Methods and systems for coating, cleaning, and inspecting pharmaceutical containers with respect to particles and defects

Abstract

The present disclosure relates to methods and systems for coating pharmaceutical containers, for example, using a coating set including an oxygen barrier layer to reduce the amount of particles present on the coated container. The present disclosure also relates to methods and systems for removing particles from a container, for example, after applying a coating to the inner surface of the container. The present disclosure also relates to methods and systems for inspecting pharmaceutical containers for particles, using machine vision analysis, prior to filling. Each of the above may be controlled and implemented by one or more processors, thereby enabling fully automated coating, cleaning, and / or inspection operations of pharmaceutical containers.

Description

Technical Field

[0001] The field of the present invention is the preparation of pharmaceutical containers, optionally containers that can be used immediately, in particular containers configured to be filled with injectables such as vials, cartridges and syringes, which have few or no visible particles. The field of the present invention is also the detection of visible particles and defects in ready-to-use pharmaceutical containers, in particular containers configured to be filled with injectables such as vials, cartridges, and syringes.

Background Art

[0002] Ready-to-use (RTU) containers are seeing increased use in the pharmaceutical industry because they provide an efficient filling process. However, RTU containers must be substantially free of visible defects, especially removable particles.

[0003] The presence of particles in injectables can pose a serious risk to patients. Therefore, the USP (United States Pharmacopeia) requires specific guidelines regarding the presence of visible particles in injectable drugs, which refers to USP <790> ("Visible Particulates in Injections") and also requires specific product quality tests for injectable products, which refers to <1> ("Injections and Implanted Drug Products (Parenterals)-Product Quality Tests"). According to USP <790>, all products intended for parenteral administration must be visually inspected for the presence of specific substances specified in Injections and Implanted Drug Products <1>. This product must be "essentially free" of visible particles as defined by USP <790> and USP <788> ("Particulate Matter in Injections") or USP <789> ("Particulate Matter in Opthalmic Solutions"). USP <790> specifies the sampling and inspection guidelines of ANSI / ASQ Z1.4 or SIO 2859-1 and specifies an AQL of 0.65%, but it should also be noted that alternative sampling plans with equivalent or better protection are also acceptable. In fact, pharmaceutical companies or CDMOs (contract development and manufacturing organizations) may require more stringent sampling plans and / or AQLs.

[0004] Typically, the inspection unit is inspected manually, without magnification (except for the optical corrections necessary to establish a normal field of view), against black and white backgrounds. An example of a workstation for manual visual inspection is shown in FIG. 1. Using a workstation as shown in FIG. 1, a trained visual inspector inspects the containers visually, under a light source 3 of 2,000 to 3,750 lux (lux), against both a black background 1 and a white background 2, and for at least 5 seconds for each background. Another exemplary workstation for manual inspection is described in U.S. Patent No. 5,940,176. This system utilizes opposing light sources above and below the vial, and the vial is placed at the midpoint between the light sources. The background can be changed between black and white backgrounds, so that as a result, the vial can be inspected without being moved from the illumination midpoint.

[0005] Manual visual inspection, even when performed correctly, is limited by the ability of the human naked eye to identify particles. Typically, the human naked eye can see particles having a size of about 80 microns or more in the case of an empty container. According to some reports, during manual visual inspection, the detection probability of particles having a size of 200 microns or more is very high (e.g., close to 100%), while the probability is significantly reduced (e.g., 50% or less) for particles having a size of about 100 microns, and close to 0% for particles having a size of less than 80 microns.

[0006] However, automated visual inspection of empty containers has been limited by the difficulty of automated visual inspection systems in accurately inspecting the transfer area of the container and / or taking into account differences in the wall thickness of the container. For these reasons, conventional automated visual inspection systems are not effective in inspecting RTU containers to the level required for injectables.

[0007] Automated visual inspection systems have found some commercial use in detecting particles within filled containers, i.e., after the containers have been filled with injectable products. In these systems, the filled containers are rotated so that any floating particles will move towards the centerline of the container. Thus, the automated visual inspection system only needs to inspect the container along its centerline. Since this depends on the fluid present within the container, such systems are not feasible for visual inspection of empty containers such as RTU containers. Such systems are also unable to inspect for visible particles that may remain adhered to the container wall or for defects in the container wall.

[0008] One important consideration in the manufacture of pharmaceutical packages or other containers, such as vials and pre-filled syringes, regarding storage or other contact with fluids, is that the contents of the pharmaceutical package or other container will desirably have a substantial shelf life. During this shelf life, it is important to isolate the material filled into the pharmaceutical package or other container from the container wall containing it, or from a barrier layer or other functional layer applied to the wall of the pharmaceutical package or other container, to avoid leaching of materials into or out of the pre-filled contents from the wall, barrier layer, or other functional layer of the pharmaceutical package or other container.

[0009] Conventional glass pharmaceutical packages or other containers are prone to breakage or degradation during manufacture, filling operations, shipping, and use, which means that glass particles can enter the drug. The presence of glass particles has led to many FDA warning letters and product recalls.

[0010] As a result, some companies have turned to plastic pharmaceutical packages or other containers that have larger dimensional tolerances and less breakage than glass, but their use in primary pharmaceutical packages is limited due to their gas permeability, i.e., because plastic allows small molecule gases such as oxygen to permeate into (or out of) the material. Many plastic materials also allow, in addition to oxygen, moisture, i.e., water vapor, to permeate into (or out of) the material. The permeability of plastic to gases such as oxygen and water vapor is significantly greater than that of glass, and for this reason, plastic has historically not been acceptable in many cases (such as with oxygen-sensitive drugs like epinephrine).

[0011] The problem of gas permeability has been addressed by adding an oxygen barrier coating or layer to plastic pharmaceutical packages. One such oxygen barrier layer is a very thin coating of SiOx, defined below, applied, for example, by plasma enhanced chemical vapor deposition. Additional layers, such as tie layers and / or pH protection layers, as described and defined in, for example, U.S. Patent No. 9,554,968, which is hereby incorporated by reference in its entirety, can also be applied as part of a coating set applied to the inner surface of the container sidewall.

[0012] However, coatings on the container, such as oxygen barrier coatings or layers, and / or improving the adhesion of the oxygen barrier coating or layer to the container wall, protecting the oxygen barrier coating or layer from dissolution by the fluid stored within the lumen of the container, or both, can lead to the presence of particles on the container wall. In particular, when using PECVD to deposit one or more coatings or layers, the coating can deposit not only on the intended container wall but also on various components of the coating system. Subsequently, flakes of the coating can be peeled off from the components of the coating system and can find their way onto the surface of the container, where they adhere as particles.

[0013] In the types of coating systems described herein, for example, flakes of one or more PECVD coating materials deposited on a source gas injection probe used during a PECVD coating process may flake off and adhere to the inner wall of the container and / or one or more surfaces of the container that are in direct contact with the system, typically the upper end surface of the container that surrounds the opening into the lumen and a portion of the outer surface of the container side wall, such as the upper and outer surfaces of a flange that surrounds the opening into the lumen.

Summary of the Invention

[0014] One aspect of the present invention is an automated system and method for visually inspecting a pharmaceutical container, such as a ready-to-use (RTU) pharmaceutical container, with respect to the presence of particles and defects.

[0015] Embodiments of the system and method may be configured to inspect the entire or substantially the entire RTU container, including all transition regions. Embodiments of the system and method may also be configured to account for wall thickness variations and distinguish particles or defects from wall thickness variations.

[0016] Embodiments of the system and method may be configured to inspect RTU containers configured for storage of injectables, such as vials, syringe barrels, or cartridges.

[0017] Embodiments of the system and method may be configured to detect particles and defects having a size as small as about 25 microns.

[0018] Embodiments of the present system and method can be configured to detect particles within a certain range of sizes, for example, particles within the size range of 25 to 500 microns, or 30 to 500 microns, or 40 to 500 microns, or 50 to 500 microns, or 60 to 500 microns, or 70 to 500 microns, or 80 to 500 microns, or 25 to 400 microns, or 30 to 400 microns, or 40 to 400 microns, or 50 to 400 microns, or 60 to 400 microns, or 70 to 400 microns, or 80 to 400 microns, or 25 to 300 microns, or 30 to 300 microns, or 40 to 300 microns, or 50 to 300 microns, or 60 to 300 microns, or 70 to 300 microns, or 80 to 300 microns.

[0019] Other embodiments of the present system and method can be configured to detect visible particles less than 500 microns, or less than 400 microns, or less than 300 microns, or less than 200 microns, or less than 150 microns, or less than 100 microns. Embodiments of the present system and method can be configured to detect particles including particles of 80 to 120 microns, 50 to 80 microns, and / or 25 to 50 microns.

[0020] Embodiments of the present system and method utilize a plurality of cameras, a plurality of illumination sources, and at least one processor. The system also includes a plurality of container holders configured to rotate the containers in a controlled manner. The processor is configured to receive inputs from the plurality of cameras and process that information into an output, namely particle detection information.

[0021] The system can include a body side camera, an angled shoulder camera, an angled top camera, an angled bottom camera, and a bottom camera. Each camera can be associated with a certain inspection station. The container can be moved between a plurality of inspection stations, which can include: a body side inspection station, a shoulder inspection station, a top inspection station, and a bottom transition area / bottom inspection station (note that the angled bottom camera that captures the bottom transition area of the container and the bottom camera that captures the bottom wall of the container can be combined at a single inspection station, but in other embodiments, there may be separate / independent bottom transition area inspection stations and bottom inspection stations).

[0022] In embodiments of the present system and method for inspecting the inner surface of a container, the container wall should be made of a transparent material, although a slight coloring may be present on the container wall and it has been found that acceptable inspection results can still be obtained. In some embodiments, the container wall can be made of glass or plastic. In some embodiments, the container wall can be made of glass. In some embodiments, the container wall can be made of plastic. In some embodiments, the container wall can be made of a plastic selected from the group consisting of polycarbonate, polystyrene, polyethylene terephthalate (PET), polypropylene, polyethylene, polyamide, cyclic olefin polymer (COP), cyclic olefin copolymer (COC), or cyclic block copolymer (CBC). In some embodiments, the container wall can be made of a plastic selected from the group consisting of cyclic olefin polymer (COP) or cyclic olefin copolymer (COC).

[0023] In some embodiments, the container wall can include one or more coatings. For example, the container wall can be made of a transparent plastic material and can include any one or more of the following coatings, each of which is configured to maintain the transparency of the container wall.

[0024] In some embodiments, for example, at least one of the container walls may further include an oxygen barrier coating or layer, which is effective for reducing the ingress of oxygen into its lumen as compared to a container without the oxygen barrier coating or layer. For example, at least one of the container walls contains SiO x or essentially consists of an oxygen barrier coating or layer containing SiO x , where x is from 1.5 to 2.9. The oxygen barrier coating or layer can be applied by plasma enhanced chemical vapor deposition (PECVD) or atomic layer deposition (ALD). In some embodiments, the oxygen barrier coating or layer can have a thickness of 1 to 1000 nm, optionally 2 to 1000 nm, optionally 10 to 1000 nm, optionally 10 to 500 nm, optionally 10 to 200 nm, optionally 20 to 100 nm. In particular, when the oxygen barrier coating or layer can be applied by ALD, the oxygen barrier coating or thickness can be a thickness of 1 to 15 nm, or a thickness of 2 to 12 nm, or a thickness of 3 to 10 nm, or a thickness of 4 to 8 nm, or a thickness of 5 to 7 nm. In some embodiments, the oxygen barrier coating or layer can be located between the inner surface of the container wall and the lumen.

[0025] At least one of the container walls may further comprise a pH protection coating located between the oxygen barrier coating or layer and the lumen, in addition to the oxygen barrier coating or layer, and the pH protection coating is effective for reducing the dissolution of the oxygen barrier coating or layer by the fluid in the lumen. The pH protection coating can contain SiOxCy or SiNxCy, where x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3. The pH protection coating can be applied by plasma enhanced chemical vapor deposition (PECVD). The pH protection coating can be 10 to 1000 nm thick. In some embodiments, the pH protection coating has at least the same extent as the oxygen barrier coating. In some embodiments, the pH protection coating has an FTIR absorption spectrum with

[0026] · the maximum amplitude of the symmetric stretching peak of Si-O-Si at about 1000 to 1040 cm-1 and

[0027] · It can be one having a ratio exceeding 0.75, optionally exceeding 0.9, between the maximum amplitude of the asymmetric stretching peak of Si-O-Si at about 1060 to about 1100 cm-1.

[0028] At least one of the container walls may also include a tie coating, in addition to an oxygen barrier coating or layer and optionally a pH protection layer, the tie coating being located between the oxygen barrier coating and the inner or outer surface of the wall. In some embodiments, the tie coating may include SiOxCy or SiNxCy, where x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3. The tie coating can be applied by plasma enhanced chemical vapor deposition (PECVD) and can have an average thickness of 5 to 200 nm.

[0029] For example, in some embodiments, at least one of the container walls may comprise a tie layer coating, such as that described in U.S. Patent No. 9,554,968, which is hereby incorporated by reference in its entirety. For example, in some embodiments, the inner surface of the container wall · An optional tie coating or tie layer comprising SiOxCy or SiNxCy, where x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3, the tie coating or tie layer having an inner surface facing the lumen and an outer surface facing the inner surface of the wall, · An optional gas barrier coating or layer optionally comprising SiOx, where x is from 1.5 to 2.9, the gas barrier coating or layer having an inner surface facing the lumen and an outer surface facing the inner surface of the tie coating or tie layer, the barrier coating or layer being effective to reduce the ingress of atmospheric gas into the lumen as compared to a container without the barrier coating or layer, · A pH protection coating or layer comprising SiOxCy or SiNxCy, where x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3, the pH protection coating or layer having an inner surface facing the lumen and an outer surface facing the inner surface of the barrier coating or layer, may be provided.

[0030] In some embodiments, at least one of the container walls may comprise a lubricious coating, such as that described in U.S. Patent No. 7,985,188, which is hereby incorporated by reference in its entirety. The lubricious coating or layer may consist essentially of SiOxCy, where x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3. The lubricious coating may be applied by plasma enhanced chemical vapor deposition (PECVD). The lubricious coating or layer may have a thickness of 10 to 1000 nm, optionally 10 to 500 nm. In some embodiments, the lubricious coating or layer has an FTIR absorption spectrum such that · the maximum amplitude of the symmetric stretching peak of Si—O—Si at about 1000 to 1040 cm−1 and · the maximum amplitude of the asymmetric stretching peak of Si—O—Si at about 1060 to about 1100 cm−1 have a ratio of at most 0.75.

[0031] In some embodiments, at least one of the container walls may include an anti-scratch and anti-static coating, such as that described in, for example, U.S. Patent Application Publication No. 2018 / 049945, which is hereby incorporated by reference in its entirety.

[0032] In some embodiments, the system and method may be adjustable and / or configurable based on the light transmission and refractive properties of the particular materials that make up the container walls.

[0033] Another aspect of the invention is an RTU container, such as a vial, syringe, or cartridge, that has been inspected for particles sized 80 to 500 microns, optionally 70 to 500 microns, optionally 60 to 500 microns, optionally 50 to 500 microns, optionally 40 to 500 microns, optionally 30 to 500 microns, optionally 25 to 500 microns and found to be free of such particles. The inspection may be performed using any of the systems and methods of the present disclosure.

[0034] Another aspect of the present invention is batches and lots of RTU containers, such as vials, syringes, or cartridges, which containers are inspected for particles sized 80 - 500 microns, optionally 70 - 500 microns, optionally 60 - 500 microns, optionally 50 - 500 microns, optionally 40 - 500 microns, optionally 30 - 500 microns, optionally 25 - 500 microns, and this batch or lot has an AQL of less than 0.5, optionally less than 0.4, optionally less than 0.3, optionally less than 0.2, optionally 0.1 or less. The inspection can be carried out using any of the systems and methods of the present disclosure.

[0035] Another aspect of the present invention is an improved system and method for applying one or more coatings or layers, such as any one or more of those described above, to the inner surface of a container. The improved system and method described herein reduce the amount of particles, such as flakes of an undesired coating, that may be present on one or more containers after a coating cycle. In some embodiments, for example, the system may be configured to reduce the contact area between the system and the container, thereby reducing the chance that particles, such as flakes of a coating, will ultimately be present on the part of the system that contacts the container and thereby adhere or embed in the container. In some embodiments, the system may also be configured to provide improved cleaning of system components, particularly those components that come into contact with the container.

[0036] Another aspect of the present invention is a system and method for removing particles from an apparatus used to deposit one or more coatings on the inner wall of a container, in particular, from components of a coating system that pose a potential for contamination of the container by particles, such as a portion of a container holder that is in direct contact with the container and / or a feed gas injection probe. In some embodiments, for example, the coating system may include an electrode cavity cleaning unit configured to create a vacuum within the electrode cavity that is suitable for removing particles, such as flakes of the coating, from within the cavity of the electrode. The cleaning unit may operate as a routine element of the coating process, and for example, cleaning of the electrode cavity may be performed after a defined number of coating cycles.

[0037] Another aspect of the present invention is a system and method for mechanical visual inspection of an apparatus used to deposit one or more coatings on the inner wall of a container, in particular, on components of a coating system that lead to potential contamination of the container by particles, such as a portion of a container holder that is in direct contact with the container and / or a feed gas injection probe. In some embodiments, for example, the coating system and method may include one or more cameras and optionally one or more lights positioned above the electrodes.

[0038] The one or more cameras may be operably connected to one or more processors such that images captured by the one or more cameras are transmitted to the one or more processors. The one or more processors may receive the images and analyze relevant portions of the images to detect the presence of particles using, for example, mechanical visual analysis (such as defining one or more inspection regions for each image and analyzing the appearance of each defined region with respect to particles) similar to that described elsewhere in this specification. The one or more processors may also be configured to determine the number of particles present within the cavity of the one or more electrodes, more specifically, on the container holder / sealing element of the cavity of the one or more electrodes, to determine the size of the one or more detected particles, or both.

[0039] In some embodiments, the electrode cleaning operation may be initiated in response to the results of the visual inspection system / method. For example, in some embodiments, the detection of particles exceeding a specific threshold by one or more processors may lead to the result that one or more processors automatically initiate an electrode cleaning process. In some embodiments, the visual inspection of the electrodes may be performed immediately after the electrode cleaning process, and if particles (any particles may be acceptable) exceeding a specific threshold are still detected, one or more processors can automatically initiate the cleaning operation cycle again.

[0040] Another aspect of the present invention is a system and method for removing particles from a container after a coating has been applied. In some embodiments, the system and method involve the inner surface of the container, i.e., the surface that defines the inner cavity and on which one or more coatings or layers are provided using a PECVD coating process and system, coming into contact with pressurized air, desirably pressurized ionized air, to remove particles that may be adhering thereto, such as flakes of the coating. The system and method may include a cleaning station. In some embodiments, the system and method involve one or more outer surfaces of the container, e.g., the outer surfaces that come into direct contact with the coating system during the coating step, coming into contact with pressurized air, desirably pressurized ionized air, to remove particles that may be adhering thereto, such as flakes of the coating. The system and method may include a cleaning station. Any or both of these coating stations may also include a vacuum line and optionally a particle collection chamber, which serves to remove any particles removed from the container during the cleaning step without compromising the cleanroom environment.

