; hemoglobin electrophoresis; hepatitis A antibody; hepatitis C antibody; IAT (indirect antiglobulin test); immunofixation (IFE); iron; lactate dehydrogenase (LDH); lactate (lactate); LDH; LH (leutinizing hormone); lipase; lupus anticoagulant; lymphocytes; magnesium; MCH (mean corpuscular hemoglobin level); MCHC (mean corpuscular hemoglobin concentration); MCV (mean corpuscular volume); methyl malonate; monocytes; MPV (mean platelet volume); myoglobin; neutrophils; parathyroid hormone (PTH); phosphorus; platelets (plt); potassium; prealbumin; prolactin; Prostate-specific antigen (PSA); Protein C; Protein S; PSA (Prostate-specific antigen); PT (Prothrombin time); PTT (Partial thromboplastin time); RDW (Red blood cell distribution width); Renin; Reticulocyte count; Reticulocytes; Rheumatoid factor (RF); ESR; Serum glutamate pyruvate transaminase (SGPT); Serum protein electrophoresis (SPEP); Sodium; T3 resin uptake rate (T3RU); Free T4; Thrombin time; Thyroid-stimulating hormone (TSH); Thyroxine (T4); Total iron-binding capacity (TIBC); Total protein; Transferrin; Transferrin saturator; Triglycerides (TG); Troponin; Uric acid; Vitamin B12; White blood cells (WBC); Widar test. [Brief explanation of the drawing]

[0211] [Figure 1]This is a schematic cross-sectional view of a container according to any embodiment of the present invention. [Figure 2] Figure 1 is a magnified detail view of a portion of the container wall and covering. [Figure 3] These are schematic diagrams of pharmaceutical packaging in the form of a syringe barrel as a container, as shown in Figures 1 and 2, containing a fluid and closed with a plunger-type closure. [Figure 4] These are schematic diagrams of pharmaceutical packaging in the form of vials, which contain fluid and are closed using a closure, as shown in Figures 1 and 2. [Figure 5] These are schematic diagrams of pharmaceutical packaging in the form of blister packaging as containers, as shown in Figures 1 and 2, containing fluid and closed with a closure in the form of a covering sheet defining an additional container wall. [Figure 6] This plot shows the relationship between silicon dissolution at pH 6 and exposure time in a glass container and a plastic container with an SiOx barrier layer coating on its inner wall. [Figure 7] This plot shows the relationship between silicon dissolution at pH 7 and exposure time in a glass container and a plastic container with an SiOx barrier layer coating on its inner wall. [Figure 8] This plot shows the relationship between silicon dissolution at pH 8 and exposure time in a glass container and a plastic container with an SiOx barrier layer coating on its inner wall. [Figure 9] This plots the initial SiOx coating thickness required to leave a 30 nm residual coating thickness when stored in solutions with different nominal pH values ​​from 3 to 9. [Figure 10] This shows the silicon dissolution rates of various PECVD coatings at pH 8 and 40°C. [Figure 11] This plot shows the ratio of Si-O-Si symmetric / asymmetric stretching modes to the energy input per unit mass (W / FM or kJ / kg) of PECVD coatings using OMCTS and oxygen as reactive precursor gases. [Figure 12] This plot shows the relationship between silicon storage life (in days) and the energy input per unit mass (W / FM or kJ / kg) of PECVD coatings using OMCTS and oxygen as reactive precursor gases. [Figure 13] This is the Fourier transform infrared spectrophotometric (FTIR) absorption spectrum of a PECVD coating. [Figure 14] This is the Fourier transform infrared spectrophotometric (FTIR) absorption spectrum of a PECVD coating. [Figure 15] This is the Fourier transform infrared spectrophotometric (FTIR) absorption spectrum of a PECVD coating. [Figure 16] This is the Fourier transform infrared spectrophotometric (FTIR) absorption spectrum of a PECVD coating. [Figure 17] This is the Fourier transform infrared spectrophotometric (FTIR) absorption spectrum of a PECVD coating, originally presented as Figure 5 in U.S. Patent No. 8,067,070, annotated to show the calculation of the O parameter mentioned in that patent. [Figure 18] Figures 1, 2, and 3 show schematic diagrams of a syringe with a three-layer coating, illustrating the cylindrical region and specific points where data was taken. [Figure 19] Figures 18, 1, 2, and 3 show a trimometric map of the relationship between the total thickness of the three-layer coating and its position within the cylindrical region of the syringe. [Figure 20] This is a micrograph cross-sectional view showing the substrate and the three-layer coating at position 2 shown in Figure 18. [Figure 21] Figure 18, Figures 1, 2, and 3 show another trimetric map of the relationship between the overall thickness of the three-layer coating and its position within the cylindrical region of the syringe. [Figure 22] Figure 18 is a plot of coating thickness representing the same coating as in Figure 21 at positions 1, 2, 3, and 4 shown in Figure 18. [Figure 23] This is a schematic diagram of the syringe showing the points on the surface where measurements were taken in the example. [Figure 24] As discussed in the examples, this photograph illustrates the advantages of this three-layer coating in preventing pinholes after attack with an alkaline reagent. [Figure 24A] This is a magnified, detailed view of the area shown in Figure 24. [Figure 25]This is a diagram of one embodiment of the coating surface described herein. [Figure 26] This is a schematic diagram illustrating an example of the atomic layer deposition process for an aluminum oxide coating consisting of multiple aluminum oxide monolayers. [Figure 27] This diagram shows various coatings applied by atomic layer deposition. [Figure 28] This graph shows the results of the water vapor transmission rate test. [Figure 29] This graph shows the results of an oxygen permeability test. [Figure 30A] This is a cross-sectional side view showing one embodiment of the vial described herein. [Figure 30B] This is a cross-sectional side view showing one embodiment of the vial described herein, including a stopper and a crimp. [Figure 31] This is a comparison diagram showing the results of ink blot testing of a standard vial and the embodiment shown in Figure 30. [Figure 32] This graph shows the embodiments of the vials described herein and the variation in the outer diameter of conventional glass vials. [Figure 33A] This graph shows the sample freeze-drying cycle. [Figure 33B] This diagram shows the location of the vial selected for testing within the 240-count tray. [Figure 34] The results of container closure integrity (CCI) testing of the vial embodiments described herein are shown. [Figure 35] The results of oxygen permeability tests of the vial embodiments described herein after being subjected to extremely low-temperature conditions are shown. [Figure 36] This is a comparison between a hydrophobic protective layer and a hydrophilic protective layer. [Figure 37] This is a comparison between a hydrophobic protective layer and a hydrophilic protective layer. [Figure 38] This graph shows the test results for hydrophobic and hydrophilic protective layers using the Kitazaki-Hata method. [Figure 39]This graph shows the results of the light shielding (LO) test of the vials described herein. [Figure 40] This graph shows the results of comparative microflow imaging (MFI) tests between the vial embodiments described herein and conventional commercially available products. [Figure 41] This graph shows the embodiment of the syringe barrel described herein and the variation in the inner diameter of conventional glass syringe barrels. [Figure 42] This graph shows the embodiment of the syringe barrel described herein and the variation in the inner diameter of conventional glass syringe barrels. [Figure 43] This graph shows the variation in the needle hub outer diameter of the syringe barrel embodiments described herein and of conventional glass syringe barrels. [Figure 44] This graph shows the variation in the overall length of the syringe barrel embodiments described herein and conventional glass syringe barrels. [Figure 45] This graph shows the variation in the overall length of the syringe barrel embodiments described herein and conventional glass syringe barrels. [Figure 46] This graph shows the variation in flange outer diameter of the syringe barrel embodiments described herein and of conventional glass syringe barrels. [Figure 47] This graph shows the weight variations of the syringe barrel embodiments described herein and conventional glass syringe barrels. [Figure 48] This graph shows the results of resonant mass measurement (RMM) tests on the embodiments of syringe barrels described herein. [Figure 49] This graph shows the results of FlowCAM® microflow digital imaging of the syringe barrel embodiment described herein. [Figure 50] This graph shows the results of a light shielding (LO) test of the syringe barrel embodiments described herein. [Figure 51]This graph shows the results of ethylene oxide (EO) barrier testing of the syringe barrel embodiments described herein. [Figure 52] This is a cross-sectional side view of one embodiment of the 1 mL staked needle syringe described herein. [Figure 53] This is a cross-sectional side view of one embodiment of the 0.5 mL staked needle syringe described herein. [Figure 54] This graph shows the test results for the sliding yield stress and sliding equilibrium stress of the syringe embodiments described herein. [Figure 55] This is a cross-sectional view showing the relationship between the inner diameter (ID) of the syringe barrel and the outer diameter (OD) of one embodiment of the lubricating gasket described herein. [Figure 56] This is a schematic cross-sectional view along the cutting line 3A-3A in Figure 55. [Figure 57] This is a detailed diagram of the structural fragment shown in Figure 56. [Figure 58] This is a top view of an embodiment of a lubricating gasket described herein, showing the approximate geometric distribution of the first and second discontinuous channels. [Figure 59] This is a top view of an embodiment of a lubricating gasket described herein, showing the approximate geometric distribution of the first, second, and third discontinuous channels. [Figure 60] This specification shows a fragment detail of one embodiment of a discontinuous channel of a lubricating gasket described herein. [Figure 61] This shows an example of the refrigeration life cycle of a vial. [Figure 62] An example of a freeze-thaw cycle used to test the vial embodiments described herein is shown. [Figure 63] Figure 62 shows the results of inspection for defects in the vial embodiments described herein after undergoing the freeze-thaw cycle. [Figure 64] This shows a partial cross-sectional side view of a syringe assembly having one embodiment of the plunger anti-backout feature described herein. [Figure 65]This is a perspective view of a syringe assembly having one embodiment of the plunger anti-backout feature described herein. [Figure 66] Figure 65 is a perspective view of one embodiment of the plunger rod of the syringe assembly shown. [Figure 67] Figure 65 is a detailed cross-sectional side view showing the interaction between one embodiment of the plunger rod and one embodiment of the backstop element of the syringe assembly shown. [Figure 68] This is a perspective view of a syringe assembly having one embodiment of the plunger anti-backout feature described herein. [Figure 69] Figure 68 is a perspective view of one embodiment of the plunger rod of the syringe assembly shown. [Figure 70] Figure 68 is a perspective view of one embodiment of the backstop element of the syringe assembly shown. [Figure 71] Figure 70 is a cross-sectional side view of the backstop element. [Figure 72] Figure 70 is a top view of the backstop element. [Figure 73] Figure 68 is a perspective view of one embodiment of the threaded housing of the syringe assembly shown. [Figure 74A] Figure 68 is a perspective view of one embodiment of the twist-lock thumb nut of the syringe assembly shown. [Figure 74B] Figure 74A is a cross-sectional side view of the twist lock thumb nut. [Figure 75] Figure 68 is a detailed cross-sectional side view showing the interaction between a plunger rod, a threaded housing, and a twist-lock thumb nut, representing one embodiment of the backstop element of a syringe assembly. [Figure 76] This is a perspective view of a syringe assembly having one embodiment of the plunger anti-backout feature described herein. [Figure 77] Figure 76 is a side view of the syringe assembly shown. [Figure 78] Figure 76 is a perspective view of one embodiment of the plunger rod of the syringe assembly shown. [Figure 79] Figure 76 is a perspective view of one embodiment of the backstop element of the syringe assembly shown. [Figure 80] Figure 79 is a cross-sectional side view of the backstop element shown. [Figure 81] Figure 76 is a perspective view of one embodiment of the lock bar of the syringe assembly shown. [Figure 82] Figure 76 shows a cross-sectional side detail view illustrating the interaction between the plunger rod and the lock bar in one embodiment of the backstop element in the syringe assembly shown in the locked position. [Figure 83] Figure 76 is a cross-sectional top view showing the interaction between the plunger rod and the lock bar, representing one embodiment of the backstop element in the syringe assembly shown in the locked position. [Figure 84] Figure 76 shows a cross-sectional side detail view illustrating the interaction between the plunger rod and the lock bar, representing one embodiment of the backstop element in the syringe assembly shown in the unlocked position. [Figure 85] Figure 76 is a cross-sectional top view showing the interaction between the plunger rod and the lock bar, representing one embodiment of the backstop element in the syringe assembly shown in the unlocked position. [Figure 86] This graph shows the water vapor transmission rate (WVTR) of an embodiment of a 10 mL vial prepared according to an embodiment of the present disclosure. [Figure 87] This graph shows the oxygen permeability (OTR) of an embodiment of a 10 mL vial prepared according to the embodiments of this disclosure. [Figure 88] This graph shows the water vapor transmission rate (WVTR) of an embodiment of a 10 mL vial prepared according to an embodiment of the present disclosure. [Figure 89] This graph shows the oxygen permeability (OTR) of an embodiment of a 10 mL vial prepared according to the embodiments of this disclosure. [Figure 90] This graph shows the oxygen permeability (OTR) of various syringes prepared according to embodiments of this disclosure. [Figure 91]This graph shows the oxygen permeability (OTR) of an embodiment of a 9 mL blood collection tube prepared according to the embodiments of this disclosure. [Figure 92] This graph shows the water vapor transmission rate (WVTR) of a 9 mL blood collection tube prepared according to an embodiment of the present disclosure. [Figure 93] This is a perspective view showing one embodiment of the blood collection tube described herein. [Modes for carrying out the invention]

[0212] In relation to the present invention, the following definitions and abbreviations are used.

[0213] ALD is atomic layer deposition, and includes both thermally supported atomic layer deposition and plasma-enhanced atomic layer deposition, sometimes called PEALD.

[0214] General-purpose resins are inexpensive, easy-to-process plastics that can be mass-produced. General-purpose resins are distinguished from specialty resins and engineering resins such as COP and COC disclosed above, particularly by their low cost and high production volume. Examples of general-purpose resins include ABS, acrylic, polyethylene, HDPE, PVC, PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN® (a product of Eastman Chemical Company), and thermoplastic olefin polymers. Although not widely available or used, CBC resins can also be considered general-purpose resins for the purposes of this disclosure.

[0215] RF stands for high frequency.

[0216] In the context of this invention, the term "at least" means the integer "greater than or equal to" that follows it. The term "including" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude plurals unless otherwise specified. Whenever a parameter range is given, it is intended to disclose the parameter values ​​given as limits to the range and all parameter values ​​within that range.

[0217] For example, “first” and “second” or similar references to lubricant deposits, processing stations, or processing devices refer to the minimum number of deposits, processing stations, or devices present, and do not necessarily represent the order or total number of deposits, processing stations, and devices, nor do they require additional deposits, processing stations, and devices beyond the number described. These terms do not limit the number of processing stations or the specific processing performed at each station. For example, “first” deposit, in the context of this specification, may be, without limitation, a single deposit or one of several deposits. In other words, the “first” deposit description may, but does not require, embodiments having second or further deposits.

[0218] For the purposes of the present invention, the "organosilicon precursor" is a compound having at least one of the following bonds, wherein the tetravalent silicon atom is bonded to an oxygen atom or nitrogen atom and an organic carbon atom (an organic carbon atom is a carbon atom bonded to at least one hydrogen atom). [ka] Volatile organosilicon precursors are defined as precursors that can be supplied as vapor to a PECVD apparatus and are optional organosilicon precursors. Optionally, organosilicon precursors are selected from the group consisting of linear siloxanes, monocyclic siloxanes, polycyclic siloxanes, polysilsesquioxanes, alkyltrimethoxysilanes, linear silazanes, monocyclic silazanes, polycyclic silazanes, polysilsesquiazanes, and any two or more combinations of these precursors.

[0219] In this specification and in the claims, the supply quantities of PECVD precursors, gaseous reactants, or process and carrier gases may be expressed in “standard volumes.” The standard volume of a charge gas or any other fixed quantity of gas is the volume occupied by that fixed quantity of gas at standard temperature and pressure (without considering the actual delivery temperature and pressure). Standard volumes can be measured using various units of volume, but still remain within the scope of this disclosure and in the claims. For example, the same fixed quantity of gas can be expressed as a value in standard cubic centimeters, standard cubic meters, or standard cubic feet. Standard volumes can also be defined using various standard temperatures and pressures, but still remain within the scope of this disclosure and in the claims. For example, the standard temperature may be 0°C and the standard pressure 760 Torr (conventional), or it may be 20°C and the standard pressure 1 Torr. However, regardless of the standards used in a given case, when comparing the relative quantities of two or more different gases without specifying certain parameters, the same units of volume, standard temperature, and standard pressure are used for each gas unless otherwise specified.

[0220] In this specification, the corresponding supply rates of PECVD precursors, gaseous reactants, or process gases and carrier gases are expressed in standard volume per unit time. For example, in the examples, the flow rate is expressed as standard cubic centimeters / minute and abbreviated as sccm. As with other parameters, other units of time such as seconds or hours may be used, but when comparing the flow rates of two or more gases, a consistent parameter should be used unless otherwise specified.

[0221] In relation to the present invention, “container” can be any type of container having at least one opening and an inner surface or a wall defining the inner surface. The substrate can be the wall of a container having a lumen. The present invention is not necessarily limited to drug packaging or other containers of a specific capacity, but drug packaging or other containers having a lumen with a void capacity of 0.5 to 50 mL, optionally 1 to 10 mL, optionally 0.5 to 5 mL, or optionally 1 to 3 mL are envisioned. The substrate surface can be the inner surface or a part or all of the inner surface of a container having at least one opening and an inner surface or an inner surface. Some examples of drug packaging include, but are not limited to, vials, plastic-coated vials, syringes, plastic-coated syringes, blister packs, ampoules, plastic-coated ampoules, cartridges, bottles, plastic-coated bottles, pouches, pumps, sprayers, stoppers, needles, plungers, caps, stents, catheters, or implants.

[0222] In relation to the present invention, the term “at least” means an integer “greater than or equal to” the integer following the preceding term. Accordingly, in relation to the present invention, a container has one or more openings. One or two openings are preferred, such as the opening (one) of a sample tube or the openings (two) of a syringe barrel. If a container has two openings, they may be the same or different in size. If there are two or more openings, one opening can be used for gas inhalation in the PECVD coating method described in the present invention, while the other openings may be covered or left open. The containers described in the present invention may be, for example, a sample tube for collecting or storing biological fluids such as blood or urine, a syringe (or part thereof such as a syringe barrel) for storing / transporting biologically active compounds or compositions, such as drugs or pharmaceutical compositions, a vial for storing biomaterials or biologically active compounds or compositions, a conduit for transporting biomaterials or biologically active compounds or compositions, such as a catheter, or a cuvette for holding a fluid such as a biomaterial or biologically active compound or composition.

[0223] The container can be of any shape, but a container having a substantially cylindrical wall adjacent to at least one of its open ends is preferred. Generally, the inner wall of the container is cylindrical, for example, inside a sample tube or syringe barrel. Sample tubes and syringes or their components (e.g., syringe barrels) are intended.

[0224] In relation to the present invention, "hydrophobic layer" means that a coating or layer reduces the wetting tension of the surface covered by the coating or layer compared to the corresponding uncoated surface. Hydrophobicity is therefore a feature of both the uncoated substrate and the coating or layer. The same applies to appropriate substitutes in other contexts in which the term "hydrophobic" is used. The term "hydrophilic" is the opposite, i.e., an increase in wetting tension compared to a reference sample. The hydrophobic layer is primarily defined by its hydrophobicity and the process conditions that provide it.

[0225] These values ​​of w, x, y, and z are used throughout this specification for the experimental composition Si w O x C y H z Applicable to: The values ​​of w, x, y, and z used throughout this specification should be understood as ratios or empirical formulas (e.g., coatings or layers), not as limitations on the number or type of atoms in the molecule. For example, molecular composition Si4O4C8H 24 Octamethylcyclotetrasiloxane having the following empirical formula: Si1O1C2H6, obtained by dividing each of the molecular formula's w, x, y, and z by their greatest common divisor, 4. The values ​​of w, x, y, and z are not limited to integers. For example, the molecular composition of (acyclic) octamethyltrisiloxane is Si3O2C8H 24 is Si1O 0.67 C 2.67 It is convertible to H8. Also, SiO x C y H z is SiO x C y It is described as an equivalent to SiO x C yTo demonstrate its presence, it is not necessary to show the presence of hydrogen in any arbitrary proportion.

[0226] "Wetting tension" is a specific measure of the hydrophobicity or hydrophilicity of a surface. In relation to the present invention, an optional method for measuring wetting tension is ASTMD2578 or an improved version of the method described therein. This method uses a standard wetting tension solution (called Dyne solution) to determine how close the solution approaches the wet state of the plastic film surface in exactly 2 seconds. This is the wetting tension of the film. The procedure used herein differs from that in ASTMD2578 in that the substrate is not a flat plastic film, but a tube manufactured according to the "Protocol for Forming PET Tubes" and coated (except for the control) according to the protocol for coating the inside of the tube with a hydrophobic coating or layer (see Example 9 of European Patent Application Publication No. 2251671A2).

[0227] The atomic ratio can be determined by XPS. Therefore, taking into account the H atoms that are not measured by XPS, the coating or layer is, in one embodiment, of the chemical formula Si w O x C y H z (or equivalent SiO x C y ) has such that, for example, w is 1, x is about 0.5 to about 2.4, y is about 0.6 to about 3, and z is about 2 to about 9. Typically, such coating or layer contains 36% to 41% carbon normalized to 100% carbon + oxygen + silicon.

[0228] The term “syringe” is broadly defined to include cartridges, “pen” type syringes, and other types of barrels or reservoirs that are assembled with one or more other components to provide a functional syringe. “Syringe” is also broadly defined to include related articles such as autoinjectors that provide a mechanism for dispensing contents.

[0229] A coating, layer, or treatment is defined as "hydrophobic" if it reduces the surface wetting tension compared to the corresponding uncoated or untreated surface. Therefore, hydrophobicity is a feature of both the untreated substrate and the treated surface.

[0230] A “pharmaceutical product” refers to a composition, typically a fluid, that comprises a pharmacologically active substance (also called a pharmacokinetic ingredient or API) and one or more excipients optionally. Reduction of the degradation rate and / or amount of a pharmaceutical product includes reduction of the degradation rate and / or amount of the pharmacologically active substance and reduction of the degradation rate and / or amount of one or more excipients. For example, reduction of the degradation rate and / or amount of a pharmaceutical product may include either reduction of only the degradation rate and / or amount of the pharmacologically active substance or reduction of only one or more excipients. Reduction of the degradation rate and / or amount of a pharmaceutical product may also include reduction of both the degradation rate and / or amount of the pharmacologically active substance and reduction of one or more excipients.

[0231] "Excipients" refer to any pharmacologically inactive substances that, when combined with a pharmacologically active substance, provide advantages to a pharmaceutical product. These advantages include, for example, (a) enhancing the solubility of the active substance, (b) enhancing the process stability and / or shelf-life stability of the active substance, (c) controlling the pH and osmotic tension of the composition, (d) maintaining a preferred stable conformation of the active protein or vaccine, including exposure of a functional epitope, (e) inhibiting aggregation or degradation of the active substance, (f) enhancing the pharmacological effect of the active substance or the ability of the antigen to stimulate the immune system, such as increasing the adjuvant, and (g) one or more of several other functions, including, but not limited to, bulking agents, antioxidants, colorants, and preservatives. Due to the complexity and fragility of biopharmaceuticals, excipients are particularly important to biopharmaceutical products, for example, to increase product stability, maintain osmotic tension, and / or facilitate drug delivery.

[0232] Common excipients include buffering agents (pH adjusters), such as acetates, citrates, citric acid, sodium citrate, tartaric acid, histidine, glutamic acid, phosphates, tris(hydroxymethyl)aminomethane ("Tris"), glycine, bicarbonates, succinic acid, sulfates and nitrates; osmotic tension modifiers, such as mannitol, sorbitol, lactose, glucose, trehalose, sucrose, sodium chloride, potassium chloride, glycerol and glycerol. Phosphorus; Bulking agents, e.g., arginine, aspartic acid, glutamic acid, lysine, proline, glycine, histidine, methionine, alanine, gelatin, PVP, PLGA, PEG, dextran, cyclodextrin and derivatives, starch derivatives, HSA and BSA; Surfactants (wetting agents and / or solubilizers), e.g., polysorbate (e.g., polysorbate 20 and polysorbate 80), poloxamer (e.g., Pluronic acid) F68 and F127), Triton X-100, Brij 30, Brij 35 and sodium lauryl sulfate: antioxidant preservatives, e.g., histamine, cysteine, methionine, ascorbic acid, glutathione, vitamin E, vitamin A, propyl gallate, retinyl palmitate, selenium and poly(ethyleneimine); antimicrobial preservatives, e.g., benzyl alcohol, metacresol, phenol, 2-phenoxyethanol and parabens (e.g., methylparaben and propylparaben); chelating and / or complexing agents (preservatives), e.g., disodium edetate, diethylenetriaminepentaacetic acid (DTPA), citric acid, hexaphosphate, thioglycolic acid and zinc; adjuvants; and colorants. In particular, sodium chloride, polysorbate (e.g., polysorbate 20 or polysorbate 80), sucrose and mannitol are present as excipients in many drug products.

[0233] The term "includes" does not exclude other elements or steps.

[0234] The indefinite article "a" or "an" does not exclude plurals.

[0235] The present invention will be described more fully hereby with reference to the accompanying drawings, which illustrate several embodiments. However, the present invention can be carried out in many different forms and should not be construed as being limited to the embodiments described herein. Rather, these embodiments are examples of the present invention, and the present invention has the entire scope as indicated by the language of the claims. Similar numbers refer to similar or corresponding elements throughout. The following disclosure relates to all embodiments unless specifically noted as being limited to a particular embodiment.

[0236] Embodiments of the present disclosure relate to the coating of containers made at least partially from one or more specialty resins or one or more general-purpose resins, for example, to achieve coated containers suitable for containing injectable solutions. This can be achieved by using a combination of ALD and PECVD coating processes to coat a variety of layers that function as oxygen barriers, optionally water vapor permeability (or moisture) barriers, and pH protective layers. By using ALD instead of PECVD, coating defects can be minimized. In contrast to PECVD deposited coatings and layers, ALD is a relatively slow and extremely precise deposition process, so films deposited by ALD do not contain as many defects as films deposited by PECVD, due to the surface roughness of the specialty and general-purpose resins.

[0237] Without being constrained by theory, if a sufficient coating or layer is deposited by ALD, the coating or layer subsequently applied by PECVD is considered not to contain the same defects as the PECVD coating applied directly to the surface of the general-purpose resin. It is also considered that defects in the subsequently applied PECVD coating or layer may have less impact on the performance attributes of the coated container than defects in the PECVD layer applied directly to the surface of the general-purpose resin, because the defects do not spread all the way to the container wall itself, but rather only to the ALD-deposited coating or layer.

[0238] Embodiments of this disclosure relate to primary drug packaging such as vials and syringes, and thermoplastic vials and syringes configured for such use, offering a variety of advantages. Vials and syringes may be provided with a gas barrier coating, for example by ALD, that functions as an oxygen barrier, water vapor barrier, nitrogen barrier, carbon monoxide barrier, carbon dioxide barrier, ethylene oxide barrier, or any combination thereof. Vials and syringes may also be prepared and configured to offer other advantages such as low particle size, improved heat exchange (vials), excellent closure integrity, a drug interface with customizable surface energy, lubricity without silicone oil or silicone baking (syringes), and improved dimensional consistency, including after very low temperatures and / or freeze-thaw cycles.

[0239] Embodiments of this disclosure relate particularly to vials and syringes configured for and suitable for the storage of lyophilized or cold-chain pharmaceuticals such as DNA and mRNA vaccines. In particular, embodiments of vials and syringes are configured to maintain container closure integrity throughout the lifespan of the lyophilized or cold-chain pharmaceuticals. In some embodiments, for example, vials and syringes may be manufactured with a degree of dimensional consistency exceeding that seen in the art, allowing for tight tolerances with stoppers, plungers, rigid needle shields, etc. Furthermore, in some embodiments, vials or syringes may include one or more features designed to maintain CCI at low temperatures, including, for example, CCI-reinforced plunger gaskets and / or plunger anti-backout features, as disclosed in detail herein. Furthermore, embodiments of vials and syringes may provide one or more barrier coatings or layers, which may be configured and / or customized to provide a gas barrier suitable for specific lyophilized or cold-chain pharmaceuticals, such as DNA or mRNA vaccines.

[0240] Embodiments of this disclosure relate to blood collection tubes. The blood collection tubes may be provided with a gas barrier coating, for example by ALD, which functions as an oxygen barrier, water vapor barrier, nitrogen barrier, carbon dioxide barrier, or any combination thereof. Due to the provision of an enhanced barrier against ambient gases, the storage life of vacuum blood collection tubes can be extended for the first time to 36 months or more. Furthermore, the inclusion of a water vapor barrier coating or layer can prevent the loss of solvent from preservatives contained within the blood collection tube.

[0241] Container and covering set One aspect of the present invention, most broadly shown in the detailed drawings of Figures 1 and 2, is a container 210 comprising a wall 214 surrounding a lumen 212 and a container covering or layer set 285 on at least a portion of the wall 214 facing the lumen 212. More specifically, the container may be a vial, syringe, blister pack, ampoule, cartridge, bottle, pouch, pump, spray, stopper, needle, plunger, cap, sten, and any other type of container or conduit for catheters, implants, or fluids. Figures 1 to 5 show containers having a single opening, and it should be understood that this includes containers having two or more openings, such as syringes, or containers without openings, such as pouches, blister packs, or ampoules.

[0242] One embodiment of the container coating or layer set 285 is at least one tie coating or layer 289, at least one barrier coating or layer 288, and at least one pH protective coating or layer 286, as shown in Figures 1 and 2. This embodiment of the container coating or layer set is sometimes known as a "three-layer coating" and is SiO x The barrier coating or layer 288 is, each, SiO as defined herein. x C y The three-layer coating is sandwiched between the organic pH protective coating or layer 286 and the tie coating or layer 289, thereby protecting it from contents with a pH that would otherwise be high enough to remove it. Specific examples of this three-layer coating are provided herein. The intended thickness of each layer in nm (preferred range in parentheses) is given in the three-layer thickness table.

[0243] [Table 1]

[0244] Several specific adjustment coating sets 285, 285a, and 285b for container 210 and the closure of Figure 1 are shown in the coating set table.

[0245] [Table 2]

[0246] [Table 3]

[0247] Sets 1-4 and 7, 8, and 10 of the coating set table are considered useful alternatives for syringes. The syringe barrel wall of Set 1 (left column) is an example of the three-layer coating described above, and Set 7 is a modification of the three-layer coating in which the PECVD or ALD lubricating coating or layer is the top layer of the set. Set 8 is one embodiment in which the tie coating or layer becomes unnecessary by the use of ALD for applying the barrier coating or layer 288. Set 10 is one embodiment in which the barrier coating or layer 288 includes both a moisture barrier layer and a gas barrier layer, and the two barrier layers are not adjacent to each other.

[0248] The three-layer coating set 285 of set 1 is shown in figure 2 and, in one embodiment, is applied to a COP syringe barrel.

[0249] The three-layer coating set 285 of Set 1 includes, as the first layer, an adhesive or tie coating or layer 289 that improves the adhesion of the barrier coating or layer to the COP substrate. The adhesive or tie coating or layer 289 is also thought to reduce stress on the barrier coating or layer 288, so that the barrier layer is less susceptible to damage from thermal expansion or contraction or mechanical shock. The adhesive or tie coating or layer 289 is also thought to decouple defects between the barrier coating or layer 288 and the COP substrate. This is thought to occur because any pinholes or other defects that may form when the adhesive or tie coating or layer 289 is applied tend not to persist when the barrier coating or layer 288 is applied, and therefore pinholes or other defects in one coating do not align with defects in another coating. The adhesive or tie coating or layer 289 has some effect as a barrier layer and is therefore blocked by the adhesive or tie coating or layer 289, even defects that would provide a leakage path extending through the barrier coating or layer 289.

[0250] The three-layer coating set 285 of set 1 includes a barrier coating or layer 288 as the second layer, which provides a barrier to oxygen that has permeated the COP barrel wall and a barrier to moisture that may optionally permeate the plastic barrel wall. The barrier coating or layer 288 also serves as a barrier to the extraction of the composition of the barrel wall 214 by the contents of the lumen 214.

[0251] The three-layer coating set 285 of set 1 includes, as a third layer, a pH protective coating or layer 286 that provides protection to the underlying barrier coating or layer 288 from the contents of the syringe with a pH of 4 to 8, including in the presence of surfactants. For pre-filled syringes that are in contact with the contents of the syringe from manufacturing to use, the pH protective coating or layer 286 prevents or inhibits attack on the barrier coating or layer 288 to the extent that it maintains an effective oxygen and / or moisture barrier over the intended shelf life of the pre-filled syringe.

[0252] Sets 5, 6, and 9 are useful, for example, for vials. The lubricant deposition as coating set 285b represents a siliconized partition where the entire surface is coated with lubricant to facilitate insertion into the vial neck, and therefore coating is not required on the contact surface of the closure, but is provided.

[0253] The container wall coating set 285, represented by set 6, is another three-layer coating set, also shown in Figure 2, and in one embodiment is applied to a COP vial. The three-layer coating has the same layers as the syringe three-layer coating of set 1 described above and provides the same performance.

[0254] Coating or layer The tie coating or layer 289 has at least two functions. One function of the tie coating or layer 289 is to improve the adhesion of the barrier coating or layer 288 to a substrate, particularly a thermoplastic substrate, but the tie layer can also be used to improve adhesion to a glass substrate or another coating or layer. For example, the tie coating or layer, also called an adhesive coating or layer, can be applied to a substrate, and a barrier layer can be applied to an adhesive layer to improve the adhesion of the barrier layer or coating to the substrate.

[0255] Another function of the tie coating or layer 289 has been discovered: the tie coating or layer 289 applied beneath the barrier coating or layer 288 can improve the function of the pH protective coating or layer 286 applied on top of the barrier coating or layer 288.

[0256] The tie coating or layer 289 is basically SiO x C y Composed of SiO x C y Contains or SiO x C y It can consist of such a ratio, where x is 0.5 to 2.4 and y is 0.6 to 3. Alternatively, the atomic ratio is given by formula Si w O x C y It can be expressed as follows, and the atomic ratios of Si, O, and C in the tie coating or layer 289 are among several options. ·Si 100:O 50~150:C 90~200 (i.e. w=1, x=0.5~1.5, y=0.9~2); ·Si 100:O 70~130:C 90~200 (i.e. w=1, x=0.7~1.3, y=0.9~2) ·Si 100:O 80~120:C 90~150 (i.e. w=1, x=0.8~1.2, y=0.9~1.5) ·Si 100:O 90~120:C 90~140 (i.e., w=1, x=0.9~1.2, y=0.9~1.4), or ·Si 100:O 92~107:C 116~133 (i.e. w=1, x=0.92~1.07, y=1.16~1.33) That is the case.

[0257] The atomic ratio can be determined by XPS. Therefore, in one embodiment, considering the H atoms that are not measured by XPS, the tie coating or layer 289 is of the formula Si w O x C y H z (or equivalent SiO x C y ) may have, for example, in the formula, w is 1, x is about 0.5 to about 2.4, y is about 0.6 to about 3, and z is about 2 to about 9. Typically, the tie coating or layer 289 contains 36% to 41% carbon normalized to 100% carbon + oxygen + silicon.

[0258] Optionally, the tie coating or layer may be similar in composition to, or identical to, the pH protective coating or layer 286 described elsewhere in this specification, but this is not a requirement.

[0259] The tie coating or layer 289 is generally intended to be 5 nm to 100 nm thick, preferably 5 to 20 nm thick, in any embodiment, especially when applied by chemical vapor deposition. These thicknesses are not critical. Generally, the tie coating or layer 289 is relatively thin, but not necessarily so, as its function is to alter the surface properties of the substrate.

[0260] In some embodiments, the tie coating or layer 289 can be omitted. For example, if the barrier coating or layer 288 is applied by ALD, the adhesion improvement of the tie coating or layer may be unnecessary.

[0261] In other embodiments, a thin tie coating or layer 289 may be applied by ALD before applying the barrier coating or layer 288. x C y In addition, the tie coating or layer 289 applied by ALD may be any material that is effective in improving the adhesion between the subsequently applied barrier coating or layer 288 and the container wall 214 or any coating already applied thereto. Such materials include metals and metal oxides, such as Al2O3, TiO2, ZrO2, HfO2, Ta2O5, Nb2, O5, Y2O3, MgO, CeO2, La2,O3, SrTiO3, BaTiO3, BixTiyOz, In2O3, In2O3:Sn, In2O3:F, In2O3:Zr, SnO2, SnO2:Sb, ZnO, ZnO:Al, Ga2O3, NiO, CoOx, YBa2Cu3O7-x, LaCoO3, LaNiO3, Si, Ge, Cu, Mo, Ta, and W. In some embodiments, zinc oxide (ZnO) or aluminum oxide (Al2O3) may be applied by ALD as a tie coating or layer 289. Due to its adhesion to the polymer film, zinc oxide (ZnO) can function as a high-quality tie coating or layer 289 in the post-processing stage.

[0262] When the tie coating or layer 289 is applied by ALD, the thickness of the tie coating or layer may be, for example, 1 to 50 nm thick, alternatively 1 to 20 nm thick, alternatively 2 to 15 nm thick, alternatively 2 to 10 nm thick, alternatively 3 to 9 nm thick, alternatively 4 to 8 nm thick, or alternatively 5 to 7 nm thick.

[0263] In some embodiments, the barrier coating or layer 288 may be divided into an oxygen barrier layer 301 and a moisture barrier layer 300, which may or may not be applied as adjacent coatings. Thus, in some embodiments, the tie coating or layer 289 may be applied between the container wall 214 and the barrier coating 288, which includes both the oxygen barrier layer 301 and the moisture barrier layer 300 (by either PECVD or ALD). However, in other embodiments, the coating or layer 289 may be applied between the oxygen barrier layer 301 and the moisture barrier layer 300 (by either PECVD or ALD). For example, the moisture barrier layer 300 may be applied to the container wall 214 by, for example, ALD, then the tie coating or layer 289 may be applied, and then the oxygen barrier layer 301 may be applied. Such a coating is shown, for example, in Figure 25.

[0264] In one example, a moisture barrier layer (e.g., of Al2O3) is applied to the container wall by ALD. Then, a tie coating or layer 289 is applied by PECVD, SiO x In another example, an oxygen barrier layer is applied by PECVD, and a pH protective coating or layer 286 is applied by PECVD. In yet another example, a moisture barrier layer is applied to the container wall by ALD, and then a tie coating or layer 289 is applied by PECVD. In yet another example, a moisture barrier layer is applied to the container wall by ALD, and then a tie coating or layer 289 is applied by ALD, an oxygen barrier layer of SiOx is applied by ALD, and a pH protective coating or layer 286 is applied by PECVD. In yet another example, a moisture barrier layer is applied to the container wall by ALD, and then a tie coating or layer 289 is applied by ALD, an oxygen barrier layer of SiOx is applied by PECVD, and a pH protective coating or layer 286 is applied by PECVD.

[0265] In other embodiments, multiple tie coatings or layers 289 may be applied. For example, a first tie coating or layer 289 may be applied by ALD, followed by a first barrier layer with a moisture barrier (e.g., Al2O3), followed by a second tie coating or layer, followed by a second barrier layer such as an oxygen barrier (e.g., SiOx), followed by a pH protective coating or layer 286.

[0266] In yet another example, a moisture barrier layer (e.g., of Al2O3) is applied to the container wall by ALD. Then, SiO x The oxygen barrier layer is applied by ALD or PECVD, and the pH protective coating or layer 286 is applied by PECVD.

[0267] Barrier layer The barrier coating or layer 288 can optionally be deposited on the container of a pharmaceutical package, particularly a thermoplastic package, by atomic layer deposition (ALD), plasma chemical vapor deposition (PECVD), or other chemical vapor deposition processes to prevent oxygen, carbon dioxide, or other gases from entering the container and / or prevent pharmaceutical materials from entering into or through the packaging wall.

[0268] The barrier coating or layer may optionally include a SiOx coating or layer applied by PECVD as shown in U.S. Patent No. 7,985,188, or by ALD as described herein. The barrier layer may optionally include a SiOx coating or layer applied by PECVD as shown in U.S. Patent No. 7,985,188, or by ALD as described herein. x Characterized as a coating, comprising silicon, oxygen and optionally other elements, where x is the ratio of oxygen atoms to silicon atoms, which is about 1.5 to about 2.9 or 1.5 to about 2.6 or about 2. These alternative definitions of x are as follows in this specification: SiO x This applies to any use of the term. The barrier coating or layer is applied, for example, to the inside of pharmaceutical packaging or other containers, such as sample collection tubes, syringe barrels, vials, or other types of containers.

[0269] In some embodiments, the barrier coating 288 is basically SiO x containing or SiOx It can consist of, where x is 1.5~2.9nm thick, 2~1000nm thick, and SiO x The barrier coating 288 has an inner surface 220 facing the lumen 212 and an outer surface 222 facing the wall 214 and the surface of the article 254, and the barrier coating 288 is effective in reducing the intrusion of atmospheric gas into the lumen 212 compared to an uncoated container 250. One suitable barrier composition is, for example, a composition in which x is 2.3. For example, a barrier coating or layer such as 288 of any embodiment may be applied with a thickness of at least 2 nm, at least 4 nm, at least 7 nm, at least 10 nm, at least 20 nm, at least 30 nm, at least 40 nm, at least 50 nm, at least 100 nm, at least 150 nm, at least 200 nm, at least 300 nm, at least 400 nm, at least 500 nm, at least 600 nm, at least 700 nm, at least 800 nm or at least 900 nm. The barrier coating or layer can have a maximum thickness of 1000 nm, a maximum of 900 nm, a maximum of 800 nm, a maximum of 700 nm, a maximum of 600 nm, a maximum of 500 nm, a maximum of 400 nm, a maximum of 300 nm, a maximum of 200 nm, a maximum of 100 nm, a maximum of 90 nm, a maximum of 80 nm, a maximum of 70 nm, a maximum of 60 nm, a maximum of 50 nm, a maximum of 40 nm, a maximum of 30 nm, a maximum of 20 nm, a maximum of 10 nm, or a maximum of 5 nm. A range of 20 to 200 nm, and optionally a range of 20 to 30 nm, is particularly intended, in which case the barrier coating or layer is applied by PECVD. A specific thickness range consisting of any one of the minimum thicknesses above plus any one of the maximum thicknesses above is also explicitly intended.

[0270] When the barrier coating or layer is applied by ALD, the thickness of the barrier coating or layer may be, for example, 1 to 50 nm thick, alternatively 1 to 20 nm thick, alternatively 2 to 15 nm thick, alternatively 2 to 10 nm thick, alternatively 3 to 9 nm thick, alternatively 4 to 8 nm thick, or alternatively 5 to 7 nm thick.

[0271] SiO xThe thickness of other barrier coatings or layers can be measured, for example, by transmission electron microscopy (TEM), and their composition can be measured by X-ray photoelectron spectroscopy (XPS). The primer coatings or layers described herein can be applied to a variety of pharmaceutical packaging or other containers made of plastic or glass, such as plastic tubes, vials, and syringes.

[0272] SiO₂ where x is between 1.5 and 2.9 x The barrier coating or layer 288 is applied directly or indirectly to the thermoplastic wall 214 by atomic layer deposition (ALD) or plasma chemical vapor deposition (PECVD) in the filled pharmaceutical packaging or other container 210, such that the barrier coating or layer 288 is positioned on the inner surface of the thermoplastic wall 214 or between the inner surface 220 and the fluid 218 (for example, a tie coating or layer 289 may be interposed between them).

[0273] SiO x The barrier coating or layer 288 is supported by the thermoplastic wall 214. The barrier coating or layer 288 described elsewhere in this specification or in U.S. Patent No. 7,985,188 may be used in any embodiment.

[0274] SiO as defined herein x Certain barrier coatings or layers 288, such as those described elsewhere in this specification, have been found to exhibit a measurable decrease in barrier improvement within six months when attacked by certain contents with a relatively high pH in coated containers, particularly those in which the barrier coating or layer comes into direct contact with the contents. This problem can be addressed using pH-protective coatings or layers discussed herein.

[0275] SiO x The barrier coating or layer 288 may also function as a primer coating or layer 283, as discussed elsewhere in this specification.

[0276] In some embodiments, the barrier coating or layer 288 may be applied by atomic layer deposition (ALD). Although ALD is a longer process than PECVD, it can provide a similar barrier coating, for example, SiO2 produced by PECVD. x Barrier coatings that are denser and have fewer defects than the barrier coating, such as the SiO mentioned above. x It can be used to generate a barrier coating (optionally SiO2). As a result, the barrier coating or layer 288 applied by ALD may have a thinner thickness than the barrier coating or layer applied by PECVD. It is also intended that even when the barrier coating or layer 288 applied by ALD is applied at a thin thickness, it may have improved gas (e.g., oxygen) barrier properties compared to a barrier coating or layer of the same composition applied by PECVD.

[0277] In some embodiments, the barrier coating or layer 288 may include one or more layers in addition to the SiOx layer described above. For example, in some embodiments, one or more additional barrier layers may be applied, regardless of whether the SiOx layer is applied by ALD or by PECVD.

[0278] In some embodiments, it may be desirable to apply an additional moisture, i.e., water vapor, barrier layer in addition to the SiOx layer, which primarily functions as an oxygen barrier. For example, depending on the plastic material that can constitute the container wall, some may have suitable moisture barrier properties for certain applications, while others may require the application of one or more moisture barrier coatings or layers. Alternatively, a plastic material that may have suitable moisture barrier properties for certain applications may be improved to be uniform or substantially uniform with glass, for example, in applications where better water vapor barrier properties are particularly desirable. In some embodiments, the water vapor barrier coating or roughening may be applied by ALD as described herein.

[0279] In some embodiments, for example, the barrier coating or layer 288 may include both (i) one or more SiOx (e.g., SiO2) oxygen barrier layers applied by ALD and (ii) one or more moisture barrier layers, e.g., Al2O3, applied by ALD. In other embodiments, for example, the barrier coating or layer 288 may include both (i) one or more SiOx oxygen barrier layers applied by PECVD and (ii) one or more moisture barrier layers, e.g., Al2O3, applied by ALD. The oxygen barrier layers and moisture barrier layers may be applied sequentially adjacent to each other, or separated by one or more additional coatings or layers (e.g., the tie coatings or layers described above). If applied sequentially, the SiOx (e.g., SiO2) oxygen barrier layers may be applied first, followed by the moisture barrier layers, or vice versa. In some embodiments, particularly when both are applied by ALD, the barrier coating or layer 288 may include multiple alternating layers of SiOx (e.g., SiO2) and Al2O3. For example, in some embodiments, the barrier coating or layer 288 may include at least two layers of SiO2, alternatively at least three layers of SiO2, alternatively at least four layers of SiO2, and / or at least two layers of Al2O3, alternatively at least three layers of Al2O3, or alternatively at least four layers of Al2O3.

[0280] In some embodiments, it has now been found that it is sometimes desirable to coat the polymer container wall with an SiO2 layer (e.g., prior to the Al2O3 layer), and it is thought that, unconstrained by theory, the chemical interaction between the specific polymer material on which the container wall is made and the SiO2 atomic layer may generate a stronger barrier coating.

[0281] In some embodiments, the water vapor barrier coating may be a metal oxide, such as aluminum oxide, applied by ALD. The water vapor barrier coating may be applied to the inner surface of the container wall, the outer surface of the container wall, or both. In some embodiments, the water vapor barrier coating may even be applied as an intermediate step during the preparation of the container wall, so that the water vapor barrier layer is sandwiched between a portion of the polymer constituting the container wall. In such embodiments, the water vapor barrier layer can be said to be located between the inner surface and the outer surface of the container wall.

[0282] In alternative embodiments, the barrier coating or layer 288 may essentially consist of any material that provides adequate oxygen and / or moisture barrier properties to the container. Such materials may include metals and metal oxides that can be deposited by ALD, such as Al2O3, TiO2, ZrO2, HfO2, Ta2O5, Nb2, O5, Y2O3, MgO, CeO2, La2,O3, SrTiO3, BaTiO3, BixTiyOz, In2O3, In2O3:Sn, In2O3:F, In2O3:Zr, SnO2, SnO2:Sb, ZnO, ZnO:Al, Ga2O3, NiO, CoOx, YBa2Cu3O7-x, LaCoO3, LaNiO3, Si, Ge, Cu, Mo, Ta, and W.

[0283] When applied in combination, one or more SiO2 layers and one or more Al2O3 layers may each contribute to the oxygen barrier properties and / or water vapor barrier properties of the coating.

[0284] In some embodiments, for example, a container coated with an oxygen barrier coating or layer may have an oxygen permeability equal to or less than that previously obtained using a PECVD-deposited SiOx coating.

[0285] In some embodiments, for example, a vial such as a 10 mL thermoplastic vial may be coated with a barrier coating or layer as described herein, and the vial (having associated stoppers) may have an oxygen permeability of 0.00030d, for example, using the oxygen permeability protocol described herein. -1Less than, alternatively 0.00025d -1 Less than, alternatively 0.00020d -1 Less than, alternatively 0.00015d -1 Less than, alternatively 0.00010d -1 It may have an OTR constant of less than . In some embodiments, the thermoplastic vial may include a polycarbonate container wall. In other embodiments, the thermoplastic vial may include a container wall made from a cyclic block copolymer (CBC) resin as described herein. In other embodiments, the thermoplastic vial may include a container wall made from a COP or COC resin.

[0286] In some embodiments, syringes such as 0.3 mL syringes, 0.5 mL syringes, or 1 mL syringes may be coated with a barrier coating or layer as described herein, and the syringes may have an OTR constant of less than 0.005 d-1, alternatively less than 0.004 d-1, alternatively less than 0.003 d-1, alternatively less than 0.002 d-1, alternatively less than 0.001 d-1, alternatively less than 0.00050 d-1, alternatively less than 0.00045 d-1, alternatively less than 0.00040 d-1, alternatively less than 0.00035 d-1, or alternatively less than 0.00030 d-1, which is determined using, for example, an oxygen permeability protocol as described herein. In some embodiments, the thermoplastic vial may include a polycarbonate container wall. In other embodiments, the thermoplastic vial may include a container wall made from a cyclic block copolymer (CBC) resin as described herein. In other embodiments, the thermoplastic vial may include a container wall made from COP or COC resin.

[0287] In some embodiments, a blood collection tube, such as a 9 mL blood collection tube, may be coated with a barrier coating or layer as described herein, and the blood collection tube may have an OTR constant of less than 0.00050d-1, alternatively less than 0.00040d-1, alternatively less than 0.00030d-1, alternatively less than 0.00030d-1, or alternatively less than 0.00015d-1, as determined using the oxygen permeability protocol described herein. In some embodiments, the thermoplastic vial may include a polycarbonate container wall. In other embodiments, the thermoplastic vial may include a container wall made from a cyclic block copolymer (CBC) resin as described herein. In other embodiments, the thermoplastic vial may include a container wall made from a COP or COC resin.

[0288] pH protective coating or layer SiO x The barrier layer or coating can be corroded or dissolved by certain fluids, such as aqueous compositions with a pH greater than approximately 5. Because coatings applied by chemical vapor deposition can be very thin—tens to hundreds of nanometers thick—even relatively slow corrosion can render the barrier layer ineffective or reduce its effectiveness in a shorter time than the desired shelf life of the product packaging. This is particularly problematic in the case of fluid pharmaceutical compositions, as many of them have a pH of approximately 7 or more broadly in the range of 5 to 9, similar to the pH of blood and other human or animal fluids. The higher the pH of the pharmaceutical, the more SiO2. x The coating corrodes or dissolves more rapidly. Optionally, this problem can be addressed by protecting the barrier coating or layer 288 or other pH-sensitive materials with a pH-protective coating or layer 286.

[0289] Optionally, the pH protective coating or layer 286 is basically the Si defined above. w O x C y H z (or its equivalent, SiO x C y ) or Si w N x C y H zOr its equivalent, Si(NH)O x C y It is composed of, contains, or may consist of. The atomic ratio of Si:O:C: or Si:N:C can be determined by XPC (X-ray photoelectron spectroscopy). Taking the H atom into consideration, the pH protective coating or layer is therefore, in one embodiment, of the formula Si w O x C y H z or its equivalent SiO x C y It may have such that, for example, in the equation, w is 1, x is approximately 0.5 to approximately 2.4, y is approximately 3, and z is approximately 2 to approximately 9.

[0290] Typically, formula Si w O x C y When expressed as such, the atomic ratios of Si, O, and C are, among several options, ·Si 100:O 50~150:C 90~200 (i.e. w=1, x=0.5~1.5, y=0.9~2); ·Si 100:O 70~130:C 90~200 (i.e. w=1, x=0.7~1.3, y=0.9~2) ·Si 100:O 80~120:C 90~150 (i.e. w=1, x=0.8~1.2, y=0.9~1.5) ·Si 100:O 90~120:C 90~140 (i.e. w=1, x=0.9~1.2, y=0.9~1.4), ·Si 100:O 92~107:C 116~133 (i.e., w=1, x=0.92~1.07, y=1.16~1.33), or Si 100:O 80~130:C 90~150 That is the case.

[0291] Alternatively, the pH protective coating or layer may have atomic concentrations of less than 50% carbon and more than 25% silicon, normalized to 100% carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS). Alternatively, the atomic concentrations may be 25-45% carbon, 25-65% silicon, and 10-35% oxygen.

[0292] Alternatively, the atomic concentrations are 30-40% carbon, 32-52% silicon, and 20-27% oxygen. Alternatively, the atomic concentrations are 33-37% carbon, 37-47% silicon, and 22-26% oxygen.

[0293] The thickness of the pH protective coating or layer can be, for example, 10nm to 1000nm; alternatively 10nm to 1000nm; alternatively 10nm to 900nm; alternatively 10nm to 800nm; alternatively 10nm to 700nm; alternatively 10nm to 600nm; alternatively 10nm to 500nm; alternatively 10nm to 400nm; alternatively 10nm to 300nm; alternatively 10nm to 200nm; alternatively 10nm to 100nm; alternatively 10nm to 50nm; alternatively 20nm to 1000nm; alternatively 50nm to 1000nm; alternatively 10nm to 1000nm; alternatively 50nm to 800nm; alternatively 100nm to 700nm; or alternatively 300nm to 600nm.

[0294] Optionally, the atomic concentration of carbon in the protective layer, normalized to 100% carbon, oxygen, and silicon as determined by X-ray photoelectron spectroscopy (XPS), can be greater than the atomic concentration of carbon in the atomic formula of the organosilicon precursor. For example, embodiments are envisioned in which the atomic concentration of carbon is increased by 1–80 atomic percent, alternatively 10–70 atomic percent, alternatively 20–60 atomic percent, alternatively 30–50 atomic percent, alternatively 35–45 atomic percent, and alternatively 37–41 atomic percent.

[0295] Optionally, the atomic ratio of carbon to oxygen in the pH protective coating or layer can be increased compared to the organosilicon precursor, and / or the atomic ratio of oxygen to silicon can be decreased compared to the organosilicon precursor.

[0296] Optionally, the pH protective coating or layer may have a silicon atom concentration lower than the silicon atom concentration in the feed gas's atomic formula, normalized to 100% carbon, oxygen, and silicon, as determined by X-ray photoelectron spectroscopy (XPS). For example, embodiments are envisioned in which the silicon atom concentration is reduced by 1 to 80 atomic percent, alternatively 10 to 70 atomic percent, alternatively 20 to 60 atomic percent, alternatively 30 to 55 atomic percent, alternatively 40 to 50 atomic percent, or alternatively 42 to 46 atomic percent.

[0297] Alternatively, in any embodiment, a pH protective coating or layer may be contemplated that features a sum formula that can increase the atomic ratio C:O and / or decrease the atomic ratio Si:O compared to the sum formula of an organosilicon compound precursor.

[0298] The pH protective coating or layer 286 is generally placed between the barrier coating or layer 288 and the fluid 218 in the finished product. The pH protective coating or layer 286 is supported by the thermoplastic wall 214.

[0299] The pH protective coating or layer 286 is optionally effective in maintaining, for a period of at least six months, that the barrier coating or layer 288 does not dissolve at least substantially even when subjected to attack by the fluid 218.

[0300] The pH protective coating or layer is specified by its X-ray reflectance (XRR) of 1.25–1.65 g / cm³. 3 Alternatively, 1.35-1.55 g / cm³ 3 Alternatively, 1.4-1.5 g / cm³ 3 Alternatively, 1.4-1.5 g / cm³ 3 Alternatively, 1.44-1.48 g / cm³ 3It can have a density of octamethylcyclotetrasiloxane as the organosilicon compound, and the pH protective coating or layer can have a density that is higher than that of the pH protective coating or layer made from HMDSO as the organosilicon compound under the same PECVD reaction conditions.

[0301] The pH protective coating or layer can optionally prevent or reduce precipitation of compounds or components of compositions in contact with the pH protective coating or layer compared to an uncoated surface and / or a barrier coating surface using HMDSO as a precursor, and in particular can prevent or reduce insulin precipitation or blood coagulation.

[0302] The pH protective coating or layer may optionally have an RMS surface roughness value (measured by AFM) of approximately 5 to approximately 9, optionally approximately 6 to approximately 8, or optionally approximately 6.4 to approximately 7.8. a The surface roughness value can be approximately 4 to 6, and optionally approximately 4.6 to 5.8. The R of the pH protective coating or layer is measured by AFM. max The surface roughness value can be approximately 70 to 160, optionally 84 to 142, or optionally 90 to 130.

[0303] The inner surface of the pH protection can have a contact angle (with distilled water) of 90° to 110°, optionally 80° to 120°, or optionally 70° to 130°, when measured by goniometer angle measurement of a water droplet on the pH protection surface, in accordance with ASTM D7334-08 "Standard Practice for Surface Wettability of Coatings, Substrates and Pigments by Advancing Contact Angle Measurement".

[0304] The passivation layer or pH protective coating or layer 286 may be optionally,

number

[0305] The O-parameter is defined in U.S. Patent No. 8,067,070, which most broadly claims O-parameter values ​​between 0.4 and 0.9. As shown in Figure 6, which is the same as Figure 5 in U.S. Patent No. 8,067,070, except that it is noted to show an O-parameter of 0.53 calculated as a result of interpolation of wavenumber and absorbance scales to obtain an absorbance of 0.0424 at 1253 cm⁻¹ and a maximum absorbance of 0.08 at 1000-1100 cm⁻¹, the O-parameter can be measured from a physical analysis of an FTIR amplitude-versus-wavenumber plot to find the numerator and denominator of the above formula. The O-parameter can also be measured from digital wavenumber-versus-absorbance data.

[0306] U.S. Patent No. 8,067,070 claims that the claimed O-parameter range provides a superior pH protective coating or layer, based solely on experiments using HMDSO and HMDSN, both of which are acyclic siloxanes. Surprisingly, the inventors have found that when the PECVD precursor is a cyclic siloxane, such as OMCTS, the O-parameter using OMCTS, outside the range claimed in U.S. Patent No. 8,067,070, can provide even better results than those obtained in U.S. Patent No. 8,067,070 using HMDSO.

[0307] Alternatively, in the embodiments shown in Figures 1 to 5, the O parameter has a value of 0.1 to 0.39, or 0.15 to 0.37, or 0.17 to 0.35.

[0308] Another aspect of the present invention is a composite material described and illustrated in Figures 1 to 5, wherein the passivation layer is

number

[0309] The N parameter is also described in U.S. Patent No. 8,067,070 and is measured similarly to the O parameter, except that the intensity at two specific wavenumbers—neither of which is a range—is used. U.S. Patent No. 8,067,070 claims an inactivating layer having an N parameter of 0.7 to 1.6. Similarly, the inventors have produced a better coating using pH protective coating or layer 286 having an N parameter below 0.7, as described above. Alternatively, the N parameter may have a value of at least 0.3, or 0.4 to 0.6, or at least 0.53.

[0310] The rate of corrosion, melting, or elution of the pH protective coating or layer 286 when in direct contact with the fluid 218 (different names in related concepts) is less than the corrosion rate of the barrier coating or layer 288 when in direct contact with the fluid 218.

[0311] In any embodiment, the thickness of the pH protective coating or layer is intended to be in the range of 50 to 500 nm, preferably 100 to 200 nm.

[0312] The pH protective coating or layer 286 is effective in separating the fluid 218 from the barrier coating or layer 288 for at least a sufficient amount of time to allow the barrier coating to function as a barrier throughout the shelf life of the pharmaceutical packaging or other container 210.

[0313] The inventors have developed a SiO2 formed from a polysiloxane precursor in which the pH protective coating or layer has a considerable amount of organic components. x C y or Si(NH) x C yIt was further found that certain pH protective coatings or layers do not erode rapidly when exposed to fluid, and in fact, erosion or dissolution is relatively slow when the fluid has a high pH in the range of 5 to 9. For example, at pH 8, the dissolution rate of the pH protective coating or layer made from the precursor octamethylcyclotetrasiloxane, i.e., OMCTS, is very slow. Therefore, SiO x C y or Si(NH) x C y These pH protective coatings or layers are SiO x It can be used to coat the barrier layer, retaining the benefits of the barrier layer by protecting it from fluids within the drug packaging. The protective layer is SiO x It is coated on at least a portion of the layer, otherwise the contents are SiO x SiO2 will come into contact with the contents stored inside the container. x Protect the layer.

[0314] Although this invention does not rely on the accuracy of the following theory, it is further believed that a pH protective coating or layer effective in avoiding erosion can be produced from the siloxanes and silazanes described herein. A cyclic siloxane or linear silazane precursor, for example, SiO deposited from octamethylcyclotetrasiloxane (OMCTS) x C y or Si(NH) x C y The coatings are thought to consist of relatively long, continuous repeating units of intact cyclic siloxane rings and precursor structures. These coatings are thought to be nanoporous, yet structured and hydrophobic, and these properties are thought to contribute to their success as pH-protective coatings or layers, and as protective coatings or layers. This is illustrated, for example, in U.S. Patent No. 7,901,783.

[0315] SiO x C y or Si(NH) x C yThe coating can also be deposited from linear siloxanes or linear silazane precursors, such as hexamethyldisiloxane (HMDSO) or tetramethyldisiloxane (TMDSO).

[0316] Optionally, the FTIR absorbance spectrum of the pH protective coating or layer 286 of any embodiment has a ratio greater than 0.75 between the maximum amplitude of the Si-O-Si symmetric stretching peak, typically located at about 1000 cm⁻¹ to 1040 cm⁻¹, and between the Si-O-Si asymmetric stretching peak, typically located at about 1060 cm⁻¹ and about 1100 cm⁻¹. Alternatively, in any embodiment, this ratio may be at least 0.8, at least 0.9, at least 1.0, at least 1.1, or at least 1.2. Alternatively, in any embodiment, this ratio may be at most 1.7, at most 1.6, at most 1.5, at most 1.4, or at most 1.3. As alternative embodiments of the invention shown in Figures 1 to 5, any minimum ratio described herein may be combined with any maximum ratio described herein.

[0317] Optionally, in any embodiment, the pH protective coating or layer 286 in the absence of the agent has a non-oily appearance. This appearance has been shown to distinguish, in some cases, an effective pH protective coating or layer from a lubricating layer which has been shown to have an oily (i.e., glossy) appearance.

[0318] Optionally, for any pH protective coating or layer 286 in any embodiment, the silicon dissolution rate in 50 mM potassium phosphate buffer at 40°C is less than 170 ppb / day, diluted with sterile water for injection, adjusted to pH 8 with concentrated nitric acid, and containing 0.2 wt.% polysorbate 80 surfactant (measured in the absence of the agent to avoid changes in the dissolving reagent). (Polysorbate 80 is a common formulation ingredient available, for example, as Tween®-80 from Uniqema Americas LLC, Wilmington, Delaware.)

[0319] Optionally, for any embodiment of the pH protective coating or layer 286, the silicon dissolution rate is less than 160 ppb / day, less than 140 ppb / day, less than 120 ppb / day, less than 100 ppb / day, less than 90 ppb / day, or less than 80 ppb / day. Optionally, for any embodiment of Figures 24-26, the silicon dissolution rate is greater than 10 ppb / day, or greater than 20 ppb / day, greater than 30 ppb / day, greater than 40 ppb / day, greater than 50 ppb / day, or greater than 60 ppb / day. For any embodiment of the pH protective coating or layer 286, any minimum rate described herein can be combined with any maximum rate described herein.

[0320] Optionally, for any embodiment of the pH protective coating or layer 286, the total silicon content of the pH protective coating or layer and barrier coating when dissolved from the container into the pH 8 test composition is less than 66 ppm, less than 60 ppm, less than 50 ppm, less than 40 ppm, less than 30 ppm, or less than 20 ppm.

[0321] The inventors of this invention provide the following theory of action of pH protective coatings or layers described herein. The present invention is not limited to the accuracy of this theory or to the embodiments that can be predicted by using this theory.

[0322] SiO x The dissolution rate of the barrier layer is thought to depend on the SiO bonds within the layer. Oxygen-bonded sites (silanols) are thought to increase the dissolution rate.

[0323] The pH protective coating or layer is SiO x The silanol moiety of the barrier layer binds to SiO x It is thought that the surface is "repaired," or passivated, which dramatically reduces the dissolution rate. In this hypothesis, the thickness of the pH protective layer is not the primary protective measure—the primary measure is SiO x This involves surface passivation. In any embodiment, the pH protective coating or layer described herein is intended to be improved by increasing the crosslinking density of the pH protective coating or layer.

[0324] Lubricant layer The "lubricating layer" according to the present invention is a coating having lower frictional resistance than the uncoated surface. In other words, the lubricating layer reduces the frictional resistance of the coated surface compared to the uncoated reference surface. This lubricating layer is mainly defined by process conditions that provide lower frictional resistance than the uncoated surface and lower frictional resistance than the uncoated surface, and optionally, empirically composed of Si as defined in the definition section. w O x C y H z The composition may be made of the following. "Friction resistance" can be static friction resistance and / or dynamic friction resistance. One optional embodiment of the present invention is a syringe component, e.g., a syringe barrel or plunger, coated with a lubricating layer. In this intended embodiment, the static friction resistance in relation to the present invention is the sliding yield stress as defined herein, and the dynamic friction resistance in relation to the present invention is the plunger sliding force as defined herein. For example, the plunger sliding force as defined and determined herein is suitable for determining the presence and lubrication characteristics of the lubricating layer in relation to the present invention whenever the coating is applied to the inner wall of any syringe or syringe component, e.g., a syringe barrel. The sliding yield stress is particularly relevant to evaluating the effect of the coating on pre-filled syringes, i.e., syringes that are filled after coating and can be stored for a certain period of time, e.g., several months or even several years, until the plunger needs to be moved again ("breakout").

[0325] In relation to the present invention, “plunger sliding force” is the force required to maintain the movement of the plunger within the syringe barrel, for example, during aspiration or dispensing. Advantageously, the plunger sliding force can be determined using the ISO 7886-1:1993 test, which is described herein and known in the art. Synonyms for “plunger sliding force,” as is often used in the art, are “plunger force” or “pressing force.”

[0326] In relation to the present invention, "sliding yield stress" is the initial force required to move the plunger within a syringe, such as a pre-filled syringe.

[0327] The "plunger sliding force" and "sliding yield stress," as well as their measurement methods, will be explained in more detail in the following sections of this description.

[0328] "Slidable" means that the plunger can slide within the syringe barrel.

[0329] The plunger sliding force test is a specialized test of the sliding friction coefficient of a plunger in a syringe. It explains that the normal force associated with the sliding friction coefficient, usually measured on a flat surface, is addressed by standardizing the fit between the plunger or other sliding element and the tube or other container in which it slides. The parallel force associated with the sliding friction coefficient, usually measured, is comparable to the plunger sliding force measured as described in this specification. The plunger sliding force can be measured, for example, as described in the ISO 7886-1:1993 test.

[0330] The plunger sliding force test can also be adapted to measure other types of frictional resistance, such as the friction that holds a stopper inside a pipe, by appropriate modifications to the apparatus and procedure. In one embodiment, the plunger can be replaced by a closure, and the withdrawal force for removing or inserting the closure can be measured as a counterpart to the plunger sliding force.

[0331] Similar to or instead of plunger sliding force, friction yield stress can be measured. Friction yield stress is the force required for a stationary plunger to begin moving within the syringe barrel, or an equivalent force required to de-seat a seated, stationary closure and initiate its movement. Friction yield stress is measured by applying a force to the plunger, starting at zero or a low value and increasing until the plunger begins to move. Friction yield stress tends to increase with syringe storage, as pre-filled syringe plungers may displace intervening lubricants or adhere to the barrel due to the decomposition of lubricants between the plunger and barrel. Friction yield stress is the force required to overcome "adhesion," which is industry terminology referring to the adhesion between the plunger and barrel that must be overcome to start the plunger and allow it to begin moving.

[0332] Some advantages of coating a container entirely or partially with a lubricating layer, for example, selectively coating surfaces that come into contact with other parts in a sliding relationship, include facilitating the insertion or removal of stoppers or the passage of sliding elements such as pistons in syringes or stoppers in sample tubes. Containers can be made from glass or polymer materials such as polyester, olefins such as polyethylene terephthalate (PET), cyclic olefin copolymer (COC), or polypropylene, or other materials. Applying a lubricating layer by PECVD generally avoids or reduces the need to coat the container walls or closures by spraying, dipping, or otherwise applying organosilicon or other lubricants in considerably larger quantities than those deposited by the PECVD process.

[0333] The power (in watts) used in PECVD also affects coating performance. Typically, higher power increases the barrier properties of the coating, while lower power increases the lubricity. For example, in the case of coating the inner wall of a syringe barrel with a volume of approximately 3 ml, power below 30 W mainly contributes to the barrier layer of the coating, while power above 30 W mainly contributes to the lubricity layer of the coating.

[0334] A further parameter determining coating properties is the ratio of O2 (or another oxidizing agent) to the precursor (e.g., an organosilicon precursor) in the gas reactants used to generate the plasma. Typically, increasing the proportion of O2 in the gas reactants improves the barrier properties of the coating, while decreasing the proportion of O2 improves the lubricity of the coating.

[0335] If a lubricating layer is desired, O2 may be present in the gas reactants in a volume-to-volume ratio of 0:1 to 5:1, 0:1 to 1:1, 0:1 to 0.5:1, or even 0:1 to 0.1:1, optionally. Most advantageously, oxygen is essentially absent from the gas reactants. Therefore, in some embodiments, the gas reactants contain less than 1 vol% O2, less than 0.5 vol% O2, and optionally, no O2.

[0336] A process is envisioned for coating a lubricating layer having the characteristics defined in the definition section onto a substrate, for example, the inside of a syringe barrel, the process comprising coating one of the described precursors on or near the substrate to a thickness of 1 to 5000 nm, optionally 10 to 1000 nm, optionally 10 to 200 nm, or optionally 20 to 100 nm, and optionally crosslinking or polymerizing (or both) the coating by a PECVD process to provide a lubricated surface.

[0337] Si as defined in the definition section w O x C yThe coating may optionally be very thin and have a thickness of at least 4 nm, at least 7 nm, at least 10 nm, at least 20 nm, at least 30 nm, at least 40 nm, at least 50 nm, at least 100 nm, at least 150 nm, at least 200 nm, at least 300 nm, at least 400 nm, at least 500 nm, at least 600 nm, at least 700 nm, at least 800 nm, or at least 900 nm. The coating can have a maximum thickness of 1000 nm, at most 900 nm, at most 800 nm, at most 700 nm, at most 600 nm, at most 500 nm, at most 400 nm, at most 300 nm, at most 200 nm, at most 100 nm, at most 90 nm, at most 80 nm, at most 70 nm, at most 60 nm, at most 50 nm, at most 40 nm, at most 30 nm, at most 20 nm, at most 10 nm, or at most 5 nm. A specific thickness range is also explicitly intended, consisting of any one of the minimum thicknesses mentioned above plus any one of the maximum thicknesses mentioned above that is greater than or equal to that minimum thickness.

[0338] A lubricating layer having the characteristics defined in the definition section can be applied as a subsequent coating after any combination of the layers described herein has been applied to the inner surface 88 of the container 80 to provide a lubricating layer.

[0339] Optionally, the lubricating layer can be post-cured after the PECVD process. Radiation curing techniques involving UV initiation (free radicals or cations), electron beam (E beam), and heat, as described in *Development Of Novel Cycloaliphatic Siloxanes For Thermal And UV-Curable Applications* (Ruby Chakraborty Dissertation, 2008), can be used.

[0340] A lubricating layer having the characteristics defined in the definition section is particularly intended for the inner surface of the syringe barrel, as will be further described later. The lubricated inner surface of the syringe barrel can reduce the sliding yield stress required to initiate plunger movement after the plunger sliding force necessary to advance the plunger within the barrel during syringe operation, or after the prefilled syringe plunger has displaced the intervening lubricant or has adhered to the barrel due to, for example, the decomposition of the lubricant between the plunger and the barrel.

[0341] Therefore, the coating 90 may include a SiOx barrier layer or a triple layer and a lubricating layer having the characteristics defined in the definition section. w O x C y H z The lubricating layer can be deposited between a layer or three layers of SiOx and the lumen of the container.

[0342] Another embodiment is a lubricating layer on the inner wall of a syringe barrel, having the characteristics defined in the Definitions section. The coating is manufactured from the PECVDPS process using the following materials and conditions. A cyclic precursor selected from monocyclic siloxanes, polycyclic siloxanes, or combinations of two or more thereof is optionally employed, as defined elsewhere in this specification for the lubricating layer. An example of a suitable cyclic precursor is octamethylcyclotetrasiloxane (OMCTS) optionally mixed with other precursor materials in any proportion. Optionally, the cyclic precursor consists essentially of octamethylcyclotetrasiloxane (OMCTS), with other precursors present in amounts that do not alter the fundamental novel properties of the resulting lubricating layer, namely the reduction of plunger sliding force or sliding yield stress on the coating surface.

[0343] Optionally, oxygen is not added to the process, at least not fundamentally. In relation to the present invention, in some embodiments, the addition of "substantially no oxygen" or (synonymously) "substantially no oxygen" to the gaseous reactants is used. This means that some residual atmospheric oxygen may be present in the reaction space, and residual oxygen supplied in a previous step that was not completely used may be present in the reaction space, which are defined herein as oxygen being substantially absent. If the oxygen content of the gaseous reactants is less than 1 vol.%, for example less than 0.5 vol.%, and optionally does not contain O2, then oxygen is substantially absent from the gaseous reactants. If oxygen is not added to the gaseous reactants, or if there is no oxygen at all during PECVD, this also falls within the range of "substantially oxygen-free".

[0344] Sufficient plasma generation power input, such as that successfully used in one or more embodiments herein, or any power level described herein, is provided to induce coating formation.