[0041] The removal of particles from the container can be performed without washing, e.g., without the surface of the container coming into contact with water.

[0042] Embodiments of the present invention can be fully automated. For example, a series of containers can be coated, cleaned, and inspected, for example, in a cleanroom environment, and the overall operation thereof is continuously controlled by one or more processors. The result is a system and method for manufacturing PECVD-coated pharmaceutical containers that are particle-free or substantially particle-free, such as RTU containers. For example, the particles are particles larger than 20 microns, or larger than 25 microns, or larger than 30 microns, or larger than 40 microns, or larger than 50 microns, and the system and method result in a very small number of containers that must be recovered due to the presence of particles or defects.

[0043] In some embodiments, the RTU containers can be filled and sealed with any of the following pharmaceutical formulations after coating, cleaning, and / or inspection: Biological agents Abatacept, abciximab, abobotulinumtoxinA, adalimumab, adalimumab - adaz, adalimumab - adbm, adalimumab - afzb, adalimumab - atto, adalimumab - bwwd, ado - trastuzumab emtansine, aflibercept, agalsidase beta, albiglutide, albumin chromated CR - 51 serum, aldesleukin, alefacept, alemtuzumab, alglucosidase alfa, alirocumab, alteplase, anakinra, aprotinin, asfotas alfa, asparaginase, asparaginase Erwinia chrysanthemi, atezolizumab, avelumab, basiliximab, becaplermin, belatacept, belimumab, benralizumab, beractant, bevacizumab, bevacizumab - awwb, bevacizumab - bvzr, bezlotoxumab, blinatumomab, brentuximab vedotin, brodalumab, brodalumab - dbll, brodalumab - twza, calaspargase pegol - mknl, calfactant, canakinumab, caplacizumab - yhdp, capromab pendetide, cemiplimab - rwlc, cenegermin - bkbj, celliponase alfa, certolizumab pegol, cetuximab, chorionic gonadotropin alfa, chorionic gonadotropin, chymopapain, collagenase, collagenase clostridium histolyticum, corticorelin ovine triflutate, crisaborole - tmca, daclizumab, daratumumab, daratumumab and hyaluronidase - fihj, darbepoetin alfa, denileukin diftitox, denosumab, desirudin, dinutuximab, dornase alfa, drotrecogin alfa, dulaglutide, dupilumab, durvalumab, ecarinase,Eclizumab, Efalizumab, Eravacycline-lvlr, Eroflurbiprofen alpha, Erotigimod, Emapalumab-lzsg, Emicizumab-kxwh, Enfortumab vedotin-ejfv, Epogen, Epogen-epbx, Enoblituzumab-aooe, Etanercept, Etanercept-szzs, Etanercept-ykro, Ebolucizumab, Trastuzumab deruxtecan-nxki (fam-trastuzumab deruxtecan-nxki), Combination of fibrinolytic enzyme and desoxyribonuclease [bovine] with chloramphenicol, Filgrastim, Filgrastim-aafi, Filgrastim-sndz, Follitropin alpha, Follitropin beta, Fremanezumab-vfrm, Galcanezumab-gnlm, Galsulfase, Gemtuzumab ozogamicin, Glucarpidase, Golgimab, Guselkumab, Hyaluronidase, Human hyaluronidase, Ibalizumab-uiyk, Ibritumomab tiuxetan, Idarucizumab, Idursulfase, Imiglucerase, Incobotulinum toxin A, Inebilizumab-cdon, Infliximab, Infliximab-abda, Infliximab-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 insulin isophane, Human insulin isophane and human insulin, Insulin lispro, Insulin lispro protamine and insulin lispro, Insulin lispro-aabc, Interferon alpha-2a, Interferon alpha-2b, Interferon alfa con-1, Interferon alpha-n3 (human leukocyte-derived), Interferon beta-1a, Interferon beta-1b, Interferon gamma-1b, Ipilimumab, Isatuximab-irfc, Ixekizumab,Ranadelumab-flyo, lanadelumab, rimexolone, ruspatelcept-aamt, mecasermin, mecasermin rinfabate, menotropins, mepolizumab, methoxypolyethylene glycol-epoetin beta, metreleptin, mogamulizumab-kpkc, moxetumomab pasudotox-tdfk, muromonab-CD3, natalizumab, nesitumumab, nivolumab, nofetumomab, obinutuzumab, obiltoxaximab, ofatumumab, olaratumab, omalizumab, onabotulinumtoxinA, oprelvekin, paricalcitol, palivizumab, pancrelipase, panitumumab, parathyroid hormone, pegademase bovine, 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, pegargatroban, pegvaliase-pqpz, pegbisomant, pembrolizumab, pertuzumab, polatuzumab vedotin-piiq, polactan alpha, prabotulinumtoxinA-xvfs, radiopharmaceutical albumin technetium Tc-99m albumin colloid kit, ramucirumab, ranibizumab, rasburicase, rubelizumab-cwvz, raxibacumab, reslizumab, reteplase, rilonacept, rimabotulinumtoxinB, risankizumab-rzaa, rituximab, rituximab and human hyaluronidase, rituximab-abbs, rituximab-pvvr, romiplostim, romosozumab-aqqg, sacituzumab govitecan-hziy, sacrosidase, sargramostim, sarilumab, sevelamer alpha, secukinumab, siltuximab, somatropin, tagraxofusp-erzs,Taliglucerase alfa, tbo-filgrastim, Technetium 99mTc fanolesomab, Tenecteplase, Teplizumab-trbw, Tesamorelin acetate, Thyroid Stimulating Hormone Alfa, Tildrakizumab-asmn, Tocilizumab, Tositumomab and Iodine I-131 Tositumomab, Trastuzumab, Trastuzumab and Hyaluronidase-oysk, Trastuzumab-anns, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-pkrb, Trastuzumab-qyyp, Urofollitropin, Urokinase, Ustekinumab, Vedolizumab, Velaglucerase alfa, Bestroneidase alfa-vjbk, Ziv-aflibercept, Amjevita (adalimumab-atto), Dupixent (dupilumab), Fulphila (pegfilgrastim-jmdb), Ilaris (canakinumab), Ixifi (infliximab-qbtx), Lantus (insulin lispro-aabc), Nyvepria (pegfilgrastim-apgf), Ogivri (trastuzumab-dkst), Semglee (insulin glargine), Uplyso (inebilizumab-cdon), A.P.L. (chorionic gonadotropin), Abrilada (adalimumab-afzb), Accretropin (somatropin), Actemra (tocilizumab), Acthrel (corticorelin ovine triflutate), Actimmune (interferon gamma-1b), Activase (alteplase), Adagen (bovine pegademase), Adakveo (crisantaspase-tmca), Adcetris (brentuximab vedotin), Adlyxin (lixisenatide), Admelog (insulin lispro), Afrezza (human insulin), Aimovig (erenumab-aooe), Ajovy (fremanezumab-vfrm), Auralzyme (laronidase), Alferon N Injection (interferon alfa-n3 (human leukocyte derived)),Amevive (alefacept), Amphadase (hyaluronidase), Anthim (obinutuzumab), Apidra (insulin glulisine), Aranesp (darbepoetin alfa), Arcalyst (rilonacept), Arzerra (ofatumumab), Asparlas (pegaspargase - mknl), Avastin (bevacizumab), Avonex (interferon beta - 1a), Avsola (infliximab - axxq), Basaglar (insulin glargine), Babencheo (avelumab), Benlysta (belimumab), Beovu (brolucizumab - dbll), Besponsa (inotuzumab ozogamicin), Betaseron (interferon beta - 1b), Bexxar (tositumomab and iodine I - 131 labeled tositumomab), Blincyto (blinatumomab), Botox (onabotulinumtoxin A), Botox Cosmetic (onabotulinumtoxin A), Bravelle (urofollitropin), Brineura (cerliponase alfa), Cabenuva (cabotegravir - yhdp), Campath (alemtuzumab), Cathflo Activase (alteplase), Cerezyme (imiglucerase), Chorionic Gonadotropin (chorionic gonadotropin), Chromalbin (chromic oxide CR - 51 serum albumin), Chymodiactin (chymopapain), Cimzia (certolizumab pegol), Cinqair (reslizumab), Cosentyx (secukinumab), Cotazym (pancreatin), Creon (pancreatin), Crisaborole (crisaborole - twza), Curosurf (poractant alfa), Cyltezo (adalimumab - adbm), Cyranza (ramucirumab), Darzalex (daratumumab), Darzalex Faspro (daratumumab and hyaluronidase - fihj), Draximage MAA (kit for the preparation of technetium Tc - 99m albumin aggregated), Dysport (abobotulinumtoxin A), Egrifta (tesamorelin acetate),Egrifta SV (Tesamorelin Acetate), Elaprase (Idursulfase), Elase-chloromycetin (Combination of Fibrinolysin and Desoxyribonuclease [Bovine] with Chloramphenicol), Elelyso (Taliglucerase Alfa), Elitek (Rasburicase), Elspar (Asparaginase), Elzonris (Tagraxofusp-e, Rzs), Emgality (galcanezumab-gnlm), Empliciti (elotuzumab), Enbrel (etanercept), Enbrel Mini (etanercept), Enhertu (trastuzumab deruxtecan-nxki (fam-trastuzumab deruxtecan-nxki)), Entyvio (vedolizumab), Epogen / Procrit (epoetin alfa), Erbitux (cetuximab), Erelzi (etanercept-szzs), Erelzi Sensoready (etanercept-szzs), Arwinaze (Erwinaze) (Aspergillus niger-derived asparaginase), Eticovo (etanercept-ykro), Evenity (romosozumab-aqqg), Extavia (interferon beta-1b), Eylea (aflibercept), Fabrazyme (agalsidase beta), Facenra (benralizumab), Fiasp (insulin aspart), Follistim (folitropin beta), Follistim AQ (folitropin beta), Follistim AQ Cartridge (folitropin beta), Gamifant (emapalumab-lzsg), Gaziva (obinutuzumab), Genotropin (somatropin), Gonal-f (folitropin alpha), Gonal-f RFF (folitropin alpha), Gonal-f RFF RediJect (folitropin alpha), Granix (tbo-filgrastim), Hadlima (adalimumab-bwwd), Hemlibra (emicizumab-kxwh), Herceptin (trastuzumab), HerceptinHylecta (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 insulin isophane and human insulin), Humulin N (human insulin isophane), Humulin R U-100 (human insulin), Humulin R U-500 (human insulin), Hydase (hyaluronidase), Hylenex recombinant (human hyaluronidase), Hyrimoz (adalimumab-adaz), Ilumya (tildrakizumab-asmn), Imfinzi (durvalumab), Increlex (mecasermin), Infasurf (calfactant), Infergen (interferon alfa-con-1), Inflectra (infliximab-dyyb), Intron A (interferon alfa-2b), Iplex (mecasermin rinfabate), Iprivask (desirudin), Jeanatope (kit for iodine I-125 albumin), Jetrea (ocriplasmin), Jeuveau (prabotulinum toxin A-xvfs), Kadcyla (ado-trastuzumab emtansineEmtansine, Kalbitor (ecallantide), Kanjinti (trastuzumab-anns), Canuma (sebelipase alfa), Kepivance (palifermin), Kebuzara (sarilumab), Keytruda (pembrolizumab), Kineret (anakinra), Kinlytic (urokinase), Krystexxa (pegrolidase), Lantus (insulin glargine), Lartruvo (olaratumab), Lemtrada (alemtuzumab), Leukine (sargramostim), Levemir (insulin detemir), Ribtaio (semi-privmab-rwlc), Lucentis (ranibizumab), Lumizyme (alglucosidase alfa), Lumoxiti (moxetumomab pasudotox-tdfk), Macrotec (kit for the preparation of technetium Tc-99m aggregated albumin), Megatope (kit for iodinated I-131 albumin), Menopur (menotropins), Mepsevii (bestatin alfa-vjbk), Microlite (radioactive labeled albumin technetium Tc-99m albumin colloid kit), Mircera (methoxypolyethylene glycol-epoetin beta), Mvasi (bevacizumab-awwb), Myalept (metreleptin), Mylotarg (gemtuzumab ozogamicin), Myobloc (rimabotulinum toxin B), Myozyme (alglucosidase alfa), Myxredlin (human insulin), N / A (laxibacumab), Naglazyme (garsulfase), Natpara (parathyroid hormone), Neulasta (pegfilgrastim), Neulasta Onpro (pegfilgrastim), Neumega (oprelvekin), Neupogen (filgrastim), NeutroSpec (technetium 99mTc fanolesomab), Nivestym (filgrastim-aafi), Norditropin (somatropin), Novarel (chorionic gonadotropin), Novolin 70 / 30 (human insulin isophane and human insulin), Novolin N (human insulin isophane), Novolin R (human insulin), Novolog (insulin aspart), Novolog Mix50 / 50 (Insulin Aspart Protamine and Insulin Aspart), Novolog Mix 70 / 30 (Insulin Aspart Protamine and Insulin Aspart), Nplate (Romiplostim), Nuvaring (Mepolizumab), Nulojix (Belatacept), Nutropin (Somatropin), Nutropin AQ (Somatropin), Ocrevus (Ocrelizumab), Omnitrope (Somatropin), Oncaspar (Pegaspargase), Ontak (Denileukin Diftitox), Ontruzant (Trastuzumab-dttb), Opdivo (Nivolumab), Orencia (Abatacept), Orthoclone OKT3 (Muromonab-CD3), Ovidrel (Choriogonadotropin Alfa), Oxervate (Cenegermin-bkbj), Padcev (Enfortumab Vedotin-ejfv), Panzyga (Pegvaliase-pqpz), Pancreaze (Pancrelipase), Pegasys (Peginterferon Alfa-2a), Pegasys Copegus Combination Pack (Peginterferon Alfa-2a and Ribavirin), PegIntron (Peginterferon Alfa-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 (Choriogonadotropin), Procrit (Epoetin Alfa), Proleukin (Aldesleukin), Prolia (Denosumab), ProstaScint (Capromab Pendetide), Pulmolite (Kit for Preparation of Technetium Tc-99m Aggregated Albumin), PulmotechMAA (Kit for the preparation of technetium Tc-99m aggregated albumin), Pulmozyme (Dornase alfa), Raptiva (Efalizumab), Rebif (Interferon beta-1a), Reblozyl (Luspatercept-aamt), Regranex (Becaplermin), Remicade (Infliximab), Renflexis (Infliximab-abda), Reopro (Abciximab), Repatha (Evolocumab), Repronex (Menotropins), Retacrit (Epoetin alfa-epbx), Retavase (Reteplease), Revcovi (Elapagenease-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), Cimzia (Certolizumab pegol-irfc), Serostim (Somatropin), Siliq (Brodalumab), Simponi (Golimumab), Simponi Aria (Golimumab), Simulect (Basiliximab), Skyrizi (Risankizumab-rzaa), Soliqua 100 / 33 (Insulin glargine and lixisenatide), Soliris (Eculizumab), Somatuline (Pegvisomant), Stelara (Ustekinumab), Strange (Aspofallas alfa (asfotasalfa)), Sucraid (Sucrase), Survanta (Beractant), Sylvant (Sirukizumab), Synaxis (Parvizumab), Takzairo (Ranadelumab-flyo), Toltz (Ixekizumab), Tanzeum (Albiglutide), Tencentrik (Atezolizumab), Tepezza (Teprotumumab-trbw), Tyrogen (Thyroid Stimulating Hormone Alfa), TNKase (Tenecteplase), Toujeo (Insulin Glargine), Trasylol (Aprotinin), Trazimera (Trastuzumab-qyyp), Tremfya (Guselkumab), Tresiba (Insulin Degludec), Trodelvy (Sacituzumab Govitecan-hziy), Trogarzo (Ibalizumab-uiyk), Tolulicity (Dulaglutide), Truxima (Rituximab-abbs), Tysabri (Natalizumab), Udenyca (Pegfilgrastim-cbqv), Ultomiris (Rablizumab-cwvz), Unistuximab (Dinutuximab), Vectibix (Panitumumab), Verluma (Nofetumomab), Bimizumab), Vitrase (Hyaluronidase), Voraxaze (Glucarpidase), VPRIV (Velaglucerase Alfa), Zeomin (Incoloynus Toxin A), Xgeva (Denosumab), Zaiyaflex (Histrix Bacterium-derived Collagenase), Xigris (Drotrecogin Alfa), Zolea (Omalizumab), Zortophi (Xultophy) 100 / 3.6 (Insulin Degludec and Liraglutide), Yarboi (Ipilimumab), Zaltrap (Ziv-Aflibercept), Zarxio (Filgrastim-sndz), Zenapax (Daclizumab), Zenpep (Pancreatin), Zevalin (Ibritumomab Tiuxetan), Ziextenzo (Pegfilgrastim-bmez), Zinbryta (Daclizumab), Geneplava (Bexlotoxumab), Zirabev (Bevacizumab-bvzr), Zomacton (Somatropin), Zorbtive / Serostim (Somatropin),

[0044] Inhalation anesthetics Alifurane, chloroform, cyclopropane, desflurane (Suprane), diethyl ether, enflurane (Ethrane), ethyl chloride, ethylene, halothane (Fluothane), isoflurane (Forane, Isoflo), isopropenyl vinyl ether, methoxyflurane, methoxyflurane, methoxypropane, nitrous oxide, loflurane, sevoflurane (Sevorane, Ultane, Sevoflo), teflurane, trichloroethylene, vinyl ether, xenon,

[0045] Injection Ablavar (gadofosveset trisodium injection), Abarelix depot, abobotulinumtoxinA injection (Dysport), ABT-263, ABT-869, ABX-EFG, Accretropin (somatropin injection), Acetadote (acetylcysteine injection), acetazolamide injection (acetazolamide injection), acetylcysteine injection (Acetadote), Actemra (tocilizumab injection), Acthrel (corticorelin ovine triflutate for injection), Actummune, Activase, acyclovir for injection (Acyclovir) (Zovirax injection), Adacel, adalimumab, Adenoscan (adenosine injection), adenosine injection (Adenoscan), Adrenaclick, AdreView (Iobenguane I 123 intravenous injection), Afluria, Ak-Fluor (fluorescein injection), Aldurazyme (laronidase), alglucerase injection (Ceredase), melphalan Hcl injection (Alkeran injection), allopurinol sodium for injection (Allopurinol Sodium) (Aloprim), Aloprim (allopurinol sodium for injection), alprostadil, Alsuma (sumatriptan injection), ALTU-238, amino acid injection, Aminosyn, Apidex, apremilast, dual chamber system for alprostadil for injection (Caverject Impulse), AMG 009, AMG 076, AMG 102, AMG 108, AMG 114, AMG 162, AMG 220, AMG 221, AMG 222, AMG 223, AMG 317, AMG 379, AMG 386, AMG 403, AMG 477, AMG 479, AMG 517, AMG 531, AMG 557, AMG 623, AMG 655, AMG 706, AMG 714, AMG 745, AMG 785, AMG 811, AMG 827, AMG 837, AMG 853, AMG 951, amiodarone HCl injection (amiodarone HCl injection), amobarbital sodium (AmobarbitalSodium) injection (Amytal Sodium), Amytal Sodium (Amobarbital Sodium injection), Anakinra, anti-Abeta, anti-Beta7, anti-Beta20, anti-CD4, anti-CD20, anti-CD40, anti-IFN alpha, anti-IL13, anti-OX40L, anti-oxLDL, anti-NGF, anti-NRP1, Aricept, Amphadase (Hyaluronidase injection), Ammonul (Sodium phenylacetate and Sodium benzoate injection), Anaprox, Anzemet injection (Dolasetron mesylate injection), Apidra (Insulin glulisine [rDNA origin] injection), Apomab, Aranesp (Darbepoetin alfa), Argatroban (Argatroban injection), Arginine hydrochloride injection (R-Gene 10), Aristocort, Aristospan, Arsenic trioxide injection (Trisenox), Articaine hydrochloride (Articane HCl) and Epinephrine injection (Septocaine), Arzerra (Ofatumumab injection), Asclera (Polidocanol injection), Ataluren, Ataluren-DMD, Atenolol injection (Tenormin intravenous injection), Atracurium besylate injection (Atracurium besylate injection), Avastin, Azactam injection (Aztreonam injection), Azithromycin (Zithromax injection), Aztreonam injection (Azactam injection), Baclofen injection (Lioresal intrathecal), Bacteriostatic water (Bacteriostatic water for injection), Baclofen injection (Lioresal intrathecal), Ampule of BAL in oil (Dimercaprol injection), BayHepB, BayTet, Benadryl, Bendamustine hydrochloride injection (Treanda), Benztropine mesylate injection (Cogentin), Betamethasone injection suspension (Celestone Soluspan), Bexxar, Bicillin C-R 900 / 300 (Penicillin G benzathine and Penicillin G procaine injection), Blenoxane (Bleomycin sulfate injection), Bleomycin sulfate injection (Blenoxane), Boniva injection (Ibandronate sodium injection), BotoxCosmetic (Onabotulinumtoxin A for injection), BR3-FC, Bravelle (urofollitropin injection), Bretylium (bretylium tosylate injection), Brevital Sodium (methohexital sodium injection), Brethine, Briobacept, BTT-1023, Bupivacaine HCI, Byetta, Ca-DTPA (calcium trisodium pentetate injection), Cabazitaxel injection (Jevtana), Caffeine Alkaloid (caffeine and sodium benzoate injection), Calcijex injection (Calcitrol), Calcitrol (Calcijex injection), Calcium Chloride (10% calcium chloride injection), Calcium Disodium Versenate (edetate calcium disodium injection), Campath (alemtuzumab), Camptosar injection (irinotecan hydrochloride), Canakinumab injection (Ilaris), Capastat Sulfate (capreomycin injection), Capreomycin injection (Capastat Sulfate), Cardiolite (technetium Tc99 sestamibi injection kit), Carticel, Cathflo, Cefazolin and Dextrose injection (cefazolin injection), Cefepime Hydrochloride, Cefotaxime, Ceftriaxone, Cerezyme, Carnitor injection, Caverject, Celestone Soluspan, Celsior, Cerebyx (phenytoin sodium injection), Ceredase (alglucerase injection), Ceretec (exametazime technetium Tc99m injection), Certolizumab, CF-101, Chloramphenicol Succinate Sodium (chloramphenicol succinate sodium injection), Chloramphenicol Succinate Sodium injection (chloramphenicol succinate sodium), Cholestagel (colesevelam hydrochloride (ColesevelamHCL)), Chorionic Gonadotropin Alfa Injection (Ovidrel), Simdiaz, Cisplatin (Cisplatin Injection), Clolar (Clofarabine Injection), Clomiphine Citrate, Clonidine Injection (Duraclon), Cogentin (Benzatropine Mesylate Injection), Colistimethate Injection (Coly-Mycin M), Coly-Mycin M (Colistimethate Injection), Compath, Conivaptan Hydrochloride Injection (Vaprisol), Conjugated Estrogen for Injection (Premarin Injection), Copaxone, Corticorelin Ovine Triflutate for Injection (Acthrel), Corvert (Ibutilide Fumarate Injection), Cubicin (Daptomycin Injection), CF-101, Cyanokit (Hydroxocobalamin for Injection), Cytarabine Liposome Injection (DepoCyt), Cyanocobalamin, Cytovene (Ganciclovir), D.H.E.45, Dacetuzumab, Dacogen (Decitabine Injection), Dalteparin, Dantrium IV (Dantrolene Sodium for Injection), Dantrolene Sodium for Injection (Dantrium IV), Daptomycin Injection (Cubicin), Darbepoietin Alfa, DDAVP Injection (Desmopressin Acetate Injection), Decavax, Decitabine Injection (Dacogen), Absolute Alcohol (Absolute Alcohol Injection), Denosumab Injection (Prolia), Delatestryl, Delestrogen, Delteparin Sodium (DelteparinSodium), Depacon (Sodium Valproate Injection), Depo-Medrol (Methylprednisolone Acetate Suspension for Injection), DepoCyt (Cytarabine Liposome Injection), DepoDur (Morphine Sulfate XR Liposome Injection), Desmopressin Acetate Injection (DDAVP Injection), Depo-Estradiol, Depo-Provera 104 mg / ml, Depo-Provera 150 mg / ml, Depo-Testosterone, Injection, Dexrazoxane (Totect) for intravenous drip only, Glucose / electrolytes, Glucose and Sodium Chloride Injection (5% Glucose in 0.9% Sodium Chloride), Glucose, Diazepam Injection (Diazepam Injection), Digoxin Injection (Lanoxin Injection), Dilaudid-HP (Hydromorphone Hydrochloride Injection), Dimercaprol Injection (Ampoule of Bal in Oil), Diphenhydramine Injection (Benadryl Injection), Dipyridamole Injection (Dipyridamole Injection), DMOAD, Docetaxel for Injection (Taxotere), Dolasetron Mesylate Injection (Anzemet Injection), Doribax (Doripenem for Injection), Doripenem for Injection (Doribax), Doxercalciferol Injection (Hectorol Injection), Doxil (Doxorubicin Hydrochloride Liposome Injection), Doxorubicin Hydrochloride Liposome Injection (Doxil), Duraclon (Clonidine Injection), Duramorph (Morphine Injection), Dysport (Botulinum Toxin A Injection), Ecallantide Injection (Kalbitor), EC-Naprosyn (Naproxen), Calcium Disodium Edetate Injection (Calcium Disodium Versenate), Edex (Alprostadil for Injection), Engerix, Edrophonium Injection (Enlon), Eliglustat Tartrate (EliglustatTartrate), Eloxatin (oxaliplatin injection), Emend injection (fosaprepitant dimeglumine injection), Enalaprilat injection (enalaprilat injection), Enlon (edrophonium injection), enoxaparin sodium injection (Lovenox), Eovist (gadoxetic acid disodium injection), Enbrel (etanercept), enoxaparin, Epicel, Epinepherine, EpiPen, EpiPen Jr. (Epipen Jr.), Epratuzumab, Arbitux, ertapenem injection (Invanz), erythropoietin (Erythropoieten), essential amino acid injection (Nephramine), estradiol cypionate, estradiol valerate, etanercept, exenatide injection (Byetta), Evlotra, Fabrazyme (Adalsidase beta), famotidine injection, FDG (fluorodeoxyglucose F18 injection), Feraheme (ferumoxytol injection), Feridex IV (Ferumoxides injection solution), Fertinex, Ferumoxid Feridex intravenous injection solution, Feraheme injection, Flagyl injection (Metronidazole injection), Fluarix, Fludara (Fludarabine phosphate), Fluorodeoxyglucose F18 injection (FDG), Fluorescein injection (Ak-Fluor), Follistim AQ Cartridge (Follitropin beta injection), Gonal-f RFF (Follitropin alpha injection), Follistim AQ Cartridge (Follitropin beta injection), Folotyn (Pralatrexate for injection solution), Fondaparinux, Forteo (Teriparatide (rDNA origin) injection), Pazopanib, Phosphacanatide dimethylglucamine injection (Emend injection), Foscarnet sodium injection (Foscavir), Foscavir (Foscarnet sodium injection), Phenytoin sodium injection (Cerebyx), Fospropofol Disodium injection (Lusedra), Fragmin, Fuzeon (Enfuvirtide), GA101, Gadobenate Dimeglumine injection (Multihance), Gadofosveset trisodium injection (Ablavar), Gadoteridol injection solution (ProHance), Gadobutrol injection (OptiMARK), Gadoxetic acid 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-fRFF (Follitropin alfa injection), Granisetron hydrochloride (Kytril injection), Gentamicin sulfate, Glatiramer acetate, Glucagen, Glucagon, HAE1, Haldol (Haloperidol injection), Havrix, Hectorol injection (Doxercalciferol injection), Hedgehog pathway inhibitor, Heparin, Herceptin, hG-CSF, Humalog, Human growth hormone, Humatrope, HuMax, Humegon, Humira, Humalin, Ibandronic acid sodium injection (Boniva injection), Ibuprofen lysine injection (NeoProfen), Ibutilide fumarate injection (Corvert), Idamycin PFS (Idarubicin hydrochloride injection), Idarubicin hydrochloride injection (Idamycin PFS), Ilaris (Canakinumab injection), Imipenem and cilastatin for injection (Primaxin IV), Imitrex, Recombinant interferon alfa-2b for injection (Intron A), Intron A (Recombinant interferon alfa-2b for injection), Invanz (Ertapenem injection), Invega Sustenna (Paliperidone palmitate extended-release injection suspension), Invirase (Saquinavir mesylate), Iobenguane I123 (Iobenguane I123) Injectable for intravenous injection (AdreView), Iopromide injection (Ultravist), Iobezole injection (Optiray injection), Iplex (Mecasermin rinfabate [rDNA origin] injection), Iprivask, Irinotecan hydrochloride (Camptosar injection), Iron sucrose injection (Venofer), Istodax (Romidepsin for injection), Itraconazole injection (Sporanox injection), Jevtana (Cabazitaxel injection), Jonexa, Kalbitor (Ecarinide injection), KCL in D5NS (Potassium chloride in 5% dextrose and sodium chloride injection), KCL in D5W, KCL in NS, Kenalog 10 injection (Triamcinolone acetonide suspension for injection), Kepivance (Palifermin), Keppra injection (Levetiracetam), Keratinocyte, KFG, Kinase inhibitor, Kineret (Anakinra), Kinlytic (Urokinase injection), Kinrix, Klonopin (Clonazepam), Kytril injection (Granisetron hydrochloride), Lacosamide tablets and injection (Vimpat), Lactated Ringer's solution, Lanoxin injection (Digoxin injection), Lansoprazole for injection (Prevacid IV), Lantus, Leucovorin calcium (Leucovorin calcium injection), Lente (L), Leptin, Levimir, Leukine Sargramostim, Leuprolide acetate, Levothyroxine, Levetiracetam (Keppra injection), Lovenox, Levocarnitine injection (Carnitor injection), Lexiscan (Regadenoson injection), Rilutek intrathecal (Baclofen injection), Liraglutide [rDNA] injection (Victoza), Lovenox (Enoxaparin sodium injection), Lucentis (Ranibizumab injection), Lumizyme, Lupron (Leuprolide acetate injection), Lusedra (FospropofolDisodium injection), Maci, Magnesium Sulfate (Magnesium Sulfate injection), Mannitol injection (Mannitol intravenous injection), Marcaine (Bupivacaine Hydrochloride and Epinephrine injection), Maxipime (Cefepime Hydrochloride for injection), Technetium injection MDP multi-dose kit (Technetium Tc 99m Medronate injection), Mecasermin [rDNA origin] injection (Increlex), Mecasermin lymphoblast [rDNA origin] injection (Iplex), Melphalan Hcl injection (Alkeran injection), Methotrexate, Menactra, Menopur (Menotropin injection), Menotropin for injection (Repronex), Methohexital Sodium for injection (Brevital Sodium), Methyldopate Hydrochloride injection (Methyldopate Hydrochloride), Methylene Blue (Methylene Blue injection), Methylprednisolone Acetate injection suspension (Depo-Medrol), MetMab, Metoclopramide injection (Reglan injection), Metrodin (Urofollitropin for injection), Metronidazole injection (Flagyl injection), Miacalcin, Midazolam (Midazolam injection), Mimpara (Cinacalet), Minocin injection (Minocycline injection), Minocycline injection (Minocin injection), Mipomersen, Mitoxantrone for injection concentrate (Novantrone), Morphine injection (Duramorph), Morphine Sulfate XR liposome injection (DepoDur), Sodium Morrhuate (Sodium Morrhuate injection), Motesanib, Mozobil (Plerixafor injection), Multihance (Gadobenate Dimethylglumine (GadobenateDimeglumine injection, multiple electrolyte and glucose injection, multiple electrolyte injection, Mylotarg (gemtuzumab ozogamicin for injection), Myozyme (alglucosidase alfa), nafcillin injection (nafcillin sodium), nafcillin sodium (nafcillin injection), naltrexone XR injection (Vivitrol), Naprosyn (naproxen), NeoProfen (ibuprofen lysine injection), nandrol decanoate, neostigmine methylsulfate (neostigmine methylsulfate injection), NEO-GAA, NeoTect (technetium Tc 99m depreotide injection), Nephramine (essential amino acid injection), Neulasta (pegfilgrastim), Neupogen (filgrastim), Novolin, NovoLog, NeoRecormon, Neutrexin (trimetrexate glucuronate injection), NPH (N), Nexterone (amiodarone HCl injection), Norditropin (somatropin injection), normal saline (sodium chloride injection), Novantrone (mitoxantrone for injection concentrate), Novolin 70 / 30 Innolet (70% NPH, human insulin isophane suspension and 30% regular human insulin injection), NovoLog (insulin aspart [rDNA origin] injection), Nplate (romiplostim), Nutropin (somatropin [rDNA origin] for injection), Nutropin AQ, Nutropin Depot (somatropin [rDNA origin] for injection), octreotide acetate injection (Sandostatin LAR), ocrelizumab, ofatumumab injection (Arzerra), olanzapine sustained-release injection suspension (ZyprexaRelprevv), Omnitarg, Omnitrope (somatropin [rDNA origin] injection), ondansetron hydrochloride injection (Zofran injection), OptiMARK (gadobenate dimeglumine injection), Optiray injection (iopamidol injection), Orenzia, Aviva with Osmitrol injection (mannitol injection in Aviva plastic container), Viaflex with Osmitrol injection (mannitol injection in Viaflex plastic container), Osteoprotegrin, Ovidrel (chorionic gonadotropin alpha injection), oxacillin (oxacillin for injection), oxaliplatin injection (Eloxatin), oxytocin injection (Pitocin), paliperidone palmitate extended-release injectable suspension (Invega Sustenna), pamidronate disodium injection (pamidronate disodium injection), panitumumab intravenous injection (Vectibix), papaverine hydrochloride injection (papaverine injection), papaverine injection (papaverine hydrochloride injection), parathyroid hormone, paricalcitol injection flip-top vial (Zemplar injection), PARP inhibitor, Pediarix, Pegintron, Peginterferon, Pegfilgrastim, penicillin G benzathine and penicillin G procaine, calcium trisodium pentetate injection (Ca-DTPA), zinc trisodium pentetate injection (Zn-DTPA), Pepcid injection (famotidine injection), Pergonal, pertuzumab, phentermine mesylate (phentermine mesylate for injection), physostigmine salicylate (physostigmine salicylate [injection]), physostigmine salicylate (injection) (physostigmine salicylate), piperacillin and tazobactam injection (Zosyn), Pitocin (oxytocin injection), Plasma-Lyte148 (multiple electrolyte injection), Plasma-Lyte56 and glucose (Multiple Electrolytes and Glucose Injection in Viaflex Plastic Container), Plasma-Lyte, Plerixafor Injection (Mozobil), Polidocanol Injection (Asclera), Potassium Chloride, Pralatrexate for Injection Solution (Folotyn), Pramlintide Acetate Injection (Symlin), Premarin injection (conjugated estrogen for injection), Technetium Tc99 Sestamibi injection kit for injection (Cardiolite), Prevacid IV (lansoprazole for injection), Primaxin IV (imipenem and cilastatin for injection), Prochymal, Procrit, progesterone, ProHance (gadoteridol injection), Prolia (denosumab injection), promethazine hydrochloride 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, Regadenoson injection (Lexiscan), Reglan injection (metoclopramide injection), Remicade, Renagel, Renvela (sevelamer carbonate), Repronex (menotropins for injection), Retrovir IV (zidovudine injection), rhApo2L / TRAIL, Ringer's and 5% dextrose injection (Ringer's solution in dextrose), Ringer's injection (Ringer's injection), Rituxan, rituximab, Rocephin (ceftriaxone), rocuronium bromide injection (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 hydrochloride injection), Septocaine (articaine hydrochloride and epinephrine injection), SerostimLQ (Somatropin (rDNA origin) 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 for Injection (rDNA origin) (Nutropin), Sporanox Injection (Itraconazole Injection), Stelara Injection (Ustekinumab), Stemgen, Sufenta (Sufentanil Citrate Injection), Sufentanil Citrate Injection (Sufenta), Sumavel, Sumatriptan Injection (Alsuma), Symlin, Symlin Pen, Systemic Hedgehog Antagonist, Synvisc-One (Hylan G-F 20 Single Intra-articular Injection), Tarceva, Taxotere (Docetaxel for Injection), Technetium Tc 99m, Telavancin for Injection (Telavancin) (Vibativ), Temsirolimus Injection (Torisel), Tenormin Intravenous Injection (Atenolol Injection), Teriparatide (rDNA origin) Injection (Forteo), Testosterone Cypionate, Testosterone Enanthate, Testosterone Propionate, Tev-Tropin (Somatropin for Injection, rDNA origin), tgAAC94, Thallous Chloride, Theophylline, Thiotepa (Thiotepa Injection), Thymoglobulin (Antithymocyte Globulin (Rabbit)), Thyrogen (Thyroid Stimulating Hormone Alpha for Injection), Ticarcillin Disodium and Clavulanate Potassium Galaxy (Timentin) Injection, Tigan Injection (Trimethobenzamide Hydrochloride for Injection), Timentin Injection (Ticarcillin Disodium and ClavulanatePotassium Galaxy)), TNKase, Tobramycin Injection (Tobramycin Injection), Tocilizumab Injection (Actemra), Torisel (Temsirolimus Injection), Totect (Dexrazoxane for Injection and Intravenous Drip Only), Trastuzumab-DM1, Travasol (Amino Acid (Injection)), Treanda (Bendamustine Hydrochloride Injection), Trelstar (Triptorelin Pamoate for Injectable Suspension), Triamcinolone Acetonide, Triamcinolone Diacetate, Triamcinolone Hexacetonide Injectable Suspension (Aristospan Injection 20mg), Triesence (Triamcinolone Acetonide Injectable Suspension), Trimethobenzamide Hydrochloride Injection (Tigan Injection), Trimetrexate Glucuronate Injection (Neutrexin), Triptorelin Pamoate for Injectable Suspension (Trelstar), Twinject, Trivaris (Triamcinolone Acetonide Injectable Suspension), Trisenox (Arsenic Trioxide Injection), Twinrix, Typhoid Vi, Ultravist (Iopromide Injection), Urofollitropin for Injection (Metrodin), Urokinase Injection (Kinlytic), Ustekinumab (Stelara Injection), Ultralente (U), Barium (Diazepam), Valproic Acid Sodium Injection (Depacon), Valtropin (Somatropin Injection), Vancomycin Hydrochloride (Vancomycin Hydrochloride Injection), Vancomycin Hydrochloride Injection (Vancomycin Hydrochloride), Vaprisol (Conivaptan Hcl Injection), VAQTA, Vasovist (Gadofosveset Trisodium for Intravenous Injection), Vectibix (Panitumumab for Intravenous Injection), Venofer (Sucrose Iron Injection), Verteporfin Injection (Visudyne), Vibativ (Telavancin for Injection), Victoza (Liraglutide [rDNA] Injection), Bimpat (Lacosamide Tablets and Injection), Vinblastine Sulfate (Vinblastine Sulfate Injection), VincasarPFS (Vincristine Sulfate Injection), Victoza, Vincristine Sulfate (Vincristine Sulfate Injection), Visudyne (Verteporfin Injection), Vitamin B-12, Vivitrol (Naltrexone XR Injection), Voluven (Hydroxyethyl Starch in Sodium Chloride Injection), Xeloda, Xenical (Orlistat), Zeomin (Injectable Incobotulinumtoxin A), Zoladex, Zantac Injection (Ranitidine Hydrochloride Injection), Zemplar Injection (Paricalcitol Injection Flip-Top Vial), Zemuron (Rocuronium Bromide Injection), Zenapax (Daclizumab), Zevalin, Zidovudine Injection (Retrovir IV), Zithromax Injection (Azithromycin), Zn-DTPA (Trisodium Zinc 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 (Olanzapine Extended Release Injectable Suspension),