[0345] The materials and conditions employed are effective in reducing the sliding force or yield stress of the syringe plunger moving through the syringe barrel by at least 25 percent, alternatively at least 45 percent, alternatively at least 60 percent, or alternatively more than 60 percent, compared to an uncoated syringe barrel. A reduction range of 20–95 percent, alternatively 30–80 percent, alternatively 40–75 percent, or alternatively 60–70 percent in the plunger sliding force or yield stress is intended.

[0346] Another embodiment is a syringe comprising a plunger, a syringe barrel, and a lubricating layer, having the features defined in the Definitions section. The syringe barrel includes an inner surface that receives the sliding plunger. The lubricating layer is disposed on the inner surface of the syringe barrel. The lubricating layer is less than 1000 nm thick and is effective in reducing the sliding yield stress or plunger sliding force required to move the plunger within the barrel. The reduction in plunger sliding force may be expressed alternatively as a reduction in the sliding friction coefficient of the plunger within the barrel or a reduction in plunger force, and these terms are considered to have the same meaning herein.

[0347] Optionally, the FTIR absorption spectrum of any embodiment of the lubricating coating or layer has a ratio of at most 0.9 between the maximum amplitude of the Si-O-Si symmetric stretching peak at about 1000–1040 cm⁻¹ and the maximum amplitude of the Si-O-Si asymmetric stretching peak at about 1060–1100 cm⁻¹. Alternatively, in any embodiment, this ratio may be at most 0.85, at most 0.8, at most 0.75, or at most 0.75.

[0348] Optionally, in any embodiment, the lubricating coating or layer may have an oily (i.e., glossy) appearance in the absence of the agent. This appearance has been recognized in some cases as distinguishing the lubricating coating or layer from the pH protective coating or layer.

[0349] Hydrophobic layer Si w O x C y or its equivalent SiO x C y The protective or lubricating coating or layer may also have usefulness as a hydrophobic layer, depending on whether or not it also functions as a pH protective coating or layer. Suitable hydrophobic coatings or layers and their applications, properties and uses are described in U.S. Patent No. 7,985,188. Dual-function protective / hydrophobic coatings or layers having the properties of both types of coatings or layers can be provided in any embodiment of the present invention.

[0350] One embodiment can be carried out under conditions effective for forming a hydrophobic pH protective coating or layer on a substrate. Optionally, the hydrophobic properties of the pH protective coating or layer can be set by setting the ratio of O2 to the organosilicon precursor in the gas reactant and / or by setting the power used to generate the plasma. Optionally, the pH protective coating or layer may have a lower wetting tension than the uncoated surface, optionally 20-72 dyne / cm, optionally 30-60 dyne / cm, optionally 30-40 dyne / cm, or optionally 34 dyne / cm. Optionally, the pH protective coating or layer may have higher hydrophobicity than the uncoated surface.

[0351] The use of coatings or layers according to any described embodiment is intended in any embodiment to be (i) a lubricating coating having lower frictional resistance than the uncoated surface, (ii) a pH-protective coating or layer that prevents dissolution of a barrier coating in contact with a fluid, and / or (iii) a hydrophobic layer that is more hydrophobic than the uncoated surface.

[0352] Atomic layer deposition coating of containers One or more of the layers described herein may be coated by atomic layer deposition. Coatings coated by atomic layer deposition are structurally different (but not necessarily chemically) from those coated by CVD or PECVD. In contrast to coatings coated by CVD or PECVD, coatings coated by atomic layer deposition consist of multiple monolayers of the deposited compound. Since each step deposits only a single monolayer, defects of the kind that can occur due to non-uniform growth in CVD or PECVD are avoided. As a result, the coating has a much higher density than coatings coated by CVD or PECVD (generally of the same chemical composition). Because the coating consists of multiple monolayers of the deposited compound, the coating may also have greater compositional purity and consistency of luminosity than coatings coated by PECVD.

[0353] In atomic layer deposition (ALD), sources, or precursors, are introduced sequentially in non-overlapping timeframes, allowing for the deposition of one material at a time. Once each possible absorption site is occupied by a particular precursor flow, the precursor can be stopped, completing the purging process, and then the next source material is introduced, with each precursor constituting one cycle with one timeframe. Since the chamber is typically under a 1-20 mmbar vacuum, the remaining precursor can be discharged once the flow is stopped. In this way, the deposition process continues in a self-limiting manner, in that there are only a finite number of sites that the reactants can absorb, and therefore, once they are filled, growth stops until the next precursor is introduced, and the total thickness of the material is controlled by the number of cycles. This process can be continued for each precursor, resulting in the deposition of a coating or layer one atomic layer at a time. Thus, ALD has excellent thickness uniformity and control, and it is possible to grow very thin conformal films with high density compared to other deposition techniques. Furthermore, precise compositional control is possible with the ALD process.

[0354] By selectively utilizing plasma, plasma can be used to enhance material deposition, sometimes called plasma-assisted atomic layer deposition (PEALD), which increases precursor dissociation, enabling lower growth temperatures, which can be useful when coatings are applied to certain thermoplastics.

[0355] ALD is useful for depositing high-density layers with low defect density. For example, a thin SiOx film can be deposited by thermal and / or plasma ALD. The deposition temperature can be in the range of 30°C to 120°C. For example, when thermal ALD is used, the deposition temperature can be in the range of 70°C to 120°C, preferably 100°C or less, and preferably 80°C or less. When PEALD is used, the temperature can be at least 30°C, for example 30°C to 80°C or 30°C to 60°C, preferably 80°C or less, and preferably 60°C or less.

[0356] The precursor for depositing SiOx (e.g., SiO2) films by ALD or PEALD comprises one or more silicon-containing precursors and one or more oxygen precursors. Examples of silicon precursors include aminosilanes; alkylaminosilanes such as tetradimethylaminosilicon; 1,2-bis(diisopropylamino)disilane; diisopropylaminosilane; tris(dimethylamino)silane; bis(ethyl-methyl-amino)silane; alkylaminosilylamines (e.g., AIR This may include ORTHRUS® (sold by LIQUIDE), hexakis(ethylamino)disilane Si2(NHEt)6(AHEAD), SiCl4(tetrasilicon chloride), SiCl4(tetrasilicon chloride) / pyridine, alkylchlorosilane, tetraethoxysilane (TEOS), 1,2-bis(diisopropylamino)disilane (BDIPADS), AP-LTO® 330, bis(diethylamino)silane (BDEAS), diisopropylaminosilane (DIPAS), tris(dimethylamino)silane (TDMAS), 3-aminopropyltriethoxysilane (APTES), bis(ethylmethylamino)silane (BEMAS), bis-dimethylaminosilane (BDMAS), bis(ethylmethylamino)silane, di(sec-butylamino)silane (DSBAS), and combinations thereof. Ozone (O3), O2, mixtures of O3 and O2, H2O, or combinations thereof may be used as oxygen precursors. In some embodiments, catalysts such as NH3, trimethylamine, and pyridine can also be provided.

[0357] Furthermore, the growth rate can be controlled by pulsing the silicon precursor (or multiple silicon precursors).

[0358] In another example, a thin aluminum oxide film may be deposited by ALD or plasma ALD. Deposition may be carried out at temperatures in the range of 25°C to 120°C. In some embodiments, the temperature may be at least 30°C, for example, 30°C to 80°C or 30°C to 60°C, preferably 100°C or less, preferably 80°C or less, preferably 60°C or less. The precursor for depositing the aluminum oxide film comprises one or more aluminum-containing precursors and one or more oxygen precursors. The aluminum-containing precursor may include, for example, trimethylaluminum (TMA) or consist of TMA. The oxygen precursor may include ozone (O3), O2, a mixture of O3 and O2, H2O, or a combination thereof. A schematic example of the process for depositing an aluminum oxide coating is shown in Figure 26. The schematic in Figure 26 also shows that the coating formed by ALD (or PEALD) may consist of multiple monolayers of the deposited compound, in this case, a monolayer of aluminum oxide.

[0359] In another example, a zirconium oxide (ZrO2) film may be deposited by ALD or plasma ALD. Deposition may be carried out at temperatures in the range of 25°C to 120°C. In some embodiments, the temperature may be at least 30°C, for example, 30°C to 80°C or 30°C to 60°C, preferably 100°C or less, preferably 80°C or less, preferably 60°C or less. The precursor for deposition of the zirconium oxide film comprises one or more zirconium-containing precursors and one or more oxygen precursors. The zirconium-containing precursor may include, for example, tetrakis(ethylmethylamino)zirconium (TEMAZ) or consist of TEMAZ. The oxygen precursor may include ozone (O3), O2, a mixture of O3 and O2, H2O, or a combination thereof.

[0360] In another example, ALD and / or PEALD can be used to deposit other barrier layer materials such as silicon nitride, silicon carbide, and aluminum oxide, or other such materials that can improve gas barrier and / or material dissociation functions. Due to the slow and controlled growth rate of ALD, which can increase material adhesion, tie layers may not be necessary.

[0361] Coating pharmaceutical containers such as syringes and vials presents a variety of problems. For example, syringes and vials typically have curved and other non-flat surfaces. Furthermore, it is generally desirable to coat only a single surface of the container, for example, the inner surface of the wall (adjacent to the lumen) or only the outer surface of the wall. Moreover, syringes typically have high aspect ratios, for example, up to 1 / 20, which can complicate the atomic layer deposition process, especially when the coating is applied to the inner surface of the wall (adjacent to the lumen).

[0362] To address these issues, the atomic layer deposition process must be carefully controlled with respect to the residence time of the gas during deposition and (b) the gas flow into the reaction chamber, including at least (a) potentially longer than conventional deposition times, to ensure that the gas passes through high aspect ratio components and reacts uniformly along the surface area of ​​the inner walls defining small diameter lumens.

[0363] Furthermore, since disposable pharmaceutical containers such as plastic syringes and vials must be manufactured in large quantities with high consistency from unit to unit, it is important that oxygen barrier coatings and / or water vapor barrier coatings can be applied simultaneously to several containers in a reactor, i.e., during a single film deposition process, with a high degree of consistency, i.e., that the thickness of the coating applied to the containers in the reactor has consistency in luminosity (the coating thickness has a low standard deviation).

[0364] Therefore, multiple containers, for example, at least 20, alternatively at least 50, alternatively at least 100, or alternatively at least 200, can be placed and arranged within the reactor, and the ALD or PEALD process can be performed such that a substantially uniform flow of precursor gas to each of the containers is achieved. As a result, a layer of coating can be built substantially uniformly across each of the multiple containers within the reactor. Examples of reactors that can be used for this process include reactors in the PICOSUN® P-1000 line, such as the PICOSUN® P-1000B PRO. To coat a large number of containers simultaneously, the containers can be arranged in a multi-level rack positioned within the reactor.

[0365] Water vapor barrier In embodiments of the present disclosure, containers made from the same thermoplastic material / resin may be coated with a water vapor barrier coating or layer to provide packaging having a water vapor transmission rate specified at 40.0°C and 75.0%RH using the water vapor transmission rate protocol described herein, such as primary drug packaging, vials, syringes, or vacuum blood collection tubes. The containers may optionally include one or more additional coatings, such as an oxygen barrier coating or layer, a tie coating or layer, a pH protective coating or layer, a lubricating coating or layer, or any combination thereof.

[0366] In embodiments of this disclosure, a container made from a thermoplastic material / resin may be coated with a water vapor barrier coating or layer, which, in combination with an oxygen barrier coating or layer described herein, provides a primary drug packaging, such as a vial, pre-filled syringe, or vacuum blood collection tube, having a shelf life of at least 3 months, alternatively at least 6 months, alternatively at least 9 months, alternatively at least 1 year, alternatively at least 1.5 years, alternatively at least 2 years, alternatively at least 2.5 years, or alternatively at least 3 years. In some embodiments, the primary drug packaging may be a vial containing a lyophilized drug product.

[0367] In some embodiments of this disclosure, containers made from general-purpose resins may be coated with a water vapor barrier coating or layer to produce the reduced water vapor transmission rates described above. As described above, special COP and COC resins used in the production of pharmaceutical containers such as vials and syringes have been selected largely due to the low water vapor transmission rates of the COP and COC container walls. Embodiments of the present invention have shown that it is possible to obtain comparable, equivalent, or better, i.e., lower water vapor transmission rates, by using lower-cost and more readily available general-purpose resins that can themselves (i.e., containers without any additional coatings) have water vapor transmission rates at least twice, alternatively at least three times, alternatively at least four times, or alternatively at least five times that of COP.

[0368] In some embodiments, for example, a container prepared from a general-purpose resin and coated with a water vapor barrier coating or layer may have a water vapor transmission rate within a commercially viable range for one or more pharmaceutical products, i.e., within a range sufficient to provide a commercially suitable shelf life for the finished pharmaceutical primary packaging. In some embodiments, a barrier coating or layer as described herein may be applied to a vial, for example, a 10 mL thermoplastic vial, and the vial (having associated stoppers) may have a WVTR of less than 2.0 mg / package / day, alternatively less than 1.5 mg / package / day, alternatively less than 1.0 mg / package / day, alternatively less than 0.9 mg / package / day, alternatively less than 0.8 mg / package / day, alternatively less than 0.7 mg / package / day, alternatively less than 0.6 mg / package / day, alternatively less than 0.5 mg / package / day, alternatively less than 0.4 mg / package / day, alternatively less than 0.3 mg / package / day, as specified using the water vapor transmission protocol described herein at 40.0 °C and 75.0% RH. In some embodiments, the thermoplastic vial may include a polycarbonate container wall. In other embodiments, the thermoplastic vial may include a container wall made from a cyclic block copolymer (CBC) as described herein.

[0369] In some embodiments, a container coated with a water vapor barrier coating or layer may be the same container made from COP resin but have a water vapor transmission rate at least equivalent to that of a container without a water vapor barrier coating or layer, optionally, the same container made from COP resin but with a water vapor transmission rate lower than that of a container without a water vapor barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower.

[0370] In some embodiments, a vacuum blood collection tube, such as a 9 mL blood collection tube having a container wall made of a general-purpose resin, may be coated with a barrier coating or layer as described herein, and the vial (with associated stopper) may have a WVTR of less than 0.5 mg / package / day, alternatively less than 0.4 mg / package / day, alternatively less than 0.3 mg / package / day, alternatively less than 0.2 mg / package / day, or alternatively less than 0.1 mg / package / day, as specified, for example, using the water vapor transmission protocol described herein at 40.0°C and 75.0% RH. For reference, an uncoated 9 mL blood collection tube made of COP may have a WVTR of about 0.1 mg / package / day. In some embodiments, the blood collection tube may include a container wall made of a cyclic block copolymer (CBC) as described herein.

[0371] Furthermore, by applying a water vapor barrier layer such as aluminum oxide to containers with walls made of general-purpose resins, such as syringes, vials, or blood collection tubes, it has been found that the water vapor transmission rate (WVTR) can be less than 0.050 mg / container / day, alternatively less than 0.040 mg / container / day, alternatively less than 0.030 mg / container / day, alternatively less than 0.020 mg / container / day, and alternatively less than 0.010 mg / container / day at 60°C and 40% relative humidity. In contrast, the water vapor transmission rate of the same container without a water vapor barrier layer can be greater than 1.0 g / container / day, optionally greater than 2.0 g / container / day, and optionally greater than 3.0 g / container / day.

[0372] In other embodiments, a container made from COP or COC resin may be coated with a water vapor barrier coating or layer to provide a water vapor transmission rate lower than that of the same container made from COP or COC resin but without the water vapor barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower. The container may optionally include one or more additional coatings, such as an oxygen barrier coating or layer, a tie coating or layer, a pH protective coating or layer, a lubricating coating or layer, or any combination thereof.

[0373] In some embodiments, for example, a vial such as a 10 mL COP vial may be coated with a barrier coating or layer as described herein, and the container (having associated stoppers) may have a WVTR of less than 0.25 mg / package / day, alternatively less than 0.22 mg / package / day, alternatively less than 0.22 mg / package / day, alternatively less than 0.20 mg / package / day, alternatively less than 0.18 mg / package / day, alternatively less than 0.16 mg / package / day, alternatively less than 0.15 mg / package / day, alternatively less than 0.13 mg / package / day, and alternatively less than 0.12 mg / package / day, as specified at 40.0°C and 75.0% RH using the water vapor transmission protocol described herein. For reference, an uncoated 10 mL vial made from COP may have a WVTR of about 0.25 mg / package / day at 40.0°C and 75.0% RH.

[0374] In some embodiments, for example, vials such as 10 mL COC vials may be coated with a barrier coating or layer as described herein, and vials (with associated stoppers) may have a WVTR of less than 0.25 mg / package / day, alternatively less than 0.22 mg / package / day, alternatively less than 0.22 mg / package / day, alternatively less than 0.20 mg / package / day, alternatively less than 0.18 mg / package / day, alternatively less than 0.16 mg / package / day, alternatively less than 0.15 mg / package / day, alternatively less than 0.13 mg / package / day, alternatively less than 0.12 mg / package / day, as specified at 40.0 °C and 75.0% RH using the water vapor transmission protocol described herein.

[0375] In some embodiments, for example, a vacuum blood collection tube such as a 9 mL blood collection tube having a container wall made from COP may be coated with a barrier coating or layer as described herein, and the container (having associated stopper) may have a WVTR of less than 0.1 mg / package / day, alternatively less than 0.09 mg / package / day, alternatively less than 0.08 mg / package / day, alternatively less than 0.07 mg / package / day, or alternatively less than 0.06 mg / package / day, as specified, for example, at 40.0°C and 75.0% RH using the water vapor transmission protocol described herein. For reference, an uncoated 9 mL blood collection tube made from COP may have a WVTR of about 0.1 mg / package / day.

[0376] The water vapor transmission rate of a container can be determined using a variety of test procedures. In some embodiments, the moisture content of a lyophilized composition stored in the lumen of a (sealed) container can be measured at various points in time to determine the rate at which the moisture content of the lyophilized composition increases over a defined time period. For example, the moisture content of a sample of the lyophilized composition may be measured over several consecutive days, e.g., at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days, etc., to obtain representative data. The water vapor transmission rate may be presented in terms of mg / container / day.

[0377] The conditions used in the test, i.e., the conditions under which the container is stored, can vary. In some embodiments, the container may be stored at 60°C and 40% relative humidity. In some embodiments, the container may be stored at 40°C and 75% relative humidity. In some embodiments, the container may be stored at room temperature (20-22°C) and 75% relative humidity. In some embodiments, the container may be stored under refrigeration, for example, at 3-8°C and 75% relative humidity.

[0378] In some embodiments, the measurement is performed using USP <921> This may be done in accordance with the USP, which is incorporated herein by reference in its entirety. <921> Method 1a is described, which is a titration of water based on the quantitative reaction of water with an aqueous solution of sulfur dioxide and iodine in the presence of a buffer that reacts with hydrogen ions. This method is also known as Karl Fischer titration. Any of the various Karl Fischer titration systems, including those manufactured by METTLER TOLEDO, can be used to perform this process, for example, under the Volumetric Compact Karl Fischer Titrator line, the Compact Coulometric Karl Fischer Titrator line, or the Titration Excellence line.

[0379] In other embodiments, measurements may be performed using a Computrac® Vapor Pro® system or a similar system operating on the same principle. The Computrac® Vapor Pro® system uses a thermosetting polymer capacitive relative humidity sensor to detect changes in relative humidity in a temperature-controlled sensor chamber resulting from the thermal evolution of sample moisture. Using this system, a sample that can be held in a vial (if the container is a vial) is heated in a sealed, temperature-controlled oven. The thermally evolved gas is transported by a dry, inert gas stream to a temperature-controlled sensor chamber housing the relative humidity sensor. This system can provide accurate and precise moisture analysis of a sample in a freeze-dried vial while limiting the sample's exposure to atmospheric moisture.

[0380] In other embodiments, the measurement is performed using USP <731> This may be done in accordance with the USP, which is incorporated herein by reference in its entirety. <731> This document describes a procedure for determining the amount of volatile substances from a sample under specified conditions. This procedure, known as the "loss on drying" test, is a thermogravimetric method in which the moisture content is determined from the weight difference before and after drying. (USP) <731> While the method described utilizes a drying oven, the loss-to-dry test can be performed more efficiently using a halogen moisture analyzer, in which the sample is heated through absorption of IR radiation from a halogen emitter, and the mass is continuously monitored during the drying process. The loss-to-dry test can be performed using any of the various halogen moisture analyzers, including, for example, those manufactured by METTLER TOLEDO. Unlike the two methods described above, the "loss-to-dry" method is not specific to the moisture content, meaning that the presence of other volatile substances in the sample may affect the accuracy of the results.

[0381] A water vapor barrier coating or layer may be applied to the outer and / or inner surfaces of the container. In some embodiments, the water vapor barrier coating or layer may even be applied as an intermediate step in the preparation of the container itself, in which case the water vapor barrier coating or layer may be nested between layers of resin and positioned between the inner and outer surfaces of the container wall. In some embodiments, the thickness of the water vapor coating or layer applied by ALD or PECVD, for example, the aluminum oxide coating or layer, may be 5-50 nm, alternatively 5-40 nm, alternatively 5-30 nm, alternatively 5-20 nm, alternatively 10-50 nm, alternatively 10-40 nm, alternatively 10-30 nm, or alternatively 10-20 nm.

[0382] The water vapor barrier coating or layer of this disclosure may also have several additional advantages with respect to pharmaceutical packaging such as syringes and vials. Specifically, in contrast to many known moisture barrier materials, this water vapor barrier coating may be inorganic. The composition of this water vapor barrier coating can also be tightly controlled, resulting in a coating consisting of a single compound and free from impurities and / or other potentially undesirable elements, compounds, etc. Therefore, for example, organic matter, impurities, or other undesirable elements are not incorporated by the liquid pharmaceutical in contact with the coating.

[0383] By providing plastic pharmaceutical packaging such as vials or syringes having a suitable water vapor barrier layer, the inventors can avoid the use of expensive specialty resins such as COP and COC. Embodiments of the present invention are thought to enable the preparation and use of containers made from general-purpose plastics that themselves may have poor water vapor permeability. In other embodiments, the inventors may provide plastic pharmaceutical packaging such as vials or syringes in which the container wall is made of COP or COC and the water vapor barrier layer provides the packaging with improved water vapor permeability. In some embodiments, for example, containers such as vials, syringes or blood collection tubes may be provided in which the container wall is made of COP or COC and the water vapor barrier layer provides the packaging with water vapor permeability equivalent to or substantially equivalent to that of the same container having a (uncoated) wall made of glass.

[0384] Furthermore, since blood collection tubes are maintained under vacuum before use, it is desirable to prevent environmental gases, including water vapor, from entering the vacuum lumen through the tube walls. A water vapor barrier layer prevents the intrusion of environmental water vapor, thereby providing a longer-lasting vacuum within the lumen of the blood collection tube. It has now been found that applying a water vapor barrier layer to the blood collection tube can significantly improve the storage life of vacuum blood collection tubes.

[0385] Applying a water vapor barrier layer to the blood collection tube can also improve the storage life of vacuum blood collection tubes by preventing solvent loss from the blood preservative contained within the lumen of the tube.

[0386] Nitrogen barrier coating or layer Since many biological drugs are susceptible to oxidation, the headspace of primary drug packaging, such as vials or syringes containing biological drugs, may be purged with an inert gas during filling. As a result, the primary drug packaging is sealed (e.g., using a stopper or plunger), and the lumen of the container contains not only the drug product but also the headspace, which is essentially composed of an inert gas as a blanket gas. However, over time, the inert gas in the headspace of a sealed package may evaporate through the container walls, reducing the inert gas content in the headspace. More common inert gases that can be used are nitrogen and argon, among others.

[0387] Furthermore, since the blood collection tube is maintained under vacuum before use, it is desirable to prevent environmental gases, including nitrogen, from passing through the tube's walls and entering the vacuum lumen.

[0388] Embodiments of the present disclosure relate to a container having a barrier coating or layer configured to prevent an inert gas such as nitrogen or argon from escaping through the container wall. Accordingly, in embodiments of the present disclosure, the gas barrier coating or layer may include one or more nitrogen barrier coatings or layers, which are effective in reducing the intrusion of nitrogen into the lumen or, as described above, the leaching of nitrogen from the lumen.

[0389] The nitrogen barrier coating or layer can optionally be deposited on the pharmaceutical packaging container by atomic layer deposition (ALD), plasma chemical vapor deposition (PECVD), or other chemical vapor deposition processes. Preferably, the nitrogen barrier coating or layer can be deposited by atomic layer deposition (ALD).

[0390] The nitrogen barrier coating or layer optionally includes an SiOx coating, comprising silicon, oxygen, and optionally other elements, where x is the ratio of oxygen atoms to silicon atoms, which is about 1.5 to about 2.9, or 1.5 to about 2.6, or about 2. The nitrogen barrier coating or layer optionally includes a metal oxide coating, such as aluminum oxide.

[0391] The nitrogen barrier coating or layer may be applied to the outer and / or inner surfaces of the container. In some embodiments, the nitrogen barrier coating or layer may even be applied as an intermediate step in the preparation of the container itself, in which case the nitrogen barrier coating or layer may be nested between layers of resin and positioned between the inner and outer surfaces of the container wall.

[0392] In embodiments of the present disclosure, a container made from a thermoplastic material / resin may be coated with a nitrogen barrier coating or layer, thereby providing packaging, such as a primary drug packaging, vial, syringe or vacuum blood collection tube, having a nitrogen permeability lower than that of identical packaging made from the same thermoplastic material / resin but without a nitrogen barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower. The container may optionally include one or more additional coatings, such as an oxygen barrier coating or layer, a water vapor barrier coating or layer, a tie coating or layer, a pH protective coating or layer, a lubricating coating or layer, or any combination thereof. In some embodiments, the container wall may be made of COP or COC resin, while in other embodiments, the container wall may be made of a general-purpose resin, such as CBC resin.

[0393] By applying such a nitrogen barrier layer to a container, such as a syringe or vial, the nitrogen permeability (NTR) is currently 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 Less than 0.00008d (optionally). -1 Less than 0.00006d (optionally). -1 Less than 0.00004d (optionally) -1 Less than 0.00003d (optionally). -1 Less than 0.00002d (optionally)-1 Less than 0.00001d (optionally). -1 It has been found that it can be less than [a certain value].

[0394] A nitrogen barrier coating or layer may be effective in reducing nitrogen intrusion into or outflow of the lumen of the primary drug packaging to less than 0.0002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00015 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00005 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.00001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar. Therefore, embodiments of vials containing a nitrogen barrier layer may be able to limit nitrogen intrusion into or leaching from the lumen to less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0001 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00005 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.00001 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar.

[0395] It has been found that applying a nitrogen barrier layer to containers, such as syringes or vials, allows for longer retention of the nitrogen blanket gas located in the container's headspace, thereby improving the shelf life of primary drug packaging.

[0396] The nitrogen barrier layer prevents the intrusion of environmental nitrogen, thereby providing a longer-lasting vacuum within the lumen of the blood collection tube. It has now been found that applying a nitrogen barrier layer to the blood collection tube can significantly improve the storage life of vacuum blood collection tubes.

[0397] Carbon monoxide barrier coating or layer Low doses of carbon monoxide are showing increasing interest as a therapeutic agent. Low doses of carbon monoxide have been shown to exhibit therapeutic effects, including anti-inflammatory and anti-apoptotic properties in sickle cell disease, kidney transplantation, and Parkinson's disease. Similarly, CO has been demonstrated to act as an effective anti-inflammatory agent in preclinical animal models of inflammation, acute lung injury, sepsis, ischemia / reperfusion injury, and organ transplantation. Additional experimental applications of this gas include pulmonary fibrosis, pulmonary hypertension, metabolic disorders, and pre-eclampsia. Low doses of carbon monoxide can be provided orally, intravenously, or inhaled. Since CO is a gas, inhalation is a natural administration consideration. However, gas inhalation presents various challenges. Consequently, formulations capable of delivering CO orally, intravenously, intraperitoneally, subcutaneously, or via other routes are under investigation and development. As with other pharmaceutical products, these formulations must be stored in containers, such as vials or pre-filled syringes. Over time, carbon monoxide within sealed packaging can evaporate through the container walls, reducing the carbon monoxide content of the pharmaceutical product.

[0398] Embodiments of the present disclosure relate to a container having a barrier coating or layer configured to prevent carbon monoxide from escaping through the container wall. Accordingly, in embodiments of the present disclosure, the gas barrier coating or layer may include one or more carbon monoxide barrier coatings or layers which are effective in reducing the ingress of carbon monoxide into the lumen or, more typically, reducing the leaching of carbon monoxide from the lumen as described above.

[0399] The carbon monoxide barrier coating or layer can optionally be deposited on the pharmaceutical packaging container by atomic layer deposition (ALD), plasma chemical vapor deposition (PECVD), or other chemical vapor deposition processes. Preferably, the carbon monoxide barrier coating or layer can be deposited by atomic layer deposition (ALD).

[0400] The carbon monoxide barrier coating or layer optionally includes an SiOx coating, comprising silicon, oxygen, and optionally other elements, where x is the ratio of oxygen atoms to silicon atoms, which is about 1.5 to about 2.9, or 1.5 to about 2.6, or about 2. The carbon monoxide barrier coating or layer optionally includes a metal oxide coating, such as aluminum oxide.

[0401] A carbon monoxide barrier coating or layer may be applied to the outer and / or inner surfaces of the container. In some embodiments, the carbon monoxide barrier coating or layer may even be applied as an intermediate step in the preparation of the container itself, in which case the carbon monoxide barrier coating or layer may be nested between layers of resin and positioned between the inner and outer surfaces of the container wall.

[0402] In embodiments of the present disclosure, a container made from a thermoplastic material / resin may be coated with a carbon monoxide barrier coating or layer, thereby providing packaging, such as a primary drug packaging, vial, syringe or vacuum blood collection tube, having a carbon monoxide transmission rate lower than that of identical packaging made from the same thermoplastic material / resin but without a carbon monoxide barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower. The container may optionally include one or more additional coatings, such as an oxygen barrier coating or layer, a water vapor barrier coating or layer, a tie coating or layer, a pH protective coating or layer, a lubricating coating or layer, or any combination thereof. In some embodiments, the container wall may be made of COP or COC resin, while in other embodiments, the container wall may be made of a general-purpose resin, such as CBC resin.

[0403] By applying such a carbon monoxide barrier layer to a container, such as a syringe or vial, the carbon monoxide transmission rate (COTR) is currently 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 Less than 0.00008d (optionally). -1 Less than 0.00006d (optionally). -1 Less than 0.00004d (optionally) -1 Less than 0.00003d (optionally). -1 Less than 0.00002d (optionally) -1 Less than 0.00001d (optionally). -1 It has been found that it can be less than [a certain value].

[0404] A carbon monoxide barrier coating or layer may be effective in reducing the intrusion of carbon monoxide into or out of the lumen of the primary drug packaging to less than 0.0002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00015 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00005 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.00001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar. Therefore, embodiments of vials containing a carbon monoxide barrier layer may be able to limit the intrusion of carbon monoxide into or out of the lumen to less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0001 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00005 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.00001 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar.

[0405] It has been found that applying a carbon monoxide barrier layer to containers, such as syringes or vials, allows for longer retention of carbon monoxide in the container's headspace, thereby improving the shelf life of primary drug packaging.

[0406] Carbon dioxide barrier coating or layer Some pharmaceutical products include liquid formulations in which the active agent (and excipients) are dissolved in a carbon dioxide-containing medium. This may be done, for example, to facilitate the stabilization of the active agent or, in some cases, simply to create a carbonated or effervescent composition. Nevertheless, when carbon dioxide is present in a formulation and the drug is packaged in a container (e.g., a vial or pre-filled syringe), it may be desirable to prevent the leaching of CO2 from the pharmaceutical product through the container wall.

[0407] Furthermore, since the blood collection tube is maintained under vacuum before use, it is desirable to prevent environmental gases, including carbon dioxide, from entering the vacuum lumen through the tube's walls.

[0408] Accordingly, embodiments of the present disclosure relate to a container having a barrier coating or layer configured to prevent carbon dioxide from escaping through the container wall. Accordingly, in embodiments of the present disclosure, the gas barrier coating or layer may include one or more carbon dioxide barrier coatings or layers which are effective in reducing the intrusion of carbon dioxide into the lumen or, more typically, reducing the leaching of carbon dioxide from the lumen as described above.

[0409] The carbon dioxide barrier coating or layer can optionally be deposited on the pharmaceutical packaging container by atomic layer deposition (ALD), plasma chemical vapor deposition (PECVD), or other chemical vapor deposition processes. Preferably, the carbon dioxide barrier coating or layer can be deposited by atomic layer deposition (ALD).

[0410] The carbon dioxide barrier coating or layer optionally includes an SiOx coating, comprising silicon, oxygen, and optionally other elements, where x is the ratio of oxygen atoms to silicon atoms, which is about 1.5 to about 2.9, or 1.5 to about 2.6, or about 2. The carbon dioxide barrier coating or layer optionally includes a metal oxide coating, such as aluminum oxide.

[0411] The carbon dioxide barrier coating or layer may be applied to the outer and / or inner surfaces of the container. In some embodiments, the carbon dioxide barrier coating or layer may even be applied as an intermediate step in the preparation of the container itself, in which case the carbon dioxide barrier coating or layer may be nested between layers of resin and positioned between the inner and outer surfaces of the container wall.

[0412] In embodiments of the present disclosure, a container made from a thermoplastic material / resin may be coated with a carbon dioxide barrier coating or layer, thereby providing packaging, such as a primary drug packaging, vial, syringe or vacuum blood collection tube, having a carbon dioxide transmission rate lower than that of identical packaging made from the same thermoplastic material / resin but without the carbon dioxide barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower. The container may optionally include one or more additional coatings, such as an oxygen barrier coating or layer, a water vapor barrier coating or layer, a tie coating or layer, a pH protective coating or layer, a lubricating coating or layer, or any combination thereof. In some embodiments, the container wall may be made of COP or COC resin, while in other embodiments, the container wall may be made of a general-purpose resin, such as CBC resin.

[0413] By applying such a carbon dioxide barrier layer to a container, such as a syringe or vial, the carbon dioxide transmission rate (CO2TR) is currently 0.005dB. -1 Less than 0.004d (optionally). -1 Less than 0.002d (optionally). -1 Less than 0.001d (optionally). -1 Less than 0.0008d (optionally). -1 Less than 0.0006d (optionally). -1 Less than 0.0005d (optionally). -1Less than 0.0004d (optio...

Claims

1. A primary drug packaging or pre-filled syringe, Thermoplastic syringe barrel, A lumen, at least partially defined by a side wall, wherein the side wall has an inner surface and an outer surface facing the lumen, Front opening and rear opening, and A gas barrier coating supported by at least one of the inner surface and outer surface of the side wall A thermoplastic syringe barrel containing, The aforementioned intraluminal drug, optionally a cold chain drug, optionally a liquid pharmaceutical of DNA type or mRNA type vaccine, A plunger that sits inside the syringe barrel and has a front surface facing the liquid pharmaceutical, Drug primary packaging or pre-filled syringes containing [the specified substance].

2. It is a syringe, Thermoplastic syringe barrel, A lumen, at least partially defined by a side wall, wherein the side wall has an inner surface and an outer surface facing the lumen, Front opening and rear opening, and A gas barrier coating supported by at least one of the inner surface and outer surface of the side wall A thermoplastic syringe barrel containing, A plunger seated in the aforementioned rear opening and Syringe containing.

3. Thermoplastic syringe barrel, A lumen defined at least partially by a side wall, wherein the side wall has an inner surface and an outer surface facing the lumen, Front opening and rear opening, A gas barrier coating supported by at least one of the inner surface and outer surface of the side wall Thermoplastic syringe barrel containing a thermoplastic syringe barrel.

4. The aforementioned front injection opening comprises a steakd needle or a Luer lock, optionally comprising a steakd needle, in the primary packaging of a drug, or a syringe or syringe barrel according to any one of claims 1 to 3.

5. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 4, further comprising a rigid needle shield.

6. A primary drug packaging or syringe according to any one of claims 1 or 2 or 4 or 5, configured to maintain container closure integrity (CCI) when circulated between -20°C and 10°C, optionally between -20°C and 20°C, optionally between -20°C and 30°C, optionally between -20°C and 40°C, optionally between -40°C and 10°C, optionally between -40°C and 20°C, optionally between -40°C and 30°C, optionally between -40°C and 40°C, optionally between -70°C and 10°C, optionally between -70°C and 20°C, optionally between -70°C and 30°C, and optionally between -70°C and 40°C.

7. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 6, wherein during each cycle, the packaging is kept at both low temperatures for 24 hours or more and at high temperatures for 24 hours or more, and optionally, during each cycle, the packaging is kept at both low temperatures for approximately 24 hours and at high temperatures for approximately 24 hours.

8. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 7, which undergoes at least three cycles and optionally three cycles.

9. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 8, wherein the filling volume of the packaging or syringe is at least 20% of the nominal capacity of the syringe, optionally, the filling volume of the packaging or syringe is at least 10% of the nominal capacity of the syringe, optionally, the filling volume of the packaging or syringe is at least 5% of the nominal capacity of the syringe.

10. The syringe is a primary drug packaging or syringe according to any one of claims 1 or 2 or 4 to 9, having a nominal filling capacity of 0.25 to 10 mL, optionally 0.5 to 5 mL, optionally 0.5 to 1 mL, optionally 0.5 mL, optionally 1 mL, or optionally 2.25 mL.

11. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 10, wherein the plunger includes a gasket attached to the distal end of the plunger.

12. The gasket comprises an elastic material, as described in claim 1 or 2 or any one of claims 4 to 11, for the primary packaging of a drug or syringe.

13. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 12, further comprising a film present on at least the circumferential outer surface portion of the gasket, optionally further comprising a fluoropolymer film.

14. The primary packaging or syringe for a drug according to claim 1 or 2 or any one of claims 4 to 13, wherein the gasket includes one or more channels on at least the circumferential outer surface portion.

15. A primary drug packaging or syringe according to any one of claims 1 or 2 or 4 to 14, wherein at least one of the one or more channels, each optionally, is discontinuous and includes a non-channel interruption portion.

16. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 15, comprising a plurality of channels on the circumferential outer surface portion of the gasket, each of which is substantially parallel to the others and spaced apart from the others in the axial direction.

17. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 16, wherein the non-channel interruption portion of each of the plurality of channels is not aligned with the non-channel interruption portion of an adjacent channel.

18. The plunger and the attached gasket have a sliding yield stress of 4 to 20 Newtons (N), as described in claim 1 or 2 or any one of claims 4 to 17, for a primary drug packaging or syringe.

19. The plunger and the attached gasket have a sliding equilibrium stress of 4 to 20 Newtons (N), as described in claim 1 or 2 or any one of claims 4 to 18, for a primary drug packaging or syringe.

20. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 19, wherein the gaskets of the syringe barrel and the plunger are sized such that, when assembled, they provide a space between the minimum inner diameter of the syringe barrel and the maximum outer diameter of the gasket that deviates from the nominal space by ±100 microns, ±50 microns, ±35 microns, ±25 microns, ±20 microns, ±15 microns, ±10 microns, ±5 microns, or ±2 microns or less.

21. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 20, wherein the plunger is configured not to move in the axial direction when the packaging or syringe is circulated at -20°C to 10°C, optionally at -20°C to 20°C, optionally at -20°C to 30°C, optionally at -20°C to 40°C, optionally at -40°C to 10°C, optionally at -40°C to 20°C, optionally at -40°C to 30°C, optionally at -40°C to 40°C, optionally at -70°C to 10°C, optionally at -70°C to 20°C, optionally at -70°C to 30°C, or optionally at -70°C to 40°C.

22. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 21, wherein the plunger is rotated between a locked position in which the plunger is prevented from moving in the axial direction and an unlocked position in which the plunger is allowed to move in the axial direction.

23. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 22, wherein at least a portion of the gas barrier coating basically consists of multiple atomic monolayers of pure elements or compounds, and optionally, at least a portion of the gas barrier coating is coated with ALD.

24. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 23, wherein at least a portion of the gas barrier coating is coated by PECVD.

25. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 24, wherein the syringe is configured such that, when the lumen is filled with Milli-Q water and undergoes one or more of the following: (i) inversion for two hours at 50 rpm, (ii) incubation for two weeks at 4°C, and (iii) five cycles of freeze-thaw at 20°C to -40°C, the contents of the lumen have fewer than 500,000 particles of size 300 nm or larger, alternatively fewer than 400,000 particles of size 300 nm or larger, or alternatively fewer than 300,000 particles of size 300 nm or larger, according to resonant mass metric.

26. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 25, wherein the syringe is configured such that, when the lumen is filled with Milli-Q water and inverted at 50 rpm for 2 hours, the contents of the syringe have fewer than 500 particles of size 2 μm or larger, alternatively fewer than 400 particles of size 2 μm or larger, alternatively fewer than 300 particles of size 2 μm or larger, and alternatively fewer than 200 particles of size 2 μm or larger, according to FlowCAM® microflow digital imaging, a light shielding test, or both.

27. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 26, wherein the syringe is configured such that, when the lumen is filled with Milli-Q water and incubated at 4°C for two weeks, the contents of the syringe contain fewer than 2,000 particles of size 2 μm or larger, alternatively fewer than 1,000 particles of size 2 μm or larger, alternatively fewer than 900 particles of size 2 μm or larger, alternatively fewer than 800 particles of size 2 μm or larger, alternatively fewer than 700 particles of size 2 μm or larger, alternatively fewer than 600 particles of size 2 μm or larger, and alternatively fewer than 500 particles of size 2 μm or larger, according to FlowCAM® microflow digital imaging, a light shielding test, or both.

28. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 27, wherein the syringe is configured such that, when the lumen is filled with Milli-Q water and subjected to five cycles of freeze-thaw at 20°C to -40°C, the contents of the syringe have fewer than 20,000 particles of size 2 μm or larger, alternatively fewer than 10,000 particles of size 2 μm or larger, alternatively fewer than 5,000 particles of size 2 μm or larger, alternatively fewer than 2,000 particles of size 2 μm or larger, alternatively fewer than 1,000 particles of size 2 μm or larger, alternatively fewer than 500 particles of size 2 μm or larger, and alternatively fewer than 300 particles of size 2 μm or larger, according to FlowCAM® microflow digital imaging, a light shielding test, or both.

29. The liquid pharmaceutical product, after the container has been rotated at 40°C for 5 minutes, followed by three freeze-thaw cycles from +5°C to -20°C at 1°C per minute for 2 or 4 weeks, or after the container has been stored at 5°C, 25°C and 60% relative humidity or 40°C and 75% relative humidity for 3 months, contains fewer than 50 particles having a size greater than 10 μm, according to claim 1 or 2 or any one of claims 4 to 28.

30. The liquid pharmaceutical product, after the container has been rotated at 40°C for 5 minutes, then for 2 weeks or 4 weeks, or after three freeze-thaw cycles from +5°C to -20°C at 1°C per minute, or after the container has been stored at 5°C, 25°C / 60% relative humidity, or 40°C / 75% relative humidity for 3 months, contains fewer than 5 particles having a size greater than 25 μm, according to claim 1 or 2 or any one of claims 4 to 29.

31. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 30, wherein there is no silicone oil or silicone coating on the syringe barrel and plunger.

32. The gas barrier coating is supported by the inner surface of the wall, in the primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 31.

33. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 32, further comprising a pH protective coating between the lumen and the gas barrier coating, wherein the pH protective coating is effective in extending the calculated storage life of the container.

34. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 33, wherein at least the surface of the pH protective coating facing the lumen has a surface energy customized for the drug formulation stored in the lumen.

35. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 34, wherein at least the surface of the pH protective coating facing the lumen has a water contact angle of 25° to 105°.

36. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 35, wherein at least the surface of the pH protective coating facing the lumen is hydrophilic and has a water contact angle of 25° to 60°, alternatively 25° to 50°, alternatively 30° to 60°, alternatively 30° to 50°, alternatively 40° to 60°, or alternatively 40° to 50°.

37. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 36, wherein at least the surface of the pH protective coating facing the lumen is hydrophobic and has a water contact angle of 70° to 105°, alternatively 75° to 105°, alternatively 80° to 105°, alternatively 85° to 105°, alternatively 90° to 105°, or alternatively 95° to 105°.

38. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 37, wherein at least the surface of the pH protective coating facing the lumen has a water contact angle of 50° to 80°, alternatively 55° to 75°, or alternatively 60° to 70°.

39. At least the surface facing the lumen of the pH protective coating has a surface free energy of 20 mJ / m 2 to 50 mJ / m 2 , alternatively 25 mJ / m 2 to 50 mJ / m 2 , alternatively 20 mJ / m 2 to 45 mJ / m 2 , alternatively 25 mJ / m 2 to 45 mJ / m 2 , alternatively 20 mJ / m 2 to 40 mJ / m 2 , alternatively 25 mJ / m 2 to 40 mJ / m 2 The primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 38, having the above surface free energy.

40. At least the surface of the pH protective coating facing the lumen is measured using the Kitazaki-Hata method to obtain a pH of 60 mJ / m 2 ~100 mJ / m 2 Alternatively, 60 mJ / m 2 ~90 mJ / m 2 Alternatively, 65 mJ / m 2 ~100 mJ / m 2 Alternatively, 65 mJ / m 2 ~90 mJ / m 2 , alternatively 70mJ / m 2 ~100 mJ / m 2 , alternatively 70mJ / m 2 ~90 mJ / m 2 A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 39, having a surface free energy of .

41. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 40, wherein the gas barrier coating includes an oxygen barrier coating or layer, and the oxygen barrier coating or layer is effective in reducing the intrusion of oxygen into the lumen to less than 0.0005 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0004 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0003 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.0001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar.

42. The gas barrier coating includes an oxygen barrier coating or layer, and the oxygen barrier coating or layer has a density of less than 0.0050d-1, alternatively less than 0.0040d-1, alternatively less than 0.0030d-1, alternatively less than 0.0020d-1, alternatively 0.0010d -1 Less than 0.0008d (optionally). -1 Less than 0.0006d (optionally). -1 Less than, alternatively less than 0.00050d-1, or optionally 0.0004d -1 Less than 0.0003d (optionally). -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 41, which is effective in providing the packaging or vial having an oxygen permeability constant of less than .

43. The gas barrier coating comprises an oxygen barrier coating or layer, the oxygen barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the oxygen barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition, according to any one of claims 1 to 42.

44. The gas barrier coating comprises an oxygen barrier coating or layer, as described in any one of claims 1 to 43, for a primary drug packaging, syringe, or syringe barrel.

45. The oxygen barrier coating or layer is applied by PECVD.

46. The oxygen barrier coating or layer is a metal oxide, optionally Al 2 O 3 A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 45, comprising or essentially consisting of the above.

47. The oxygen barrier coating or layer is SiO x A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 46, comprising or essentially consisting of, where x is 1.5 to 2.

9.

48. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 47, wherein the gas barrier coating includes a water vapor barrier coating or layer, and the water vapor barrier coating or layer is effective in reducing the intrusion of water vapor into the lumen to less than 0.05 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / package / day at 60°C and 40% relative humidity, and optionally less than 0.01 mg / package / day at 60°C and 40% relative humidity.

49. The gas barrier coating includes a water vapor barrier coating or layer, the water vapor barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the water vapor barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition, according to any one of claims 1 to 48.

50. The water vapor barrier coating or layer may be made of a metal oxide, optionally Al 2 O 3 A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 49, comprising or essentially consisting of the above.

51. The water vapor barrier coating or layer is SiO x A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 50, comprising or essentially consisting of, where x is 1.5 to 2.

9.

52. The lumen further contains nitrogen gas, the gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer limits the leakage of the nitrogen gas from the lumen to less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally 0.0001 cc / package at 25°C, 60% relative humidity, and 0.21 bar. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 51, which is effective in reducing the amount to less than 1 packing / day, optionally less than 0.00005 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.00001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar.

53. The gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer is 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 Less than 0.00008d (optionally). -1 Less than 0.00006d (optionally). -1 Less than 0.00004d (optionally) -1 Less than 0.00003d (optionally). -1 Less than 0.00002d (optionally). -1 Less than 0.00001d (optionally). -1 A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 52, which is effective in providing the packaging or vial having a nitrogen permeability constant (NTR) of less than 1.

54. The primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 53, wherein the gas barrier coating includes a nitrogen barrier coating or layer, the nitrogen barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the nitrogen barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

55. The nitrogen barrier coating or layer is a metal oxide, optionally Al 2 O 3 A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 54, comprising or essentially consisting of the above.

56. The nitrogen barrier coating or layer is SiO x A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 55, comprising or essentially consisting of, where x is 1.5 to 2.

9.

57. The lumen further contains carbon monoxide, the gas barrier coating includes a carbon monoxide barrier coating or layer, and the carbon monoxide barrier coating or layer limits carbon monoxide leakage from the lumen to less than 0.0002 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally 0.0001 cc / A primary drug packaging, syringe, or thermoplastic syringe barrel according to any one of claims 1 to 56, which is effective in reducing the amount to less than packaging / day, optionally less than 0.00005 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.00001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar.

58. The gas barrier coating includes a carbon monoxide barrier coating or layer, and the carbon monoxide barrier coating or layer is 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 Less than 0.00008d (optionally). -1 Less than 0.00006d (optionally). -1 Less than 0.00004d (optionally) -1 Less than 0.00003d (optionally). -1 Less than 0.00002d (optionally). -1 Less than 0.00001d (optionally). -1 A primary drug packaging, syringe, or thermoplastic syringe barrel according to any one of claims 1 to 57, which is effective in providing the packaging or vial having a carbon monoxide transmission rate (COTR) of less than 1 / 2.

59. The gas barrier coating comprises a carbon monoxide barrier coating or layer, the carbon monoxide barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the carbon monoxide barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition, according to any one of claims 1 to 58.

60. The carbon monoxide barrier coating or layer may be made of a metal oxide, optionally Al 2 O 3 A primary drug packaging, syringe, or thermoplastic syringe barrel according to any one of claims 1 to 59, comprising or essentially consisting of the same.

61. The carbon monoxide barrier coating or layer is SiO x A primary drug packaging, syringe, or thermoplastic syringe barrel according to any one of claims 1 to 60, comprising or essentially consisting of, where x is 1.5 to 2.

9.

62. The lumen further contains carbon dioxide, the gas barrier coating includes a carbon dioxide barrier coating or layer, and the carbon dioxide barrier coating or layer limits the leakage of carbon dioxide from the lumen to less than 0.005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.004 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.003 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally 25°C, relative humidity A primary drug packaging, syringe, or thermoplastic syringe barrel according to any one of claims 1 to 61, which is effective in reducing the amount to less than 0.002 cc / package / day at 60% and 0.21 bar, optionally less than 0.001 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0008 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, and optionally less than 0.0005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar.

63. The gas barrier coating comprises a carbon dioxide barrier coating or layer, and the carbon dioxide barrier coating or layer is effective in providing the packaging or vial having a carbon dioxide transmission rate (CO2TR) of less than 0.005d-1, optionally less than 0.004d-1, optionally less than 0.002d-1, optionally less than 0.001d-1, optionally less than 0.0008d-1, optionally less than 0.0006d-1, optionally less than 0.0005d-1, optionally less than 0.0004d-1, optionally less than 0.0003d-1, optionally less than 0.0002d-1, or optionally less than 0.0001d-1, according to any one of claims 1 to 62.

64. The gas barrier coating comprises a carbon dioxide barrier coating or layer, the carbon dioxide barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the carbon dioxide barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition, according to any one of claims 1 to 63.

65. The carbon dioxide barrier coating or layer is a metal oxide, optionally Al 2 O 3 A primary drug packaging, syringe, or thermoplastic syringe barrel according to any one of claims 1 to 64, comprising or essentially consisting of the above.

66. The carbon dioxide barrier coating or layer is SiO x A primary drug packaging, syringe, or thermoplastic syringe barrel according to any one of claims 1 to 65, comprising or essentially consisting of, where x is 1.5 to 2.

9.

67. The gas barrier coating comprises an ethylene oxide barrier coating or layer, as described in any one of claims 1 to 66, for a primary drug packaging, syringe, or syringe barrel.

68. The primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 67, wherein the primary drug packaging is optionally sterilized in the final step using ethylene oxide.

69. The pH protective coating or layer is SiO x C y or SiN x C y A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 68, comprising, where x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

70. The pH protective coating or layer is deposited by PECVD, in the primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 69.

71. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 70, wherein, in the presence of a fluid composition having a pH of 5 to 9 contained in the lumen, the calculated storage life of the packaging is more than 6 months at a storage temperature of 4°C.

72. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 71, wherein the fluid composition having a pH of 5 to 9 is removed at a rate of 1 nm or less in thickness of the pH protective coating or layer per 44 hours of contact with the fluid composition.

73. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, - The maximum amplitude of the Si-O-Si asymmetric stretching peak is approximately 1060 to 1100 cm⁻¹. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 72, having a ratio of more than 0.75 between them.

74. The syringe barrel is made of a thermoplastic material selected mainly from PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN™, cyclic block copolymer (CBC) resin, thermoplastic olefin polymer, COP, COC, or any combination thereof, as described in any one of claims 1 to 73.

75. The syringe barrel is mainly made of a cyclic block copolymer (CBC) resin, as described in any one of claims 1 to 74, for a primary drug packaging, syringe, or syringe barrel.

76. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 75, further comprising a lubricating coating or layer supported by the inner surface of the wall, a portion of the plunger, or both.

77. The primary packaging of a drug, or a syringe, or a syringe barrel according to any one of claims 1 to 76, wherein the lubricating coating or layer basically consists of SiOxCy, x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

78. The lubricating coating or layer is deposited by plasma chemical vapor deposition (PECVD) in the primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 77.

79. The primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 78, wherein the lubricating coating or layer is deposited by PECVD of a linear siloxane, monocyclic siloxane, polycyclic siloxane, polysilsesquioxane, or any combination thereof, optionally by PECVD of a monocyclic siloxane, or optionally by PECVD of octamethylcyclotetrasiloxane (OMCTS).

80. The primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 79, wherein the lubricating coating or layer has a thickness of 10 to 1000 nm, optionally 10 to 500 nm, optionally 10 to 200 nm, optionally 10 to 100 nm, or optionally 20 to 100 nm.

81. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 80, wherein the lubricating coating or layer provides (i) a lower plunger sliding force, (ii) a lower plunger sliding yield stress, or (iii) both (i) and (ii) compared to the same primary packaging or syringe barrel without the lubricating coating or layer.

82. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 81, wherein the lubricating coating or layer provides at least 45%, and optionally at least 60%, a reduction in (i) plunger sliding force, (ii) plunger sliding yield stress, or both (i) and (iii) compared to the same primary packaging or syringe barrel without the lubricating coating or layer.

83. The primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 82, wherein the lubricating coating or layer is disposed between the pH protective coating or layer and the lumen.

84. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, - The maximum amplitude of the Si-O-Si asymmetric stretching peak is approximately 1060 to 1100 cm⁻¹. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 83, having a ratio of greater than 0.75, optionally greater than 0.8, optionally greater than 0.85, or optionally greater than 0.9 in the range of .

85. The FTIR absorbance spectrum of the lubricating coating or layer is - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, - The maximum amplitude of the Si-O-Si asymmetric stretching peak is approximately 1060 to 1100 cm⁻¹. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 84, having a ratio of at most 0.75 among them.

86. The inner surface of the wall is - A tie coating or layer comprising SiOxCy or SiNxCy, wherein x is approximately 0.5 to approximately 2.4 and y is approximately 0.6 to approximately 3, and the tie coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the wall, A gas barrier coating or layer containing SiOx, wherein x is 1.5 to 2.9, the gas barrier coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the coating or layer, and the barrier coating or layer is effective in reducing the intrusion of atmospheric gas into the lumen compared to a container without a barrier coating or layer, A pH protective coating or layer comprising SiOxCy or SiNxCy, wherein x is about 0.5 to about 2.4 and y is about 0.6 to about 3, and the pH protective coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the barrier coating or layer. A primary drug packaging, syringe, or syringe barrel according to any one of claims 1 to 85, including the above.

87. The syringe barrel has an inner diameter that varies by ±0.05 mm or less, and is one of a plurality of drug primary packaging, syringes, or syringe barrels according to any one of claims 1 to 86.

88. A plurality of drug primary packaging, syringes, or syringe barrels according to any one of claims 1 to 87, wherein the syringe barrel has a consistent inner diameter having a standard deviation of less than 0.03 mm, optionally less than 0.02 mm, optionally less than 0.01 mm, optionally less than 0.008 mm, optionally less than 0.006 mm, optionally less than 0.005 mm, or optionally less than 0.004 mm.

89. A plurality of primary drug packaging, syringes, or syringe barrels according to any one of claims 1 to 88, wherein the syringe barrel has a needle hub or Luer hub outer diameter that varies by ±0.07 mm or less, and optionally by ±0.05 mm or less.

90. A plurality of primary drug packaging, syringes, or syringe barrels according to any one of claims 1 to 89, wherein the syringe barrel has a consistent needle hub or Luer hub outer diameter having a standard deviation of less than 0.15 mm, optionally less than 0.10 mm, optionally less than 0.08 mm, optionally less than 0.05 mm, optionally less than 0.02 mm, optionally less than 0.008 mm, or optionally less than 0.005 mm.

91. The syringe barrel has a length that varies by ±0.20 mm or less, and is a plurality of primary drug packaging, syringes, or syringe barrels according to any one of claims 1 to 90.

92. A plurality of drug primary packaging, syringes, or syringe barrels according to any one of claims 1 to 91, wherein the syringe barrel has a consistent length having a standard deviation of less than 0.06 mm, optionally less than 0.05 mm, optionally less than 0.04 mm, optionally less than 0.03 mm, optionally less than 0.02 mm, or optionally less than 0.01 mm.

93. A plurality of drug primary packaging, syringes, or syringe barrels according to any one of claims 1 to 92, wherein the syringe barrel has a consistent weight having a standard deviation of less than 0.025 g, optionally less than 0.020 g, optionally less than 0.015 g, optionally less than 0.010 g, optionally less than 0.0075 g, or optionally less than 0.005 g.

94. The variance or standard deviation is calculated over a sample of at least 20 units, optionally at least 50 units, optionally at least 100 units, optionally at least 200 units, optionally at least 300 units, optionally at least 500 units, or optionally at least 1000 units, for a plurality of primary drug packaging, syringes, or syringe barrels according to any one of claims 1 to 93.

95. Each of the plurality of packages or syringes is configured to maintain container closure integrity (CCI) when the plurality of packages or syringes are circulated at -20°C to 10°C, optionally at -20°C to 20°C, optionally at -20°C to 30°C, optionally at -20°C to 40°C, optionally at -40°C to 10°C, optionally at -40°C to 20°C, optionally at -40°C to 30°C, optionally at -40°C to 40°C, optionally at -70°C to 10°C, optionally at -70°C to 20°C, optionally at -70°C to 30°C, or optionally at -70°C to 40°C, as described in claim 1 or 2 or any one of claims 4 to 94.

96. A plurality of primary drug packaging or syringes according to claim 1 or 2 or any one of claims 4 to 95, wherein each cycle is maintained at both low temperatures for 24 hours or more and high temperatures for 24 hours or more, and optionally maintained at both low temperatures for approximately 24 hours and high temperatures for approximately 24 hours during each cycle.

97. A plurality of primary drug packaging or syringes according to claim 1 or 2 or any one of claims 4 to 96, which undergo at least three cycles and optionally three cycles.

98. A plurality of primary drug packaging or syringes according to claim 1 or 2 or any one of claims 4 to 97, wherein the filling volume of each packaging or syringe is at least 20% of the nominal capacity of the syringe, optionally, the filling volume of each packaging or syringe is at least 10% of the nominal capacity of the syringe, and optionally, the filling volume of each packaging or syringe is at least 5% of the nominal capacity of the syringe.

99. A plurality of primary drug packaging or syringes according to claim 1 or 2 or any one of claims 4 to 98, each syringe having a nominal filling capacity of 0.25 to 10 mL, optionally 0.5 to 5 mL, optionally 0.5 to 1 mL, optionally 0.5 mL, optionally 1 mL, or optionally 2.25 mL.

100. A plurality of primary drug packaging or syringes according to claim 1 or 2 or any one of claims 4 to 99, comprising at least 50 untested packages or syringes, optionally comprising 50 samples of untested packages or syringes, optionally comprising at least 100 untested packages or syringes, optionally comprising 100 samples of untested packages or syringes, optionally comprising at least 500 untested packages or syringes, optionally comprising 500 samples of untested packages or syringes, optionally comprising at least 1000 untested packages or syringes, optionally comprising 1000 samples of untested packages or syringes.

101. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 100, further comprising a plunger rod and a backstop element for preventing axial backward movement of the plunger.

102. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 101, wherein the backstop element prevents the plunger from moving backward in the axial direction when the packaged or filled syringe is subjected to a temperature of -20°C or lower, optionally -30°C or lower, optionally -40°C or lower, optionally -50°C or lower, optionally -60°C or lower, or optionally -70°C or lower.

103. The backstop element prevents the plunger from moving backward in the axial direction when the package or filled syringe is circulated at -20°C to 10°C, optionally at -20°C to 20°C, optionally at -20°C to 30°C, optionally at -20°C to 40°C, optionally at -40°C to 10°C, optionally at -40°C to 20°C, optionally at -40°C to 30°C, optionally at -40°C to 40°C, optionally at -70°C to 10°C, optionally at -70°C to 20°C, optionally at -70°C to 30°C, or optionally at -70°C to 40°C, according to claim 1 or 2 or any one of claims 4 to 102.

104. The backstop element is attached to the syringe barrel and extends over the upper part of the rear opening, as described in claim 1 or 2 or any one of claims 4 to 103, for a primary drug packaging or syringe.

105. The backstop element includes an extended finger flange, as described in claim 1 or 2 or any one of claims 4 to 104, for a primary drug packaging or syringe.

106. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 105, wherein the plunger rod includes one or more backstop engagement features.

107. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 106, wherein the backstop engagement feature is a radially protruding portion, optionally a radially protruding continuous ring, or a radially protruding discontinuous ring.

108. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 107, wherein the backstop engagement feature is wedge-shaped.

109. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 108, wherein the backstop element includes an aperture, the aperture is aligned with the rear opening of the syringe barrel.

110. The primary drug packaging or syringe according to claim S108, wherein the aperture is defined by an inner wall, and optionally, at least a portion of the inner wall moves toward the rear opening of the syringe barrel and inclined inward.

111. When the plunger rod is inserted into the syringe barrel to its stopping position, the rearward force on the plunger rod causes the backstop engagement feature to abut against the contact surface of the backstop element, thereby preventing further rearward movement of the plunger rod, and optionally the contact surface of the backstop element includes the lower edge of the inner wall of the aperture, as described in claim 1 or 2 or any one of claims 4 to 110.

112. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 111, wherein the backstop engagement feature is located, when the plunger is in its resting position within the syringe barrel, adjacent to the contact surface of the backstop, optionally within about 1.5 mm, optionally within about 1.0 mm, optionally within about 0.75 mm, optionally within about 0.5 mm, and optionally within about 0.25 mm.

113. The position of the backstop engagement feature on the plunger rod is coordinated with the plunger insertion depth in the syringe barrel corresponding to the filling volume of the filled and fully assembled drug primary packaging or a drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 112.

114. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 113, wherein the backstop element further comprises a locking collet, a threaded housing, and a twist-lock thumb nut.

115. The plunger rod is a primary drug packaging or syringe according to any one of claims 1 or 2 or 4 to 114, wherein the plunger rod does not include a backstop engagement feature.

116. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 115, wherein the backstop element includes an aperture, the aperture is aligned with the rear opening of the syringe barrel, and at least a portion of the aperture is defined by a flexible lock collet.

117. The flexible lock collet is configured such that the inner surface of the lock collet is compressed to compress a portion of the plunger rod that does not extend into the aperture, according to claim 1 or 2 or any one of claims 4 to 116.

118. The lock collet is divided into a plurality of sections by a circumferential gap, as described in claim 1 or 2 or any one of claims 4 to 117, for a primary drug packaging or syringe.

119. The primary packaging or syringe for a drug according to claim 1 or 2 or any one of claims 4 to 118, wherein the upper part of the lock collet is varied such that the diameter of the upper part of the lock collet increases as it moves downward.

120. The lower part of the twist-lock thumb nut is configured to interface with the upper part of the lock collet to compress the lock collet, as described in claim 1 or 2 or any one of claims 4 to 119.

121. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 120, further comprising a threaded housing that at least partially surrounds the lock collet.

122. The primary packaging or syringe for a drug according to claim 1 or 2 or any one of claims 4 to 121, wherein the threaded housing includes an inner wall, and at least a portion of the inner wall is threaded.

123. The threaded housing is configured to engage with a portion of the backstop element to optionally fix the threaded housing in a predetermined position by a snap-fit ​​connection, according to claim 1 or 2 or any one of claims 4 to 122.

124. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 123, further comprising a twist-lock thumb nut having a threaded portion that engages with the threaded housing.

125. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 124, wherein the twist-lock thumb nut includes a lower wall portion configured to interface with the upper part of the lock collet and compress the lock collet.

126. The lower wall portion of the twist-lock thumb nut is varied such that the aperture defined by the lower wall portion of the thumb nut has a diameter that increases as it moves downward, according to claim 1 or 2 or any one of claims 4 to 125.

127. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 126, wherein the twist-lock thumb nut includes a gripping outer surface comprising a plurality of ribs configured to provide an improved user grip.

128. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 127, wherein the backstop element comprises a lock block cavity and a lock block slidable within the lock block cavity.

129. The backstop element includes a central aperture aligned with the rear opening of the syringe barrel, and the lock block cavity spans the central aperture, according to claim 1 or 2 or any one of claims 4 to 128.

130. The lock block comprises an aperture including a large cross-sectional portion and a small cross-sectional portion, as described in claim 1 or 2 or any one of claims 4 to 129.

131. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 130, wherein the effective diameter of the large cross-sectional portion is greater than the diameter of the one or more backstop engagement features.

132. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 131, wherein the effective diameter of the small cross-sectional portion is smaller than the diameter of the one or more backstop engagement features.

133. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 132, wherein the inner wall defining at least partially the small cross-sectional portion has a radius of curvature substantially corresponding to the radius of curvature of the plunger rod.

134. The large cross-sectional portion and the small cross-sectional portion are separated by one or more ribs, or optionally pairs of opposing ribs arranged on the side walls, as described in claim 1 or 2 or any one of claims 4 to 133.

135. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 134, wherein each of the one or more ribs includes an inclined or curved surface facing the large cross-sectional portion of the aperture.

136. The primary drug packaging or syringe according to claim S134, wherein the inclined or curved surface is configured to facilitate the movement of the rib surface across the plunger rod when the lock block is moved from the unlocked position to the locked position.

137. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 136, wherein each of the one or more ribs includes an inclined or curved surface facing the small cross-sectional portion of the aperture.

138. The primary drug packaging or syringe according to claim S136, wherein the inclined or curved surface is configured to facilitate the movement of the rib surface across the plunger rod when the lock block is moved from the locked position to the unlocked position.

139. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 138, wherein sliding the lock block to the locked position aligns the small cross-sectional portion of the aperture with the rear opening of the syringe barrel, and sliding the lock block to the unlocked position aligns the large cross-sectional portion of the aperture with the rear opening of the syringe barrel.

140. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 139, wherein the lock block includes a first end and a second end, and the lock block is configured such that (i) a user can slide the lock block to an unlocked position by pressing the first end, and (ii) a user can slide the lock block to a locked position by pressing the second end.

141. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 140, wherein the first end includes a mark that indicates that pressing the first end causes the lock block to move to the unlocked position.

142. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 141, wherein the second end includes a mark that indicates that pressing the second end brings the lock block to the locked position.

143. The plunger rod comprises one or more backstop engagement features, optionally two or more backstop engagement features, in the primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 142.

144. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 143, wherein when the lock block is in the locked position, a rearward force on the plunger rod causes one of the one or more backstop engagement features to abut against the lower contact surface of the lock block, thereby preventing further rearward movement of the plunger rod.

145. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 144, wherein one of the one or more backstop engagement features is located, when the plunger is in its resting position within the syringe barrel, adjacent to the lower contact surface of the lock block, optionally within about 1.5 mm, optionally within about 1.0 mm, optionally within about 0.75 mm, optionally within about 0.5 mm, or optionally within about 0.25 mm.

146. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 145, wherein when the lock block is in the locked position, a forward force on the plunger rod causes the second of the one or more backstop engagement features to abut against the upper contact surface of the lock block, thereby preventing further forward movement of the plunger rod.

147. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 156, wherein the second of the one or more backstop engagement features is located adjacent to the upper contact surface of the lock block, optionally within about 1.5 mm, optionally within about 1.0 mm, optionally within about 0.75 mm, optionally within about 0.5 mm, and optionally within about 0.25 mm, when the plunger is in its stop position within the syringe barrel.

148. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 147, wherein the plunger rod does not include any backstop engagement feature, and the small cross-sectional portion of the aperture is configured to create an interlocking fit with the plunger rod.

149. (i) One or more retaining elements that require the application of a threshold force to slide the lock block from the locked position, (ii) One or more retaining elements that require the application of a threshold force to slide the lock block from the unlocked position, (iii) Both (i) and (ii) A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 148, further comprising:

150. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 149, wherein at least one of the inner surface defining the lock block cavity and the outer surface of the lock block includes one or more retaining ribs, and the other of the inner surface defining the lock block cavity and the outer surface of the lock block includes one or more recesses, at least one of the one or more recesses is configured to receive at least one of the one or more retaining ribs when the lock block is in the locked position.

151. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 150, wherein at least one of the inner surface defining the lock block cavity and the outer surface of the lock block includes one or more retaining ribs, and the other of the inner surface defining the lock block cavity and the outer surface of the lock block includes one or more recesses, at least one of the one or more recesses is configured to receive at least one of the one or more retaining ribs when the lock block is in the unlocked position.

152. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 151, wherein the backstop element is configured to prevent the movement of the plunger in both the rearward and forward directions.

153. The backstop element allows the user to insert the packaging or syringe. A locking mechanism that prevents the plunger rod from moving within the syringe barrel, Unlock configuration in which the plunger rod moves within the syringe barrel A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 152, configured to enable the following:

154. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 153, wherein the backstop element is configured to move between the locked configuration and the unlocked configuration by a user rotating a rotatable component of the backstop element, optionally a twist-lock thumb nut.

155. The rotatable component of the backstop element, optionally a twist-lock thumb nut, includes markings indicating (i) a first rotational direction corresponding to the locked position, (ii) a second rotational direction corresponding to the unlocked position, or (iii) both (i) and (ii), as described in claim 1 or 2 or any one of claims 4 to 154.

156. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 155, wherein the backstop element is configured to move between the locked configuration and the unlocked configuration by the user optionally pressing a lock block, a movable component of the backstop element, in a direction traversing the longitudinal axis of the syringe barrel.

157. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 156, wherein the movable component of the backstop element, optionally the lock block, includes (i) a first push direction corresponding to the locked position, (ii) a second push direction corresponding to the unlocked position, or (iii) a mark indicating both (i) and (ii).

158. A primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 157, wherein, when the backstop element is in an unlocked configuration, the plunger rod is configured to move within the syringe barrel with little to no resistance from the backstop element.

159. The primary drug packaging or syringe according to claim 1 or 2 or any one of claims 4 to 158, wherein, when the backstop element is in an unlock configuration, the plunger sliding force is configured to be the same as or substantially the same as the plunger sliding force of the same packaging or syringe but without the backstop element, and optionally, the plunger sliding force is within 10%, optionally within 5%, optionally within 3%, or optionally within 1% of the plunger sliding force of the same packaging or syringe but without the backstop element.

160. The drug primary packaging or syringe according to claim 1 or 2 or any one of claims 4 to 159, wherein, when the backstop element is in an unlock configuration, the plunger sliding yield stress is configured to be the same as or substantially the same as the plunger sliding force of the same packaging or syringe but without the backstop element, and optionally, the plunger sliding yield stress is within 10%, optionally within 5%, optionally within 3%, or optionally within 1% of the plunger sliding yield stress of the same packaging or syringe but without the backstop element.

161. Use of one or more packages or syringes according to claim 1 or 2 or any one of claims 4 to 160 for storing pharmaceuticals, optionally cold chain drugs, optionally DNA-type or mRNA-type vaccines, wherein during their lifespan, the drug-containing packages or syringes are kept at -20°C to 5°C, optionally -20°C to 10°C, optionally -20°C to 20°C, optionally -20°C to 30°C, optionally Use is permitted for exposure to a temperature range including selectively -20°C to 40°C, optionally -40°C to 5°C, optionally -40°C to 10°C, optionally -40°C to 20°C, optionally -40°C to 30°C, optionally -40°C to 40°C, optionally -70°C to 5°C, optionally -70°C to 10°C, optionally -70°C to 20°C, optionally -70°C to 30°C, and optionally -70°C to 40°C.

162. An automatic injector comprising a primary drug packaging or thermoplastic syringe as described in claim 1 or 2 or any one of claims 4 to 160.

163. Primary packaging for pharmaceuticals, Thermoplastic vial, A lumen that is at least partially defined by the lateral and bottom walls, The side wall has an inner surface and an outer surface facing the inner lumen, The bottom wall has an upper surface and a lower surface facing the lumen, An opening to the lumen, which is positioned opposite the bottom wall, A gas barrier coating supported by at least one of the inner surface and outer surface of the wall. A thermoplastic vial containing, A stopper seated in the aforementioned opening, The aforementioned intraluminal drug, optionally a cold chain drug, optionally a liquid pharmaceutical of DNA or mRNA type vaccine Primary packaging of pharmaceuticals including the drug.

164. Primary packaging for pharmaceuticals, Thermoplastic vial, A lumen that is at least partially defined by the lateral and bottom walls, The side wall has an inner surface and an outer surface facing the inner lumen, The bottom wall has an upper surface and a lower surface facing the lumen, An opening to the lumen, which is positioned opposite the bottom wall, A gas barrier coating supported by at least one of the inner surface and outer surface of the wall. A thermoplastic vial containing, A stopper seated in the aforementioned opening, The freeze-dried agent in the lumen and Primary packaging of pharmaceuticals including the drug.

165. It is packaging, Thermoplastic vial, A lumen that is at least partially defined by the lateral and bottom walls, The side wall has an inner surface and an outer surface facing the inner lumen, The bottom wall has an upper surface and a lower surface facing the lumen, An opening to the lumen, which is positioned opposite the bottom wall, A gas barrier coating supported by at least one of the inner surface and outer surface of the wall. A thermoplastic vial containing, A stopper seated in the aforementioned opening and Packaging including.

166. Thermoplastic vial, A lumen that is at least partially defined by the lateral and bottom walls, The side wall has an inner surface and an outer surface facing the inner lumen, The bottom wall has an upper surface and a lower surface facing the lumen, An opening to the lumen, which is positioned opposite the bottom wall, A gas barrier coating supported by at least one of the inner surface and outer surface of the wall. Thermoplastic vials containing [a specific component].