[0046] Liquid (Non-Injectable) Evirex, AccuNeb (Albuterol Sulfate Inhalation Solution), Actidose Aqua (Activated Charcoal Suspension), Activated Charcoal Suspension (Actidose Aqua), Advair, Agenerase Oral Solution (Amprenavir Oral Solution), Akten (Lidocaine Hydrochloride Ophthalmic Gel), Alamast (Pemirolast Potassium Ophthalmic Solution), Albumin (Human) 5% Solution (Buminate 5%), Albuterol Sulfate Inhalation Solution, Alinia, Alocril, Alphagan, Alrex, Alvesco, Amprenavir Oral Solution, Analpram-HC, Arformoterol Tartrate Inhalation Solution (Brovana), Aristospan Injection 20mg (Triamcinolone Hexacetonide Injection Suspension), Asacol, Azmanex, Astepro, Astepro (Azelastine Hydrochloride Nasal Spray), Atrovent Nasal Spray (Ipratropium Bromide Nasal Spray), Atrovent Nasal Spray.06, Augmentin ES-600, Azasite (Azithromycin Ophthalmic Solution), Azelaic Acid (Finacea Gel), Azelastine Hydrochloride Nasal Spray (Astepro), Azelex (Azelaic Acid Cream), Eysopto (Brimonidine Ophthalmic Suspension), Bacteriostatic Saline, Balanced Salts, Bepotastine, Bactroban Nasal, Bactroban, Beclovent, Benzac W, Betimol, Betoptic S, Bepreve, Bimatoprost Ophthalmic Solution, Bleph 10 (Sulfacetamide Sodium Ophthalmic Solution 10%), Brimonidine Ophthalmic Suspension (Eysopto), Bromfenac Ophthalmic Solution (Xibrom), Bromhist, Brovana (Arformoterol Tartrate Inhalation Solution), Budesonide Inhalation Suspension (Pulmicort Respules), Cambia (Diclofenac Potassium for Oral SolutionPotassium, Capex, Carac, Carboxine - PSE, Carnitor, Cayston (aztreonam for inhalation solution), CellCept, Centany, Cerumenex, Ciloxan eye drops (ciprofloxacin hydrochloride eye drops), Ciprodex, ciprofloxacin hydrochloride eye drops (Ciloxan eye drops), clemastine fumarate syrup, CoLyte (PEG electrolyte solution), Combiven, Comtan, Condylox, Cordran, Cortisporin ophthalmic suspension, Cortisporin otic suspension, cromolyn sodium inhalation solution (Intal nebulizer solution), cromolyn sodium eye drops (Opticrom), crystalline amino acid solution containing electrolyte (Aminosyn electrolyte), Cutivate, Cuvposa (glycopyrrolate oral solution), cyanocobalamin (CaloMist nasal spray), cyclosporine oral solution (Gengraf oral solution), Cyclogyl, Cysview (hexaminolevulinate hydrochloride bladder solution), DermOtic oil (fluocinolone acetonide otic drops), desmopressin acetate nasal spray, DDAVP, Derma - Smoothe / FS, dexamethasone Intensol, Dianeal Low Calcium, Dianeal PD, diclofenac potassium for oral solution (Cambia), didanosine pediatric powder for oral solution (Videx), deferiprone, Dilantin 125 (phenytoin oral suspension), Ditropan, dorzolamide hydrochloride eye drops (Trusopt), dorzolamide hydrochloride - timolol maleate eye drops (Cosopt), Dovonex Scalp (calcipotriene solution), doxycycline calciumCalcium) Oral Suspension (for Oral Use of Vibramycin), Efudex, Elaprase (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), Oilax, Extraneal (Icodextrin Peritoneal Dialysis Solution), Felbatol, Feridex IV (Ferumoxides Injection), Flovent, Floxin for Otic Use (Ofloxacin Otic Solution), Flo-pred (Prednisolone Acetate Oral Suspension), Fluoroplex, Flunisolide Nasal Spray (Flunisolide Nasal Spray 0.025%), Fluorometholone Eye Suspension (FML), Flurbiprofen Sodium Eye Drops (Ocufen), FML, Foradil, Formoterol Fumarate Inhalation Solution (Perforomist), Fosamax, Furadantin (Nitrofurantoin Oral Suspension), Furoxone, Gamma-Gard Liquid (Immune Globulin IV (Human) 10%), Gantrisin (Acetyl Sulfisoxazole Pediatric Suspension), Gatifloxacin Eye Drops (Zymar), Gengraf Oral Solution (Cyclosporine Oral Solution), Glycopyrrolate Oral Solution (Cuvposa), Halcinonide Topical Solution (Halog Solution), Halog Solution (Halcinonide Topical Solution), HEP-LOCK U / P (Heparin Lock Flush Solution without Preservative), Heparin Lock Flush Solution (Hepflush 10), Hexaminolevulinate Hydrochloride Intravesical Solution (Cysview), Hydrocodone BitartrateBitartrate), 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), Ketorolac Tromethamine Ophthalmic Solution (Acular LS), Kaletra, Lanoxin, Lexiva, Leuprolide Acetate for Depot Suspension (Lupron Depot 11.25mg), Levobetaxolol Hydrochloride Ophthalmic Suspension (Betaxon), Tablets, Oral Solution, Sugar-Free of Levocarnitine (Carnitor), Levofloxacin Ophthalmic Solution 0.5% (Quixin), Lidocaine HCl Sterile Solution (Xylocaine MPF Sterile Solution), Lok Pak (Heparin Lock Flush Solution), Lorazepam Intensol, Lortab Elixir (Hydrocodone Bitartrate and Acetaminophen Oral Solution), Lotemax (Loteprednol Etabonate Ophthalmic Suspension), Loteprednol Etabonate Ophthalmic Suspension (Alrex), Low Calcium Peritoneal Dialysis Solution (Dianeal Low Calcium), Lumigan (Bimatoprost Ophthalmic Solution 0.03% for Glaucoma), Lupron Depot 11.25mg (Leuprolide Acetate for Depot Suspension), Megestrol Acetate Oral Suspension (Megestrol Acetate Oral Suspension), MEK Inhibitor, Mepron, Mesnex, Mestinon, Mesalamine Rectal Suspension Enema (Rowasa), Melquin-3 Topical Solution (Hydroquinone 3% Topical Solution), MetMab, Methyldopate Hcl (Methyldopate Hydrochloride Injection, Solution), Methylin Oral Solution (MethylphenidateOral solution of HCl (5 mg / 5 mL and 10 mg / 5 mL), methylprednisolone acetate injection suspension (Depo-Medrol), oral solution of methylphenidate HCl (5 mg / 5 mL and 10 mg / 5 mL) (Methylin oral solution), sodium succinate methylprednisolone (Solu-Medrol), metipranolol eye drops (Optipranolol), Migranal, Miochol-E (intraocular acetylcholine chloride solution), Micro-K for liquid suspension (sustained-release potassium chloride preparation for liquid suspension), Minocin (oral suspension of minocycline hydrochloride), Nasacort, neomycin and polymyxin B sulfate and hydrocortisone, nepafenac eye drop suspension (Nevanac), Nevanac (nepafenac eye drop suspension), oral suspension of nitrofurantoin (Furadantin), Noxafil (oral suspension of posaconazole), nystatin (for oral use) (oral suspension of nystatin), oral suspension of nystatin (nystatin (for oral use)), Ocufen (flurbiprofen sodium eye drops), ofloxacin eye drops (ofloxacin eye drops), ofloxacin for otology (Floxin for otology), olopatadine hydrochloride eye drops (Pataday), Opticrom (sodium cromoglycate eye drops), Optipranolol (metipranolol eye drops), Patanol, Pediapred, PerioGard, oral suspension of phenytoin (Dilantin 125), Phisohex, oral suspension of posaconazole (Noxafil), sustained-release potassium chloride preparation for liquid suspension (Micro-K for liquid suspension), Pataday (olopatadine hydrochloride eye drops), Patanase nasal spray (olopatadine hydrochloride nasal spray), PEG electrolyte solution (CoLyte), pemirolast potassium eye drops (Alamast), Penlac (topical solution of ciclopirox), PENNSAID (topical solution of diclofenac sodium), Perforomist (inhalation solution of formoterol fumarate), peritoneal dialysis solution, phenylephrine hydrochloride eye drops (Neo-Synephrine), phospholine iodide (PhospholineIodide) (Echothiophate Iodide for eye drops), Podofilox (Podofilox topical solution), Pred Forte (Prednisolone acetate eye suspension), Pralatrexate injection solution (Folotyn), Pred Mild, Prednisone Intensol, Prednisolone acetate eye suspension (Pred Forte), Prevacid, PrismaSol solution (sterile hemodiafiltration solution for hemodiafiltration), ProAir, Proglycem, ProHance (gadoteridol injection solution), Proparacaine hydrochloride Alcaine eye drops, Propine, Pulmicort, Pulmozyme, Quixin (0.5% levofloxacin eye drops), QVAR, Rapamune, Levotol, Relacon-HC, Rotarix (oral rotavirus live vaccine suspension), oral rotavirus live vaccine suspension (Rotarix), Rowasa (Mesalamine rectal suspension enema), Sabril (vigabatrin oral solution), Sucraid (sacrosidase oral solution), Sandimmune, Sepra, Serevent Diskus, Solu-Cortef (sodium hydrocortisone succinate), Solu-Medrol (sodium methylprednisolone succinate), Spiriva, Sporanox oral solution (itraconazole oral solution), Staticin (1.5% erythromycin topical solution), Stalevo, Starlix, PrismaSol solution (sterile hemodiafiltration solution for blood filtration), Stimate, Carafate suspension, 10% Sulfacetamide Sodium eye drops (Bleph 10), Synarel nasal spray (napharelin acetate nasal spray for endometriosis), Taclonex Scalp (calcipotriene and betamethasone dipropionate topical suspension), Tamiflu, Tobi, TobraDex, Tobradex ST (0.3% / 0.05% tobramycin / dexamethasone ophthalmic suspension), 0.3% / 0.05% (Tobradex ST), Timolol, Timoptic, Travatan Z, Tyvaso (treprostinil inhalation solution), Trusopt (dorzolamide hydrochloride ophthalmic solution), Tyvaso (treprostinil inhalation solution), Ventolin, Bufend, Vibramycin Oral (doxycycline calcium oral suspension), Videx (didanosine pediatric powder for oral solution), Vigabatrin Oral Solution (Sabril), Viokase, Virasept, Viramune, Vitamin K1 (fluid colloidal solution of vitamin K1), Voltaren Eye (diclofenac sodium ophthalmic solution), Zarontin Oral Solution (ethosuximide oral solution), Ziagen, Zyvox, Zymar (gatifloxacin ophthalmic solution), Zymaxid (gatifloxacin ophthalmic solution),.

[0047] Drug Class 5-alpha-reductase inhibitors, 5-aminosalicylic acid, 5HT3 receptor antagonists, adamantane antiviral agents, adrenal corticosteroids, adrenal cortical corticosteroid inhibitors, adrenergic bronchodilators, medications for hypertensive emergencies, medications for pulmonary hypertension, aldosterone receptor antagonists, alkylating agents, alpha-adrenergic receptor antagonists, alpha-glucosidase inhibitors, alternative medicine, antiamebic drugs, aminoglycosides, aminopenicillins, 5-aminosalicylic acid, amylin analogs, combinations of analgesics, analgesics, androgens and anabolic steroids, angiotensin-converting enzyme inhibitors, angiotensin II inhibitors, anorectal preparations, appetite suppressants, antacids, anthelmintics, anti-angiogenic ophthalmic agents, anti-CTLA-4 monoclonal antibodies, anti-infective agents, centrally acting antiadrenergic drugs, peripherally acting antiadrenergic drugs, antiandrogenic drugs, antianginal agents, antiarrhythmic agents, combinations of anti-asthmatic agents, antineoplastic / antineoplastic agents, anticholinergic antiemetics, anticholinergic antiparkinsonian drugs, anticholinergic bronchodilators, anticholinergic chronotropic agents, anticholinergic agents / antispasmodics, anticoagulants, anticonvulsants, antidepressants, antidiabetic agents, combinations of antidiabetic agents, antidiarrheal drugs, antidiuretic hormone, antidotes, antiemetics / antivertigoagent), antifungal agent, anti-gonadotropin agent, antigout agent, antihistamine agent, anti-dyslipidemic agent, combination of anti-dyslipidemic agents, combination of antihypertensive agents, uric acid-lowering agent, antimalarial agent, combination of antimalarial agents, antimalarial quinoline, antimetabolite, anti-migraine agent, anti-cancer detoxifying agent, anti-cancer interferon, anti-tumor monoclonal antibody, anti-cancer agent, anti-Parkinson's disease agent, antiplatelet agent, anti-Pseudomonas aeruginosa penicillin, psoriasis treatment agent, antipsychotic agent, anti-rheumatic agent, disinfectant and bactericide, anti-thyroid agent, antitoxin and anti-snake venom agent, anti-tuberculosis agent, combination of anti-tuberculosis agents, antitussive agent, antiviral agent, combination of antiviral agents, antiviral interferon, anti-anxiety agent, sedative and hypnotic agent, aromatase inhibitor, atypical antipsychotic agent, azole antifungal agent, bacterial vaccine, barbiturate anti-convulsant, barbiturate, BCR-ABL tyrosine kinase inhibitor, benzodiazepine anti-convulsant, benzodiazepine, beta-adrenergic blocker, beta-lactamase inhibitor, bile acid sequestrant, biological preparation, bisphosphonate, bone resorption inhibitor, combination of bronchodilators, bronchodilator, calcitonin, calcium channel blocker, carbamate anti-convulsant, carbapenem, carbonic anhydrase inhibitor anti-convulsant, carbonic anhydrase inhibitor, cardiac stressing agent, cardioselective beta blocker, cardiovascular agent, catecholamine, CD20 monoclonal antibody, CD33 monoclonal antibody, CD52 monoclonal antibody, central nervous system agent, cephalosporin, earwax solution, chelating agent, chemokine receptor antagonist, chloride ion channel activator, cholesterol absorption inhibitor, cholinergic agent, cholinergic muscle stimulant, cholinesterase inhibitor, CNS stimulant, coagulation regulator (coagulationmodifier), colony-stimulating factor, contraceptive, corticotropin, coumarin and indandione, cox-2 inhibitor, blood-removing agent, dermatological agent, diagnostic radiopharmaceutical, dibenzazepine anticonvulsant, digestive enzyme, dipeptidyl peptidase 4 inhibitor, diuretic, dopamine-acting antiparkinson agent, drug used in alcohol dependence, echinocandin, EGFR inhibitor, estrogen receptor antagonist, estrogen, expectorant, factor Xa inhibitor, fatty acid derivative anticonvulsant, fibrin acid derivative, first-generation cephalosporin, fourth-generation cephalosporin, functional bowel disorder drug, gallstone dissolution aid, gamma-aminobutyric acid analogue, gamma-aminobutyric acid reuptake inhibitor, gamma-aminobutyric acid transaminase inhibitor, gastrointestinal drug, general anesthetic, genitourinary tract agent, GI stimulant, glucocorticoid, glucose elevating agent, glycopeptide antibiotic, glycoprotein platelet inhibitor, glycylcycline, gonadotropin-releasing hormone, gonadotropin-releasing hormone antagonist, gonadotropin, class I antiarrhythmic drug, class II antiarrhythmic drug, class III antiarrhythmic drug, class IV antiarrhythmic drug, class V antiarrhythmic drug, growth hormone receptor blocker, growth hormone, Helicobacter pylori eradication drug, H2 antagonist, hematopoietic stem cell mobilizing agent, heparin antagonist, heparin, HER2 inhibitor, herbal product, histone deacetylase inhibitor, hormone replacement therapy, hormone, hormone / antineoplastic drug, hydantoin anticonvulsant, illegal (street) drug, immunoglobulin, immunologic agent, immunosuppressant, infertility drug, in vivo diagnostic biological preparation, incretin mimetic, inhaled anti-infective, inhaled corticosteroid, cardiotonic, insulin, insulin-like growth factor, integrase strand transfer inhibitor, interferon, intravenous nutritionalproduct), iodine contrast agent, ionic iodine contrast agent, iron product, ketolide, laxative, anti-rabies drug, leukotriene regulator, lincomycin derivative, lipoglycopeptide, local anesthetic for injection, loop diuretic, pulmonary surfactant, lymphatic staining agent, lysosomal enzyme, macrolide derivative, macrolide, magnetic resonance imaging contrast agent, mast cell stabilizer, medical gas, meglitinide, metabolic agent, methylxanthine, mineralocorticoid, minerals and electrolytes, various drugs, various analgesics, various antibiotics, various anticonvulsants, various antidepressants, various antidiabetic agents, various antiemetics, various antifungal agents, various antihyperlipidemic agents, various antimalarial agents, various antineoplastic drugs, various antiparkinsonian agents, various antipsychotic agents, various antituberculosis agents, various antiviral agents, various anxiolytics, sedatives and hypnotics, various biological agents, various bone resorption inhibitors, various cardiovascular agents, various central nervous system agents, various coagulation modifiers, various diuretics, various genitourinary tractagent), various GI drugs, various hormones, various metabolic agents, various ophthalmic agents, various otologic agents, various respiratory drugs, various sex hormones, various topical agents, various unclassified agents, various vaginal drugs, mitotic inhibitors, monoamine oxidase inhibitors, monoclonal antibodies, oral and throat products, mTOR inhibitors, mTOR kinase inhibitors, mucolytics, multi-kinase inhibitors, muscle relaxants, mydriatics, combinations of narcotic analgesics, narcotic analgesics, nasal anti-infectives, nasal antihistamines and decongestants, nasal lubricants and cleansers, nasal drops, nasal steroids, natural penicillins, neuraminidase inhibitors, neuromuscular blockers, next-generation cephalosporins, nicotinic acid derivatives, nitrates, NNRTIs, non-selective beta blockers, non-iodinated contrast agents, non-ionic iodinated contrast agents, non-sulfonylurea agents, non-steroidal anti-inflammatory agents, norepinephrine reuptake inhibitors, norepinephrine-dopamine reuptake inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), nutritional supplements, nutritional products, ophthalmic anesthetics, ophthalmic anti-infectives, ophthalmic anti-inflammatories, ophthalmic antihistamines and decongestants, ophthalmic diagnostic agents, ophthalmic glaucoma agents, ophthalmic lubricants and cleansers, eye drops, ophthalmic steroids, ophthalmic steroids containing anti-infectives, ophthalmic surgical agents, oral nutritional supplements, otologic anesthetics, otologic anti-infectives, otologic preparations, otologic steroids, otologic steroids containing anti-infectives, oxazolidinedione anticonvulsants, parathyroid hormone and analogs, penicillinase-resistant penicillins, penicillins, peripheral opioid receptor antagonists, peripheral vasodilators, peripherally acting anti-obesity agents, phenothiazine antiemetics, phenothiazine antipsychotics, phenylpiperazine antidepressants, plasma volume expanders, platelet aggregation inhibitors, platelet stimulants, polyenes, potassium-sparing diuretics, probiotics, progesterone receptor modulators, progestins, prolactin inhibitors, prostaglandin D2 antagonists, protease inhibitors, proton pump inhibitors, psoralen, psychotherapeutic agents, combinations of psychotherapeutics, purine nucleosides, pyrrolidine anticonvulsants, quinolones, radiologic contrast agents, radiologic adjuncts, radiologic drugs, radiologic conjugatingagent), radiopharmaceuticals, RANK ligand inhibitors, recombinant human erythropoietin, renin inhibitors, respiratory agents, respiratory inhalation products, rifamycin derivatives, salicylic acid agents, hardeners, second-generation cephalosporins, selective estrogen receptor modulators, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, serotonin-acting neuroenteric regulators, combinations of sex hormones, sex hormones, combinations of skeletal muscle relaxants, skeletal muscle relaxants, smoking cessation medications, somatostatin and somatostatin analogs, spermicides, statins, sterile irrigating solutions, streptomyces derivatives, succinimide anticonvulsants, sulfonamides, sulfonylureas, synthetic ovulation stimulants, tetracyclic antidepressants, tetracyclines, therapeutic radiopharmaceuticals, thiazide diuretics, thiazolidinediones, thioxanthenes, third-generation cephalosporins, thrombin inhibitors, thrombolytics, thyroid medications, uterine contraction inhibitors, topical acne medications, topical agents, local anesthetics, topical anti-infectives, topical antibiotics, topical antifungals, topical antihistamines, topical psoriasis treatments, topical antivirals, topical astringents, topical pus-promoting agents, topical depigmenting agents, topical emollients, topical keratolytics, topical steroids, topical steroids containing anti-infectives, toxoids, triazine anticonvulsants, tricyclic antidepressants, trifunctional monoclonal antibodies, tumor necrosis factor (TNF) inhibitors, tyrosine kinase inhibitors, ultrasound contrast agents, upper airway combinations, urea anticonvulsants, urinary anti-infectives, urinary antispasmodics, urinary pH regulators, uterine stimulants, vaccines, combinations of vaccines, vaginal anti-infectives, vaginal preparations, vasodilators, vasopressin antagonists, pressor agents, VEGF / VEGFR inhibitors, viral vaccines, viscosupplementation agents, combinations of vitamins and minerals, vitamins, protein-based vaccines, DNA-based vaccines, mRNA-based vaccines,