167. A primary drug packaging or packaging according to any one of claims 163 to 165, configured to maintain container closure integrity (CCI) when circulated at -20°C to 10°C, optionally circulated at -20°C to 20°C, optionally circulated at -20°C to 30°C, optionally circulated at -20°C to 40°C, optionally circulated at -40°C to 10°C, optionally circulated at -40°C to 20°C, optionally circulated at -40°C to 30°C, optionally circulated at -40°C to 40°C, optionally circulated at -70°C to 10°C, optionally circulated at -70°C to 20°C, optionally circulated at -70°C to 30°C, or optionally circulated at -70°C to 40°C.

168. A primary drug packaging or packaging according to any one of claims 163 to 165 or 167, wherein during each cycle, it is kept at both low temperatures for 24 hours or more and at high temperatures for 24 hours or more, and optionally, during each cycle, it is kept at both low temperatures for about 24 hours and at about 24 hours.

169. A primary drug packaging or packaging according to any one of claims 163 to 165 or 167 or 168, which undergoes at least three cycles, and optionally three cycles.

170. The primary packaging or packaging of a drug according to any one of claims 163 to 165 or 167 to 169, wherein the filling volume of the vial is at least 20% of the nominal volume of the vial, optionally, the filling volume of the vial is at least 10% of the nominal volume of the vial, and optionally, the filling volume of the vial is at least 5% of the nominal volume of the vial.

171. The vial has a nominal capacity of either 10 mL or 2 mL, and optionally, the vial has a nominal capacity of 10 mL, and optionally, the vial has a nominal capacity of 2 mL, as described in any one of claims 163 to 165 or 167 to 170.

172. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 171, wherein at least a portion of the gas barrier coating basically consists of multiple atomic monolayers of pure elements or compounds, and optionally, at least a portion of the gas barrier coating is coated with ALD.

173. The primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 172, wherein at least a portion of the gas barrier coating is coated by PECVD.

174. The lower surface of the thermoplastic vial is flat or substantially flat, the primary packaging of a drug, or packaging, or thermoplastic vial according to any one of claims 163 to 173.

175. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 174, wherein the lower surface of the thermoplastic vial generates an ink blot covering at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 75%, optionally at least 80%, optionally at least 85%, or optionally at least 90% of the surface area corresponding to the footprint of the vial.

176. During lyophilization, the vial contains at least 3.3 cal / s / cm³ 2 / ℃, or alternatively, at least 3.4 cal / s / cm 2 / ℃, or alternatively, at least 3.5 cal / s / cm 2 Heat transfer coefficient at / °C (Kv × 10) 4 A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 175, configured to have )

177. During freeze-drying, the heat transfer coefficient of the plurality of packages is 0.15 cal / s / cm². 2 Below 0.12 cal / s / cm², alternatively 0.12 cal / s / cm² 2 Below ℃, alternatively 0.10 cal / s / cm 2 Below ℃, alternatively 0.08 cal / s / cm 2 A plurality of primary drug packaging, or packaging, or thermoplastic vials according to any one of claims 163 to 176, having a standard deviation of less than / °C.

178. The standard deviation is calculated over a sample of at least 20 units, optionally at least 50 units, optionally at least 100 units, optionally at least 200 units, or optionally at least 300 units, according to any one of claims 163 to 177, for a plurality of primary drug packaging, or packaging, or thermoplastic vials.

179. A primary drug packaging or packaging according to any one of claims 163 to 165 or 167 to 178, configured to maintain container closure integrity for at least 3 months, optionally at least 6 months, optionally at least 9 months, or optionally at least 12 months when stored at -80°C.

180. The packaging is stored at -80°C for at least 3 months, optionally at least 6 months, optionally at least 9 months, optionally at least 12 months, and then 0.005d -1 Less than 0.004d (optionally). -1 Less than 0.003d (optionally). -1 Less than 0.002d (optionally). -1 Less than 0.001d (optionally). -1 Less than 0.0005d (optionally). -1 A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 179, having an oxygen permeability constant of less than .

181. The gas barrier coating is supported by the inner surface of the wall, the primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 180.

182. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 181, further comprising a pH protective coating between the lumen and the gas barrier coating, wherein the pH protective coating is effective in extending the calculated shelf life of the packaging.

183. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 182, wherein at least the surface of the pH protective coating facing the lumen has a surface energy customized for the drug stored in the lumen, or optionally the DNA-type or mRNA-type vaccine product stored in the lumen.

184. The primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 183, wherein at least the surface of the pH protective coating facing the lumen has a water contact angle of 25° to 105°.

185. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 184, wherein at least the surface of the pH protective coating facing the lumen is hydrophilic and has a water contact angle of 25° to 60°, alternatively 25° to 50°, alternatively 30° to 60°, alternatively 30° to 50°, alternatively 40° to 60°, or alternatively 40° to 50°.

186. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 185, wherein at least the surface of the pH protective coating facing the lumen is hydrophobic and has a water contact angle of 70° to 105°, alternatively 75° to 105°, alternatively 80° to 105°, alternatively 85° to 105°, alternatively 90° to 105°, or alternatively 95° to 105°.

187. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 186, wherein at least the surface of the pH protective coating facing the lumen has a water contact angle of 50° to 80°, alternatively 55° to 75°, or alternatively 60° to 70°.

188. At least the surface facing the lumen of the pH protective coating has a surface free energy of 20 mJ / m 2 to 50 mJ / m 2 alternatively 25 mJ / m 2 to 50 mJ / m 2 alternatively 20 mJ / m 2 to 45 mJ / m 2 alternatively 25 mJ / m 2 to 45 mJ / m 2 alternatively 20 mJ / m 2 to 40 mJ / m 2 alternatively 25 mJ / m 2 to 40 mJ / m 2 and is the primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 187.

189. At least the surface facing the lumen of the pH protective coating has a surface free energy of 60 mJ / m 2 to 100 mJ / m 2 , alternatively 60 mJ / m 2 to 90 mJ / m 2 , alternatively 65 mJ / m 2 to 100 mJ / m 2 , alternatively 65 mJ / m 2 to 90 mJ / m 2 , alternatively 70 mJ / m 2 to 100 mJ / m 2 , alternatively 70 mJ / m 2 to 90 mJ / m 2 The pharmaceutical primary packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 188, having.

190. The thermoplastic vial having the gas barrier coating contains less than 50 particles per mL that are 2 μm or larger in size, optionally less than 40 particles per mL that are 2 μm or larger in size, optionally less than 30 particles per mL that are 2 μm or larger in size, optionally less than 25 particles per mL that are 2 μm or larger in size, optionally less than 20 particles per mL that are 2 μm or larger in size, optionally less than 15 particles per mL that are 2 μm or larger in size, optionally less than 12 particles per mL that are 2 μm or larger in size, and optionally less than 10 particles per mL that are 2 μm or larger in size, according to any one of claims 163 to 189.

191. The primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 190, wherein the gas barrier coating comprises an oxygen barrier coating or layer, and the oxygen barrier coating or layer is effective in reducing the intrusion of oxygen into the lumen to less than 0.0005 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0004 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0003 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.0002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar.

192. The gas barrier coating includes an oxygen barrier coating or layer, and the oxygen barrier coating or layer is 0.0010d -1 Less than 0.0008d (optionally). -1 Less than 0.0006d (optionally). -1 Less than 0.0004d (optionally). -1 Less than 0.0003d (optionally). -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 191, which is effective in providing the packaging or vial having an oxygen permeability constant of less than .

193. The primary packaging of a drug, or packaging, or thermoplastic vial according to any one of claims 163 to 192, wherein the gas barrier coating includes an oxygen barrier coating or layer, the oxygen barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the oxygen barrier coating or layer is deposited by atomic layer deposition, or optionally by plasma-assisted atomic layer deposition.

194. The primary packaging of a drug, or packaging, or thermoplastic vial according to any one of claims 163 to 193, wherein the gas barrier coating comprises an oxygen barrier coating or layer, and the oxygen barrier coating or layer is applied by PECVD.

195. The oxygen barrier coating or layer is a metal oxide, optionally Al 2 O 3 A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 194, comprising or essentially consisting of the above.

196. The oxygen barrier coating or layer is SiO x A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 195, comprising or essentially consisting of, where x is 1.5 to 2.

9.

197. The primary drug packaging, packaging, or thermoplastic vial according to any one of claims 163 to 196, wherein the gas barrier coating includes a water vapor barrier coating or layer, and the water vapor barrier coating or layer is effective in reducing the intrusion of water vapor into the lumen to less than 0.05 mg / packaging / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / packaging / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / packaging / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / packaging / day at 60°C and 40% relative humidity, and optionally less than 0.01 mg / packaging / day at 60°C and 40% relative humidity.

198. When the gas barrier coating is stored at 40.0°C and 75.0% relative humidity, the penetration of water vapor into the lumen is less than 2.0 mg / package / day, alternatively less than 1.5 mg / package / day, alternatively less than 1.0 mg / package / day, alternatively less than 0.9 mg / package / day, alternatively less than 0.8 mg / package / day, alternatively less than 0.7 mg / package / day, alternatively less than 0.6 mg / package / day, alternatively less than 0.5 mg / package / day, alternatively less than 0.4 mg / package / day, alternatively less than 0.3 mg / package / day. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 197, which reduces the amount to less than 0.25 mg / package / day, less than 0.22 mg / package / day, less than 0.22 mg / package / day, less than 0.20 mg / package / day, 0.18 mg / package / day or less, less than 0.16 mg / package / day or less, 0.15 mg / package / day or less, 0.13 mg / package / day or less, or 0.12 mg / package / day or less.

199. The gas barrier coating includes a water vapor barrier coating or layer, the water vapor barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the water vapor barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition, according to any one of claims 163 to 198.

200. The water vapor barrier coating or layer may be made of a metal oxide, optionally Al 2 O 3 A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 199, comprising or essentially consisting of the above.

201. The water vapor barrier coating or layer is SiO x A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 200, comprising or essentially consisting thereof, where x is 1.5 to 2.

9.

202. The headspace of the lumen further contains nitrogen gas, the gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer limits the leakage of the nitrogen gas from the lumen to less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally 0.0001 cc at 25°C, 60% relative humidity, and 0.21 bar. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 201, which is effective in reducing to less than c / packaging / day, optionally less than 0.00005 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, and optionally less than 0.00001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar.

203. The gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer is 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 Less than 0.00008d (optionally). -1 Less than 0.00006d (optionally). -1 Less than 0.00004d (optionally) -1 Less than 0.00003d (optionally). -1 Less than 0.00002d (optionally). -1 Less than 0.00001d (optionally). -1 A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 202, which is effective in providing the packaging or vial having a nitrogen permeability constant (NTR) of less than 0.

204. The primary packaging of a pharmaceutical product, or packaging, or thermoplastic vial according to any one of claims 163 to 203, wherein the gas barrier coating includes a nitrogen barrier coating or layer, the nitrogen barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the nitrogen barrier coating or layer is deposited by atomic layer deposition, or optionally by plasma-assisted atomic layer deposition.

205. The nitrogen barrier coating or layer is a metal oxide, optionally Al 2 O 3 A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 204, comprising or essentially consisting of the above.

206. The nitrogen barrier coating or layer is SiO x A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 205, comprising or essentially consisting thereof, where x is 1.5 to 2.

9.

207. The lumen further contains carbon monoxide, the gas barrier coating includes a carbon monoxide barrier coating or layer, and the carbon monoxide barrier coating or layer limits the leakage of carbon monoxide from the lumen to less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally 0.0001 cc at 25°C, 60% relative humidity, and 0.21 bar. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 206, which is effective in reducing the amount to less than 0.00005 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00002 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00001 cc / packaging / day at 25°C, 60% relative humidity, and 0.21 bar.

208. The gas barrier coating includes a carbon monoxide barrier coating or layer, and the carbon monoxide barrier coating or layer is 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 Less than 0.00008d (optionally). -1 Less than 0.00006d (optionally). -1 Less than 0.00004d (optionally) -1 Less than 0.00003d (optionally). -1 Less than 0.00002d (optionally). -1 Less than 0.00001d (optionally). -1 A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 207, which is effective in providing the packaging or vial having a carbon monoxide transmission rate (COTR) of less than 1 / 200.

209. The gas barrier coating comprises a carbon monoxide barrier coating or layer, the carbon monoxide barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the carbon monoxide barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition, according to any one of claims 163 to 208.

210. The carbon monoxide barrier coating or layer may be made of a metal oxide, optionally Al 2 O 3 A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 209, comprising or essentially consisting of the above.

211. The carbon monoxide barrier coating or layer is SiO x A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 210, comprising or essentially consisting of, where x is 1.5 to 2.

9.

212. The lumen further contains carbon dioxide, the gas barrier coating includes a carbon dioxide barrier coating or layer, and the carbon dioxide barrier coating or layer limits the leakage of carbon dioxide from the lumen to less than 0.005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.004 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.003 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally 25°C, relative humidity A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 211, which is effective in reducing the amount to less than 0.002 cc / packaging / day at 60% temperature and 0.21 bar, optionally less than 0.001 cc / packaging / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0008 cc / packaging / day at 25°C, 60% relative humidity and 0.21 bar, or optionally less than 0.0005 cc / packaging / day at 25°C, 60% relative humidity and 0.21 bar.

213. The gas barrier coating comprises a carbon dioxide barrier coating or layer, and the carbon dioxide barrier coating or layer is effective in providing the packaging or vial having a carbon dioxide transmission rate (CO2TR) of less than 0.005d-1, optionally less than 0.004d-1, optionally less than 0.002d-1, optionally less than 0.001d-1, optionally less than 0.0008d-1, optionally less than 0.0006d-1, optionally less than 0.0005d-1, optionally less than 0.0004d-1, optionally less than 0.0003d-1, optionally less than 0.0002d-1, or optionally less than 0.0001d-1, according to any one of claims 163 to 212.

214. The gas barrier coating comprises a carbon dioxide barrier coating or layer, the carbon dioxide barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the carbon dioxide barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition, according to any one of claims 163 to 213.

215. The carbon dioxide barrier coating or layer is a metal oxide, optionally Al 2 O 3 A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 214, comprising or essentially consisting of the above.

216. The carbon dioxide barrier coating or layer is SiO x A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 215, comprising or essentially consisting of, where x is 1.5 to 2.

9.

217. The gas barrier coating comprises an ethylene oxide barrier coating or layer, as described in any one of claims 163 to 216, for a primary drug packaging, or packaging, or thermoplastic vial.

218. The primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 217, wherein the primary drug packaging is optionally sterilized in the final step using ethylene oxide.

219. The pH protective coating or layer is SiO x C y or SiN x C y A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 218, comprising, x being about 0.5 to about 2.4, and y being about 0.6 to about 3.

220. The pH protective coating or layer is deposited by PECVD, as described in any one of claims 163 to 219, for a primary drug packaging, or packaging, or thermoplastic vial.

221. If a fluid composition having a pH of 5 to 9 is contained in the lumen, the calculated storage life of the packaging is more than 6 months at a storage temperature of 4°C, according to any one of claims 163 to 220, a primary drug packaging, or packaging, or thermoplastic vial.

222. A primary pharmaceutical packaging, packaging, or thermoplastic vial according to any one of claims 163 to 221, wherein the fluid composition having a pH of 5 to 9 is removed at a rate of 1 nm or less in thickness of the pH protective coating or layer per 44 hours of contact with the fluid composition.

223. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, - The maximum amplitude of the Si-O-Si asymmetric stretching peak is approximately 1060 to 1100 cm⁻¹. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 222, having a ratio of more than 0.75 between them.

224. The vial is made of a thermoplastic material selected mainly from PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN™, cyclic block copolymer (CBC) resin, thermoplastic olefin polymer, COP, COC, or any combination thereof, as described in any one of claims 163 to 223, which is a primary drug packaging, or packaging, or thermoplastic vial.

225. The vial is a primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 224, wherein the vial is mainly made of a cyclic block copolymer (CBC) resin.

226. The inner surface of the wall is - A tie coating or layer comprising SiOxCy or SiNxCy, wherein x is approximately 0.5 to approximately 2.4 and y is approximately 0.6 to approximately 3, and the tie coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the wall, A gas barrier coating or layer containing SiOx, wherein x is 1.5 to 2.9, the gas barrier coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the coating or layer, and the barrier coating or layer is effective in reducing the intrusion of atmospheric gas into the lumen compared to a container without a barrier coating or layer, A pH protective coating or layer comprising SiOxCy or SiNxCy, wherein x is about 0.5 to about 2.4 and y is about 0.6 to about 3, and the pH protective coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the barrier coating or layer. A primary drug packaging, or packaging, or thermoplastic vial according to any one of claims 163 to 225, including the above.

227. A plurality of primary drug packaging, or packaging, or thermoplastic vials according to any one of claims 163 to 226, wherein each of the plurality of packaging is configured to maintain container closure integrity (CCI) when the plurality of packaging is circulated at -20°C to 10°C, optionally at -20°C to 20°C, optionally at -20°C to 30°C, optionally at -20°C to 40°C, optionally at -40°C to 10°C, optionally at -40°C to 20°C, optionally at -40°C to 30°C, optionally at -40°C to 40°C, optionally at -70°C to 10°C, optionally at -70°C to 20°C, optionally at -70°C to 30°C, or optionally at -70°C to 40°C.

228. During each cycle, the plurality of packagings are kept at both low temperatures for 24 hours or more and high temperatures for 24 hours or more, and optionally, during each cycle, the plurality of packagings are kept at both low temperatures for about 24 hours and high temperatures for about 24 hours, wherein the plurality of primary drug packagings, packaging, or thermoplastic vials are as described in any one of claims 163 to 227.

229. A plurality of primary drug packaging, or packaging, or thermoplastic vials according to any one of claims 163 to 228, wherein the plurality of packaging undergoes at least three cycles, and optionally, the plurality of packaging undergoes three cycles.

230. A plurality of primary drug packaging, or packaging, or thermoplastic vials according to any one of claims 163 to 229, wherein the filling volume of each vial is at least 20% of the nominal capacity of the vial, optionally, the filling volume of each vial is at least 10% of the nominal capacity of the vial, and optionally, the filling volume of each vial is at least 5% of the nominal capacity of the vial.

231. A plurality of primary drug packaging, or packaging, or thermoplastic vials according to any one of claims 163 to 230, wherein each vial has a nominal capacity of either 10 mL or 2 mL, and optionally each vial has a nominal capacity of either 10 mL or 2 mL.

232. A plurality of primary drug packaging, or packaging, or thermoplastic vials according to any one of claims 163 to 231, wherein the plurality of packaging comprises at least 50 untested packaging, optionally comprising samples of 50 untested packaging, optionally comprising at least 100 untested packaging, optionally comprising samples of 100 untested packaging, optionally comprising at least 500 untested packaging, optionally comprising samples of 500 untested packaging, optionally comprising at least 1000 untested packaging, optionally comprising samples of 1000 untested packaging.

233. A use of one or more packages or thermoplastic vials according to any one of claims 163 to 232 for storing a drug, optionally lyophilized drug, optionally cold chain drug, optionally DNA-type or mRNA-type vaccine, wherein during its lifespan, the drug-containing package is kept at -20°C to 5°C, optionally -20°C to 10°C, optionally -20°C to 20°C, optionally -20°C to 30°C Use is permitted to expose the product to a temperature range including, optionally, -20°C to 40°C, optionally -40°C to 5°C, optionally -40°C to 10°C, optionally -40°C to 20°C, optionally -40°C to 30°C, optionally -40°C to 40°C, optionally -70°C to 5°C, optionally -70°C to 10°C, optionally -70°C to 20°C, optionally -70°C to 30°C, and optionally -70°C to 40°C.

234. The lumen is as follows: Biologics Abatacept; Absiximab; Avobotulinum toxin A; Adalimumab; Adalimumab-adaz; Adalimumab-adbm; Adalimumab-afzb; Adalimumab-atto; Adalimumab-bwwd; Ado-trastuzumab emtansine; Aflibercept; Agalsidase beta; Albiglutide; Chromium-51 serum albumin; Aldesleukin; Alphacept; Alemtuzumab; Alglucosidase alfa; Alirocumab; Alteplase; Anakinra; Aprotinin; Asfotase alfa; Asparaginase; Asparagus Ginaze erwinia chrysanthemum; atezolizumab; avelumab; basiliximab; becaprelmin; beratacept; belimumab; benralizumab; belactant; bevacizumab; bevacizumab-awwb; bevacizumab-bvzr; bezlotoxumab; blinatumomab; brentuximab vedotin; brodalumab; brolucizumab-dbll; brosumab-twza; caraspargaze pegol-mknl; calfactant; canakinumab; capracizumab-yhdp; capromab pendetide; semiprimab-rwlc; senegermin-bkbj; se Luliponase alfa; certolizumab pegol; cetuximab; choriogonadotropin alfa; chorionic gonadotropin; chymopapain; collagenase; collagenase Clostridium histolyticum; corticolellin overvine triflutate; chryzanlizumab-tmca; daclizumab; daratumumab; daratumumab and hyaluronidase-fihj; darbepoetin alfa; denileukin difutitox; denosumab; decilidine; dinutuximab; dorunase alfa; dorotrecogin alfa; dulaglutide; dupilumab; durvalumab Ecalantid; Eculizumab; Ephalizumab; Elapegademase-lvr; Elosulfase alfa; Elotuzumab; Emapalmab-lzsg; Emicizumab-kxwh; Enfortumab vedotin-ejfv; Epoetin alfa; Epoetin alfa-epbx; Erenumab-aooe; Etanercept; Etanercept-szzs; Etanercept-ykro; Evolocumab; Fam-trastuzumab deruxtecan-nxki; Fibrinolysin and deoxyribonuclease mixture with chloramphenicol [bovine]; Filgrastim;Filgrastim-aafi; Filgrastim-sndz; Follitropin alfa; Follitropin beta; Fremanezumab-vfrm; Galcanezumab-gnlm; Galsulfase; Gemtuzumab ozogamicin; Glucarpidase; Golimumab; Guselkumab; Hyaluronidase; Human hyaluronidase; Ibalizumab-uiyk; Ibritumomab tiuxetan; Idarucizumab; Idursulfase; Imiglucerase; Incobotulinum toxin A; Rinebilizumab-cdon; Infliximab; Infliximab-abda; Infl Liximab-axxq; Infliximab-dyyb; Infliximab-qbtx; Inotuzumab ozogamicin; Insulin aspart; Insulin aspart protamine and insulin aspart; Insulin degludec; Insulin degludec and insulin aspart; Insulin degludec and liraglutide; Insulin detemir; Insulin glargine; Insulin glargine and lixisenatide; Insulin glulisine; Human insulin; Human isofenstein insulin; Human isofenstein insulin and human insulin; Insulin lispro Insulin lisproprotamine and insulin lispro; insulin lispro-aabc; interferon alpha-2a; interferon alpha-2b; interferon alpha-con-1; interferon alpha-n3 (derived from human leukocytes); interferon beta-1a; interferon beta-1b; interferon gamma-1b; ipilimumab; isatuximab-irfc; ixekizumab; lanadermab-flyo; laronidase; lixisenatide; ruspatercept-aamt; mecasermin; mecasermin linfaber To; menotropins; mepolizumab; methoxypolyethylene glycol-epoetin beta; metreleptin; mogamulizumab-kpkc; moxetumomab-passudotox-tdfk; muromanab-CD3; natalizumab; necitumumab; nivolumab; nofetumomab; obiltoxaximab; obinutuzumab; ocrelizumab; ocuriplasmin; ofatumumab; olaratumab; omalizumab; onabotulinumtoxin A; oprelbequin; parifermin; palivizumab; pancrelipase; panitumumab; parathyroid hormone; cowpeguademase;Pegaspargase; Pegfilgrastim; Pegfilgrastim-apgf; Pegfilgrastim-bmez; Pegfilgrastim-cbqv; Pegfilgrastim-jmdb; Peginterferon alpha-2a; Peginterferon alpha-2a and ribavirin; Peginterferon alpha-2b; Peginterferon alpha-2b and ribavirin; Peginterferon beta-1a; Pegroticase; Pegvariase-pqpz; Pegvisomant; Pembrolizumab; Pertuzumab; Polatuzumab vedotin-piiq; Polactant alpha; Prabotulinum toxin A-xvfs; Radiolabeled albumin technetium Tc -99m albumin colloid kit; ramucirumab; ranibizumab; rasburicase; ravulizumab-cwvz; laxibakumab; reslizumab; leteplase; lilonacept; botulinum toxin type B; risankizumab-rzaa; rituximab; rituximab and human hyaluronidase; rituximab-abbs; rituximab-pvvr; romiplostim; romosozumab-aqqg; sacituzumab govitecan-hziy; sacrosidase; salglamostim; sarilumab; seberipase alfa; secukinumab; siltuximab; somatropin; taglaxofusp-erzs; taliglucerase alfa; tbo-filgrastim; technetium-99m tcphanolesomab; tenecteplase; teprotumumab-trbw; tesamorelin acetate; human thyrotropin alpha; tildrakizumab-asmn; tocilizumab; tocitumomab and iodine I-131 tocitumomab; trastuzumab; trastuzumab and hyaluronidase-oysk; trastuzumab-anns; trastuzumab-dkst; trastuzumab-dttb; trastuzumab-pkrb; trastuzumab-qyyp; urof Folitropin; urokinase; ustekinumab; vedolizumab; veraglucerase alfa; bestronidase alfa-vjbk; Ziv-aflibercept; Amjevita (adalimumab-atto); Dupixent (dupilumab); Fulphila (pegfilgrastim-jmdb); Ilaris (canakinumab); Ixifi (infliximab-qbtx); Lyumjev (insulin lispro-aabc);Nyvepria (pegfilgrastim-apgf); Ogivri (trastuzumab-dkst); Semglee (insulin glargine); Uplizna (inebilizumab-cdon); A.P.L. (human chorionic gonadotropin); Abrillada (adalimumab-afzb); Accretropin (somatropin); Actemra (tocilizumab); Acthrel (corticolin overtriflutate); Actimune (interferon gamma-1b); Activase (alteplase); Adagen (bovine pegademase); Adakveo (chryzanlizumab-tmca); Adcetris (Brentuximab vedotin); Adlyxin (lixisenatide); Admelog (insulin lispro); Afrezza (human insulin); Aimovig (erenumab-aooe); Ajovy (fremanezumab-vfrm); Aldurazime (laronidase); AlferonN injection (interferon alpha-n3 (derived from human leukocytes)); Amevive (alefacept); Amphadase (human leukocytes) Alronidase); Anthim (Obiltoxaximab); Apidra (Insulin glulisine); Aranesp (Darbepoetin alfa); Arcalist (Rilonacept); Arzerra (Ofatumumab); Asparlas (Caraspargase pegol-mknl); Avastin (Bevacizumab); Avonex (Interferon beta-1a); Avsola (Infliximab-axq); Bas aglar (insulin glargine); Bavencio (avelumab); Benlysta (belimumab); Beovu (brolucizumab-dbll); Besponsa (inotuzumab ozogamicin); Betaseron (interferon beta-1b); Bexxar (tositumomab and iodine I-131 tositumomab); Blincyto (blinatumomab); Botox (onabotulinum toxin A); Botox Cosmetic (Onabotulinum toxin A); Bravelle (Urofolitropin); Brineura (Cerliponase alfa); Cabrivi (Caplacizumab-yhdp); Campath (Alemtuzumab); Cathfloxacin (Alteplase);Cerezyme (imiglucerase); Chorionic Gonadotropin; Chromalbin (chromium-oxidized CR-51 serum albumin); Chymodiactin (chymopapain); Cimzia (certolizumab pegol); Cinqair (resulizumab); Cosentyx (secukinumab); Cotazym (pancrelipase); Creon (pancrelipase); Crysvita (brosumab-twza); Curosurf (polactant alfa); Cyltez (adalimumab-adbm); Cyramza (ramucirumab); Darzalex (daratumumab); Darzalex Faspro (daratumumab and hyaluronider-fihj); Draximage MAA (kit for preparing technetium Tc-99m albumin agglutination); Dysport (avobotulinum toxin A); Egrifta (tesamorelin acetate); Egrifta SV (tesamorelin acetate); Elaprase (idursulfase); Elase-chloromycetin (a mixture of chloramphenicol, fibrinolysin, and deoxyribonuclease [bovine]); Eleryso (taliglucerase alfa); Elitek (rasburicase); Elspar (asparaginase); Elzonris (taglaxofusp-erzs); Emgality (galcanezumab-gnlm); Empliciti (elotuzumab); Enbrel (etanercept); Enbrel Mini (etanercept); Enhertu (fam-trastuzumab deruxtecan-nxki); Entyvio (vedolizumab); Epogen / Procrit (epoetin alfa); Erbitux (cetuximab); Erelzi (etanercept-szzs); Erelzi Sensoready (etanercept-szzs); Erwinaze (asparaginase erwinia chrysanthemum); Eticovo (etanercept-ykro); Evenity (romosozumab-aqqg); Extavia (interferon beta-1b); Eyela (aflibercept); Fabrazyme (agalsidase beta); Fasenra (benralizumab); Fiasp (insulin aspart);Follistim (Follitropin beta); Follistim AQ (Follitropin beta); Follistim AQ Cartridge (Follitropin beta); Gamiphant (Emapalmab-lzsg); Gazyva (Obinutuzumab); Genotropin (Somatropin); Gonal-f (Fol; Litropin alfa; Gonal-f RFF (Follitropin alfa); Gonal-f RFF RediJect (Follitropin alfa); Granix (tbo-filgrastim); Hadlimuma (adalimumab-bwwd); Hemlibra (emisizumab-kxwh); Herceptin (trastuzumab); Herceptin Hylecta (trastuzumab and hyaluronidase-oysk); Herzuma (trastuzumab-pkrb); Humalog (insulin lispro); Humalog Mix 50 / 50 (insulin lispro, protamine and insulin lispro); Humalog Mix 75 / 25 (insulin lispro, protamine and insulin lispro); Humatrope (somatropin); Humegon (menotropins); Humira (adalimumab); Humulin 70 / 30 (human isophene insulin and human insulin); Humulin N (human isophene insulin); Humulin RU-100 (human insulin); Humulin RU-500 (human insulin); Hydase (hyaluronidase); Hylenex recombinant (human hyaluronidase); Hyrimoz (adalimumab-adaz); Ilumya (tildrakizumab-asmn); Imfinzi (durvalumab); Increlex (mecasermin); Infasurf (calfactant); Infergen (interferon alphacon-1); Inflectra (infliximab-dyyb); Intron A (Interferon alpha-2b); Iplex (Mecasermin linfaber); Iprivask (Desildin); Jeanatope (Iodide albumin I-125 kit); Jetrea (Ocliplasmin); Jeuveau (Prabotulinum toxin A-xvfs); Kadcyla (ado-trastuzumab emtansine); Kalbitor (Ecalantide); Kanjinti (Trastuzumab-anns); Kanuma (Seberipase alpha); Kepivance (Parifermin); Kevzara (Sarilumab); Keytruda (Pembrolizumab); Kineret (Anakinra); Kinlytic (Urokinase);Krystexa (pegroticase); Lantus (insulin glargine); Lartruvo (olaratumab); Lemtrada (alemtuzumab); Leukine (salglamostim); Levemir (insulin detemir); Libtayo (semiprimab-rwlc); Lucentis (ranibizumab); Lumizyme (alglucosidase alfa); Lumoxiti (moxetumomab pasudotox-tdfk); Macrotec (kit for preparing technetium Tc-99m albumin agglutination); Megatope (iodide albumin I131 kit); Menopur (menotropins); Mepsevii (be Stronidase alpha-vjbk); Microlite (Radiolabeled albumin technetium Tc-99m albumin colloid kit); Mircera (Methoxypolyethylene glycol-epoetin beta); Mvasi (Bevacizumab-awwb); Myalept (Metreleptin); Mylotarg (Gemtuzumab ozogamicin); Myoblock (Botulinum toxin type B); Myozyme (Alglucosidase alpha); Myxredlin (Human insulin); N / A (Laxibacumab); Naglazyme (Galsulfase); Natpara (Parathyroid hormone); Neulasta (Pegfilgrastim); Neulasta Onpro (pegfilgrastim); Neumega (oprelbequine); Neupogen (filgrastim); NeutroSpec (technetium-99m tcphanolesomab); Nivestym (filgrastim-aafi); Norditropin (somatropin); Novarel (human chorionic gonadotropin); Novolin 70 / 30 (human isophene insulin and human insulin); Novolin N (human isophene insulin); Novolin R (human insulin); Novolog (insulin aspart); Novolog Mix 50 / 50 (insulin aspart protamine and insulin aspart); Novolog Mix 70 / 30 (insulin aspartoprotamine and insulin aspart); Nplate (romiplostim); Nucala (mepolizumab); Nulojix (beratacept);Nutropin (somatropin); Nutropin AQ (somatropin); Ocrevus (ocrelizumab); Omnitrope (somatropin); Oncaspar (peguaspar gauze); Ontak (deniloquin difutitox); Ontruzant (trastuzumab-dttb); Opdivo (nivolumab); Orencia (abatacept); Orthoclone OKT3 (Muromanab-CD3); Ovidrel (Coriogonadotropin alpha); Oxervate (Senegermin-bkbj); Padcev (Enfortumab vedotin-ejfv); Palynziq (Pegvariase-pqpz); Pancreaze (Pancrelipase); Pegasys (Peginterferon alpha-2a); Pegasys Copegus Combination Pack (Peginterferon alpha-2a and ribavirin); Pegintron (Peginterferon alpha-2b); PegIntron / Rebetol Combo Pack (pegylated interferon alpha-2b and ribavirin); Pergonal (menotropins); Perjeta (pertuzumab); Pertzye (pancrelipase); Plegridy (pegylated interferon beta-1a); Polivy (polatuzumab vedotin-piiq); Portrazza (nesitumumab); Poteligeo (mogamulizumab-kpkc); Pral uent (alirocumab); Praxbind (idarucizumab); Pregnyl (chorionic gonadotropin); Procrit (epoetin alfa); Proleukin (aldesleukin); Prolia (denosumab); ProstaScint (capromab pendetide); Pulmolite (kit for preparing technetium Tc-99m albumin agglutination); Pulmotech MAA (Kit for preparing technetium Tc-99m albumin agglutination); Pulmozyme (Dornase Alpha); Raptiva (Ephalizumab); Rebif (Interferon Beta-1a); Reblozyl (Ruspatercept-aamt); Regranex (Becaprelmin); Remicade (Infliximab); Renflexis (Infliximab-abda);Reopro (absiximab); Repatha (evolocumab); Repronex (menotropins); Retacrit (epoetin alfa-epbx); Retavase (reteplase); Revcovi (ellapeguademase-lvr); Rituxan (rituximab); Rituxan Hycela (rituximab and human hyaluronidase); Roferon-A (interferon alfa-2a); Ruxience (rituximab-pvvr); Ryzodeg 70 / 30 (insulin degludec and insulin aspart); Saizen (somatropin); Santyl (collagenase); Sarclisa (isatuximab-irfc); Serostim (somatropin); Siliq (brodalumab); Simponi (golimumab); Simponi Aria (golimumab); Simulect (basiliximab); Skyrizi (risankizumab-rzaa); Soliqua 100 / 33 (insulin glargine and lixisenatide); Soliris (eculizumab); Somavert (pegvisomant); Stellara (ustekinumab); Strensiq (asfotase alfa); Sucraid (sacrosidase); Survanta (bellactant); Sylvant (siltuximab); Synagis (palivizumab); Takhzyro (lanadermab-flyo); Taltz (ixekizumab); Tanzeum (albiglutide); Tecentriq (atezolizumab); Tepezza (teprotumumab-trbw); Thyrogen (human thyrotropin alfa) ;TNKase (tenecteplase); Toujeo (insulin glargine); Trasyol (aprotinin); Trazimera (trastuzumab-qyyp); Tremfya (guselkumab); Tresiba (insulin degludec); Trodelvy (sacituzumab govitecan-hziy); Trogarzo (ibalizumab-uiyk); Trulicity (dulaglutide); Truxima (rituximab-abbs); Tysabri (natalizumab); Udenyca (pegfilgrastim-cbqv); Ultomiris (ravulizumab-cwvz); Unituxin (dinutuximab);Vectibix (panitumumab); Verluma (nofetumomab); Vimizim (elosulfase alfa); Viokace (pancrelipase); Vitrase (hyaluronidase); Voraxaze (glucarpidase); VPRIV (veraglucerase alfa); Xeomin (incobotulinum toxin A); Xgeva (denosumab); Xiaflex (collagenase Clostridium histolyticum); Xigris (drotolecogin alfa); Xolair (omalizumab); Xultophy 100 / 3.6 (insulin degludec and liraglutide); Yervoy (ipilimumab); Zaltrap (Ziv-aflibercept); Zarxio (filgrastim-sndz); Zenapax (daclizumab); Zenpep (pancrelipase); Zevalin (ibritumomab tiuxetan); Ziextenzo (pegfilgrastim-bmez); Zinbryta (daclizumab); Zinplava (bezlotoxumab); Zirabev (bevacizumab-bvzr); Zomacton (somatropin); Zorbtive / Serostim (somatropin); Inhaled anesthetics Aliflurane; chloroform; cyclopropane; desflurane (Suprane); diethyl ether; enflurane (Ethrane); ethyl chloride; ethylene; halothane; isoflurane (Forane, Isoflo); isopropenyl vinyl ether; methoxyflurane; methoxyflurane; methoxypropane; nitrous oxide; loflurane; sevoflurane (Sevorane, Ultane, Sevoflo); teflurane; trichloroethylene; vinyl ether; xenon, Injectable drug Ablavar (Gadophosbecet trisodium injection); Abarelix Depot; Avobotulinum toxin A injection (Dysport); ABT-263; ABT-869; ABX-EFG; Accretropin (Somatropin injection); Acetadote (Acetazolamide injection); Acetazolamide injection; Acetadote (Acetazolamide injection); Actemra (Tocilizumab injection); Acthrel (Corticoleline overtriflutate for injection); Actumune; Activase; Acyclovir for injection (Zovirax injection); Adacel; Adalimumab; Adenoscan (Adenosine injection) ); Adenosine injection (Adenoscan); Adrenaclick; AdreView (Iobenguan I123 injection for intravenous use); Afluria; Ak-Fluor (Fluorescein injection); Audrazyme (Laronidase); Alglucerase injection (Ceredes); Alkeran injection (Melphalan HCl injection); Allopurinol sodium for injection (Aloprim); Aloprim (Allopurinol sodium for injection); Alprostadil; Alsuma (Sumatriptan injection); ALTU-238; Amino acid injection; Aminosyn; Apidra; Apremilast; Alprostadil dual chamber system for injection (Caverject) AMG009; AMG076; AMG102; AMG108; AMG114; AMG162; AMG220; AMG221; AMG222; AMG223; AMG317; AMG379; AMG386 ;AMG403;AMG477;AMG479;AMG517;AMG531;AMG557;AMG623;AMG655;AMG706;AMG714;AMG745;AMG785;AMG811;AMG827; AMG837; AMG853; AMG951; Amiodarone HCl injection; Amobarbital sodium injection; Amobarbital sodium injection; Anakinra; Anti-Abeta; Anti-Beta7; Anti-Beta20; Anti-CD4; Anti-CD20; Anti-CD40; Anti-IFNalpha; Anti-IL13;Anti-OX40L; Anti-OXLDS; Anti-NGF; Anti-NRP1; Arixtra; Amphadase (hyaluronidase injection); Ammonul (sodium phenylacetate and sodium benzoate injection); Anaprox; Anzemet injection (drasetron mesylate injection); Apidra (insulin glulisine [rDNA derived] injection); Apomab; Aranesp (darbepoetin alfa); Argatroban (argatroban injection); Arginine hydrochloride injection (R-Gene 10; Aristocort); Aristospan; Arsenic trioxide injection (Trisenox); Alticane HCl and epinephrine injection (Septocaine); Arzera (ofatumumab injection); Asclera (polidocanol injection); Atalen; Atalen-DMD; Atenolol injection (Tenormin I.V. injection); Atracurium besylate injection (Atracurium besylate injection); Avastin; Azactam injection (Aztreonam injection); Azithromycin (Zithromax injection); Aztreonam injection (Azactam injection); Baclofen injection (Lioresal intrathecal injection); Bacteriostatic water (Bacteriostatic water for injection); Baclofen injection (Lioresal intrathecal injection); Bal in Oil Ampules (Dimelcarprole injection); BayHepB; BayTet; Benadryl; Bendamustine hydrochloride injection (Treanda); Benztropine mesylate injection (Cogentin); Betamethasone suspension injection (Celestone Soluspan); Bexal; Bicillin C-R900 / 300 (Penicillin G benzathine and Penicillin G procaine injection); Blenoxan (Bleomycin sulfate injection); Blenoxan (Bleomycin sulfate injection); Boniva injection (Ibandronate sodium injection); Botox Cosmetic (Onabotulinum toxin A for injection); BR3-FC; Bravelle (Urofolitropin injection); Bretilium (Bretillium tosylate injection); Brevital sodium (Methhexital sodium injection); Brethine; Briobacept; BTT-1023; Bupivacaine HCl; Byetta; Ca-DTPA (Calcium trisodium pentetate injection); Cabazitaxel injection (Jevtana);Caffeine alkaloids (caffeine and sodium benzoate injection); Calcijex injection (calcitriol); Calcitriol (calcijex injection); Calcium chloride (calcium chloride injection 10%); Calcium disodium bersenate (calcium disodium edetate injection); Campus (artemtuzumab); Camptosar injection (irinotecan hydrochloride); Canakinumab injection (irinotecan hydrochloride); RIS); Capreomycin sulfate (for injection); Capreomycin (for injection) (Capreomycin sulfate); Cardiolite (Preparation kit for Technetium Tc99 Cestamivi for injection); Carticel; Cathflo; Cefazolin and glucose for injection (Cefazolin injection); Cefepime hydrochloride; Cefotaxime; Ceftriaxone; Cerezyme; Carnitor injection; Caverject; Celestone Soluspan; Celsior; Cerebyx (fosphenytoin sodium injection); Ceredes (alglucerase injection); Ceretec (technetium Tc99m examethadim injection); certolizumab; CF-101; chloramphenicol sodium succinate (chloramphenicol sodium succinate injection); chloramphenicol sodium succinate injection (chloramphenicol sodium succinate injection); Cholestagel (coloseveram HCl); chorionic gonadotropin alpha injection (Ovidrel); Cimzia; cisplatin (cisplatin injection); chloral (clofarabine injection); clomifin citrate; clonidine injection (Duraclon); cogentin (benztropine mesylate injection); colistimethate injection (Cory-Mycin) M); Coly-Mycin M (colistimetate injection); Compath; Conivaptan HCl injection (vaprizol); Conjugated estrogen for injection (Premarin injection); Copaxone; Corticolerin overtriflutate injection (Acthrel); Colbert (ibutylide fumarate injection); Cubicin (daptomycin injection); CF-101; Cyanokit (hydroxocobalamin injection); Cytarabine liposomal injection (Depoty); Cyanocobalamin; Cytoben (ganciclovir); D.H.E. 45; Dasetuzumab;Dacogen (decitabine injection); dalteparin; danthorene IV (dantrolene sodium for injection); dantrolene sodium for injection (danthorene IV); daptomycin injection (cubicin); darbepoetin alfa; DDAVP injection (desmopressin acetate injection); Decavax; decitabine injection (dacogen); anhydrous alcohol (anhydrous alcohol injection); denosumab injection (prolia); delatestril; delestrone; delteparin sodium; Depacon (sodium valproate injection); depomedrol (methylprednisolone acetate suspension injection); Deposite (Sitara) Bin liposome injection; Depodul (morphine sulfate XR liposome injection); Desmopressin acetate injection (DDAVP injection); Depo-estradiol; Depo-Provera 104 mg / ml; Depo-Provera 150 mg / ml; Depo-testosterone; Dexrazoxane for injection, intravenous only (Totect); Glucose / electrolytes; Glucose and sodium chloride injection (5% glucose in 0.9% sodium chloride); Glucose; Diazepam injection (Diazepam injection); Digoxin injection (Lanoxine injection); Dilauzide-HP (Hydromorphone hydrochloride injection); Dimercarprole injection (Ba in Oil) Amples; Diphenhydramine injection (Benadryl injection); Dipyridamole injection (Dipyridamole injection); DMOAD; Docetaxel injection (Taxotere); Dracetron mesylate injection (Anzemet injection); Doribax (Doripenem injection); Doripenem injection (Doribax); Doxelcalciferol injection (Hectorol injection); Doxil (Doxorubicin HCl liposomal injection); Doxorubicin HCl liposomal injection (Doxil) Duraclon (clonidine injection); Duramorph (morphine injection); Dysport (avobotulinum toxin A injection); Ecalantide injection (Kalbitor); EC-Naprosin (naproxen); Calcium disodium edetate injection (calcium disodium bersenate); Edex (alprostadil for injection); Engerix; Edrophonium injection (Enlon); Eliglustat terate; Eloxatin (oxaliplatin injection);Emend injection (fosaprepitant dimeglumine injection); Enalaprilate injection (enalaprilate injection); Enlon (edrophonium injection); Enoxaparin sodium injection (labnox); Eovist (gadoxetate disodium injection); Enbrel (etanercept); Enoxaparin; Epicel; Epinephrine; EpiPen; EpiPen Jr. Epratuzumab; Erbitux; Ertapenem injection (Invanz); Erythropoieten; Essential amino acid injection (Nephramine); Estradiol cypionate; Estradiol valerate; Etanercept; Exenatide injection (Byetta); Ebrotra; Fabrazyme (Adalusidase beta); Famotidine injection; FDG (Fludeoxyglucose F18 injection); Ferhem (Fermoxytol injection); Feridex I.V. (Fermoxides Injection Solution); Fertinex; Fermoxides Injection Solution (Feridex I.V.); Fermoxytol Injection (Ferahem); Flagyl Injection (Metronidazole Injection); Fluarix; Fludara (Fludarabine Phosphate); Fludeoxyglucose F18 Injection (FDG); Fluorescein Injection (Ak-Fuor); Follistim AQ Cartridge (Follitropin Beta Injection); Follitropin Alpha Injection (Gonal-f RFF); Follitropin beta injection (Follistim AQ cartridge); Forotin (pralatrexate solution for intravenous injection); Fondaparinux; Forteo (teriparatide (rDNA-derived) injection); Fostamatibinb; Fosaprepitant dimeglumine injection (Emend injection); Foscarnet sodium injection (Foscavir); Foscavir (Foscarnet sodium injection); Fosphenytoin sodium injection (Cerebyx); Fospropofol disodium injection (Lusedra); Fragmin; Fuzeon (Enfvirtide); GA101; Gadopentate meglumine injection (Multihance); Gadophosbecet trisodium injection (Ablavar); Gadoteridol injection solution (Prohance); Cadvercetamide injection (OptiMARK); Gadoxetate disodium injection (Eovist); Ganirelix (Ganirelix acetate injection); Gardasil; GC1008;GDPD; gemtuzumab ozogamicin for injection (Mylotarg); genotropin; gentamicin injection; GENZ-112638; golimumab injection (Simponi injection); Gonal-f RFF (follitropin alpha injection); granisetron hydrochloride (Kytril injection); gentamicin sulfate; glatiramer acetate; Glucagen; glucagon; HAE1; H; aldol (haloperidol injection); Havrix; Hectorol injection (doxelcalciferol injection); Hedgehog pathway inhibitors; heparin; Herceptin; hG-CSF; Humalog; human growth hormone; Humatrope; HuMax; Humegon; Humira; Humulin; ibandronate sodium injection (boniva injection); ibuprofen lysin injection (NeoProfen); ibutylide fumarate injection (Colbert); idamycin PFS (idarubicin hydrochloride injection); idarubicin hydrochloride injection (idamycin PFS); iraris (canakinumab injection); imipenem and cilastatin for injection (primaxin I.V.); imi Torex; Incobotulinum toxin A for injection (Xeomin); Increlex (Mecasermin [rDNA-derived] injection); Indomethacin IV (Indomethacin injection); Indomethacin injection (Indomethacin IV); Infanrix; Inohep; Insulin; Insulin aspart [rDNA-derived] injection (NovoLog); Insulin glargine [rDNA-derived] injection (Lantus); Insulin glulisine [rDNA-derived] injection (Apidra) for injection; Interferon alpha-2b, recombinant (Intron A); Intron A (Interferon alpha-2b for injection, recombinant); Invanz (Ertapene injection); Invega Sustenna (paliperidone palmitate sustained-release suspension injection); Invirase (saquinavir mesylate); Iobenguan I123 injection for intravenous use (AdreView); Iopromide injection (Ultravist); Ioversol injection (Optiray injection); Iplex (mecasermine linfaber [rDNA derived] injection); Iprivask; Irinotecan hydrochloride (Camptosar injection); Iron oxide injection (Venofar); Istodax (romidepsin for injection); Itraconazole injection (Sporanox injection); Jevtana (cabazitaxel injection); Jonexa; Kalbitor (ecalantide injection); KCL in D5NS (5% glucose and sodium chloride injectable solution); KCL in D5W; KCL in NS; Kenalog 10 injection (triamcinolone acetonide suspension injection); Kepivans (palifermin);Keppra injection (levetiracetam); keratinocyte; KFG; kinase inhibitor; Kineret (anakinra); Kinlytic (urokinase injection); Kinrix; clonopin (clonazepam); Kytril injection (granisetron hydrochloride); lacosamide tablets and injection (Vinpat); Ringer's lactate solution; lanoxin injection (digoxin injection); lansoprazole injection (prevacid I.V.); Lantus; leucovorin calcium (leucovorin calcium injection); Lente (L); leptin; levemir; leukain salglamostim; Leuprolide acetate; levothyroxine; levetiracetam (Keppra injection); Rabnox; levocarnitine injection (Carnitor injection); Lexcan (Legadenosone injection); Lioresal intrathecal injection (baclofen injection); liraglutide [rDNA] injection (Victoza); Rabnox (enoxaparin sodium injection); Lucentis (ranibizumab injection); Lumizyme; Lupron (leuprolide acetate injection); Lucedra (fospropofol disodium injection); Maci; magnesium sulfate (magnesium sulfate Injectable drugs); Mannitol Injection (Mannitol IV); Marcaine (Bupivacaine Hydrochloride and Epinephrine Injection); Maxipime (Cefepime Hydrochloride for Injection); Technetium Injection MDP High-Dose Kit (Technetium Tc99m Medronate Injection); Mecasermin [rDNA-derived] Injection (Increx); Mecasermin Rinfaber [rDNA-derived] Injection (Iplex); Melphalan HCl Injection (Alkeran Injection); Methotrexate; Menactra; Menopur (Menotropins Injection); Menotropins for Injection (Rep ronex); Methhexital sodium for injection (Brevital sodium); Methyldopert hydrochloride injection, solution (Methyldopert HCl); Methylene blue (Methylene blue injection); Methylprednisolone acetate suspension injection (Depo-Medrol); MetMab; Metoclopramide injection (Reglan injection); Metrodin (Urofolitropin for injection); Metronidazole injection (Flagyl injection); Miacalcin; Midazolam (Midazolam injection); Minpara (Cinacareto); Minosin injection (Minocycline injection);Minocycline injection (Minosin injection); Mipomersen; Mitoxantrone concentrate for injection (Novantrone); Morphine injection (Duramorph); Morphine sulfate XR liposomal injection (Depodul); Sodium molinate (Sodium molinate injection); Motesanib; Mozovir (Prelixafor injection); Multihance (Gadopentate meglumine injection); Polyelectrolyte and glucose injection; Polyelectrolyte injection; Mylotarg (Gemtuzumab ozogamicin for injection); Ma Iozyme (alglucosidase alfa); Nafcillin injection (nafcillin sodium); Nafcillin sodium (nafcillin injection); Naltrexone XR injection (Vivitrol); Naprosin (naproxen); NeoProfen (ibuprofen lysine injection); Nandroldecanoate; Neostigmine methylsulfate (neostigmine methylsulfate injection); NEO-GAA; NeoTect (technetium Tc99m depreotide injection); Nephramine (essential amino acid) (NO acid injection); Neulasta (pegfilgrastim); Neupogen (filgrastim); Novolin; Novolog; NeoRecormon; Neutrexin (trimethrexate gluconate injection); NPH (N); Nexterone (amiodarone HCl injection); Norditropin (somatropin injection); Physiological saline (sodium chloride injection); Novantrone (mitoxantrone concentrate for injection); Novolin 70 / 30 Inolet (70% NPH, human ingredient) Slinisophene suspension and 30% regular (human insulin injection); NovoLog (insulin aspart [rDNA-derived] injection); Nplate (romiplostim); Neutropin (somatropin for injection (rDNA-derived)); Neutropin AQ; Neutropin Depot (somatropin for injection (rDNA-derived)); Octreotide acetate injection (Sandostatin LAR); Ocrelizumab; Ofatumumab injection (Arzera); Sustained-release olanzapine suspension injection (Zyplexa Reprevv); Omnitarg; Omnitrope (somatropin [rDNA-derived] injection); Ondansetron hydrochloride injection (Zofran injection); OptiMARK (cadvercetamide injection); Optiray injection (iobersol injection); Orencia;Osmitrol injection in Aviva (mannitol injection in Aviva plastic container); Osmitrol injection in Viaflex (mannitol injection in Viaflex plastic container); Osteoprotegrin; Ovidrel (human chorionic gonadotropin alpha injection); Oxacillin (oxacillin for injection); Oxaliplatin injection (eloxatin); Oxytocin injection (pitosin); Paliperidone palmitate sustained-release suspension injection (Invega Sustenna); Pamidronate disodium injection; Panitumumab injection for intravenous injection (Vectibix); Papaverine hydrochloride injection (Papaverine injection); Papaverine injection (Papaverine hydrochloride injection); Parathyroid hormone; Palicalcitol injection flip-top vial (Zemplar injection); PARP inhibitors; Pediarix; PegIntron; Peginterferon; Pegfilgrastim; Penicillin G benzathine and Penicillin G procaine; Pentetic acid Calcium trisodium injection (Ca-DTPA); zinc trisodium pentetate injection (Zn-DTPA); pepsid injection (famotidine injection); Pergonal; pertuzumab; phentolamine mesylate (phentolamine mesylate for injection); physostigmine salicylate (physostigmine salicylate (injectable)); physostigmine salicylate (injectable) (physostigmine salicylate); piperacillin and tazobactam injection (zosyn); pitosin (oxytocin injection); Plasma-Lyte 148 (Polyelectrolyte Injection); Plasma-Lyte 56 and Glucose (Polyelectrolyte and Glucose Injection in Viaflex Plastic Container); PlasmaLyte; Prelixafor Injection (Mozovir); Polidocanol Injection (Asclera); Potassium Chloride; Plalatrexate Solution for Intravenous Injection (Forotin); Pramulintide Acetate Injection (Symlin); Premarin Injection (Conjugated Estrogen for Injection); Technetium Tc99 Cestamivi Preparation Kit for Injection (Cardiolite); Prevacid I.V. (Lansoprazole for Injection); Primaxin I.V. (Imipenem and Cilastatin for Injection); Prochymal; Procrit; Progesterone; Prohans (Gadoteridol Injection Solution);Prolia (denosumab injection); promethazine HCl injection (promethazine hydrochloride injection); propranolol hydrochloride injection (propranolol hydrochloride injection); quinidine gluconate injection (quinidine injection); quinidine injection (quinidine gluconate injection); R-Gene 10 (arginine hydrochloride injection); ranibizumab injection (Lucentis); ranitidine hydrochloride injection (Zantac injection); Raptiva; Reclast (zoledronic acid injection); Recombivarix HB; Legadenoson injection (Lexcan); Reglan injection (metoclopramide injection); Remicade; Renagel; Renvela (sevelamer carbonate); Repronex (menotropins for injection); Retrovir IV (zidovudine injection); rhApo2L / TRAIL; Ringer's solution and 5% glucose injection (Ringer's solution with glucose); Ringer's injection (Ringer's injection); Rituxan; Rituximab; Rocephin (ceftriaxone); Rocuronium bromide injection Drugs (Zemuran); Roferon-A (Interferon alpha-2a); Romazicon (Flumazenil); Romidepsin for injection (Istodax); Saizen (Somatropin injection); Sandostatin LAR (Octreotide acetate injection); Sclerostin Ab; Sensipar (Cinacalcet); Sensorcaine (Bupivacaine HCl injection); Septocaine (Alticane HCl and Epinephrine injection); Serostim LQ (Somatropin (rDNA-derived) injection); Simponi injection (Golimumab injection); Sodium acetate (Sodium acetate injection); Sodium bicarbonate (5% sodium bicarbonate injection); Sodium lactate (Sodium lactate injection in AVIVA); Sodium phenylacetate and sodium benzoate injection (Ammonul); Somatropin (rDNA-derived) for injection (Neutropin); Sporanox injection (Itraconazole injection); Stelara injection (Ustekinumab); Stemgen; Sufenta (Sufentanyl citrate injection); Sufentanyl citrate injection (Sufenta); Sumavel; Sumatriptan injection (Alsuma); Symlin; Symlin Pen; Systemic Hedgehog Antagonist; Synvisc-One (Hiran G-F20 Single Intra-articular Injection);Tarceva; Taxotere (Docetaxel for injection); Technetium Tc99m; Teravancin for injection (Vivativ); Temsirolimus injection (Torisel); Tenormin I.V. injection (Atenolol injection); Teriparatide (rDNA-derived) injection (Forteo); Testosterone cypionate; Testosterone enanthate; testosterone propionate; Tev-Tropin (somatropin for injection, derived from rDNA); tgAAC94; thallium chloride; theophylline; thiotepa (thiotepa injection); thymoglobulin (anti-thymocyte globulin (rabbit)); thyrogen (thyrotropin alpha for injection); ticalcillin sodium and potassium clavulanate Galaxy (timentin injection); Tigan injection (trimethobenzamide hydrochloride injection); timentin injection (ticalcillin sodium and potassium clavulanate MuGalaxy); TNKase; Tobramycin injection; Tocilizumab injection (Actemra); Torisel (Temsirolimus injection); Totect (Dexrazoxane for injection, intravenous only); Trastuzumab-DM1; Travasol (Amino acid (injectable)); Treanda (Bendamustine hydrochloride injection); Torelstar (Triptorelympamoate suspension injection); Triamcinolone acetonide; Triamcinolone acetate; Triamcinolone hexaacetonide suspension injection (Aristospan injection 20 mg); Triesen ce (triamcinolone acetonide suspension injection); Trimethobenzamide hydrochloride injection (Tigan injection); Trimethrexate gluconate injection (Neutrexin); Triptrelymphamoate suspension injection (Torelstar); Twinjet; Trivaris (triamcinolone acetonide suspension injection); Trisenox (arsenic trioxide injection); Twinrix; Typhoid Vi; Ultravist (iopromide injection); Urofolliculartropin for injection (Metrodin); Urokinase injection (Kinlytic); Uste Numab (Stelara injection); Ultralente (U); Barium (diazepam); Sodium valproate injection (Depacon); Valtropin (Somatropin injection); Vancomycin hydrochloride (Vancomycin hydrochloride injection); Vancomycin hydrochloride injection (Vancomycin hydrochloride); Vaprizol (Conivaptan HCl injection); VAQTA; Vasovist (Gadophos veset trisodium injection for intravenous injection); Vectibix (Panitumumab injection for intravenous injection); Venofar (Iron sucrose injection); Verteporfin injection (Visudyne);Vivativ (Teravancin for injection); Victoza (Liraglutide [rDNA] injection); Vinpat (Lacosamide tablets and injection); Vinblastine sulfate (Vinblastine sulfate injection); Vincasar PFS (Vincristine sulfate injection); Victoza; Vincristine sulfate (Vincristine sulfate injection); Visudyne (Verteporfin injection); Vitamin B-12; Vivitrol (Naltrexone XR injection); Voluben (Hydroxyethyl starch in sodium chloride injection); Xeloda; Xenical (Orlistat); Xeomin (Incobotulinum toxin A for injection); Xolair; Zantac injection (Ranitidine hydrochloride injection); Zemplar injection (Paricalcitol injection) (Putop-type vial); Zemuron (Rocuronium bromide injection); Zenapax (Daclizumab); Zevalin; Zidovudine injection (Retrovir IV); Zithromax injection (Azithromycin); Zn-DTPA (Zinc trisodium pentetate injection); Zofran injection (Ondansetron hydrochloride injection); Zingo; Zoledronic acid for injection (Zometa); Zoledronic acid injection (Reclast); Zometa (Zoledronic acid for injection); Zosyn (Piperacillin and tazobactam injection); Zyprexa Reprevv (Sustained-release olanzapine suspension injection); Liquid formulation (non-injectable) Abilify; AccuNeb (albuterol sulfate inhalation solution); Actidose Aqua (activated carbon suspension); Activated carbon suspension (Actidose Aqua; Advere; Agenerase Oral Solution (Amprenavir Oral Solution); Akten (Lidocaine Hydrochloride Ophthalmic Gel); Alamast (Pemirolast Potassium Ophthalmic Solution); Albumin (Human) 5% Solution (Buminet 5%); Albuterol Sulfate Inhalation Solution; Alinia; Alocrill; Alphagan; Alrex; Alvesco; Amprenavir Oral Solution; Analpram-HC; Alformoterol Tartrate Inhalation Solution (Brovana); Aristospan Injection 20 mg (Triamcinolone Hexaacetonide Suspension Injection); Asacol; Asmanex; Astepro; Astepro (Azelastine Hydrochloride Nasal Spray); Atrovent Nasal Spray (Ipratropium Bromide Nasal Spray); Atrovent Nasal Spray. 06; Augmentin ES-600; Azasite (azithromycin eye drops); Azelaic acid (Finacea gel); Azelastine hydrochloride nasal spray (Astepro); Azelex (azelaic acid cream); Azopt (brinzolamide suspension eye drops); Bacteriostatic physiological saline; Balanced salts; Bepotastine; Bactroban for nasal cavity; Bactroban; Beclovent; Benzac W; Betimol; Betoptic S; Bepreve; Bimatoprost eye drops; Bleph 10 (Sulfacetamide sodium ophthalmic solution 10%); Brinzolamide suspension ophthalmic solution (Azopt); Bromfenac ophthalmic solution (Xibrom); Bromhist; Brovana (Alformoterol tartrate inhalation solution); Budesonide inhalation suspension (Pulmicort inhalation solution); Cambia (Diclofenac potassium for oral use); Capex; Carac; Carboxine-PSE; Carnitor; Cays ton (Aztreonam for inhalation); CellCept; Centany; Cerumenex; Ciloxan eye drops (Ciprofloxacin HCl eye drops); Ciprodex; Ciprofloxacin HCl eye drops (Ciloxan eye drops); Clemastine fumarate syrup (Clemastine fumarate syrup); CoLyte (PEG electrolyte solution); Combiven; Comtan; Condylox; Cordran;Cortisporin suspension eye drops; Cortisporin ear suspension; Cromolyn sodium inhalation solution (Intal Nebulizer solution); Cromolyn sodium eye drops (Opticrom); Electrolyte-added crystalline amino acid solution (Aminosyn electrolyte); Cutivate; Cuvposa (glycopyrrolate oral solution); Cyanocobalamin (CaloMist nasal spray); Cyclosporine oral solution (Gengraf oral solution); Cyclozil; Cysview (hexaminolevulinate hydrochloride intravesical solution) (Liquid); DermOtic Oil (Fluocinolone Acetonide Oil Ear Drops); Desmopressin Acetate Nasal Spray; DDAVP; Derma-Smoothe / FS; Dexamethasone Intensol; Dianyl Hypocalcium; Dianyl PD; Diclofenac Potassium Oral Solution (Cambia); Didanosine Powder for Children Oral Solution (Videx); Differin; Dirantin 125 (Phenytoin Oral Suspension); Ditropan; Dorzolamide Hydrochloride Eye Drops (Trusopt); Dorzolamide Hydrochloride-Timolol Maleate Eye Drops (Cosopt); Dovonex Scalp (Calcipotriene Solution); Doxycycline Calcium Oral Suspension (Vibramycin Oral Solution); Efudex; Elaprace (Idursulfase Solution); Elestat (Epinastine HCl Eye Drops) (Solution); Elocon; Epinastine HCl eye drops (Elestat); Epivir HBV; Epogen (epoetin alfa); Erythromycin topical solution 1.5% (Staticin); Ethiodol (ethodized oil); Ethosuximide oral solution (Zarontin oral solution); Oylax; Extraneal (icodextrin peritoneal dialysis solution); Felbatol; Feridex I.V. (Fermoxides Injection Solution); Flovent; Floxin Oto Solution (Ofloxacin Oto Solution); Flo-Pred (Prednisolone Acetate Oral Suspension); Fluoroplex; Flunisolid Nasal Spray (Flunisolid Nasal Spray 0.25%); Fluorometholone Suspension Eye Drops (FML); Flurbiprofen Sodium Eye Drops (Ocufen); FML; Foradil; Formoterol Fumarate Inhalation Solution (Performomist); Fosamax; Fladantin (Nitrofurantoin Oral Suspension); Floxone;Gammaguard Solution (10% Human Immunoglobulin for Intravenous Injection); Gantricin (Acetylsulfisoxazole Suspension for Children); Gatifloxacin Eye Drops (Zymar); Gengraf Oral Solution (Cyclosporine Oral Solution); Glycopyrrolate Oral Solution (Cuvposa); Haloc Solution (Haloc Solution); Haloc Solution (Haloc Solution); HEP-LOCK U / P (Preservative-Free Heparin Lock Flush Solution); Heparin Lock Flush Solution (Hepflush 10); Hexaminolevulinate Hydrochloride Intravesical Solution (Cysview); Hydrocodone Bitartrate and Acetaminophen Oral Solution (Lortab) Elixir); Hydroquinone 3% topical solution (Melquin-3 topical solution); IAP antagonist; Isopto; Ipratropium bromide nasal spray (Atrovent nasal spray); Itraconazole oral solution (Sporanox oral solution); Ketrolactromethamine eye drops (Acular LS); Kaletra; Lanoxin; Lexiva; Leuprolide acetate for depot suspension (Lupron Depot 11.25 mg); Levobetaxolol hydrochloride suspension eye drops (Betaxone); Levocarnitine tablets, oral solution, sugar-free (Carnitor); Levofloxacin eye drops 0.5% (Quixin); Lidocaine HCl sterile solution (Xylocaine MPF sterile solution); Lok Pak (Heparin Lock Flush Solution); Lorazepam Intensol; Lortab Elixir (Hydrocodone Bisarthrate and Acetaminophen Oral Solution); Lotemax (Loteprednol Ethavonate Suspension Eye Drops); Loteprednol Ethavonate Suspension Eye Drops (Alrex); Hypocalcium Peritoneal Dialysis Solution (Dianyl Hypocalcium); Lumigan (Bimatoprost Eye Drops for Glaucoma 0.03%); Lupron Depot 11.25 mg (Leuprolide Acetate for Depot Suspension); Megestrol Acetate Salt oral suspension (megestrol acetate oral suspension); MEK inhibitors; Mepron; Mesnex; Mestinon; Mesalamine suspension enema (Rowasa); Melquin-3 topical solution (hydroquinone 3% topical solution); MetMab; Methyldopert HCl (methyldopert hydrochloride injection, solution); Methylin oral solution (methylphenidate HCl oral solution 5 mg / 5 mL and 10 mg / 5 mL);Methylprednisolone acetate suspension injection (Depo-Medrol); Methylphenidate HCl oral solution 5 mg / 5 mL and 10 mg / 5 mL (Methylin oral solution); Methylprednisolone succinate sodium (Solmedrol); Metipranolol eye drops (Optipranolol); Migranal; Miochol-E (Acetylcholine chloride intraocular solution); Micro-K for liquid suspension (potassium chloride sustained-release preparation for suspension); Minosin (Minocycline hydrochloride oral suspension); Nasacort; Neoma Isin sulfate, polymyxin B sulfate, and hydrocortisone; Nepafenac suspension eye drops (Nevanac); Nevanac (Nepafenac suspension eye drops); Nitrofurantoin oral suspension (Fludantin); Noxafil (Posaconazole oral suspension); Nistatin (oral) (Nistatin oral suspension); Nistatin oral suspension (Nistatin (oral)); Ocufen (Flurbiprofen sodium eye drops); Ofloxacin eye drops (Ofloxacin eye drops); Ofloxacin otological solution (Flox (Ear medicine); Olopatadine hydrochloride eye drops (Pataday); Opticrom (Cromolin sodium eye drops); Optipranolol (Metipranolol eye drops); Patanol; Pediapred; PerioGard; Phenytoin oral suspension (Dirantin 125); Phisohex; Posaconazole oral suspension (Noxafil); Potassium chloride sustained-release preparation for liquid suspension (Micro-K liquid for suspension); Pataday (Olopatadine hydrochloride eye drops); Patanase nasal Pre (olopatadine hydrochloride nasal spray); PEG electrolyte solution (CoLyte); pemirolast potassium eye drops (Alamast); Penlac (cyclopirox topical solution); PENNSAID (diclofenac sodium topical solution); Performist (formoterol fumarate inhalation solution); peritoneal dialysis solution; phenylephrine hydrochloride eye drops (neo-synephrine); phosphorine iodide (ecothiopat iodide for eye drops); podophyllox (podophyllox topical solution); Pred Forte (prednisolone acetate suspension eye drops); pralatrexate solution for intravenous injection (Forotin); Pred Mild; Prednisone Intensol;Prednisolone acetate suspension eye drops (Pred Forte); Prevacid; PrismaSol solution (sterile hemofiltration hemodialysis solution); Proair; Proglycem; ProHance (gadoteridol injection solution); Proparacaine hydrochloride eye drops (Alcaine); Propine; Pulmicort; Pulmozyme; Quixin (levofloxacin eye drops 0.5%); QVAR; Rapammune; Rebetol; Relacon-HC; Rotarix (oral live rotavirus vaccine suspension); Oral live rotavirus vaccine suspension (Rotarix); Rowasa (mesalamine suspension enema); Sabril (vigabatrin oral solution); Sacrosidase oral solution (Sucraid); Sandimmune; Sepra; Serevent Diskus; Solu-Cortef (hydrocortisone sodium succinate); Solu-Medrol (methylprednisolone sodium succinate); Spiriva; Sporanox oral solution (itraconazole oral solution); Staticin (erythromycin topical solution 1.5%); Stalevo; Starlix; Sterile hemofiltration hemodialysis solution (PrismaSol solution); Stimate; Sucralfate (Calafate suspension); Sulfacetamide sodium eye drops 10% (Bleph 10); Synarel nasal spray (nafarelin acetate nasal spray for endometriosis); Taclonex Scalp (calcipotriene and betamethasone dipropionate topical suspension); Tamiflu; Toby; TobraDex; Tobradex ST (Tobramycin / Dexamethasone Suspension Ophthalmic Solution 0.3% / 0.05%); Tobramycin / Dexamethasone Suspension Ophthalmic Solution 0.3% / 0.05% (Tobradex ST); Timolol; Timoptic; Travatans; Treprostinil Inhalation Solution (Tyvaso); Trusopt (Dorzolamide Hydrochloride Ophthalmic Solution); Tyvaso (Treprostinil Inhalation Solution); Ventolin; Vfend; Vibramycin Oral (Doxycycline Calcium Oral Suspension); Videx (Didanosine Oral Solution for Children); Vigabatrin Oral Solution (Sabril); Viokase; Viracept; Viramune; Vitamin K1 (Fluid Colloidal Solution of Vitamin K1); Voltaren Ophthalmic Solution (Diclofenac Sodium Ophthalmic Solution); Zarontin Oral Solution (Ethosuximide Oral Solution); Ziagen;Zyvox; Zymar (gatifloxacin eye drops); Zymaxid (gatifloxacin eye drops); drugs 5α-reductase inhibitors; 5-aminosalicylates; 5HT3 receptor antagonists; adamantane antiviral drugs; corticosteroids; corticosteroid inhibitors; adrenergic bronchodilators; drugs for hypertensive emergencies; drugs for pulmonary hypertension; aldosterone receptor antagonists; alkylating agents; α-adrenergic receptor antagonists; α-glucosidase inhibitors; alternative drugs; Amoebicides; aminoglycosides; aminopenicillins; aminosalicylates; amylin analogs; analgesic combinations; analgesics; androgens and anabolic steroids; angiotensin-converting enzyme inhibitors; angiotensin II inhibitors; anorectal preparations; appetite suppressants; antacids; anthelmintics; antivascular ophthalmic agents; anti-CTLA-4 monoclonal antibodies; antiinfectives; centrally acting antiadrenergic agonists; peripherally acting antiadrenergic agonists; antiandrogens; antianginic drugs; antiarrhythmics; antiasthmatic combinations; antibiotics / antineoplastics; anticholinergic antiemetics; anticholinergic antiparkin Son's drugs; anticholinergic bronchodilators; anticholinergic tropic drugs; anticholinergic agonists / antispasmodics; anticoagulants; anticonvulsants; antidepressants; antidiabetic drugs; antidiabetic combination drugs; antidiarrheals; antidiuretic hormones; detoxification drugs; antiemetics / anti-vertigo drugs; antifungal drugs; antigonadotropins; gout treatment drugs; antihistamines; drugs for hyperlipidemia; combination drugs for hyperlipidemia; antihypertensive combination drugs; uric acid lowering drugs; antimalarial drugs; antimalarial combination drugs; antimalarial quinolines; antimetabolites; antimigraine drugs; antitumor detoxification agents; antitumor interferons; antitumor monoclonal antibodies; antitumor drugs; antiparkinsonian drugs; antiplatelet drugs; anti-pseudosuperfluous drugs Bacterial penicillin drugs; antipsoriatic drugs; antipsychotic drugs; antirheumatic drugs; antiseptics and antibacterial drugs; antithyroid drugs; antitoxin drugs and antisnake venom drugs; antituberculosis drugs; antituberculosis drug combinations; antitussives; antiviral drugs; antiviral drug combinations; antiviral interferons; anxiolytics, sedatives and hypnotics; aromatase inhibitors; atypical antipsychotics; azol antifungal drugs; bacterial vaccines; barbiturate anticonvulsants; barbiturates; BCR-ABL tyrosine kinase inhibitors; benzodiazepine anticonvulsants; benzodiazepines; β-adrenergic blockers; β-lactamase inhibitors; bile acid metal ion sequestering agents; bile Physical preparations; bisphosphonate preparations; bone resorption inhibitors; bronchodilator combination preparations; bronchodilators; calcitonin; calcium channel blockers; carbamate anticonvulsants; carbapenems; carbonic anhydrase inhibitor anticonvulsants; carbonic anhydrase inhibitors; cardiotonic agents; cardiac-selective beta-blockers; cardiovascular agents; catecholamines; CD20 monoclonal antibodies; CD33 monoclonal antibodies; CD52 monoclonal antibodies; central nervous system drugs; cephalosporins; earwax solution; chelating agents; chemokine receptor antagonists; chloride channel activators; cholesterol absorption inhibitors; cholinergic agents;Cholinergic muscle stimulants; cholinesterase inhibitors; central nervous system stimulants; coagulation regulators; colony-stimulating factors; contraceptives; adrenocorticotropic hormone; coumarins and indanedions; cox-2 inhibitors; decongestants; topical medications; diagnostic radiopharmaceuticals; dibenzazepine anticonvulsants; digestive enzymes; dipeptidyl peptidase-4 inhibitors; diuretics; dopaminergic antiparkinsonian drugs; drugs used for alcohol dependence; echinocandin; EGFR inhibitors; estrogen receptor antagonists; estrogen; expectorants; factor Xa inhibitors; fatty acid derivative anticonvulsants; fibrinic acid derivatives; first-generation cephalosporins Phosphorus; fourth-generation cephalosporins; functional bowel disease drugs; gallstone solubilizers; gamma-aminobutyric acid analogs; gamma-aminobutyric acid reuptake inhibitors; gamma-aminobutyric acid transaminase inhibitors; gastrointestinal drugs; general anesthetics; urogenital tract drugs; gastrointestinal stimulants; glucocorticoids; glucose-raising agents; glycopeptide antibiotics; glycoprotein platelet inhibitors; glycylcyclines; gonadotropin-releasing hormone; gonadotropin-releasing hormone antagonists; gonadotropins; Class I antiarrhythmic drugs; Class II antiarrhythmic drugs; Class III antiarrhythmic drugs; Class IV antiarrhythmic drugs; Class V antiarrhythmic drugs; growth hormone receptor blockers; growth hormone; H. pylori eradication drugs; H2 antagonists; hematopoietic stem cell mobilizers; heparin antagonists; heparin; HER2 inhibitors; plant products; histone deacetylase inhibitors; hormone replacement therapy; hormones; hormone / antineoplastic drugs; hydantoin anticonvulsants; illegal (street) drugs; immunoglobulins; immunotherapy drugs; immunosuppressants; impotence drugs; in vivo diagnostic biological agents; incretin mimetics; inhaled infection drugs; inhaled corticosteroids; cardiac stimulants; insulin; insulin-like growth factor; integrase chain transfer inhibitors; interferon; intravenous nutritional products Iodine contrast agents; ionized iodine contrast agents; iron products; ketolides; laxatives; antileprosy agents; leukotriene regulators; lincomycin derivatives; lipid-containing glycopeptides; local injection anesthetics; loop diuretics; pulmonary surfactants; lymphatic staining agents; lysosomal enzymes; macrolide derivatives; macrolides; magnetic resonance imaging contrast agents; mast cell stabilizers; medical gases; meglitinides; metabolites; methylxanthines; mineralocorticoids; minerals and electrolytes; other drugs; other analgesics; other antibiotics; other anticonvulsants; other antidepressants; other antidiabetic drugs Drugs; other antiemetics; other antifungal drugs; other antihyperlipidemia drugs; other antimalarial drugs; other antitumor drugs; other antiparkinsonian drugs; other antipsychotics; other antituberculosis drugs; other antiviral drugs; other anxiolytics, sedatives and hypnotics; other biological agents; other bone resorption inhibitors; other cardiovascular drugs; other central nervous system drugs; other coagulation regulators; other diuretics; other urogenital drugs; other gastrointestinal drugs; other hormones; other metabolites; other ophthalmic drugs; other ophthalmic drugs; other ophthalmic drugs; other respiratory drugs; other sex hormones; other pharmacologics Drugs; other unclassified drugs; other vaginal preparations; mitotic inhibitors; monoamine oxidase inhibitors; monoclonal antibodies; oral and pharyngeal products; mTOR inhibitors; mTOR kinase inhibitors; mucolytics; multikinase inhibitors; muscle relaxants; mydriatics; narcotic analgesic combination preparations; narcotic analgesics; nasal anticongestives; nasal antihistamines and decongestants; nasal lubricants and irrigants; nasal preparations; nasal steroids; natural penicillin-based drugs; neuraminidase inhibitors; neuromuscular blockers; next-generation cephalosporins; nicotinic acid derivatives; nitrates; NNRTIs; non-cardiac-selective beta-blockers; non-iodine contrast agents;Nonionic iodine contrast agents; nonsulfonylurea; nonsteroidal anti-inflammatory drugs; norepinephrine reuptake inhibitors; norepinephrine-dopamine reuptake inhibitors; nucleoside reverse transcriptase inhibitors (NRTIs); nutritional supplements; nutritional products; ophthalmic anesthetics; ophthalmic infection drugs; ophthalmic anti-inflammatory drugs; ophthalmic antihistamines and decongestants; ophthalmic diagnostic agents; ophthalmic glaucoma drugs; ophthalmic lubricants and irrigants; ophthalmic preparations; ophthalmic steroids; additional ophthalmic steroids for infections; ophthalmic surgical drugs; oral nutritional supplements; ear anesthetics; ear infection drugs; ear preparations; ear steroids; additional ear steroids for infections; oxazolidinedione anticonvulsants; parathyroid hormones and analogues; penicillinase-resistant penicillin; penicillin-based drugs; peripheral Sexual opioid receptor antagonists; peripheral vasodilators; peripheral-acting anti-obesity drugs; phenothiazine antiemetics; phenothiazine antipsychotics; phenylpiperazine antidepressants; plasma expanders; platelet aggregation inhibitors; platelet stimulants; polyenes; potassium-sparing diuretics; probiotics; progestins; prolactin inhibitors; prostaglandin D2 antagonists; protease inhibitors; proton pump inhibitors; psoralens; psychotropic drugs; combination psychotropic drugs; purine nucleosides; pyrrolidine anticonvulsants; quinolones; contrast agents; radioactive adjuvants; radioactive agents; radioconjugates; radiopharmaceuticals; RANK ligand inhibitors; recombinant human erythropoietin; renin inhibitors; respiratory drugs; Respiratory inhalant products Products; Rifamycin derivatives; Salicylates; Sclerosing agents; Second-generation cephalosporins; Selective estrogen receptor modulators; Selective serotonin reuptake inhibitors; Serotonin-norepinephrine reuptake inhibitors; Serotonergic neurointestinal modulators; Sex hormone combinations; Sex hormones; Skeletal muscle relaxant combinations; Skeletal muscle relaxants; Smoking cessation drugs; Somatostatin and somatostatin analogs; Spermicides; Statins; Sterile washing solutions; Streptomyces derivatives; Succinimid anticonvulsants; Sulfonamides; Sulfonylurea; Synthetic ovulation inducers; Tetracyclic antidepressants; Tetracycline; Therapeutic radiopharmaceuticals; Thiazide diuretics; Thiazolidinediones; Thioxanthene; Third-generation cephalosporins; Thrombin inhibitors; Thrombolytic agents; Thyroid agents; Labor suppressants; Topical acne medications; Topical drugs; Local anesthesia Intoxicants; topical infection agents; topical antibiotics; topical antifungal agents; topical antihistamines; topical antipsoriasis agents; topical antiviral agents; topical astringents; topical pus-draining agents; topical depigments; topical emollients; topical keratolytic agents; topical steroids; additional topical steroids for infections; toxoids; triazine anticonvulsants; tricyclic antidepressants; trifunctional monoclonal antibodies; tumor necrosis factor (TNF) inhibitors; tyrosine kinase inhibitors; ultrasound contrast agents; upper respiratory tract combination agents; urea anticonvulsants; urinary tract infection agents; urinary tract antispasmodics; urine pH adjusters; uterine contraction agents; vaccines; combination vaccines; vaginal antiinfection agents; vaginal suppositories; vasodilators; vasopressors; VEGF / VEGFR inhibitors; viral vaccines; intra-articular replacement agents; vitamin and mineral complexes; vitamins; protein-based vaccines; DNA vaccines; mRNA vaccines; Diagnostic test 17-Hydroxyprogesterone; ACE (Angiotensin I-converting enzyme); Acetaminophen; Acid phosphatase; ACTH; Active clotting time; Activated protein C resistance; Adrenocorticotropic hormone (ACTH); Alanine aminotransferase (ALT); Albumin; Aldolase; Aldosterone; Alkaline phosphatase; Alkaline phosphatase (ALP); α1-Antitrypsin; α-Fetoprotein; α-Fetoprotein; Ammonia level; Amylase; ANA (Antinuclear Antbody); ANA (Antinuclear Antibody); Angiotensin Electrolyte-converting enzyme (ACE); anion gap; anti-cardiolipin antibody; anti-cardiolipin antibody (ACA); anti-centromere antibody; antidiuretic hormone; anti-DNA; anti-DNA-B; anti-gliadin antibody; anti-glomerular basement membrane antibody; anti-HBc (hepatitis B core antibody); anti-HBs (hepatitis B surface antibody); antiphospholipid antibody; anti-RNA polymerase; anti-Smith (Sm) antibody; anti-smooth muscle antibody; anti-streptolysin O value (ASO); anti-thrombin III; anti-Xa activity; anti-Xa assay; apolipoprotein; arsenic; aspartate aminotransferase (AST); B1 2; basophilic leukocytes; β2-microglobulin; β-hydroxybutyrate; B-HCG; bilirubin; direct bilirubin; indirect bilirubin; total bilirubin; bleeding time; blood gas (arterial); blood urea nitrogen (BUN); BUN; BUN (blood urea nitrogen); CA125; CA15-3; CA19-9; calcitonin; calcium; calcium (ionized); carbon monoxide (CO); carcinoembryonic antigen (CEA); CBC; CEA; CEA (carcinoembryonic antigen); ceruloplasmin; CH50 chloride; cholesterol; cholesterol, HDL; thrombolysis time; blood clot release Time reduction; CMP; CO2; cold agglutinin; complement component 3; copper; corticotropin-releasing hormone (CRH) stimulation test; cortisol; cortrosine stimulation test; C peptide; CPK (total); CPK-MB; C-reactive protein; creatinine; creatinine kinase (CK); cryoglobulin; DAT (direct antiglobulin test); D-dimer; dextamethasone suppression test; DHEA-S; diluted Russell's chain snake venom; oval erythrocytes; eosinophils; erythrocyte sedimentation rate (ESR); estradiol; estriol; ethanol; ethylene glycol; euglobulin solubility;Factor V Leiden; Factor VIII inhibitor; Factor VIII level; Ferritin; Fibrin degradation products; Fibrinogen; Folate; Folate (serum); Sodium fractional excretion rate (FENA); FSH (Follicle-stimulating factor); FTA-ABS; Gamma-glutamyltransferase (GGT); Gastrin; GGTP (Gamma-glutamyltransferase); Glucose; Growth hormone; Haptoglobin; HBeAg (Hepatitis B e antigen); HBs-Ag (Hepatitis B surface antigen); Helicobacter pylori pylori); hematocrit; hematocrit (HCT); hemoglobin; hemoglobin A1C; hemoglobin electrophoresis; hepatitis A antibody; hepatitis C antibody; IAT (indirect antiglobulin test); immunofixation (IFE); iron; lactate dehydrogenase (LDH); lactate (lactate); LDH; LH (routinizing hormone); lipase; lupus anticoagulant; lymphocyte; magnesium; MCH (mean corpuscular hemoglobin level); MCHC (mean corpuscular hemoglobin concentration); MCV (mean corpuscular volume); methyl malonate; monocyte; MPV (mean platelet volume); myoglobin; neutrophil; parathyroid hormone (PTH); phosphorus; platelets (plt); potassium; prealbumin; prolactin; prostate-specific antibody Prostaglandin (PSA); Protein C; Protein S; PSA (Prostate-Specific Antigen); PT (Prothrombin Time); PTT (Partial Thromboplastin Time); RDW (Red Blood Cell Distribution Width); Renin; Reticulocyte Count; Reticulocytes; Rheumatoid Factor (RF); ESR (Erythrocyte Sedimentation Rate); Serum Glutamate Pyruvate Transaminase (SGPT); Serum Protein Electrophoresis (SPEP); Sodium; T3 Resin Uptake Rate (T3RU); Free T4; Thrombin Time; Thyroid-Stimulating Hormone (TSH); Thyroxine (T4); Total Iron-Binding Capacity (TIBC); Total Protein; Transferrin; Transferrin Saturated Agent; Triglycerides (TG); Troponin; Uric Acid; Vitamin B12; White Blood Cells (WBC); Widar Test; A container, or primary packaging for a drug, or vial, or syringe, or method, according to any one of claims 1 to 233, comprising a material selected from the group consisting of the following.