[0048] Diagnostic tests 17-Hydroxyprogesterone, ACE (angiotensin I converting enzyme), Acetaminophen, Acid phosphatase, ACTH, Activated clotting time, Activated protein C resistance, Adrenocorticotropic hormone (ACTH), Alanine aminotransferase (ALT), Albumin, Aldolase, Aldosterone, Alkaline phosphatase, Alkaline phosphatase (ALP), Alpha1-antitrypsin, Alpha-fetoprotein, Alpha-fetoprotien, Ammonia concentration, Amylase, ANA (antinuclear antibody), ANA (antinuclear antibody), Angiotensin converting enzyme (ACE), Anion gap, Anticardiolipin antibody, Anticardiolipin antibody (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 (ASO), Antithrombin III, Anti-Xa activity, Anti-Xa assay, Apolipoprotein, Arsenic, Aspartate aminotransferase (AST), B12, Basophil, Beta-2-microglobulin, Beta-hydroxybutyric acid, 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, HDL cholesterol, Clot lysis time, Clot retraction time, CMP, CO2, Cold agglutinin, Complement C3, Copper, Corticotropin-releasing hormone (CRH) stimulation test, Cortisol, Cosyntropin stimulation test, C-peptide, CPK (total), CPK-MB, C-reactive protein, Creatinine, Creatine kinase (CK), Cryoglobulin, DAT (direct antiglobulin test), D-dimer, Dexamethasone suppression test, DHEA-S, Dilute Russell viper venom, Elliptocyte,Good acid ball, erythrocyte sedimentation rate (ESR), estradiol, estriol, ethanol, ethylene glycol, euglobulin lysis, factor V Leiden, factor VIII inhibitor, factor VIII concentration, ferritin, fibrin degradation product, fibrinogen, folic acid, folic acid (serum, fractional excretion of sodium (FENA), FSH (follicle-stimulating hormone), FTA-ABS, gamma-glutamyl transferase (GGT), gastrin, GGTP (gamma-glutamyl transferase), glucose, growth hormone, haptoglobin, HBeAg (hepatitis B e antigen), HBs-Ag (hepatitis B surface antigen), Helicobacter 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), lactic acid (lactate), LDH, LH (luteinizing hormone), lipase, lupus anticoagulant factor, lymphocyte, magnesium, MCH (mean corpuscular hemoglobin), MCHC (mean corpuscular hemoglobin concentration), MCV (mean corpuscular volume), methylmalonic acid, monocyte, MPV (mean platelet volume), myoglobin, neutrophil, parathyroid hormone (PTH), phosphorus, platelet count (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, renin, reticulocyte count, reticulocyte, rheumatoid factor (RF), erythrocyte sedimentation rate (Sed 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 amount, transferrin, transferrin saturation, triglyceride (TG), troponin, uric acid, vitamin B12, white blood cell (WBC), Widal test.

Brief Description of the Drawings

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Figure 1

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[0087] In the context of the present invention, the following definitions and abbreviations are used.

[0088] In the context of the present invention, the term "at least" means "greater than or equal to" the integer that follows the term. The word "comprising" does not exclude other elements or steps, and the indefinite articles "a" or "an" do not exclude a plurality unless otherwise indicated. Whenever a range of parameters is indicated, it is intended to disclose the parameter values given as the limits of the range and all values of the parameters that fall within the range.

[0089] For example, references to "first" and "second" or similar with respect to a processing station or processing apparatus refer to the minimum number of processing stations or apparatuses present, but do not necessarily represent an order or total number of processing stations and apparatuses, nor do they require additional processing stations and apparatuses beyond the specified number. These terms do not limit the number of processing stations or the particular processing performed at each station. For example, the "first" station in the context of this specification can be either the only station or any one of a plurality of stations, but is not limited thereto. In other words, the recitation of a "first" station permits, but does not require, embodiments that also have a second station or additional stations.

[0090] The phrase "comprising" does not exclude other elements or steps.

[0091] The term "ready-to-use" or "RTU" refers to containers such as vials, syringe barrels, cartridges, etc., which are empty, clean, and sterilized so as to be configured to be filled without additional processing. RTU containers are typically cleaned (e.g., washed), and then packaged in a nested and tabbed configuration with trays and tabs sealed with Tyvek® seals. Next, the nested and tabbed configuration of the containers is sterilized. An example of the nested and tabbed configuration of an RTU vial is shown in FIG. 2. As shown in the illustrated embodiment, a typical nested and tabbed configuration of an RTU vial may include a nest 4 that holds a plurality of vials 400, and tabs 5, inlays 6, and seals 7 that surround the nest and the vials.

[0092] An exemplary vial 400 is shown in FIG. 3. The vial 400 of the present disclosure may include a bottom wall 401, a side wall 402 extending upward from the bottom wall, a curved lower edge joining the bottom wall and the side wall 403, a radially inwardly extending shoulder 404 formed at the upper part of the side wall, and a neck 405 extending upward from the shoulder, the neck having a neck flange 405a defining an opening 406 at its upper end, and the opening 406 leading to the inside of the vial, i.e., the lumen 212. The bottom wall 401 may have a flat or substantially flat lower surface 407 as shown in FIG. 3. Alternatively, the bottom wall 401 may have an outer resting ring and a central curved raised bottom region as in the case of a conventional vial as shown in FIG. 4. Vials having both types of bottoms may be coated, cleaned, and inspected using the methods and systems disclosed herein. The vial 400 may be made of borosilicate glass or a transparent thermoplastic material such as cyclic olefin polymer (COP) or cyclic olefin copolymer (COC).

[0093] Exemplary syringes are shown in FIGS. 5 and 6. In particular, FIG. 5 shows a syringe having a needle hub 506 and a needle, which is shown to be covered and protected by a rigid needle shield 511. FIG. 6 shows a syringe having a luer hub 507 instead of a needle, which is shown to be covered by a tip cap. In both examples, the syringe barrel 500 comprises a side wall 501 extending between a rear end including an opening to the lumen and a front end portion including the needle hub 506 or the luer hub 507. The rear end of the syringe barrel comprises a flange 508 having an upper surface surrounding the opening to the lumen and an outer surface extending beyond the body portion of the side wall 501. At the front end of the syringe barrel, the side wall portion 501 includes a shoulder 510, where the side wall transitions from the body side wall portion to the needle hub 506 or the luer hub 507 portion. Both syringes are also shown as including a plunger 509, although the plunger is not part of the syringe barrel 500.

[0094] For the purposes of the coating, cleaning, and container inspection techniques described herein, the rear end of the syringe barrel should be considered to correspond to the upper portion of the vial since both syringes include an opening to the lumen. Further, although the shoulder 510 of the syringe barrel is located towards the front end, it is contemplated that the same or substantially the same inspection techniques as described with respect to the shoulder 404 of the vial 400 may be applied to the shoulder 510 of the syringe barrel. Generally, although such embodiments are not illustrated, it is contemplated that the same or substantially the same inspection techniques as shown and described with respect to the vial may be applied to various portions of the syringe barrel.

[0095] An exemplary blood collection tube 274 is shown in FIG. 7. The blood collection tube includes a side wall 268 extending between a closed bottom end and an open top end. The open top end, which includes an opening to a central lumen, is shown as being covered by a cap 270. The open top end may or may not include a small flange. The closed bottom end comprises a small bottom wall 269. The blood collection tube also includes a transition region 271 between the side wall 268 and the bottom wall 269.

[0096] For the purposes of the coating, cleaning, and inspection techniques described herein, the blood collection tube 274 should be considered similar to the exemplary vial 400 in that it includes both a side wall portion 268, an opening into the lumen at the upper end of the container, and a bottom end in a closed state. Similar to the vial, the blood collection tube 274 also has a transition region 271 between the side wall 268 and the bottom wall 269. Unlike the vial 400, the blood collection tube 274 typically does not include a shoulder. Although such embodiments are not illustrated, it is contemplated that the same or substantially the same inspection techniques, as shown and described with respect to the vial 400, can be applied to various parts of the blood collection tube 274.

[0097] RTU containers are supplied to pharmaceutical companies or CDMOs (Contract Development and Manufacturing Organizations) for filling. The pharmaceutical company or CDMO opens the seals of the trays and tabs, fills the containers, and, for example, inserts a rubber stopper 411 into the opening of the vial and optionally applies an additional cap 412 typically made of a metal such as aluminum and crimped over the stopper and the upper part of the neck flange 405a of the vial, or inserts a plunger 509 into the barrel of the syringe or cartridge, or seals the container with a blood collection tube cap 270, within a sterile environment. RTU containers eliminate the need for the pharmaceutical company to process the containers prior to filling, for example, by washing or sterilization.

[0098] The term "syringe" is meant to include syringes with a needle embedded therein, such as a syringe with a fixed needle, as well as syringes having an alternative Luer lock or Luer cone fluid outlet. The term "syringe barrel" means the barrel of the syringe, including any embedded needle and / or any removable cap or needle shield, if present, but excluding the plunger inserted after filling.

[0099] The term "in-specification quality" or "AQL" means the maximum percentage of defects (or the maximum number of defects per 100 units) that can be considered acceptable. AQL is measured in terms of defects per 100 units. AQL specifies the maximum number of defective containers that would exclude the batch or lot from which it is drawn.

[0100] Here, the present invention will be described more fully with reference to the accompanying drawings showing several embodiments. However, the present invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are examples of the present invention that fall within all of the scopes indicated by the language of the claims. Like reference numerals throughout refer to like or corresponding elements.

[0101] A plurality of vials 400 were inspected using the system illustrated in FIGS. 13A-17 and described herein.

[0102] Vial 400 is moved between various inspection stations including a body side inspection station 101, an angled shoulder inspection station 102, an angled upper inspection station 103, an angled bottom inspection station 104, and a bottom inspection station 105. In some embodiments, including the illustrated embodiment, the angled bottom inspection station and the bottom inspection station may be combined in a single station 104, 105. The transport between each station 101, 102, 103, 104, 105 of the plurality of vials 400 can be automated so as to allow for the placement and positioning of the vials within each inspection station. In some embodiments, the plurality of vials 400 are transported along one or more transport lines until at least one of the vials reaches a predetermined point where it is retrieved from the transport line by one of a container holder or a container transport unit (depending on which inspection station). The container holder or container transport unit can then transport the container to inspection stations 101, 102, 103, 104, 105, or specific components of the inspection station, such as a bottom light and a side light, can be brought adjacent to the container holder so as to partially form the container compartment of the inspection station, for example, directly above the transport line. When a container transport unit is used, the container transport unit can also position the vial on the container holder of the inspection station for inspection. Once an image is captured, the container holder or container transport unit can then return the vial to the transport unit, and the vial can be transported to subsequent inspection stations until each inspection is performed.

[0103] Further, in any of the embodiments, a number of identical inspection stations can be arranged adjacent to each other such that a plurality of vials 400 are inspected at a given time.

[0104] Inspection of the body side part Figures 13A and 13B show the main body side inspection station 101, which is also called the side wall inspection station. The main body side inspection station 101 includes a main body side camera 110, a bottom light 111, a side light 112, and a container holder 113.

[0105] The bottom light 111 is configured and positioned such that the bottom light is below the vial 400 and light shines upward, for example, passing through the bottom of the vial and shining around the entire side of the vial. In some embodiments, the bottom light 111 can be a direct type backlight, such as a 63mm×60mm direct type backlight, a blue LED light, an M12 light, or a similar light. The use of blue light is optional but desirable for reasons such as highlighting the color of plasma flake particles that may be present from one or more coatings on the side wall of the vial 400. The side light 112 is positioned such that the side light is behind the vial 400 from the perspective of the camera 110 (i.e., on the opposite side of the vial from the camera), and when viewed from the camera, the light shines through the side wall of the vial and beyond the side of the vial. In some embodiments, the side light 112 can be a direct type backlight, such as a 100mm×100mm high-power planar light, a blue light, an M12 light, or a similar light. Again, the use of blue light is optional but desirable for reasons such as highlighting the color of plasma flake particles that may be present from one or more coatings on the side wall of the vial 400. The high-power planar light is preferably used in place of the type of direct type backlight used as the bottom light 111 in this embodiment because the main body side camera 110 includes a telecentric lens 114.

[0106] In the illustrated embodiment, the bottom light 111 and the side light 112 define the bottom and rear surfaces of a container compartment 115 within which the vial 400 is held. Here, the sides and front of the container compartment 115 are completely open. However, in other embodiments, one or both of the sides and / or the front may be partially or completely closed.

[0107] The body side camera 110 is located in front of the container compartment 115, and the lens is directed towards the container compartment. The body side camera 110 is preferably an area scan camera. Preferably, the body side camera 110 is an area scan camera that captures at least a 60° arc of the vial sidewall, such that the entire vial sidewall 402 can be inspected using six or fewer image captures. For example, the body side camera 110 can be an area scan camera that captures at least a 65° arc of the container sidewall (this provides overlap with adjacent arcs and thus ensures that the entire sidewall is captured and inspected). In some embodiments, the body side camera 110 can be a Cognex In-Sight 9912M, 12.0MP camera.

[0108] The body side camera 110 can also include a high-resolution telecentric lens 114 (as well as associated lens brackets and bandpass filters). The use of a telecentric lens 114 is desirable because the area of the vial sidewall 402 captured at this inspection station 101 is relatively large. When using a standard lens, the captured image is likely to be subject to a slight fisheye effect that hinders accurate measurement of particle size, i.e., particles present at the top and bottom of the sidewall 402 will appear different from particles present in the central portion of the sidewall. By using the telecentric lens 114, the system can be calibrated to measure particle size evenly across the entire sidewall 402 of the vial 400. In other (not shown) embodiments, multiple cameras with standard lenses may be used instead of a single camera 110 with a telecentric lens 114, or a single camera with a standard lens may be used, and it is assumed that the system can be calibrated to account for the resulting fisheye effect. If the telecentric lens 114 is not used, the side lights 112 may not need to be as bright as those used in the illustrated embodiment.

[0109] The container holder 113 is configured to hold the vial 400 from above without contacting the side wall 402 of the vial or, alternatively, without interfering with the line of sight around the side wall of the vial, including the sides of the neck 405 and the neck flange 405a. In the illustrated embodiment, for example, the container holder 113 interacts with the upper portion of the neck flange 405a of the vial, such as by clamping, suction, etc., such that the vial 400 is suspended from the container holder within the container compartment 115. As such, the container holder 113 forms at least a partial upper surface of the container compartment 115.

[0110] The container holder 113 is also configured to rotate the vial such that the entire 360° of the side wall 402 can be imaged and inspected. In some embodiments, the container holder 113 is configured to rotate continuously, which enables a high-throughput inspection process. For example, the container holder 116 of the illustrated embodiment is configured to rotate at a speed of up to approximately 120 rpm. Of course, continuous rotation requires the camera 110 to open the shutter for a very short time. For example, the camera 110 can be selected and the lights 111, 112 can be positioned such that the shutter remains open for less than one millisecond when capturing an image. In other embodiments, the vial 400 can be rotated discontinuously, i.e., the vial is held stable between each image capture and can be rotated between image captures.

[0111] In the illustrated embodiment, the container holder 113 is movable relative to the camera 110 and the lights 111, 112. In this way, the container holder 113 can pick up a vial 400, for example, from a transport line or a different inspection station and position the vial within the scope of the container compartment 115 for inspection. In other embodiments, certain components such as the lights 111, 112 may instead be moved to a location adjacent to the container holder 113. For example, the container holder can pick out a vial 400 from a transport line, and then the lights 111, 112 can be brought to a position that is very close to (e.g., directly above) the transport line to form the container compartment 115 of the inspection station 101.