235. Vacuum blood collection tube, A lumen at least partially defined by a thermoplastic sidewall, wherein the thermoplastic sidewall has an inner surface and an outer surface facing the lumen, A gas barrier coating supported by at least one of the inner surface and outer surface of the side wall, wherein at least a portion of the gas barrier coating is basically composed of multiple atomic monolayers of pure elements or compounds, The upper part that defines the opening, A stopper that sits in the opening and seals the lumen Vacuum blood collection tubes, including those included.

236. The vacuum blood collection tube according to claim 235, wherein the gas barrier coating includes an oxygen barrier coating or layer, and the oxygen barrier coating or layer is effective in reducing the intrusion of oxygen into the lumen to less than 0.0005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0004 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0003 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0002 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, and optionally less than 0.0001 cc / package / day at 25°C, 60% relative humidity and 0.21 bar.

237. The gas barrier coating includes an oxygen barrier coating or layer, and the oxygen barrier coating or layer is 0.0010d -1 Less than 0.0008d (optionally). -1 Less than 0.0006d (optionally). -1 Less than 0.0005d (optionally). -1 Less than 0.0004d (optionally). -1 Less than 0.0003d (optionally). -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 The vacuum blood collection tube according to claim 235 or 236, which is effective in providing the vacuum blood collection tube having an oxygen permeability constant of less than .

238. The vacuum blood collection tube according to any one of claims 235 to 237, wherein the gas barrier coating includes an oxygen barrier coating or layer.

239. The oxygen barrier coating or layer basically consists of multiple atomic monolayers, and optionally, the oxygen barrier coating or layer is deposited by atomic layer deposition, or optionally, by plasma-assisted atomic layer deposition.

240. The oxygen barrier coating or layer is a metal oxide, optionally Al 2 O 3 A vacuum blood collection tube according to any one of claims 235 to 239, comprising or essentially consisting of the above.

241. The oxygen barrier coating or layer is SiO x A vacuum blood collection tube according to any one of claims 235 to 240, comprising or essentially consisting of, where x is 1.5 to 2.

9.

242. The vacuum blood collection tube according to any one of claims 235 to 241, wherein the gas barrier coating includes a water vapor barrier coating or layer, and the water vapor barrier coating or layer is effective in reducing the intrusion of water vapor into the lumen to less than 0.05 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / package / day at 60°C and 40% relative humidity, and optionally less than 0.01 mg / package / day at 60°C and 40% relative humidity.

243. The vacuum blood collection tube according to any one of claims 235 to 242, wherein the gas barrier coating reduces the intrusion of water vapor into the lumen to less than 0.5 mg / package / day, alternatively less than 0.4 mg / package / day, alternatively less than 0.3 mg / package / day, alternatively less than 0.2 mg / package / day, alternatively 0.1 mg / package / day or less, alternatively less than 0.1 mg / package / day, alternatively less than 0.09 mg / package / day, alternatively less than 0.08 mg / package / day, alternatively less than 0.07 mg / package / day, or alternatively 0.06 mg / package / day or less when stored at 40°C and 75% relative humidity.

244. The vacuum blood collection tube according to any one of claims 235 to 243, wherein the gas barrier coating includes a water vapor barrier coating or layer, the water vapor barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the water vapor barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

245. The water vapor barrier coating or layer may be made of a metal oxide, optionally Al 2 O 3 A vacuum blood collection tube according to any one of claims 235 to 244, comprising or essentially consisting of the same.

246. The water vapor barrier coating or layer is SiO x A vacuum blood collection tube according to any one of claims 235 to 245, comprising or essentially consisting of, where x is 1.5 to 2.

9.

247. The gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer prevents nitrogen gas from entering the lumen at less than 0.0002 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally less than 0.00015 cc / package / day at 25°C, 60% relative humidity, and 0.21 bar, optionally 0.0001 cc / package / A vacuum blood collection tube according to any one of claims 235 to 246, which is effective in reducing the amount to less than 0.00005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.00002 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.00001 cc / package / day at 25°C, 60% relative humidity and 0.21 bar.

248. The gas barrier coating includes a nitrogen barrier coating or layer, and the nitrogen barrier coating or layer is 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 Less than 0.00008d (optionally). -1 Less than 0.00006d (optionally). -1 Less than 0.00004d (optionally) -1 Less than 0.00003d (optionally). -1 Less than 0.00002d (optionally). -1 Less than 0.00001d (optionally). -1 A vacuum blood collection tube according to any one of claims 235 to 247, which is effective in providing the vacuum blood collection tube having a nitrogen permeability constant (NTR) of less than .

249. The vacuum blood collection tube according to any one of claims 235 to 248, wherein the gas barrier coating includes a nitrogen barrier coating or layer, the nitrogen barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the nitrogen barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

250. The nitrogen barrier coating or layer is a metal oxide, optionally Al 2 O 3 A vacuum blood collection tube according to any one of claims 235 to 249, comprising or essentially consisting of the same.

251. The nitrogen barrier coating or layer is SiO x A vacuum blood collection tube according to any one of claims 235 to 250, comprising or essentially consisting of, where x is 1.5 to 2.

9.

252. The gas barrier coating includes a carbon dioxide barrier coating or layer, which prevents carbon dioxide from entering the lumen at less than 0.005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.004 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.003 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally 25°C, relative humidity A vacuum blood collection tube according to any one of claims 235 to 251, which is effective in reducing the amount to less than 0.002 cc / package / day at 60% and 0.21 bar, optionally less than 0.001 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0008 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, and optionally less than 0.0005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar.

253. The vacuum blood collection tube according to any one of claims 235 to 252, wherein the gas barrier coating includes a carbon dioxide barrier coating or layer, and the carbon dioxide barrier coating or layer is effective in providing the vacuum blood collection tube having a carbon dioxide transmission rate (CO2TR) of less than 0.005d-1, optionally less than 0.004d-1, optionally less than 0.002d-1, optionally less than 0.001d-1, optionally less than 0.0008d-1, optionally less than 0.0006d-1, optionally less than 0.0005d-1, optionally less than 0.0004d-1, optionally less than 0.0003d-1, optionally less than 0.0002d-1, and optionally less than 0.0001d-1.

254. The vacuum blood collection tube according to any one of claims 235 to 253, wherein the gas barrier coating includes a carbon dioxide barrier coating or layer, the carbon dioxide barrier coating or layer basically consists of a plurality of atomic monolayers, and optionally the carbon dioxide barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

255. The carbon dioxide barrier coating or layer is a metal oxide, optionally Al 2 O 3 A vacuum blood collection tube according to any one of claims 235 to 254, comprising or essentially consisting of the above.

256. The carbon dioxide barrier coating or layer is SiO x A vacuum blood collection tube according to any one of claims 235 to 255, comprising or essentially consisting of, where x is 1.5 to 2.

9.

257. The thermoplastic sidewall mainly consists of a general-purpose resin selected from COP, COC, PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN™, cyclic block copolymer (CBC) resin, thermoplastic olefin polymer, or any combination thereof, and optionally the thermoplastic sidewall mainly consists of cyclic block copolymer (CBC) resin, optionally VIVION™ 0510, VI A vacuum blood collection tube according to any one of claims 235 to 256, comprising a CBC resin selected from the group consisting of VION (trademark) 0510HF and VIVION (trademark) 1325, optionally from the group consisting of VIVION (trademark) 0510 and VIVION (trademark) 0510HF, optionally from VIVION (trademark) 0510, and optionally from VIVION (trademark) 0510HF, wherein optionally the thermoplastic sidewall is mainly composed of COP or COC.

258. The vacuum blood collection tube according to any one of claims 235 to 257, wherein the gas barrier coating is effective in maintaining a vacuum level in the lumen sufficient to draw blood from a patient's vein into the lumen against ambient pressure at sea level for at least 28 months, optionally at least 30 months, optionally at least 32 months, optionally at least 34 months, and optionally at least 36 months.

259. The gas barrier coating is effective in extending the storage life of the vacuum blood collection tube to at least 28 months, optionally at least 30 months, optionally at least 32 months, optionally at least 34 months, or optionally at least 36 months, and the storage life, defined by the amount of time since the tube was vacuumed, maintains an intake capacity of at least 90% of the intake capacity of a newly vacuumed container of the same type, according to any one of claims 235 to 258.

260. The vacuum blood collection tube according to any one of claims 235 to 259, further comprising a blood preservative in the lumen.

261. The vacuum blood collection tube according to any one of claims 235 to 260, wherein the gas barrier coating is effective in reducing the amount of solvent loss of the blood preservative over the storage life of the blood collection tube.

262. The vacuum blood collection tube according to any one of claims 235 to 261, wherein the gas barrier coating is supported by the inner surface of the wall.

263. The vacuum blood collection tube according to any one of claims 235 to 262, further comprising a pH protective coating between the lumen and the gas barrier coating.

264. The pH protective coating or layer is SiO x C y or SiN x C y A vacuum blood collection tube according to any one of claims 235 to 263, comprising, where x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

265. The vacuum blood collection tube according to any one of claims 235 to 264, wherein the pH protective coating or layer is deposited by PECVD.

266. A vacuum blood collection tube according to any one of claims 235 to 265, wherein the fluid composition having a pH of 5 to 9 is removed at a rate of 1 nm or less in thickness of the pH protective coating or layer per 44 hours of contact with the fluid composition.

267. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, - The maximum amplitude of the Si-O-Si asymmetric stretching peak is approximately 1060 to 1100 cm⁻¹. A vacuum blood collection tube according to any one of claims 235 to 266, having a ratio of more than 0.75 between them.

268. Primary packaging for pharmaceuticals, A container comprising a lumen at least partially defined by a wall, wherein the wall has an inner surface and an outer surface facing the lumen, - An oxygen barrier coating or layer supported by at least one of the inner surface and outer surface of the wall, which is effective in reducing the intrusion of oxygen into the lumen to less than 0.0005 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0004 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0003 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0002 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, optionally less than 0.0001 cc / package / day at 25°C, 60% relative humidity and 0.21 bar, - A water vapor barrier coating or layer supported by at least one of the inner surface and outer surface of the wall, which is effective in reducing the intrusion of water vapor into the lumen to less than 0.05 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / package / day at 60°C and 40% relative humidity, optionally less than 0.01 mg / package / day at 60°C and 40% relative humidity, Basically, at least one of the oxygen barrier coating or layer and the water vapor barrier coating or layer, which consist of multiple atomic monolayers of pure elements or compounds, - The fluid drug stored in the lumen and Primary packaging of pharmaceuticals including the drug.

269. The primary drug packaging according to claim 268, wherein at least one of the oxygen barrier coatings or layers or at least one of the water vapor barrier coatings or layers is supported by the inner surface of the wall.

270. The primary drug packaging according to claim 268 or 269, wherein the water vapor barrier coating or layer and the oxygen barrier coating or layer are disposed between the inner surface of the wall and the lumen.

271. The primary drug packaging according to any one of claims 268 to 270, wherein the water vapor coating or layer is disposed between the inner surface of the wall and the oxygen barrier coating or layer, and the oxygen barrier coating or layer is disposed between the water vapor coating or layer and the lumen.

272. The primary drug packaging according to any one of claims 268 to 271, further comprising a pH protective film or layer between the lumen and at least one of the water vapor barrier coating or layer and the oxygen barrier coating or layer, or optionally between the lumen and both the water vapor barrier coating or layer and the oxygen barrier coating or layer, wherein the pH protective film or layer is effective in extending the calculated storage life of the container.

273. The primary packaging of the drug according to claim Bx-C, wherein the fluid drug is in contact with the pH protective coating.

274. The primary drug packaging according to any one of claims 268 to 273, wherein the oxygen barrier coating or layer basically consists of multiple atomic monolayers of pure elements or compounds.

275. The primary pharmaceutical packaging according to any one of claims 268 to 274, wherein the water vapor barrier coating or layer basically consists of multiple atomic monolayers of pure elements or compounds.

276. The primary drug packaging according to any one of claims 268 to 275, wherein the wall is basically made of a thermoplastic material.

277. The primary packaging for pharmaceuticals according to claim Bx-F, wherein the thermoplastic material is basically made of a general-purpose resin.

278. The pharmaceutical primary packaging according to claim Bx-D1, wherein the general-purpose resin basically consists of PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN™, cyclic block copolymer (CBC) resin, thermoplastic olefin polymer, or any combination thereof.

279. The primary packaging of a pharmaceutical product according to any one of claims 268 to 278, wherein the pure element or compound of at least one atomic monolayer is a metal oxide, a metal nitride, or an elemental metal.

280. The primary packaging of a pharmaceutical product according to any one of claims 268 to 279, wherein the pure element or compound of at least one atomic monolayer is Al2O3, AlxTiyOz, HfO2, In2O3, MgO, SiO2, SrTiOx, Ta2O5, TiO2, Y2O3, ZnO, ZnO:Al, ZrO2, La2O3, or CeO2.

281. The primary packaging of a pharmaceutical product according to any one of claims 268 to 280, wherein the pure element or compound of at least one atomic monolayer is AlN, TiAlCN, TiN, or TaNx.

282. The primary packaging of a pharmaceutical product according to any one of claims 268 to 281, wherein the pure element or compound of at least one atomic monolayer is Ir, Pd, Pt, Si, Al, or Ru.

283. The primary pharmaceutical packaging according to any one of claims Bx-C to Bx-G3, wherein the pH protective coating basically consists of a PEG-CVD coating of SiOxCy, x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

284. The primary packaging of a pharmaceutical agent according to any one of claims 268 to 283, wherein the fluid pharmaceutical agent has a pH of 5 to 9, and the calculated storage life of the container is more than 6 months at a storage temperature of 4°C.

285. The primary packaging of a pharmaceutical agent according to any one of claims 268 to 284, wherein the fluid agent has a pH of 5 to 9, and the fluid agent removes the pH protective coating or layer at a rate of 1 nm or less in thickness per 44 hours of contact with the fluid agent.

286. The primary drug packaging according to any one of claims 268 to 285, wherein the lumen has a volume of 10 mL or less, optionally a volume of 5 mL or less, or optionally a volume of 2 mL or less.

287. The primary drug packaging according to any one of claims 268 to 286, further comprising a lubricating coating or layer supported by the inner surface of the wall.

288. The primary packaging of a pharmaceutical product according to claim Bx-L, wherein the lubricating coating or layer basically consists of SiOxCy, x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

289. The primary packaging of a pharmaceutical product according to claim Bx-M, wherein the lubricating coating or layer is deposited by plasma chemical vapor deposition (PECVD).

290. The primary pharmaceutical packaging according to claim Bx-N, wherein the lubricating coating or layer is deposited by PECVD of a linear siloxane, monocyclic siloxane, polycyclic siloxane, polysilsesquioxane, or any combination thereof, optionally by PECVD of a monocyclic siloxane, or optionally by PECVD of octamethylcyclotetrasiloxane (OMCTS).

291. The primary packaging for pharmaceuticals according to any one of claims Bx-L to Bx-O, wherein the lubricating coating or layer has a thickness of 10 to 1000 nm, optionally 10 to 500 nm, optionally 10 to 200 nm, optionally 10 to 100 nm, or optionally 20 to 100 nm.

292. The lubricating coating or layer is determined by the X-ray reflectance (XRR) to be 1.25 to 1.65 g / cm³. 3 A primary drug packaging according to any one of claims Bx-L to Bx-P, having the density of .

293. The primary drug packaging according to any one of claims Bx-L to Bx-Q, wherein the container is a syringe barrel, and the lubricating coating or layer provides (i) a lower plunger sliding force, (ii) a lower plunger sliding yield stress, or (iii) both (i) and (ii) compared to the same syringe barrel without the lubricating coating or layer.

294. The primary drug packaging according to claim Bx-R, wherein the lubricating coating or layer provides (i) a plunger sliding force, (ii) a plunger sliding yield stress, or (iii) both (i) and (ii) that are reduced by at least 45%, and optionally at least 60%, compared to the same syringe barrel without the lubricating coating or layer.

295. The primary drug packaging according to any one of claims 268 to 294, wherein the lubricating coating or layer is disposed between the pH protective coating or layer and the lumen.

296. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, - The maximum amplitude of the Si-O-Si asymmetric stretching peak is approximately 1060 to 1100 cm⁻¹. A primary drug packaging according to any one of claims 268 to 295, having a ratio of greater than 0.75, optionally greater than 0.8, optionally greater than 0.85, and optionally greater than 0.9 in the range.

297. The FTIR absorbance spectrum of the lubricating coating or layer is - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and A primary drug packaging according to any one of claims 268 to 296, having a ratio of at most 0.75 among them.

298. A container having a lumen at least partially defined by a wall, wherein the wall comprises a general-purpose resin, and the wall has an inner surface facing the lumen, an outer surface, and a coating set on the inner surface including at least one barrier coating or layer and at least one pH protective coating or layer. - The barrier coating or layer is SiO x The barrier coating or layer is applied by atomic layer deposition and has an inner surface facing the lumen and an outer surface facing the inner surface of the wall, and the barrier coating or layer is effective in reducing the intrusion of atmospheric gas into the lumen compared to a container without a barrier coating or layer. - The pH protective coating or layer is SiO x C y or SiN x C y The pH protective coating or layer is coated by PECVD and has an inner surface facing the lumen and an outer surface facing the inner surface of the barrier coating or layer, and A container in which, if a fluid composition having a pH of 5 to 9 is present in the lumen, the calculated storage life of the container is more than 6 months at a storage temperature of 4°C.

299. The container according to claim 298, wherein the covering set further comprises a tie covering or layer, the tie covering or layer having an inner surface facing the barrier covering or layer and an outer surface facing the inner surface of the wall.

300. The container according to claim 299, wherein the tie coating or layer comprises SiOxCy or SiNxCy, where x is about 0.5 to about 2.4 and y is about 0.6 to about 3.

301. The tie coating or layer is Al 2 O 3 The container according to claim 299, or comprising ZnO.

302. The container according to any one of claims 299 to 301, wherein the tie coating or layer is applied by atomic layer deposition.

303. The container according to any one of claims 299 to 302, wherein the tie coating or layer is 1 to 15 nm thick, alternatively 2 to 12 nm thick, alternatively 3 to 10 nm thick, alternatively 4 to 8 nm thick, or alternatively 5 to 7 nm thick.

304. The container according to any one of claims 298 to 303, wherein the coating set further comprises a water vapor barrier coating or layer.

305. The container according to claim 304, wherein the water vapor barrier coating or layer includes a metal oxide coating applied by atomic layer deposition.

306. The container according to claim 304 or 305, wherein the water vapor barrier coating or layer comprises aluminum oxide.

307. The container according to claim 306, wherein the aluminum oxide is deposited by atomic layer deposition using a trimethylaluminum precursor.

308. The container according to any one of claims 304 to 306, wherein the water vapor barrier coating or layer has an inner surface facing the barrier coating or layer and an outer surface facing the inner surface of the wall.

309. The container according to any one of claims 304 to 307, wherein the water vapor barrier coating or layer is 1 to 15 nm thick, alternatively 2 to 12 nm thick, alternatively 3 to 10 nm thick, alternatively 4 to 8 nm thick, or alternatively 5 to 7 nm thick.

310. The container according to any one of claims 298 to 309, wherein the SiOx barrier coating or layer is deposited using a silicon-containing precursor selected from the group consisting of aminosilanes, alkylaminosilanes, 1,2-bis(diisopropylamino)disilane, diisopropylaminosilane, tris(dimethylamino)silane, bis(ethyl-methyl-amino)silane, and any combination thereof.

311. The container according to any one of claims 298 to 310, wherein the barrier coating or layer is 1 to 15 nm thick, alternatively 2 to 12 nm thick, alternatively 3 to 10 nm thick, alternatively 4 to 8 nm thick, or alternatively 5 to 7 nm thick.

312. A container having a lumen at least partially defined by a wall, wherein the wall comprises a general-purpose resin, and the wall has an inner surface facing the lumen, an outer surface, and a coating set on the inner surface comprising at least one barrier coating or layer and a pH protective coating or layer, wherein at least one of the one or more barrier coatings or layers is coated by atomic layer deposition.

313. The container according to claim 312, wherein the coating set includes a water vapor barrier coating or layer applied by atomic layer deposition.

314. The container according to claim 313, wherein the water vapor barrier coating or layer comprises aluminum oxide.

315. The container according to any one of claims 312 to 314, wherein the coating set includes an oxygen barrier coating or layer applied by atomic layer deposition.

316. The container according to claim 315, wherein the oxygen barrier coating or layer comprises SiOx, and x is 1.5 to 2.

9.

317. The container according to any one of claims 312 to 316, wherein the pH protective coating or layer comprises SiOxCy or SiNxCy, where x is about 0.5 to about 2.4 and y is about 0.6 to about 3.

318. The container according to any one of claims 312 to 317, wherein at least one of the one or more barrier coatings or layers applied by atomic layer deposition has a thickness of 1 to 15 nm, alternatively 2 to 12 nm, alternatively 3 to 10 nm, alternatively 4 to 8 nm, or alternatively 5 to 7 nm.

319. The container according to any one of claims 312 to 318, further comprising at least one tie layer or coating.

320. A container having a lumen at least partially defined by a wall, wherein the wall comprises a general-purpose resin and has an inner surface facing the lumen, an outer surface, and a coating set on the inner surface comprising at least one oxygen barrier coating or layer, at least one water vapor barrier coating or layer, and at least one pH protective coating or layer. - The water vapor barrier coating or layer has an inner surface facing the oxygen barrier coating or layer and an outer surface facing the inner surface of the container wall, and the water vapor barrier coating or layer is effective in reducing the intrusion of water vapor into the lumen compared to a container without a water vapor barrier coating or layer. - The oxygen barrier coating or layer is SiO x The oxygen barrier coating or layer includes, where x is 1.5 to 2.9, and the oxygen barrier coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the water vapor barrier coating or layer, and the oxygen barrier coating or layer is effective in reducing the intrusion of atmospheric gas into the lumen compared to a container without an oxygen barrier coating or layer. - The pH protective coating or layer is SiO x C y or SiN x C y The pH protective coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the barrier coating or layer, and A container in which, if a fluid composition having a pH of 5 to 9 is present in the lumen, the calculated storage life of the container is more than 6 months at a storage temperature of 4°C.

321. The container according to claim 320, wherein the steam coating or layer is deposited by atomic layer deposition.

322. The aforementioned water vapor barrier coating or layer is Al 2 O 3 The container according to claim 320 or 321, including the above.

323. The container according to any one of claims 320 to 322, wherein the oxygen barrier coating or layer is deposited by atomic layer deposition.

324. The container according to any one of claims 320 to 323, wherein at least a portion of the wall of the container comprises PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN®, cyclic block copolymer (CBC), or thermoplastic olefin polymer: optionally PET, polycarbonate, polypropylene, or any combination thereof: cyclic block copolymer (CBC); optionally a CBC resin selected from the group consisting of VIVION® 0510, VIVION® 0510HF, and VIVION® 1325.

325. A container according to any one of claims 320 to 324, comprising a syringe barrel, a vial, or blister packaging.

326. The container according to any one of claims 320 to 325, wherein the pH protective coating or layer is applied by PECVD of a precursor feed comprising any two or more combinations of acyclic siloxane, monocyclic siloxane, polycyclic siloxane, polysilsesquioxane, monocyclic silazane, polycyclic silazane, polysilsesquiazane, silatoran, silk acilatran, silproatoran, azasilatoran, azasilacilatran, azasilproatoran, or the precursor.

327. The container according to any one of claims 320 to 326, wherein the pH protective coating or layer applied is 10 to 1000 nm thick.

328. The container according to any one of claims 320 to 327, wherein the pH protective coating or layer has at least the same extent as the barrier coating or layer.

329. The container according to any one of claims 320 to 328, wherein the fluid composition removes the pH protective coating or layer at a rate of 1 nm or less in thickness per 44 hours of contact with the fluid composition.

330. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and A container according to any one of claims 320 to 329, having a ratio of more than 0.75 between them.

331. The container according to any one of claims 320 to 330, further comprising a lubricating coating or layer supported by the inner surface of the wall.

332. The container according to claim 331, wherein the lubricating coating or layer basically consists of SiOxCy, x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

333. The container according to claim 332, wherein the lubricating coating or layer is deposited by plasma chemical vapor deposition (PECVD).

334. The container according to claim 333, wherein the lubricating coating or layer is deposited by PECVD of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, or any combination thereof, optionally by PECVD of a monocyclic siloxane, or optionally by PECVD of octamethylcyclotetrasiloxane (OMCTS).

335. The container according to any one of claims 331 to 334, wherein the lubricating coating or layer has a thickness of 10 to 1000 nm, optionally 10 to 500 nm, optionally 10 to 200 nm, optionally 10 to 100 nm, or optionally 20 to 100 nm.

336. The lubricating coating or layer is determined by the X-ray reflectance (XRR) to be 1.25 to 1.65 g / cm³. 3 A container according to any one of claims 331 to 335, having the density of .

337. A syringe barrel, and the lubricating coating or layer provides (i) a lower plunger sliding force, (ii) a lower plunger sliding yield stress, or (iii) both (i) and (ii), compared to the same syringe barrel without the lubricating coating or layer, according to any one of claims 331 to 336.