[0112] The inspection station 101 is described in the orientation in the drawing. In other non-illustrated embodiments, the container compartment 115 may be inverted 180 degrees such that the bottom light 111 forms the upper part of the container compartment and the container holder 113 forms at least a partial bottom of the container compartment. In fact, the components can be oriented in any desired manner as long as the relationship between the camera 110, the lights 111, 112, and the vial 400 that enables accurate image capture is maintained.

[0113] Also contemplated in other non-illustrated embodiments is the ability to combine the body side inspection station 101 and the angled shoulder inspection station 102 such that the angled shoulder camera 120 can capture an image during the same rotation as the body side camera 110 of the vial 400. This can be done, for example, by temporally offsetting the image capture of the two cameras 110, 120 from each other and varying the required light characteristics, such as intensity, between the light characteristics used for image capture by the body side camera 110 and the light characteristics used for image capture by the angled shoulder camera 120. This can also be done by using one or more cameras with a standard lens for body side inspection (or a camera with a telemetric lens for the angled shoulder camera, although this may not be desirable for other reasons).

[0114] To inspect the side wall 402 of a vial, the vial 400 is lifted by a container holder 113 and placed within the confines of a container compartment 115 of a side wall inspection station 101. While the bottom light 111 and side lights 112 are illuminated, the vial 400 is rotated 360° about its longitudinal axis. During that rotation, a camera 110 captures a number of images, for example six images, of the body side portion of the vial. The captured images together show the entire 360° surface of the vial body side portion. The captured images are processed by one or more system processors to identify (i) the presence of particles within a specified body side inspection region and (ii) the size of any identified particles.

[0115] An example of an image captured by the body side camera 110 during this inspection process is shown in FIG. 8A. FIG. 8B shows the same image as processed by the system, particularly by one or more processors. The processor is one that identifies separate inspection regions, examples of which are shown in FIG. 8B as boxes 201, 202, and 203. To ensure that the inspection regions 201, 202, 203 are properly identified, the system may not rely only on the center of the image (which would require the container holder 113 to position the vial 400 perfectly aligned with the center of the camera lens). Rather, as shown as boxes 204, 205, and 206 in FIG. 8B, the system may be configured to identify image elements corresponding to specific portions of the vial 400, such as the side of the vial within the captured image (within box 204), the top of the vial within the captured image (within box 205), and / or the shadow within the captured image representing the shoulder of the vial (within box 206). Next, the system may determine the exact placement of the inspection regions 201, 202, 203 based on the positions of those image elements.

[0116] As shown in FIG. 8B, the body side portion of vial 400 can be divided into three body side inspection regions: a body portion 201, a neck portion 202, and a neck flange side portion 203. The system can be calibrated separately for each inspection region to account for surface features, etc. For example, the system can be calibrated to account for image elements caused by surface features present on the neck flange side portion 203 so as not to be misidentified as particles or defects. The presence of similar image elements in the body portion 201 can be correctly identified as particles or defects.

[0117] As shown in FIG. 8B, the shoulder 404 of the vial is subject to significant shadow effects and thus cannot be inspected using the camera and light configuration of the body side inspection station 101. Similarly, the transition region 403 between the body and the bottom wall 401 of the side wall 402 of the vial is distorted and cannot be inspected using the camera and light configuration of the body side inspection station 101. Thus, vial 400 is transported to a further inspection station.

[0118] In other embodiments of the container inspection systems and methods disclosed herein, for example, when the system is configured to inspect a syringe barrel, the inspection regions defined by one or more processors can be different, e.g., a different number of inspection regions can be defined by one or more processors, the inspection regions can have different dimensions, etc. For example, the side wall of a blood collection tube typically has few, if any, geometric features such as shoulders or necks, so only a single inspection region (of relatively high aspect ratio) can be applied to each image. Further, minor modifications may be made to the system components to accommodate the different geometric shapes of the particular vessels / containers being inspected. However, notwithstanding these distinctions, the inspection systems and methods of the present disclosure can be applied to any of a variety of containers, including syringe barrels (and cartridge barrels) and blood collection tubes.

[0119] Inspection of the shoulder FIG. 14 shows a shoulder inspection station 102, also known as an angled shoulder inspection station. The angled shoulder inspection station 102 includes an angled shoulder camera 120, a bottom light 121, a side light 122, and a container holder 123.

[0120] The bottom light 121 is configured and positioned such that the bottom light is below the vial 400 and light shines upwardly, for example through the bottom of the vial and around the entire side of the vial. In some embodiments, the bottom light 121 can be a direct type backlight, such as a 63 mm × 60 mm direct type backlight, a blue LED light, an M12 light, or a similar light. The use of a blue light is optional, but is desirable for reasons such as highlighting the color of plasma flake particles that may be present from one or more coatings on the sidewall of the vial. The side light 122 is positioned such that the side light is behind the vial 400 from the perspective of the camera 120 (i.e., the side light and the camera are on opposite sides of the vial), and light shines through the sidewall of the vial and over the side of the vial when viewed from the camera. In some embodiments, the side light 122 can be a direct type backlight, such as an 83 mm × 75 mm direct type backlight, a blue LED light, an M12 light, or a similar light. Again, the use of a blue light is optional, but is desirable for reasons such as highlighting the color of plasma flake particles that may be present from one or more coatings on the sidewall of the vial.

[0121] In the illustrated embodiment, the bottom light 121 and the side light 122 define the bottom and rear surfaces of a container compartment 125 within which the vial 400 is held. Here, the sides and front of the container compartment 125 are completely open. However, in other embodiments, one or both of the sides and / or front may be partially or fully closed.

[0122] The angled shoulder camera 120 is positioned forward and above the vial 400 and the container compartment 125, and the lens is directed towards the vial, more generally towards the container compartment. More specifically, the angled shoulder camera 120 is positioned and oriented within the container compartment 125 in such a manner as to capture an image of the vial shoulder 404 without shadow or other interference. The angled shoulder camera 120 is desirably an area scan camera. Preferably, the angled shoulder camera 120 is an area scan camera that captures at least a 60° arc of the vial shoulder, such that the entire vial shoulder 404 can be inspected using six image captures. For example, the angled shoulder camera 120 can be an area scan camera that captures at least a 65° arc of the vial shoulder 404, which provides overlap with adjacent arcs and thus ensures that the entire shoulder is captured and inspected. For example, the angled shoulder camera 120 can be a Cognex In-Sight 9912M, 12.0MP camera, or a similar camera. The angled shoulder camera 120 can also include a 50mm lens (along with associated lens spacers (20mm) and band pass filters).

[0123] The container holder 123 is configured to hold the vial 400 from above without contacting the sidewall of the vial or otherwise interfering with the line of sight around the sidewall of the vial. In the illustrated embodiment, for example, the container holder 123 interacts with the upper portion of the neck flange 405a of the vial 400, such that the vial is suspended from the container holder within the container compartment 125, for example by means of a clamp, suction, or the like. As such, the container holder 123 forms at least a partial upper surface of the container compartment 125.

[0124] The container holder 123 is also configured to rotate the vial so that the entire 360° of the shoulder 404 can be imaged and inspected. In some embodiments, the container holder 123 is configured to rotate continuously, which enables a high-throughput inspection process. For example, the container holder 123 can be configured to rotate at a speed of up to about 120 rpm. Of course, continuous rotation requires that the camera 120 open the shutter for a very short time. For example, the camera 120 can be selected and the lights 121, 122 can be configured and positioned such that the shutter remains open for less than one millisecond when capturing an image. In other embodiments, the vial 400 can be rotated discontinuously, i.e., the vial can be held steady between each image capture and rotated between image captures.

[0125] In the illustrated embodiment, the container holder 123 is movable relative to the camera 120 and the lights 121, 122. In this way, the container holder 123 can pick up a vial 400, for example, from a transport line or a different inspection station and position the vial within the confines of the container compartment 125 for inspection. In other embodiments, certain components such as the lights 121, 122 may instead be moved to a location adjacent to the container holder 123. For example, the container holder can remove a vial 400 from a transport line and then the lights 121, 122 can be brought to a position that is very close to (e.g., directly above) the transport line to form the container compartment 125 of the inspection station 102.

[0126] Although inspection station 102 is described in the orientation in the drawing, in other non-illustrated embodiments, the container compartment 125 may be inverted 180 degrees such that the bottom light 121 forms the upper part of the container compartment and the container holder 123 forms at least a partial bottom of the container compartment. In such embodiments, the angled shoulder camera 120 will of course be located forward and downward of the vial 400, or more generally of the container compartment 125. In fact, the components can be oriented in any desired manner as long as the relationship between the camera 120, lights 121, 122, and the vial 400 that enables accurate image capture is maintained.

[0127] Also contemplated in other non-illustrated embodiments is the ability to combine the body side inspection station 101 and the angled shoulder inspection station 102 such that the angled shoulder camera 120 can capture an image during the same rotation as the body side camera 110 of the vial. This can be done, for example, by temporally offsetting the image capture of the two cameras 110, 120 from each other and varying the optical properties, such as intensity, of the light required between the optical properties used for image capture by the body side camera and the optical properties used for image capture by the angled shoulder camera. This can also be done by using one or more cameras with a standard lens for body side inspection (or a camera with a telemetric lens for the angled shoulder camera, although this may not be desirable for other reasons).

[0128] To inspect the shoulder 404 of a vial, the vial 400 is lifted by a container holder 123 and placed within the container compartment 125 of the shoulder inspection station 102. While the bottom light 121 and the side light 122 are irradiated, the vial 400 is rotated 360° about its longitudinal axis. During that rotation, the angled shoulder camera 120 captures a number of images, e.g., six images, of the shoulder 404 of the vial. The captured images together show the entire 360° surface of the vial shoulder 404. The captured images are processed by one or more system processors to (i) identify the presence of particles within a specified shoulder inspection area and (ii) identify the size of any identified particles.

[0129] An example of an image captured by the angled shoulder camera 120 during this inspection process is shown in FIG. 9A. FIG. 9B shows the same image when processed by the system. The processor is one that identifies independent inspection areas, examples of which are shown in FIG. 9B as boxes 211, 212 (subtracting the area indicated by the cross-hatching 213). To ensure that the inspection areas 211, 212 are properly identified, the system may not rely only on the center of the image (which would require the container holder 123 to position the vial 400 perfectly aligned with the center of the camera lens). Rather, as shown as boxes 214 and line 215 in FIG. 9B, the system may be configured to identify image elements corresponding to specific portions of the vial 400, such as the side of the vial within the captured image, more specifically the side of the neck flange 405a of the vial (e.g., as determined from line 215), and / or the bottommost portion of the neck flange 405a of the vial within the captured image (e.g., as shown in box 214). Next, the system may determine the exact placement of the inspection areas 211, 212 based on the positions of those image elements.

[0130] As shown in FIG. 9B, the shoulder 404 of the vial can be divided into a plurality of inspection regions 211, 212 to account for shadow effects or other interferences. For example, the box 212 shown in FIG. 9B has a smaller width than the box 211 due to the shadows immediately adjacent to the left and right sides of the box 212. Optionally, the system can also be calibrated separately for each of the inspection regions 211, 212 to account for surface features, etc.

[0131] In other embodiments of the container inspection systems and methods disclosed herein, for example, when the system is configured to inspect a syringe barrel, the inspection regions defined by one or more processors can be different. Further, minor modifications may be made to the system components to accommodate different geometric shapes of the particular vessels / containers being inspected. For example, since the shoulder of the syringe barrel is located towards the front end and the opening into the lumen is located at the rear end, the container holder can hold the syringe barrel with a needle shield or tip cap, i.e., the opening into the lumen becomes the downwardly suspended end. However, notwithstanding these distinctions, the inspection systems and methods of the present disclosure can be applied to any of a variety of containers, including syringe barrels (and cartridge barrels) and blood collection tubes.

[0132] Upper inspection FIG. 15 shows an upper inspection station 103, also known as an angled upper inspection station. The angled upper inspection station 103 includes an angled upper camera 130, a bottom light 131, a side light 132, a container holder 133, and a reflective wall 134.

[0133] The bottom light 131 is configured and positioned such that the bottom light is below the vial 400 and light shines upward, for example through the bottom of the vial and around the entire side of the vial. The bottom light 131 can be a direct-type backlight, such as a 63 mm × 60 mm direct-type backlight, a blue LED light, an M12 light, or a similar light. The use of a blue light is optional, but it is desirable for reasons such as emphasizing the color of plasma flake particles, which may be present from one or more coatings on the sidewall of the vial. The side light 132 is positioned such that the side light is behind the vial 400 from the perspective of the camera 130 (i.e., the side light and the camera are on opposite sides of the vial), and when viewed from the camera, the light shines through the sidewall of the vial and over the side of the vial. The side light 132 can be a direct-type backlight, such as a 51 mm × 51 mm direct-type backlight, a blue LED light, an M12 light, or a similar light. Again, the use of a blue light is optional, but it is desirable for reasons such as emphasizing the color of plasma flake particles, which may be present from one or more coatings on the sidewall of the vial.

[0134] In the illustrated embodiment, the bottom light 131 and the side light 132 define the bottom and the rear surface of a container compartment 135 within which the vial 400 is held. The upper inspection station 103 also includes a reflective wall 134 located on the opposite side of the container holder 133 and the vial 400 from the side light 132. Thus, the reflective wall 134 forms at least a partial front surface of the container compartment 135. As shown in FIG. 15, the reflective wall 134 can also include a concave surface 136 configured to at least partially extend around the vial 400. Thereby, the reflective wall 134 forms at least partial left and right side surfaces of the container compartment 135. The reflective wall 134 is configured to reflect light irradiated from the side light 132 and the bottom light 131 and to prevent a shadow from appearing on the upper surface of the vial, i.e., the upper surface of the neck flange 405a, during image capture.

[0135] The angled upper camera 130 is positioned in front of and above the vial 400, more generally the container compartment 135, with the lens directed toward the vial, more generally the container compartment. More specifically, the angled upper camera 130 is positioned and oriented within the container compartment 135 in a manner that captures an image of the upper surface of the vial free of shadows or other interference. The angled upper camera 130 is desirably an area scan camera. Preferably, the angled upper camera 130 is an area scan camera that captures at least a 60° arc of the upper surface of the vial, such that the entire upper surface of the vial can be inspected using six image captures. For example, the angled upper camera 130 can be an area scan camera that captures at least a 65° arc of the upper surface of the vial (which provides overlap with adjacent arcs and thus ensures that the entire upper surface is captured and inspected). For example, the angled upper camera 130 can be a Cognex In-Sight 9912M, 12.0MP camera, or a similar camera. The angled upper camera 130 of this embodiment can also include a 50 mm lens (as well as associated lens spacers (20 mm) and bandpass filters).

[0136] The container holder 133 is configured to rotate the vial 400 such that the entire 360° of the upper portion can be image captured and inspected. In some embodiments, the container holder 133 is configured to rotate continuously, which enables a high throughput inspection process. For example, the container holder 133 can be configured to rotate at a maximum speed of about 120 rpm. Of course, continuous rotation requires that the camera 130 open the shutter for a very short time. For example, the camera 130 can be selected and the lights 131, 132 can be positioned such that the shutter remains open for less than one millisecond when capturing an image. In other embodiments, the vial 400 can be rotated discontinuously, i.e., the vial is held stable between each image capture and rotated between image captures.

[0137] As shown in FIG. 16, the container holder 133 may include a rotatable platform 137 that supports the bottom surface or bottom 401 of the vial. The rotatable platform 137 is preferably configured so as not to interrupt or distort the bottom light 131. For example, the rotatable platform 137 may be made of a material such that the bottom light 131 fluoresces without causing any significant distortion that would result in a shadow or the like during image capture. Alternatively, the rotatable container holder 133, such as the platform 137, may itself include at least a portion of the bottom light 131. In some embodiments, for example, the bottom light 131 or a portion thereof may function as the rotatable container holder 133.

[0138] In contrast to the inspection stations 101, 102 on the body side and shoulder, the container holder 133 of the inspection station 103 on the upper surface of the illustrated embodiment is not movable to transport the vial 400 in and out of the inspection station, although in other (not shown) embodiments it may be movable. Rather, the inspection station 103 may also include a container transport element 138 configured to pick up a vial 400, for example from a transport line or a different inspection station, and position the vial within the container compartment 135, more specifically on the container holder 133. Once an image is obtained, the container transport element 138 may then pick up the vial 400 and return it to the transport line or transport it directly to a different inspection station.

[0139] Although the inspection station 103 is described in the orientation shown in the drawings, in other (not shown) embodiments, the container compartment 135 may be inverted 180 degrees such that the bottom light 131 forms the upper part of the container compartment. In such embodiments, the angled upper camera 130 will, of course, be located in front of and below the vial 400, more generally the container compartment 135. In fact, the components may be oriented in any desired manner as long as the relationship between the camera 130, lights 131, 132, and the vial 400 that allows for accurate image capture is maintained.

[0140] To inspect the upper portion of the vial, the vial 400 is placed upright on the container holder 133, i.e., its bottom 401 is placed on the container holder and within the container compartment 135 of the upper inspection station 103. While the bottom light 131 and the side light 132 are being irradiated, the vial 400 is rotated 360° about the longitudinal axis of the vial by the operation of the rotatable container holder 133, which is, for example, the platform 137. During this rotation, the angled upper camera 130 captures a number of images, e.g., six images, of the upper portion of the vial, i.e., the upper surface of the neck flange 405a of the vial. The captured images together show the entire 360° surface of the upper portion of the vial. The captured images are processed by one or more system processors to (i) identify the presence of particles within a specified upper inspection region and (ii) identify the size of any identified particles.

[0141] An example of an image captured by the angled upper camera 130 during this inspection process is shown in FIG. 10A. FIG. 10B shows the same image when processed by the system. The processor is one that identifies separate inspection regions, examples of which are shown as boxes 221, 222 in FIG. 10B. To ensure that the inspection regions are properly identified, the system may not rely solely on the center of the image (this would require the container holder 133 and / or the container transport element 138 to position the vial 400 perfectly aligned with the center of the camera lens). Rather, as shown by lines 223 and / or boxes 224, 225 in FIG. 10B, the system may be configured to identify image elements corresponding to specific portions of the vial, such as the outer edge of the vial within the captured image, more specifically the outer edge of the neck flange 405a of the vial (shown by lines 223 and box 224), and / or a portion of the inner surface of the vial within the captured image (e.g., the hatched area shown by box 225). Next, the system can determine the exact placement of the inspection regions 221, 222 based on the positions of those image elements.

[0142] As shown in FIG. 10B, the upper surface of the vial can be divided into a plurality of inspection regions 221, 222 to account for shadow effects or other interferences. For example, the inspection regions identified by box 222 shown in FIG. 10B may need to be calibrated separately from the inspection regions identified by box 221 to account for surface features, shadows, etc.