338. The container according to claim 337, wherein the lubricating coating or layer provides (i) a plunger sliding force, (ii) a plunger sliding yield stress, or (iii) both (i) and (ii) that are reduced by at least 45%, and optionally at least 60%, compared to the same syringe barrel without the lubricating coating or layer.

339. The container according to any one of claims 320 to 338, wherein the lubricating coating or layer is disposed between the pH protective coating or layer and the lumen.

340. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and A container according to any one of claims 320 to 339, having a ratio of more than 0.75, optionally more than 0.8, optionally more than 0.85, and optionally more than 0.9 in between.

341. The FTIR absorbance spectrum of the lubricating coating or layer is - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and A container according to any one of claims 320 to 340, having a ratio of at most 0.75 among them.

342. It is a container, A container having a lumen at least partially defined by a wall, wherein the wall has an inner surface and an outer surface facing the lumen, and the wall is made mainly of a general-purpose resin, A water vapor barrier coating or layer that is effective in reducing the intrusion of water vapor into the lumen, A container that includes, and is the same container, but has a water vapor transmission rate that is lower than the water vapor transmission rate of the container without the water vapor barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, optionally at least 90% lower.

343. The container according to claim 342, which is an identical container made of COP resin and has a water vapor permeability at least equal to that of a container without a water vapor barrier coating or layer, and optionally has a water vapor permeability lower than that of an identical container made of COP resin and without a water vapor barrier coating or layer.

344. The container according to claim 343, wherein, in the absence of the water vapor barrier or layer, the container is made of COP resin and has a water vapor transmission rate greater than that of the container without the water vapor barrier coating or layer.

345. It is a container, A container having a lumen at least partially defined by a wall, wherein the wall has an inner surface and an outer surface facing the lumen, and the wall is made mainly of a general-purpose resin, Compared to a container without a water vapor barrier coating or layer, a water vapor barrier coating or layer is effective in reducing the intrusion of water vapor into the lumen. A container containing and having a water vapor transmission rate of less than 0.05 mg / container / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / container / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / container / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / container / day at 60°C and 40% relative humidity, and optionally less than 0.01 mg / container / day at 60°C and 40% relative humidity.

346. A container according to any one of claims 342 to 345, having a volume of 10 mL or less, optionally 5 mL or less, or optionally 2 mL or less.

347. The container according to claim 345 or 346, wherein, in the absence of the water vapor barrier or coating, the container has a water vapor transmission rate of more than 1.0 g / container / day, optionally more than 2.0 g / container / day, and optionally more than 3.0 g / container / day.

348. It is a container, A container having a lumen at least partially defined by a wall, wherein the wall has an inner surface and an outer surface facing the lumen, and the wall is mainly made of COP resin, A water vapor barrier coating or layer that is effective in reducing the intrusion of water vapor into the lumen, A container comprising the same container made from COP resin, having a water vapor transmission rate that is lower than the water vapor transmission rate of the container without the water vapor barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower.

349. It is a container, A container having a lumen at least partially defined by a wall, wherein the wall has an inner surface and an outer surface facing the lumen, and the wall is mainly made of COC resin, A water vapor barrier coating or layer that is effective in reducing the intrusion of water vapor into the lumen, A container comprising the same container made from COC resin, having a water vapor transmission rate that is lower than the water vapor transmission rate of the container without the water vapor barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, and optionally at least 90% lower.

350. The container according to any one of claims 342 to 349, wherein the container is a syringe, a vial, or a blood collection tube.

351. The container according to any one of claims 342 to 350, wherein the general-purpose resin is selected from PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN™, cyclic block copolymer (CBC) resin, thermoplastic olefin polymer, or any combination thereof.

352. The container according to claim 351, wherein the general-purpose resin is selected from PET, polycarbonate, polypropylene, or any combination thereof.

353. The container according to claim 351, wherein the general-purpose resin is a cyclic block copolymer (CBC) resin.

354. The container according to claim 353, wherein the CBC resin is selected from the group consisting of VIVION® 0510, VIVION® 0510HF, and VIVION® 1325, optionally from the group consisting of VIVION® 0510 and VIVION® 0510HF, optionally from VIVION® 0510, and optionally from VIVION® 0510HF.

355. The container according to any one of claims 342 to 354, wherein the water vapor barrier coating or layer includes or is basically composed of a metal oxide coating.

356. The container according to any one of claims 342 to 355, wherein the water vapor barrier coating or layer contains or is basically composed of aluminum oxide.

357. The container according to any one of claims 342 to 356, wherein the water vapor barrier coating or layer comprises or is essentially composed of a plurality of atomic monolayers, and optionally the water vapor barrier coating or layer is applied by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

358. The container according to any one of claims 342 to 357, wherein the water vapor barrier coating or layer has an inner surface facing the inner surface of the cavity and an outer surface facing the inner surface of the wall.

359. The container according to any one of claims 342 to 357, wherein the water vapor barrier coating or layer has an inner surface facing the outer surface of the wall.

360. The container according to any one of claims 342 to 357, wherein the water vapor barrier coating or layer has an inner surface facing the inner surface of the wall and an outer surface facing the outer surface of the wall.

361. The container according to any one of claims 342 to 360, wherein the water vapor barrier coating or layer is 1 to 50 nm thick, alternatively 5 to 50 nm thick, alternatively 10 to 50 nm thick, alternatively 1 to 40 nm thick, alternatively 5 to 40 nm thick, alternatively 10 to 40 nm thick, alternatively 1 to 30 nm thick, alternatively 5 to 30 nm thick, or alternatively 10 to 30 nm thick.

362. A container according to any one of claims 342 to 361, further comprising an oxygen barrier coating or layer, the oxygen barrier coating or layer being effective in reducing the intrusion of atmospheric gas into the lumen compared to a container without an oxygen barrier coating or layer.

363. The container according to claim 362, wherein the oxygen barrier coating or layer comprises SiOx, and x is 1.5 to 2.

9.

364. The container according to claim 362 or 363, wherein the oxygen barrier coating or layer comprises or consists essentially of a plurality of atomic monolayers, and optionally the oxygen barrier coating or layer is applied by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

365. The container according to claim 362 or 363, wherein the oxygen barrier coating or layer is applied by PECVD.

366. The container according to any one of claims 362 to 365, wherein the oxygen barrier coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the wall.

367. The container according to claim 366, wherein the water vapor barrier coating or layer is located between the oxygen barrier coating or layer and the inner surface of the wall.

368. A container according to any one of claims 362 to 367, further comprising a pH protective coating or layer, the pH protective coating or layer being effective in extending the calculated storage life of the container.

369. The container according to claim 368, wherein the pH protective coating or layer comprises SiOxCy or SiNxCy, where x is about 0.5 to about 2.4 and y is about 0.6 to about 3.

370. The container according to any one of claims 342 to 369, wherein, if a fluid composition having a pH of 5 to 9 is contained in the lumen, the calculated storage life of the container is more than 6 months at a storage temperature of 4°C.

371. The container according to any one of claims 342 to 370, further comprising a liquid pharmaceutical in the lumen.

372. The container according to any one of claims 342 to 371, further comprising a lubricating coating or layer supported by the inner surface of the wall.

373. The container according to claim 372, wherein the lubricating coating or layer basically consists of SiOxCy, x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

374. The container according to claim 373, wherein the lubricating coating or layer is deposited by plasma chemical vapor deposition (PECVD).

375. The container according to claim 374, wherein the lubricating coating or layer is deposited by PECVD of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, or any combination thereof, optionally by PECVD of a monocyclic siloxane, optionally by PECVD of octamethylcyclotetrasiloxane (OMCTS).

376. The container according to any one of claims 372 to 375, wherein the lubricating coating or layer has a thickness of 10 to 1000 nm, optionally 10 to 500 nm, optionally 10 to 200 nm, optionally 10 to 100 nm, or optionally 20 to 100 nm.

377. The lubricating coating or layer is determined by the X-ray reflectance (XRR) to be 1.25 to 1.65 g / cm³. 3 A container according to any one of claims 372 to 376, having the density of .

378. The container according to any one of claims 372 to 377, wherein the container is a syringe barrel, and the lubricating coating or layer provides (i) a lower plunger sliding force, (ii) a lower plunger sliding yield stress, or (iii) both (i) and (ii) compared to the same syringe barrel without the lubricating coating or layer.

379. The container according to claim 378, wherein the lubricating coating or layer provides (i) plunger sliding force, (ii) plunger sliding yield stress, or (iii) both (i) and (ii) that are reduced by at least 45%, and optionally at least 60%, compared to the same syringe barrel without the lubricating coating or layer.

380. The container according to any one of claims 342 to 379, wherein the lubricating coating or layer is disposed between the pH protective coating or layer and the lumen.

381. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and A container according to any one of claims 342 to 380, having a ratio of greater than 0.75, optionally greater than 0.8, optionally greater than 0.85, and optionally greater than 0.9 between the two.

382. The FTIR absorbance spectrum of the lubricating coating or layer is - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and A container according to any one of claims 342 to 381, having a ratio of at most 0.75 among them.

383. It is a container, A lumen, at least partially defined by a wall, wherein the wall is mainly made of a general-purpose resin and has an inner surface and an outer surface facing the lumen, Compared to a container without an oxygen barrier coating or layer, an oxygen barrier coating or layer is effective in reducing the intrusion of atmospheric gas into the lumen, A water vapor barrier coating or layer that is effective in reducing the intrusion of water vapor into the lumen, Optionally, a pH protective coating or layer which is effective in extending the calculated storage life of the container and A container containing...

384. It is a container, A lumen, at least partially defined by a wall, wherein the wall is mainly made of COP or COC resin and has an inner surface and an outer surface facing the lumen, Compared to a container without an oxygen barrier coating or layer, an oxygen barrier coating or layer is effective in reducing the intrusion of atmospheric gas into the lumen, A water vapor barrier coating or layer that is effective in reducing the intrusion of water vapor into the lumen, Optionally, a pH protective coating or layer which is effective in extending the calculated storage life of the container and A container containing...

385. The container according to claim 383 or 384, wherein the water vapor barrier coating or layer comprises or consists essentially of a plurality of atomic monolayers, and optionally the water vapor barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

386. The water vapor barrier coating or layer is a metal oxide coating, optionally Al 2 O 3 A container according to any one of claims 383 to 385, which includes or basically consists of the same.

387. The oxygen barrier coating or layer is SiO x Includes 、 The container according to any one of claims 383 to 386, wherein x is 1.5 to 2.

9.

388. The container according to any one of claims 383 to 387, wherein the oxygen barrier coating or layer comprises or consists essentially of a plurality of atomic monolayers, and optionally the oxygen barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

389. The pH protective coating or layer is SiO x C y or SiN x C y A container according to any one of claims 383 to 388, comprising, where x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

390. The container according to any one of claims 383 to 389, wherein the pH protective coating or layer is deposited by PECVD.

391. The container according to any one of claims 383 to 390, wherein, if a fluid composition having a pH of 5 to 9 is contained in the lumen, the calculated storage life of the container is more than 6 months at a storage temperature of 4°C.

392. The container according to any one of claims 383 to 391, wherein at least the oxygen barrier coating or layer and the pH protective coating or layer are located between the inner surface of the wall and the lumen.

393. The container according to any one of claims 383 to 392, wherein the water vapor permeable coating or layer is located (i) between the inner surface of the wall and the lumen, (ii) on another surface of the wall, or (iii) between the inner surface of the wall and the outer surface of the wall.

394. A container according to any one of claims 383 to 393, having a water vapor transmission rate that is at least equal to the water vapor transmission rate of an identical container made from COP resin and without the water vapor barrier coating or layer, and optionally lower than the water vapor transmission rate of an identical container made from COP resin and without the water vapor barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower.

395. The container according to any one of claims 383 to 393, which is the same container made of COP or COC resin and has a water vapor transmission rate that is lower than the water vapor transmission rate of the container without the water vapor barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower.

396. The container according to claim 394, which, in the absence of the aforementioned water vapor barrier coating or layer, is made of COP resin and has a water vapor transmission rate that is optionally at least twice, optionally at least three times, optionally at least four times, or optionally at least five times higher than the water vapor transmission rate of the one without the aforementioned water vapor barrier coating or layer.

397. A container according to any one of claims 383 to 396, having a water vapor transmission rate of less than 0.05 mg / container / day at 60°C and 40% relative humidity, optionally less than 0.04 mg / container / day at 60°C and 40% relative humidity, optionally less than 0.03 mg / container / day at 60°C and 40% relative humidity, optionally less than 0.02 mg / container / day at 60°C and 40% relative humidity, and optionally less than 0.01 mg / container / day at 60°C and 40% relative humidity.

398. The container according to claim 397, wherein the internal lumen of the container has a volume of 10 mL or less, optionally 5 mL or less, or optionally 2 mL or less.

399. A container according to any one of claims 397 to B13984, having a water vapor transmission rate of more than 1.0 g / container / day, optionally more than 2.0 g / container / day, or optionally more than 3.0 g / container / day, in the absence of the aforementioned water vapor barrier or coating.

400. A container according to any one of claims 383 to 399, which is a syringe, or a vial, or a blood collection tube.

401. The container according to any one of claims 383 to 400, wherein the general-purpose resin is selected from PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN™, cyclic block copolymer (CBC) resin, thermoplastic olefin polymer, or any combination thereof.

402. The container according to claim 401, wherein the general-purpose resin is selected from PET, polycarbonate, polypropylene, or any combination thereof.

403. The container according to claim 401, wherein the general-purpose resin is a cyclic block copolymer (CBC) resin.

404. The container according to claim 403, wherein the CBC resin is selected from the group consisting of VIVION® 0510, VIVION® 0510HF, and VIVION® 1325, optionally from the group consisting of VIVION® 0510 and VIVION® 0510HF, optionally from VIVION® 0510, and optionally from VIVION® 0510HF.

405. The container according to any one of claims 383 to 404, wherein the water vapor barrier coating or layer is 1 to 50 nm thick, alternatively 5 to 50 nm thick, alternatively 10 to 50 nm thick, alternatively 1 to 40 nm thick, alternatively 5 to 40 nm thick, alternatively 10 to 40 nm thick, alternatively 1 to 30 nm thick, alternatively 5 to 30 nm thick, or alternatively 10 to 30 nm thick.

406. The container according to any one of claims 383 to 405, wherein the oxygen barrier coating or layer is 1 to 15 nm thick, alternatively 2 to 12 nm thick, alternatively 3 to 10 nm thick, alternatively 4 to 8 nm thick, or alternatively 5 to 7 nm thick.

407. The container according to any one of claims 383 to 406, wherein the pH protective coating or layer is 10 to 1000 nm thick.

408. The container according to any one of claims 383 to 407, wherein the pH protective coating or layer has at least the same extent as the oxygen barrier coating or layer.

409. A container according to any one of claims 383 to 408, wherein the fluid composition having a pH of 5 to 9 is removed at a rate of 1 nm or less in thickness of the pH protective coating or layer per 44 hours of contact with the fluid composition.

410. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, - The maximum amplitude of the Si-O-Si asymmetric stretching peak is approximately 1060 to 1100 cm⁻¹. A container according to any one of claims 383 to 409, having a ratio of more than 0.75 between them.

411. 0.0010d -1 Less than 0.0008d (optionally). -1 Less than 0.0006d (optionally). -1 Less than 0.0004d (optionally). -1 Less than 0.0002d (optionally). -1 A container according to any one of claims 383 to 410, having an oxygen permeability constant of less than .

412. The container according to any one of claims 383 to 411, further comprising a liquid pharmaceutical in the lumen.

413. The container according to any one of claims 383 to 412, further comprising a lubricating coating or layer supported by the inner surface of the wall.

414. The container according to claim 413, wherein the lubricating coating or layer basically consists of SiOxCy, x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

415. The container according to claim 414, wherein the lubricating coating or layer is deposited by plasma chemical vapor deposition (PECVD).

416. The container according to claim 415, wherein the lubricating coating or layer is deposited by PECVD of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, or any combination thereof, optionally by PECVD of a monocyclic siloxane, optionally by PECVD of octamethylcyclotetrasiloxane (OMCTS).

417. The container according to any one of claims 413 to 416, wherein the lubricating coating or layer has a thickness of 10 to 1000 nm, optionally 10 to 500 nm, optionally 10 to 200 nm, optionally 10 to 100 nm, or optionally 20 to 100 nm.

418. The lubricating coating or layer is determined by the X-ray reflectance (XRR) to be 1.25 to 1.65 g / cm³. 3 A container according to any one of claims 413 to 417, having the density of .

419. A syringe barrel, and the lubricating coating or layer provides (i) a lower plunger sliding force, (ii) a lower plunger sliding yield stress, or (iii) both (i) and (ii), compared to the same syringe barrel without the lubricating coating or layer, according to any one of claims 413 to 418.

420. The container according to claim 419, wherein the lubricating coating or layer provides (i) a plunger sliding force, (ii) a plunger sliding yield stress, or (iii) both (i) and (ii) that are reduced by at least 45%, and optionally at least 60%, compared to the same syringe barrel without the lubricating coating or layer.

421. The container according to any one of claims 413 to 420, wherein the lubricating coating or layer is disposed between the pH protective coating or layer and the lumen.

422. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and A container according to any one of claims 384 to 421, having a ratio of greater than 0.75, optionally greater than 0.8, optionally greater than 0.85, and optionally greater than 0.9 in between.

423. The FTIR absorbance spectrum of the lubricating coating or layer is - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and A container according to any one of claims 384 to 422, having a ratio of at most 0.75 among them.

424. A container comprising a lumen at least partially defined by a wall, the wall having an inner surface and an outer surface facing the lumen, and a covering set on the inner surface, the covering set comprising an oxygen barrier coating or layer, The oxygen barrier coating or layer has a thickness of 1 nm to 15 nm, optionally 1 nm to 10 nm. The aforementioned container has an oxygen permeability constant of 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 A container that is less than [amount missing].

425. The container according to claim 424, wherein the oxygen barrier coating or layer comprises or consists essentially of a plurality of atomic monolayers, and optionally the oxygen barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

426. A container comprising a lumen at least partially defined by a wall, the wall having an inner surface and an outer surface facing the lumen, and a covering set on the inner surface, the covering set comprising an oxygen barrier coating or layer, The oxygen barrier coating or layer comprises or is essentially composed of multiple atomic monolayers, and optionally the oxygen barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition. The container is coated by PECVD with an oxygen barrier coating or layer having substantially the same composition and thickness, and has an oxygen permeability constant that is lower than that of an otherwise uniform container, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower.

427. The container according to claim 426, wherein the oxygen barrier coating or layer has a thickness of 1 nm to 15 nm, and optionally 1 nm to 10 nm.

428. The oxygen barrier coating or layer is SiO x A container according to any one of claims 424 to 427, which includes, mainly consists of, or is the same as, and x is between 1.5 and 2.

9.

429. The container according to any one of claims 424 to 428, further comprising a water vapor barrier coating or layer, the water vapor barrier coating or layer being effective in reducing the intrusion of water vapor into the lumen.

430. The container according to claim 429, wherein the water vapor barrier coating or layer comprises or consists essentially of a plurality of atomic monolayers, and optionally the water vapor barrier coating or layer is deposited by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

431. The aforementioned water vapor coating or layer is a metal oxide, optionally Al 2 O 3 The container according to claim 429 or 430, including the above.

432. The container according to any one of claims 429 to 431, wherein the water vapor barrier coating or layer is 1 to 50 nm thick, alternatively 5 to 50 nm thick, alternatively 10 to 50 nm thick, alternatively 1 to 40 nm thick, alternatively 5 to 40 nm thick, alternatively 10 to 40 nm thick, alternatively 1 to 30 nm thick, alternatively 5 to 30 nm thick, or alternatively 10 to 30 nm thick.

433. The container according to any one of claims 429 to 432, wherein the water vapor permeable coating or layer is located (i) between the inner surface of the wall and the oxygen barrier coating or layer, (ii) between the oxygen barrier coating or layer and the lumen, (iii) on the outer surface of the wall, or (iv) between the inner surface of the wall and the outer surface of the wall.

434. A container according to any one of claims 424 to 433, further comprising a pH protective coating or layer, the pH protective coating or layer being effective in extending the calculated storage life of the container.

435. The pH protective coating or layer is SiO x C y or SiN x C y The container according to claim 434, wherein x is about 0.5 to about 2.4 and y is about 0.6 to about 3.

436. The container according to claim 434 or 435, wherein the pH protective coating or layer is deposited by PECVD.

437. The container according to any one of claims 434 to 436, wherein the pH protective coating or layer is 10 to 1000 nm thick.

438. The container according to any one of claims 434 to 437, wherein the pH protective coating or layer has at least the same extent as the barrier coating or layer.

439. A container according to any one of claims 434 to 438, wherein the fluid composition having a pH of 5 to 9 is removed at a rate of 1 nm or less in thickness of the pH protective coating or layer per 44 hours of contact with the fluid composition.

440. The container according to any one of claims 434 to 439, wherein, if a fluid composition having a pH of 5 to 9 is contained in the lumen, the calculated storage life of the container is more than 6 months at a storage temperature of 4°C.

441. A container according to any one of claims 424 to 440, which is a syringe or a vial.

442. The container according to any one of claims 424 to 441, wherein the container wall is mainly made of a general-purpose resin, and optionally the general-purpose resin is selected from PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN™, cyclic block copolymer (CBC) resin, thermoplastic olefin polymer, or any combination thereof.

443. The container according to claim 442, wherein the general-purpose resin is selected from PET, polycarbonate, polypropylene, or any combination thereof.

444. The container according to claim 442, wherein the general-purpose resin is a cyclic block copolymer (CBC) resin.

445. The container according to claim 444, wherein the CBC resin is selected from the group consisting of VIVION® 0510, VIVION® 0510HF and VIVION® 1325; optionally selected from the group consisting of VIVION® 0510 and VIVION® 0510HF; optionally selected from VIVION® 0510; and optionally selected from VIVION® 0510HF.

446. The container according to any one of claims 424 to 441, wherein the container wall is mainly made of COP resin or COC resin.

447. The container according to any one of claims 424 to 446, further comprising a liquid drug solution within the lumen.

448. The container according to any one of claims 424 to 447, further comprising a lubricating coating or layer supported by the inner surface of the wall.

449. The container according to claim 448, wherein the lubricating coating or layer basically consists of SiOxCy, x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

450. The container according to claim 449, wherein the lubricating coating or layer is deposited by plasma chemical vapor deposition (PECVD).

451. The container according to claim 450, wherein the lubricating coating or layer is deposited by PECVD of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, or any combination thereof, optionally by PECVD of a monocyclic siloxane, or optionally by PECVD of octamethylcyclotetrasiloxane (OMCTS).

452. The container according to any one of claims 448 to 451, wherein the lubricating coating or layer has a thickness of 10 to 1000 nm, optionally 10 to 500 nm, optionally 10 to 200 nm, optionally 10 to 100 nm, or optionally 20 to 100 nm.

453. The lubricating coating or layer is determined by the X-ray reflectance (XRR) to be 1.25 to 1.65 g / cm³. 3 A container according to any one of claims 448 to 452, having the density of .

454. A syringe barrel, and the lubricating coating or layer provides (i) a lower plunger sliding force, (ii) a lower plunger sliding yield stress, or (iii) both (i) and (ii), compared to the same syringe barrel without the lubricating coating or layer, according to any one of claims 448 to 453.

455. The container according to claim 454, wherein the lubricating coating or layer provides (i) plunger sliding force, (ii) plunger sliding yield stress, or (iii) both (i) and (ii) compared to the same syringe barrel but without the lubricating coating or layer, which is reduced by at least 45%, and optionally at least 60%.

456. The container according to any one of claims 448 to 455, wherein the lubricating coating or layer is disposed between the pH protective coating or layer and the lumen.

457. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and A container according to any one of claims 424 to 456, having a ratio of greater than 0.75, optionally greater than 0.8, optionally greater than 0.85, and optionally greater than 0.9 in between.

458. The FTIR absorbance spectrum of the lubricating coating or layer is - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and A container according to any one of claims 424 to 457, having a ratio of at most 0.75 among them.

459. A method for preparing a barrier container suitable for storing a liquid drug formulation over a period of time, To provide a container having a lumen at least partially defined by a wall, wherein the wall is mainly made of a general-purpose resin and has an inner surface and an outer surface facing the lumen, A water vapor barrier coating is applied by atomic layer deposition, wherein the water vapor barrier coating is effective in reducing the intrusion of water vapor into the lumen. A method that includes this.

460. A method for preparing a barrier container suitable for storing a liquid drug formulation over a period of time, To provide a container having a lumen at least partially defined by a wall, wherein the wall is mainly made of COP or COC resin and has an inner surface and an outer surface facing the lumen, A water vapor barrier coating is applied by atomic layer deposition, wherein the water vapor barrier coating is effective in reducing the intrusion of water vapor into the lumen. A method that includes this.

461. The method according to claim 459 or 460, wherein the water vapor barrier coating includes a metal oxide coating.

462. The method according to claim 461, wherein the water vapor barrier coating or layer comprises aluminum oxide.

463. The method according to claim 462, wherein the atomic layer deposition utilizes a trimethylaluminum precursor.

464. The method according to any one of claims 459 to 463, wherein the water vapor barrier coating is applied by plasma-assisted atomic layer deposition.

465. The method according to any one of claims 459 to 464, wherein the wall is maintained at a temperature of less than 100°C, optionally less than 80°C, during the deposition of the coating.

466. The method according to any one of claims 459 to 465, wherein the outer surface of the wall is masked during deposition so that the coating is deposited only on the inner surface of the wall.

467. The method according to any one of claims 459 to 465, wherein the inner surface of the wall is masked during deposition so that the coating is deposited only on the outer surface of the wall.

468. The method according to any one of claims 459 to 467, wherein the water vapor barrier coating or layer is deposited to a thickness of 1 to 50 nm, alternatively 5 to 50 nm, alternatively 10 to 50 nm, alternatively 1 to 40 nm, alternatively 5 to 40 nm, alternatively 10 to 40 nm, alternatively 1 to 30 nm, alternatively 5 to 30 nm, or alternatively 10 to 30 nm.

469. To provide at least 20 containers, optionally at least 50 containers, optionally at least 100 containers, optionally at least 150 containers, optionally at least 200 containers, optionally at least 500 containers, optionally at least 800 containers, optionally at least 1000 containers in the reactor, optionally at least PICOSUN (trademark) P-1000B PRO, Provide a substantially uniform flow of the precursor gas to each of the containers under conditions sufficient to construct the layer of the water vapor barrier coating substantially uniformly across the plurality of containers, with optionally at least 95% uniformity, optionally at least 96% uniformity, and optionally at least 97% uniformity. The method according to any one of claims 459 to 467, further comprising:

470. The method according to claim 469, wherein the container is placed in a multi-level rack located inside the reactor.

471. The method according to any one of claims 459 to 470, which provides a container having a water vapor transmission rate that is at least equal to the water vapor transmission rate of an identical container made from COP resin and without the water vapor barrier coating or layer, and optionally lower than the water vapor transmission rate of an identical container made from COP resin and without the water vapor barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower.

472. The method according to any one of claims 459 to 470, wherein the water vapor barrier coating is the same container made of COP or COC resin, and the container has a water vapor transmission rate that is lower than the water vapor transmission rate of the container without the water vapor barrier coating or layer, optionally at least 5% lower, optionally at least 10% lower, optionally at least 20% lower, optionally at least 30% lower, optionally at least 40% lower, optionally at least 50% lower, optionally at least 60% lower, optionally at least 70% lower, optionally at least 80% lower, or optionally at least 90% lower.

473. The method according to claim 471, wherein, in the absence of the water vapor barrier coating or layer, the container is made of COP resin and has a water vapor transmission rate at least twice, optionally at least three times, optionally at least four times, or optionally at least five times the water vapor transmission rate of the container without the water vapor barrier coating or layer.

474. The method according to any one of claims 459 to 473, wherein the lumen of the container has a volume of 10 mL or less, optionally 5 mL or less, or optionally 2 mL or less.

475. The method according to any one of claims 459 to 474, which provides a container having a water vapor transmission rate of 0.05 mg / container / day at 60°C and 40% relative humidity, optionally 0.04 mg / container / day at 60°C and 40% relative humidity, optionally 0.03 mg / container / day at 60°C and 40% relative humidity, optionally 0.02 mg / container / day at 60°C and 40% relative humidity, and optionally 0.01 mg / container / day at 60°C and 40% relative humidity.

476. The container according to claim 475, wherein, in the absence of the aforementioned water vapor barrier or coating, the container has a water vapor transmission rate of more than 1.0 g / container / day, more than 2.0 g / container / day, and more than 3.0 g / container / day.

477. The method according to any one of claims 459 to 476, wherein the container is a syringe or a vial.

478. The method according to any one of claims 459 to 477, wherein the general-purpose resin is selected from PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN™, cyclic block copolymer (CBC) resin, thermoplastic olefin polymer, or any combination thereof.

479. The method according to claim 478, wherein the general-purpose resin is selected from PET, polycarbonate, polypropylene, or any combination thereof.

480. The container according to claim 478, wherein the general-purpose resin is a cyclic block copolymer (CBC) resin.

481. The method according to claim 480, wherein the CBC resin is selected from the group consisting of VIVION® 0510, VIVION® 0510HF and VIVION® 1325; optionally selected from the group consisting of VIVION® 0510 and VIVION® 0510HF; optionally selected from VIVION® 0510; and optionally selected from VIVION® 0510HF.

482. The method according to any one of claims 459 to 481, further comprising applying an oxide barrier coating, wherein the oxide barrier coating is effective in reducing the penetration of oxygen into the lumen.

483. The method according to claim 482, wherein the oxygen barrier coating or layer is applied by atomic layer deposition, optionally by plasma-assisted atomic layer deposition.

484. The oxygen barrier coating contains SiOx. 、 The method according to claim 482 or 483, wherein x is 1.5 to 2.

9.

485. The method according to claim 484, wherein the SiOx barrier coating or layer is deposited using a silicon-containing precursor selected from the group consisting of aminosilanes, alkylaminosilanes, 1,2-bis(diisopropylamino)disilane, diisopropylaminosilane, tris(dimethylamino)silane, bis(ethyl-methyl-amino)silane, and any combination thereof.

486. The method according to any one of claims 482 to 485, wherein the oxygen barrier coating or layer is applied to a thickness of 1 nm to 15 nm, optionally to a thickness of 1 nm to 10 nm.

487. The method according to any one of claims 482 to 486, wherein the oxygen barrier coating is applied on top of the water vapor barrier coating, or the water vapor barrier coating is applied on top of the oxygen barrier coating.

488. The method according to any one of claims 482 to 487, wherein the oxygen barrier coating is applied in the same reactor as the water vapor barrier coating.

489. The oxygen barrier is less than 0.0010d-1, optionally less than 0.0008d-1, optionally less than 0.0006d-1, optionally less than 0.0004d-1, optionally less than 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 The method according to any one of claims 482 to 488, which provides the container having an oxygen permeability constant of less than .

490. The method according to any one of claims 482 to 489, wherein the container has an oxygen permeability constant that is lower than that of an otherwise uniform container, which is coated by PECVD with an oxygen barrier coating or layer having substantially the same composition and thickness, optionally at least 10%, optionally at least 20%, optionally at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 80%, or optionally at least 90% lower.

491. A method for preparing a barrier container suitable for storing a liquid drug formulation over a period of time, To provide a container having a lumen at least partially defined by a wall, wherein the wall is mainly made of a general-purpose resin and has an inner surface and an outer surface facing the lumen, The method involves applying an oxygen barrier coating by atomic layer deposition, wherein the oxygen barrier coating is effective in reducing the penetration of oxygen into the lumen. A method that includes this.

492. The oxygen barrier coating contains SiOx. 、 The method according to claim 491, wherein x is between 1.5 and 2.

9.

493. The method according to claim 492, wherein the SiOx barrier coating or layer is deposited using a silicon-containing precursor selected from the group consisting of aminosilanes, alkylaminosilanes, 1,2-bis(diisopropylamino)disilane, diisopropylaminosilane, tris(dimethylamino)silane, bis(ethyl-methyl-amino)silane, and any combination thereof.

494. The method according to any one of claims 491 to 493, wherein the oxygen barrier coating or layer is applied to a thickness of 1 nm to 15 nm, optionally 1 nm to 10 nm.

495. The oxygen barrier coating is less than 0.0010d-1, optionally less than 0.0008d-1, optionally less than 0.0006d-1, optionally less than 0.0004d-1, optionally less than 0.0003d -1 Less than 0.0002d (optionally). -1 Less than 0.0001d (optionally). -1 The method according to any one of claims 491 to 494, which provides the container having an oxygen permeability constant of less than .

496. The method according to any one of claims 491 to 495, wherein the container has an oxygen permeability constant that is lower than that of an otherwise uniform container, which is coated by PECVD with an oxygen barrier coating or layer having substantially the same composition and thickness, optionally at least 10%, optionally at least 20%, optionally at least 30%, optionally at least 40%, optionally at least 50%, optionally at least 60%, optionally at least 70%, optionally at least 80%, or optionally at least 90% lower.

497. The method according to any one of claims 491 to 496, wherein the oxygen barrier coating is deposited by plasma-assisted atomic layer deposition.

498. The method according to any one of claims 491 to 497, wherein the wall is maintained at a temperature of less than 100°C, optionally less than 80°C, during the deposition of the oxygen barrier coating.

499. The method according to any one of claims 491 to 498, wherein the outer surface of the wall is masked during deposition so that the oxygen barrier coating is deposited only on the inner surface of the wall.

500. The method according to any one of claims 491 to 499, wherein the container is a syringe or a vial.

501. The method according to any one of claims 491 to 500, wherein the general-purpose resin is selected from PET, PETG, polypropylene, polyamide, polystyrene, polycarbonate, TRITAN™, cyclic block copolymer (CBC) resin, thermoplastic olefin polymer, or any combination thereof.

502. The method according to claim 501, wherein the general-purpose resin is selected from PET, polycarbonate, polypropylene, or any combination thereof.

503. The container according to claim 501, wherein the general-purpose resin is a cyclic block copolymer (CBC) resin.

504. The method according to claim 503, wherein the CBC resin is selected from the group consisting of VIVION® 0510, VIVION® 0510HF and VIVION® 1325; optionally selected from the group consisting of VIVION® 0510 and VIVION® 0510HF; optionally selected from VIVION® 0510; and optionally selected from VIVION® 0510HF.

505. To provide at least 20 containers, optionally at least 50 containers, optionally at least 100 containers, optionally at least 150 containers, optionally at least 200 containers, optionally at least 500 containers, optionally at least 800 containers, optionally at least 1000 containers in the reactor, optionally at least PICOSUN (trademark) P-1000B PRO, Provide a substantially uniform flow of precursor gas to each of the containers under conditions sufficient to construct the layer of water vapor barrier coating substantially uniformly across the plurality of containers, with optionally at least 95% uniformity, optionally at least 96% uniformity, and optionally at least 97% uniformity. The method according to any one of claims 491 to 504, further comprising:

506. The method according to claim 505, wherein the container is placed in a multi-level rack located inside the reactor.

507. The method according to any one of claims 491 to 506, further comprising the step of applying a lubricating coating or layer to the inner surface of the container wall.

508. The method according to claim 507, wherein the lubricating coating or layer basically consists of SiOxCy, x is about 0.5 to about 2.4, and y is about 0.6 to about 3.

509. The method according to claim 508, wherein the lubricating coating or layer is applied by plasma chemical vapor deposition (PECVD).

510. The method according to claim 509, wherein the lubricating coating or layer is applied by PECVD of a linear siloxane, a monocyclic siloxane, a polycyclic siloxane, a polysilsesquioxane, or any combination thereof, optionally by PECVD of a monocyclic siloxane, optionally by PECVD of octamethylcyclotetrasiloxane (OMCTS).

511. The method according to any one of claims 507 to 510, wherein the lubricating coating or layer has a thickness of 10 to 1000 nm, optionally 10 to 500 nm, optionally 10 to 200 nm, optionally 10 to 100 nm, or optionally 20 to 100 nm.

512. The lubricating coating or layer is determined by the X-ray reflectance (XRR) to be 1.25 to 1.65 g / cm³. 3 The method according to any one of claims 507 to 511, wherein the lubricating coating or layer having a density is applied under conditions effective for providing such a coating or layer.

513. The method according to any one of claims 507 to 512, wherein the container is a syringe barrel, and the lubricating coating or layer provides (i) a lower plunger sliding force, (ii) a lower plunger sliding yield stress, or (iii) both (i) and (ii) compared to the same syringe barrel without the lubricating coating or layer.

514. The method according to claim 513, wherein the lubricating coating or layer provides (i) plunger sliding force, (ii) plunger sliding yield stress, or (iii) both (i) and (ii) compared to the same syringe barrel but without the lubricating coating or layer, which is reduced by at least 45%, and optionally at least 60%.

515. The method according to any one of claims 507 to 514, wherein the lubricating coating or layer is disposed between the pH protective coating or layer and the lumen.

516. The FTIR absorbance spectrum of the pH protective coating or layer is as follows: - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and The method according to any one of claims 491 to 515, wherein the ratio between these two values ​​is greater than 0.75, optionally greater than 0.8, optionally greater than 0.85, and optionally greater than 0.

9.

517. The FTIR absorbance spectrum of the lubricating coating or layer is - The maximum amplitude of the Si-O-Si symmetric stretching peak is approximately 1000-1040 cm⁻¹, ・Approx. 1060~1100cm -1 The maximum amplitude of the Si-O-Si asymmetric stretching peak and The method according to any one of claims 491 to 516, wherein the ratio among them is at most 0.75.

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