[0143] In other embodiments of the container inspection systems and methods disclosed herein, for example, when the system is configured to inspect a syringe barrel or a blood collection tube, the inspection regions defined by one or more processors may be different. Further, minor modifications may be made to the system components to accommodate different geometric shapes of the particular vessel / container being inspected (note that the rear end of the syringe barrel should be considered equivalent to the upper portion of the vial for the purposes of this inspection process, both defining an opening into the lumen and typically having a flange). However, despite these distinctions, the inspection systems and methods of the present disclosure can be applied to any of a variety of containers, including syringe barrels (and cartridge barrels) and blood collection tubes.

[0144] Inspection of the bottom transition area FIG. 17 shows a combination of the bottom transition region and the inspection stations 104, 105 of the bottom surface. However, in other embodiments, the bottom surface inspection station 105 may be separated from the bottom transition region inspection station 104. The combined bottom transition region and bottom surface inspection stations 104, 105 (or, if separated, the bottom transition region inspection station 104) include an angled bottom camera 140, a bottom light 141, a side light 412, and a container holder 143.

[0145] The bottom light 141 is configured and positioned such that the bottom light is below the vial 400 and light shines upward, for example through the upper part of the vial (with the upper part being oriented upside down in a state closer to the bottom light than its bottom), around the entire side of the vial. The bottom light 141 can be a direct-type backlight, such as a 63 mm × 60 mm direct-type backlight, a blue LED light, an M12 light, or a similar light. The use of a blue light is optional, but it is desirable for reasons such as emphasizing the color of plasma flake particles that may be present from one or more coatings on the side wall and / or bottom wall of the vial. The side light 142 is positioned such that the side light is behind the vial 400 from the perspective of the camera 140 (i.e., the side light and the camera are on opposite sides of the vial), and light shines through the side wall of the vial and beyond the side of the vial when viewed from the camera. The side light 142 can be a direct-type backlight, such as a 51 mm × 51 mm direct-type backlight, a blue LED light, an M12 light, or a similar light. Again, the use of a blue light is optional, but it is desirable for reasons such as emphasizing the color of plasma flake particles that may be present from one or more coatings on the side wall and / or bottom wall of the vial.

[0146] In the illustrated embodiment, the bottom light 141 and the side light 142 define the bottom and the rear surface of a container compartment 145 within which the vial 400 is held. Here, the sides and the front of the container compartment 145 are completely open. However, in other embodiments, one or both of the sides and / or the front may be partially or fully closed.

[0147] The angled bottom camera 140 is positioned in front of and above the vial 400, more generally the container compartment 145, and the lens is directed towards the vial, more generally the container compartment. More specifically, the angled bottom camera 140 is positioned and oriented within the container compartment 145 in such a manner as to capture an image of the transition region 403 between the body side wall 402 and the bottom wall 401 of the vial body without shadow or other interference. The angled bottom camera 140 is desirably an area scan camera. Preferably, the angled bottom camera 140 is an area scan camera that captures at least a 60° arc of the transition region 403, such that the entire vial transition region can be inspected using six image captures. For example, the angled bottom camera 140 can be an area scan camera that captures at least a 65° arc of the transition region 403, which provides overlap with adjacent arcs and thus ensures that the entire transition region is captured and inspected. For example, the angled bottom camera 140 can be a Cognex In-Sight 9912M, 12.0MP camera, or similar camera. The angled bottom camera 140 of this embodiment can also include a 50 mm lens (along with associated lens spacer (20 mm) and bandpass filter).

[0148] The container holder 143 is configured to rotate the vial 400 such that the entire 360° of the transition region 403 can be image captured and inspected. In some embodiments, the container holder 143 is configured to rotate continuously, which enables a high-throughput inspection process. For example, the container holder 143 can be configured to rotate at a maximum speed of about 120 rpm. Of course, continuous rotation requires the camera 140 to open the shutter for a very short time. For example, the camera 140 can be selected and the lights 141, 142 can be positioned such that the shutter remains open for less than one millisecond when capturing an image. In other embodiments, the vial 400 can be rotated discontinuously, i.e., the vial is held steady between each image capture and rotated between image captures.

[0149] The container holder 143 may comprise a rotatable platform 147 that supports the upper surface of the vial, e.g., the upper surface of the neck flange 405a of the vial (the vial is disposed upside down on the container holder as shown in FIG. 13). The rotatable platform 147 is preferably configured so as not to interrupt or distort the bottom light 141. For example, the rotatable platform 147 can be made of a material such that the bottom light fluoresces without causing significant distortion that would result in a shadow or the like during image capture. Alternatively, the rotatable platform 147 itself may comprise at least a portion of the bottom light 141. In some (not shown) embodiments, for example, the bottom light 141 or a portion thereof may function as the container holder 143, e.g., the rotatable platform 147.

[0150] In contrast to the inspection stations 101, 102 for the body side and shoulder, the illustrated embodiment of the container holder 143 of the angled bottom inspection station 104 is not movable to bring the vial 400 in and out of the inspection station, although in other (not shown) embodiments it may be movable. Rather, the angled bottom inspection station 104 may also comprise a container transport element 148 configured to pick up a vial 400, e.g., from a transport line or a different inspection station, and position the vial within the container compartment 145, more specifically, on the container holder 143. Once an image is obtained, the container transport element 148 can then pick up the vial 400 and return it to the transport line or transport it directly to a different inspection station.

[0151] Although inspection station 104 is depicted in the orientation shown in the drawings, in other embodiments not shown, the container compartment 145 may be inverted 180 degrees such that the bottom light 141 forms the top of the container compartment. In such embodiments, the angled bottom camera 140 will, of course, be positioned forward and downward of the vial 400, and more particularly of the container compartment 145, and the vial will not be oriented upside down. In fact, the components may be oriented in any desired manner as long as the relationship between the camera 140, lights 141, 142, and vial 400 that enables accurate image capture is maintained.

[0152] To inspect the transition region 403 of the vial, the vial 400 is placed on the container holder 143 and within the range of the container compartment 145 of the angled bottom inspection station 104. While the bottom light 141 and side lights 142 are illuminated, the vial 400 is rotated 360° about the longitudinal axis of the vial by the operation of the rotatable container holder 143, which is, for example, the platform 147. During that rotation, the angled bottom camera 140 captures a number of images, e.g., six images, of the transition region 403 of the vial. The captured images together show the entire 360° surface of the transition region 403 of the vial. The captured images are processed by one or more system processors to (i) identify the presence of particles within a specified transition region inspection area and (ii) identify the size of any identified particles.

[0153] An example of an image captured by the angled bottom camera 140 during this inspection process is shown in FIG. 11A. FIG. 11B shows the same image when processed by the system. The processor identifies the inspection area, which in this example is a single inspection area shown as box 231 in FIG. 11B (subtracting the portion shown by the cross-hatching 232). To ensure that the inspection area 231 is properly identified, the system may not rely solely on the center of the image (this would require the container holder 143 and / or the container transport element 148 to position the vial 400 perfectly aligned with the center of the camera lens). Instead, as shown as box 233 and lines 234, 235 in FIG. 11B, the system may be configured to identify image elements corresponding to specific portions of the vial, such as the side edges of the vial sidewall in the captured image (e.g., shown by line 234), the side edges of the vial base in the captured image (e.g., shown by line 235), and / or the center of the vial base (e.g., shown in box 233). Next, the system can determine the exact placement of the inspection area 231 based on the positions of those image elements.

[0154] In other illustrated embodiments not shown, the transition region 403 of the vial can be divided into multiple inspection areas to account for shadow effects or other interferences. Optionally, the system can also be calibrated separately for each inspection area to account for surface features and the like.

[0155] In other embodiments of the container inspection system and method disclosed herein, for example, when the system is configured to inspect blood collection tubes, the inspection areas defined by one or more processors may be different. Additionally, minor modifications may be made to the system components to accommodate different geometric shapes of the particular vessels / containers being inspected. However, despite these differences, the inspection system and method of the present disclosure can be applied to any of a variety of containers, including syringe barrels (and cartridge barrels) and blood collection tubes.

[0156] Bottom inspection As described above, FIG. 17 shows the combined bottom transfer region station and bottom inspection stations 104, 105. However, in other embodiments, the bottom inspection station 105 may be separated from the bottom transfer region inspection station 104. The combined bottom transfer region and bottom inspection stations 104, 105 (or the bottom inspection station 105 if separated) include a bottom camera 150, a bottom light 141, optionally a side light 142, and a container holder 143.

[0157] The bottom light 141 is configured and positioned such that the bottom light is below the vial 400 and the light is upward, for example passing through the upper part of the vial (the upper part of the vial is arranged upside down so that it is closer to the bottom light than the base of the vial), and shines around the entire side of the vial. The bottom light 141 can be a direct-type backlight, such as a 63 mm × 60 mm direct-type backlight, a blue LED light, an M12 light, or a similar light. The use of a blue light is optional, but it is desirable for reasons such as highlighting the color of plasma flake particles that may be present from one or more coatings on the sidewall and / or bottom wall of the vial. The side light 142 is optional. Here, the side light 142 is a direct-type backlight, particularly a 51 mm × 51 mm direct-type backlight, a blue LED, an M12. Again, the use of a blue light is optional, but it is desirable for reasons such as highlighting the color of plasma flake particles that may be present from one or more coatings on the sidewall and / or bottom wall of the vial.

[0158] In the illustrated embodiment, the bottom light 141 and optionally the side lights 142 used during inspection of the vial bottom wall 401 define the bottom and rear surfaces of the container compartment 145 within which the vial is held. Here, the sides and front of the container compartment are completely open. However, in other embodiments, one or both of the sides and / or front may be partially or fully closed. Alternatively, if the bottom inspection station 105 is independent of the bottom transition region inspection station 104, the side lights 142 may not be present and all sides of the container compartment 145 may be open.

[0159] The bottom camera 150 is positioned above the container compartment 145 and the lens is directed towards the container compartment. More specifically, the bottom camera 150 is positioned and oriented within the container compartment in such a manner as to capture an image of the bottom wall 401 of the vial without shadow or other interference. The bottom camera 150 is preferably an area scan camera. For example, the bottom camera 150 can be a Cognex In-Sight 9912M, 12.0MP camera, or a similar camera. The bottom camera 150 can also include a 50 mm lens (as well as the associated lens spacer (15 mm) and band pass filter). In contrast to the other cameras 110, 120, 130, 140 described herein, the bottom camera 150 may be able to capture the entire bottom wall 401 of the vial in a single image capture.

[0160] The bottom wall inspection station 105 may also include a container holder 143. For example, when the bottom wall inspection station 105 is combined with the transition region inspection station 104, the bottom wall inspection station may include a rotatable container holder 143 as described above. In other embodiments where the bottom wall inspection station 105 is independent of the transition region inspection station 104, the container holder 143 need not be rotatable (since the entire bottom wall can be captured in a single image capture, and thus there is no need to rotate the vial). For example, the vial 400 may be placed directly on the bottom light 141 that can function as a container holder, or on a fixed (non-rotatable) platform that does not interfere with the bottom light.

[0161] In some embodiments, the bottom wall inspection station 105 also includes a container transport element 148 configured to pick up a vial 400, for example from a transport line or a different inspection station, and position the vial within the container compartment and, if present, on the container holder 143. Once an image is obtained, the container transport element 148 can then pick up the vial 400 and return it to the transport line or transport it directly to a different inspection station.

[0162] Although the inspection station 105 is described in the orientation shown in the drawings, in other non-illustrated embodiments, the container compartment 145 may be inverted 180 degrees such that the bottom light 141 forms the upper part of the container compartment. In such embodiments, the bottom camera 150 will of course be located below the container compartment 145, and the vial 400 will not be oriented upside down. In fact, the components can be oriented in any desired manner as long as the relationship between the camera 150, the light 141, and the vial 400 that allows for accurate image capture is maintained.

[0163] To inspect the bottom wall 401 of a vial, the vial 400 is placed on the container holder 143 of the bottom wall inspection station 105 within the scope of the container compartment 145, if present. While the bottom light 141 and optionally the side lights 142 are irradiated, the bottom camera 150 captures at least one image of the bottom wall 401 of the vial, which shows the entire bottom wall of the vial either alone (e.g., if there is one) or together (e.g., if there are two or more). The captured images are processed by one or more system processors to (i) identify the presence of particles within a specified bottom wall inspection area and (ii) identify the size of any identified particles.

[0164] An example of an image captured by the bottom camera 150 during this inspection process is shown in FIG. 12A. FIG. 12B shows the same image when processed by the system. The processor is the one that identifies the inspection area, which in this example is a single inspection area shown as circle 241 in FIG. 12B. To ensure that the inspection area is properly identified, the system may not rely only on the center of the image (which would require positioning the vial 400 perfectly aligned with the center of the camera lens). Rather, as shown in FIG. 12B, the system can be configured to identify image elements corresponding to specific parts of the vial, such as the side edges of the vial in the captured image (shown by line 242) and / or the center of the bottom wall of the vial in the captured image. Next, the system can determine the exact placement of the inspection area based on the positions of those image elements.

[0165] In other illustrated embodiments not shown, the bottom wall 401 of the vial can be divided into multiple inspection areas to account for shadow effects or other interferences. Optionally, the system can also be calibrated separately for each inspection area to account for surface features and the like.

[0166] In other embodiments of the container inspection systems and methods disclosed herein, for example, when the system is configured to inspect blood collection tubes, the inspection regions defined by one or more processors may be different. Further, minor modifications may be made to the system components to accommodate different geometric shapes of the particular vessels / containers being inspected. However, notwithstanding these distinctions, the inspection systems and methods of the present disclosure may be applied to any of a variety of containers, including syringe barrels (and cartridge barrels) and blood collection tubes.

[0167] With the exception of the bottom camera 150 that captured a single image of the bottom wall 401 of the vial 400 while the vial was stationary, each vial was rotated continuously and images of the vial were captured by each of the cameras 110, 120, 130, 140 while the vial was rotating.

[0168] In all of the above embodiments, it has been described that the vial (or other container) is rotated during the image capture process. However, in alternative embodiments, it is also contemplated that the camera and / or side lights may be rotated around the vial to capture images over the entire circumference of the vial. In other embodiments, multiple cameras may be present at different positions around the container compartment of a given inspection station, and either (i) multiple side lights may be provided and illuminated at different times to provide a desired light profile to each of the cameras, or (ii) one or more side lights may be rotated around the vial to provide a desired light profile to each of the cameras.

[0169] The application of one or more inspection regions to each image can be performed by one or more processors. Determining whether there are particles or defects in one or more inspection regions, the number of particles or defects in one or more inspection regions, the size of any identified particles or defects, or any combination thereof can also be performed by one or more processors. For example, one or more processors can be configured to receive one or more images from each camera, apply one or more inspection regions to each image, and determine whether there are particles and / or defects in each of the one or more inspection regions.

[0170] In some embodiments, one or more processors can be configured to determine whether there are particles or defects within the scope of each of the one or more inspection regions that are 25 microns or more, or 30 microns or more, or 40 microns or more, or 50 microns or more, or 60 microns or more, or 70 microns or more, or 25 - 500 microns, or 30 - 500 microns, or 40 - 500 microns, or 50 - 500 microns, or 60 - 500 microns, or 70 - 500 microns, or 80 - 500 microns, or 25 - 400 microns, or 30 - 400 microns, or 40 - 400 microns, or 50 - 400 microns, or 60 - 400 microns, or 70 - 400 microns, or 80 - 400 microns, or 25 - 300 microns, or 30 - 300 microns, or 40 - 300 microns, or 50 - 300 microns, or 60 - 300 microns, or 70 - 300 microns, or 80 - 300 microns.

[0171] The surface area of a particle can be an important criterion for determining whether a particular container meets quality standards with respect to the presence of the particle. In some embodiments, one or more processors can be configured to determine, e.g., quantify, the surface area of a particular identified particle, e.g., by equipping with an image analysis tool. One or more processors can then compare the surface area of the identified particle to a threshold value. If the surface area of the identified particle exceeds the threshold value, the container, e.g., vial, can be removed from the transport line. In some embodiments, the particle surface area threshold above which removal of the container, e.g., vial, is required can be 0.0019 mm 2 can be.

[0172] In some embodiments, a vial (or other container) can be removed from the transport line if it is discovered that the vial contains particles and / or defects within the scope of one or more inspection regions. In other embodiments, a vial can be removed from the transport line if it is discovered that the vial contains particles and / or defects that are determined to exceed a threshold value (e.g., the number of particles or defects can be zero, or the number of particles or defects of a minimum size can be zero). For example, the threshold value can be related to the number of particles or defects, the threshold value can be related to the size of the particles or defects, or the threshold value can be related to a combination of the number of particles or defects and the size of each particle or defect. One or more processors can be configured to determine whether a vial exceeds the threshold value of particles and / or defects based on the analysis of one or more images.

[0173] In some embodiments, one or more processors can be configured to determine whether a detected defect is a surface defect or a critical defect. If the defect is determined to be a critical defect, the vial can be removed from the transport line. Determining whether a defect is a surface defect or a critical defect by at least one processor can include analyzing the shape of the defect, the depth of the defect, or a combination thereof.

[0174] In some embodiments, one or more of the inspection stations may compensate for changes in ambient illumination in one or more of the following. For example, one or more of the body side cameras, angled shoulder cameras, angled top cameras, angled bottom cameras, and bottom cameras, and optionally each of them, may be configured to compensate for changes in ambient illumination. One way this can be done is for one or more of the cameras, and optionally each of them, to include a bandpass filter such as a bandpass filter that passes only light having wavelengths necessary for the detection of particles and / or defects.

[0175] Further, in some embodiments, the intensity of one or more backlights, the intensity of one or more side lights, or both may be monitored to ensure that the intensity remains within a defined range. That monitoring may also be performed by one or more processors. To ensure that each vial has appropriate illumination during inspection, the inspection may be stopped if the intensity of one or more backlights, one or more side lights, or both is outside the defined range.

[0176] System and method for applying a coating set to a container Another aspect of the present invention is an improved method and system for manufacturing a container, such as a vial, syringe (or cartridge) barrel, blood collection tube, etc., e.g., an RTU pharmaceutical container, having a coating set consisting of one or more coatings on the inner surface of the container, and which is reduced in particles, e.g., particle-free or substantially particle-free. The one or more coatings can be applied by any of a variety of techniques, such as plasma enhanced chemical vapor deposition (PECVD) and atomic layer deposition (ALD). Many of the embodiments described herein are such that at least one of the coatings is applied by PECVD. In some embodiments, for example, at least a gas barrier layer and a pH protection layer can be applied by PECVD. However, in other embodiments, the gas barrier layer (e.g., SiO2, Al2O3, or a combination thereof) may be applied by atomic layer deposition and the pH protection layer may be applied by PECVD. Further details regarding the deposition of a gas barrier layer on the inner surface of a pharmaceutical container by ALD can be found in International Patent Application No. PCT / US2021 / 038548, which is hereby incorporated by reference in its entirety. Further details regarding the deposition of one or more layers on the inner surface of a pharmaceutical container by PECVD can be found in International Patent Application No. PCT / US2021 / 045819, which is hereby incorporated by reference in its entirety herein.

[0177] FIG. 18 shows a pulsed RF PECVD reactor according to an exemplary embodiment of the present disclosure. Referring to FIG. 18, a pulsed RF PECVD reactor 600 is shown comprising an RF power source 601, an electrode 603, a chamber cavity 605, a camera 607, an exhaust manifold 609, a gas injection manifold 611, and a vacuum line 613. At the bottom of each chamber cavity 605 are container holders 1105, 1107, to which the opening of the container is disposed, through which a precursor gas flows into the container (from the gas injection manifold 611) and the exhaust from the container flows out (to the exhaust manifold 609). The container holders will be described in more detail with reference to FIGS. 22-23.

[0178] The RF power supply 601 may include appropriate circuitry for providing an RF signal at a desired power level, duty cycle, pulse duration, and frequency to, for example, the electrode 603. The RF power supply 601 may include an adjustable matching impedance network for adjusting its output impedance to match the output impedance of the electrode 603. The RF power supply 601 may provide a resolution of 100 mV to the RF voltage for optimal control of the plasma. Further, the generated RF signal may have high-power pulses of 250 W to 1000 W, but the power may be increased to several kW depending on other parameters. The low-power pulses may be 0 W, and for example, the power frequency may be 13.65 MHz. The duty cycle may vary from 1% to 99%, preferably from 50% to 99%. The pulse train frequency may be in the range of 250 Hz to 5000 Hz, which may be extended to 10,000 Hz. The coating system described herein utilizes pulsed RF power, but in other embodiments, different power sources may be utilized. In other words, the power source need not be an RF power source, but rather may be a different power source, such as a microwave power source.

[0179] The electrode 603 may include a metallic component for transmitting a signal from the power source to an individual PECVD chamber defined by the container cavity 605 and the container itself. The electrode 603 includes a plurality of openings on an upper surface in which the container to be coated is disposed within the individual container cavity 605.

[0180] The container cavity 605 includes a portion of the electrode 603, in which a portion of the container to be coated is disposed, and each of the electrodes 603 substantially surrounds the container wall. The potential between the electrode 603 and a ground plane (not shown) is configured such that plasma is generated by the input gas provided by the gas injection manifold 611. In this example, there are sixteen container cavities 605 arranged in two rows of eight, but the present disclosure is not limited thereto.

[0181] In some embodiments, the vessel cavity 605 may have a "window" opening in the wall of the electrode 603 that defines the vessel cavity, whereby the camera 607 can view the plasma generated by the applied RF signal within each vessel.

[0182] The camera 607 may comprise, for example, a CCD or CMOS imaging sensor for monitoring deposition. The camera 607 can be utilized to monitor the intensity, uniformity, and / or color of the plasma to ensure, for example, that the plasma state is properly configured and / or maintained for deposition during coating deposition. In some embodiments as shown in FIG. 18, two or more cameras may be required to monitor the deposition of all chambers, for example, sixteen in number. In the illustrated embodiment, for example, the camera 607 may be disposed on each side of the electrode 603. In other embodiments, the vessel cavity 605 can be arranged and configured such that a single camera 607 can be utilized to monitor the plasma in all vessels being coated. By staggering the vessel cavities 605 in the first row with those in the second row, each cavity can have a single window with all of its windows facing in the same direction. Thus, one or more cameras 607, preferably one camera, can be disposed on one side of the electrode 603 and used to monitor the plasma state within the vessels contained in the cavities of both rows during a PECVD coating process.

[0183] In one embodiment, the camera 607 can capture and examine an image of the plasma in the visible light region. In another embodiment, the camera 607 can capture and examine an image of the plasma in the infrared region. In another embodiment, the camera 607 can capture and examine an image of the plasma in the ultraviolet (UV) region. Light in any one or more of these wavelength regions can be captured and examined to evaluate the quality of the plasma process.

[0184] The inspection of the captured image can be performed by a processor that is operably coupled to the camera 607 and optionally further operably coupled to a display and / or user interface. By inspecting the image captured by the camera 607, if it is determined that the plasma in one or more containers is not within a predetermined acceptable range of one or more characteristics, such as intensity, uniformity, or color, the operator may be warned, one or more of the PECVD variables (e.g., gas flow rate, vacuum level, RF power level, pulse rate, etc.) may be adjusted, and / or the process may be stopped for system maintenance. Containers in which the plasma is considered unacceptable may be discarded.

[0185] The exhaust manifold 609 comprises a network of gas flow lines that enables combining a plurality of exhaust outputs into one, thereby enabling a single vacuum system / pump to exhaust a plurality of chambers equally, thereby providing a uniform and consistent reproducible vacuum within each of the plurality of container cavities. In this example, each of the two sides of the exhaust manifold 609 combines the outputs from eight container cavities into one output line, and each output line is connected together by a vacuum line 613.

[0186] The vacuum line 613 can bring a vacuum to the container cavity via the exhaust manifold 609, and the vacuum can be enabled by one or more pumps (not shown). By providing the same pressure in each container, uniformity between containers in the deposition process can be ensured.

[0187] The gas injection manifold 611 comprises a network of gas flow lines that enables branching a single input gas line into a plurality of input lines for supplying gas to the containers to be coated, thereby enabling a single input port 611A to supply gas equally to each container, thereby providing a uniform and consistent reproducible flow of precursor gas to each of the plurality of container cavities. In this example, the gas injection manifold equally branches the output of the gas input port 611A among sixteen containers.

[0188] FIG. 19 shows a pulsed RF PECVD vessel deposition arrangement according to an exemplary embodiment of the present disclosure. Referring to FIG. 19, shown herein are a cross-sectional view and an enlarged cross-sectional view of a vessel 210, which is a vial, disposed within a vessel cavity 605 with an opening of the vessel 210 oriented downwardly within a vessel holder 1105. In this example, a gas delivery probe 1101 for supplying one or more precursor gases into the vessel 210 during a pulsed PECVD deposition process is also shown. Further, the gas delivery probe 1101 can act as an internal electrode (e.g., may comprise metal and may be grounded), such that when the electrode 603 provides an RF signal, an electric field is generated, thereby igniting a plasma within the vessel 210 during the deposition process.

[0189] FIG. 19 also shows a plasma screen 1107 that extends across the opening of the vacuum port 1103 and ensures that the plasma is confined above the screen 1107 and within the vessel 210. In any embodiment, the plasma screen 1107 can take any of a variety of forms. In some embodiments, for example, the plasma screen 1107 can comprise a perforated grid, such as a perforated metal disk or plate, as shown in the illustrated embodiment. In other embodiments, the plasma screen 1107 can comprise a metal mesh.

[0190] During a pulsed plasma PECVD coating process, one or more precursor gases flow from a gas injection manifold 611 into a gas delivery probe 1101 and into a container 210, and a plasma is generated by a pulsed RF signal, thereby causing the deposition of a desired coating on the inner surface of the wall of the container 210. A desired level of vacuum is maintained by the flow of gas through the vacuum port 1103 to the aforementioned exhaust manifold 609. Since the outlet of the gas delivery probe 1101 is located near the end of the container on the opposite side of the opening through which the vacuum is drawn, the precursor gas flows along the length of the container, providing a substantially uniform gas distribution and enabling the coating to be applied substantially uniformly along the wall of the container.

[0191] The gas delivery probe 1101 can provide a uniform gas distribution within the container 210. However, in other embodiments, it may be possible to remove the probe 1101 by pulsing the RF field that generates the plasma, because this pulsing (as well as the flow of the precursor gas) can be controlled to provide a time between pulses sufficient for the precursor gas to be distributed within the container before each pulse. An example of such an embodiment is shown in FIG. 20.

[0192] FIG. 20 shows a pulsed RF PECVD container coating system without a gas delivery probe according to an exemplary embodiment of the present disclosure. Referring to FIG. 20, a cross-sectional view and an enlarged cross-sectional view of a container 210, here a vial, disposed within a container cavity 605 are shown, similar to that of FIG. 19 but without a gas delivery probe within the container 210. In this example, there is a precursor gas injection line 1201, but it does not extend into the lumen of the container 210. Instead, the gas injection line 1201 extends across the opening of the gas injection line and is separated from the lumen of the container by a plasma screen 1107 that ensures that the plasma is confined above the screen 1107 and within the container 210.

[0193] Similar to the arrangement shown in FIG. 19, the opening of the container 210 is oriented downward within the container holder 1105. In this embodiment, the electrode 603 provides an RF signal, generating an electric field between the electrode 603 and the plasma screen 1107, which can act as an "internal" (not in this case the inside of the container) electrode (e.g., it may comprise metal and may be grounded), thereby igniting plasma within the container 210 during the deposition process. In the illustrated embodiment, the plasma screen 1107 extends across both the outlet of the gas injection line 1201 and the inlet of the vacuum port 1103. However, in other embodiments, a first plasma screen 1107 may be associated with the gas injection line 1201, and a second plasma screen 1107 may be associated with the vacuum port 1103.

[0194] FIG. 22 shows a detailed view of the first embodiment of the container holder 1105 described above. The illustrated embodiment is sized and configured for coating a syringe barrel, but the same components and component arrangements are used for coating any container, such as a vial (although the sizes of the components may of course be different).

[0195] The container holder 1105, which is located at the bottom of the container cavity 605 of the electrode 603, comprises the container 210 and, more specifically, a portion of the container surrounding the opening to the inner cavity, and a sealing unit 700 configured to form a seal. This seal is important because it allows evacuation of the inner cavity and ensures that ambient air does not enter the inner cavity of the container during the coating process. The sealing unit comprises a pack 701 and a flexible seal 702.

[0196] The pack 701 has an upper surface 703 for a portion of the container surrounding the opening into the lumen, and is adapted to contact the opening into the lumen when the container is placed within the cavity 605. The portion of the container surrounding the opening into the lumen is an end face of the container, such as the upper surface of a vial, the rear face of a syringe barrel, etc. In some embodiments as illustrated, the container 210 may have a flange at, for example, the upper end of a vial, the rear end of a syringe barrel, etc., so that its end face may be the end face of the flange.

[0197] The pack 701 also has a central opening 704 defined by an inner wall 705. A vacuum port 1103 through which the lumen of the container is evacuated passes through the central opening 704. Similarly, as illustrated, a source gas injection probe 1101 may pass through the central opening 704. In alternative embodiments where the source gas injection probe 1101, such as that shown in FIG. 12, is excluded, the precursor gas injection line 1201 may extend into, but not through, the central opening 704. Finally, the plasma screen 1107 may be positioned within the central opening 704 of the pack 701. For example, the pack 701 may include a thinner portion near its upper end, thereby providing the inner wall 705 with a ledge that can support the plasma screen 1107 thereon.

[0198] The pack 701 can be made of any heat-resistant non-conductive material, such as, for example, a ceramic material or a thermoplastic material. In addition to ceramic materials, polyetheretherketone (PEEK) has been found to be a desirable material for the pack 701.

[0199] The sealing unit 700 also comprises a flexible seal 702. The flexible seal 702 is positioned vertically above the pack 701 and is configured to contact a portion of the container sidewall when the container is placed within the electrode cavity 605. In some embodiments, such as those illustrated, this portion of the container sidewall can be a flange, more specifically the outer surface of the flange. The seal is configured and positioned such that when the container 210 is inserted into the cavity 605 and contacts the pack 701, the portion of the sidewall that contacts the flexible seal 702, such as the outer surface of the flange, will apply pressure to the flexible seal, which creates an airtight or substantially airtight seal between the container sidewall and the sealing unit 700 (this means that if any gas were to pass through the flexible seal, it would not be sufficient to have a measurable effect on the coating process conditions or on one or more of the resulting coatings). As shown in the illustrated embodiment, the flexible seal 702 can be an O-ring, such as a silicone or elastomeric polymer O-ring.

[0200] The container holder 1105 can also comprise a housing 706 that at least partially encloses the sealing unit 700, i.e., the pack 701 and the flexible seal 702, and prevents unwanted movement of the components, particularly the flexible seal. The container holder 1105 can also comprise an intermediate element 707 between the pack 701 and the housing 705. As shown in the illustrated embodiment, the intermediate element 707 and the housing 706 can form a recess for holding the flexible seal 702. In other (not shown) embodiments, the pack 701 can have an increased thickness such as to replace the intermediate element 707.

[0201] FIG. 23 shows a detailed view of a second embodiment of the container holder 1105 described above. Here again, while the illustrated embodiment is sized and configured for covering a syringe barrel, the same components and component arrangements are used for covering any container, such as a vial (although, of course, the sizes of the components may be different). This embodiment is similar to the first embodiment described above, but unlike the first embodiment, the second embodiment includes a pack 701 configured to prevent accumulated particles from contacting the container and / or to enable more effective cleaning of the container contact area of the sealing unit 700.

[0202] During application of one or more coatings to the inner surface of the container, it has been observed that one or more coatings also deposit on the raw gas injection probe 1101. The coating deposited on the raw gas injection probe 1101 flakes off over time and accumulates on the container holder 1105, including the upper surface 703 of the pack 701 and the flexible seal 702, which are the surfaces of the sealing unit 700 that the container 210 contacts. Similarly, in embodiments where the raw gas injection probe 1101 is excluded, such as that shown in FIG. 20, flakes of the coating may likewise ultimately deposit on the container holder 1105, including the surfaces of the sealing unit 700 that contact the container 210, or it is expected that the coating may deposit on those portions of the container holder 1105. Flakes of the coating and other particles present on the surface of the sealing unit 700 that contacts the container 210 may become embedded in the container during the coating process, for example, during a subsequent coating process, which leads to a container having potentially critical defects that render it unusable.

[0203] As shown in FIG. 23, the pack 701 includes an upper surface 703, at least a portion of which is inclined at an angle greater than 10 degrees, or greater than 15 degrees, or greater than 20 degrees, or greater than 25 degrees, or greater than 30 degrees, or greater than 35 degrees, or greater than 40 degrees, or 45 degrees or more from the inner wall 705 (and the central opening 704). In contrast, the corresponding portion of the upper surface 703 of the pack 701 in the embodiment shown in FIG. 22 has an inclination of only about 10 degrees.

[0204] By increasing the inclination angle of a portion of the upper surface 703, the pack 701 is configured to reduce the surface area that comes into contact with the container 210. As the inclination angle of a portion of the upper surface 703 increases, flakes or other particles are directed towards the central opening and also away from the container contact surface. Thus, the particles falling onto the pack 701 accumulate on the surface that does not contact the container, and thus are less likely to be incorporated into the container 210 during the coating process.

[0205] By increasing the inclination angle of a portion of the upper surface 703, the pack 701 can also facilitate more effective cleaning of the sealing unit 700, for example using methods such as those described elsewhere in this specification. In particular, by increasing the inclination angle of at least a portion of the upper surface 703, a more powerful flow profile, such as a vacuum flow, can be generated in the vicinity of the flexible seal 702 during the cleaning process. The increase in the inclination angle can also direct particles towards the center of the pack 701, which can be subjected to the most powerful flow profile, such as a vacuum flow, during the cleaning process.

[0206] The following is an exemplary process for coating a container using the system described above, particularly an exemplary process for providing a three-layer coating on the inner surface of the container.

[0207] A container 210 is provided that includes a wall 214 that consists essentially of a thermoplastic polymer material that defines an interior cavity 212. Optionally, in any embodiment, the wall comprises polyester, polyethylene terephthalate (PET), polyethylene naphthalate (PEN), polyolefin, cyclic block copolymer (CBC), cyclic olefin polymer (COP), cyclic olefin copolymer (COC), polypropylene (PP), or polycarbonate, preferably COP, COC, or CBC. Optionally, in any embodiment, the container interior cavity has a volume of 2 to 12 mL, optionally 3 to 5 mL, optionally 8 to 10 mL. The wall 214 has an inner surface 303 and an outer surface 305 that face the interior cavity.

[0208] The container is disposed in one of the cavities 605 of the electrode 603 such that the opening to the container interior cavity is oriented downward and a portion of the sidewall of the container, such as the outer surface of a flange, makes sealing contact with a flexible seal 702.

[0209] A partial vacuum is drawn within the interior cavity. In some embodiments, for example, the partial vacuum can be from about 20 to about 60 mTorr, or from about 30 to about 50 mTorr.

[0210] While maintaining the partial vacuum within the interior cavity so as not to break it, a SiOC x C y coating or layer 289 is optionally applied by a pulsed PECVD layer coating step that includes applying a pulsed RF power (alternatively, the same concept is referred to herein as "energy") sufficient to generate a plasma within the interior cavity while supplying a precursor gas that includes a siloxane precursor that is preferably a linear siloxane precursor, optionally oxygen, and optionally an inert gas diluent to stabilize the plasma. In some embodiments, the precursor gas may be introduced prior to ignition of the plasma to stabilize the ratio of the gas components. Next, while maintaining the partial vacuum within the interior cavity so as not to break it, the plasma can be extinguished, which has the effect of stopping the application of the SiOC x C y coating or layer.

[0211] The tie coating or tie layer, if present, may comprise SiOxCy or Si(NH)xCy. In either formula, x is from about 0.5 to about 2.4 and y is from about 0.6 to about 3. The tie coating or tie layer has an inner surface facing the lumen and an outer surface facing the inner surface of the wall.

[0212] After the plasma used in the tie PECVD coating process has disappeared and before the blocking PECVD coating process is started, stop and exchange the gas supply used in the tie PECVD coating process, or simply change to an appropriate gas supply by, for example, increasing the ratio of oxygen to the siloxane precursor and optionally reducing or removing an inert gas (e.g., argon) from the gas supply, by deposition of a blocking coating or layer.

[0213] While maintaining the partial vacuum within the lumen, a pulsed PECVD blocking coating step is applied that includes applying a pulsed RF power sufficient to generate a plasma within the lumen while supplying a precursor gas comprising a siloxane, preferably a linear siloxane, and oxygen. In some embodiments, the precursor gas may be introduced prior to plasma ignition to stabilize the ratio of gas components. After applying the blocking coating or layer, the plasma can be extinguished while maintaining the partial vacuum within the lumen, which has the effect of stopping the application of the blocking coating or layer. SiO x wherein x is from 1.5 to 2.9 when determined by XPS, SiO x The blocking coating or layer of SiO is created between the tie coating or tie layer and the lumen as a result of the blocking coating step. The blocking layer can be from 2 to 1000 nm thick. It can have an inner surface facing the lumen and an outer surface facing the inner surface of the tie coating or tie layer. The blocking coating or layer is effective in reducing the ingress of atmospheric gas into the lumen compared to a container without the blocking coating or layer.

[0214] After the plasma used in the blocking PECVD coating process has disappeared and before the pH-protected PECVD coating process is started, stop and replace the supply of the gas used in the blocking PECVD coating process, or simply change to a gas supply suitable for the deposition of the pH-protected coating or layer, for example, by reducing the ratio of oxygen to the siloxane precursor and optionally increasing or introducing an inert gas (e.g., argon) into the gas supply.

[0215] Next, while maintaining the partial vacuum in the lumen without breaking it, the pH-protected coating or layer 286 of SiO x C y can be applied by the pH-protected coating step of pulsed RF PECVD. The pH-protected coating or layer is applied between the blocking coating or layer and the lumen. The pH-protected PECVD step preferably includes applying pulsed RF power sufficient to generate plasma in the lumen while supplying a precursor gas containing a siloxane precursor, which is preferably a linear siloxane precursor, optionally oxygen, and optionally an inert gas diluent to stabilize the plasma. In some embodiments, the precursor gas may be introduced before the plasma is ignited to stabilize the ratio of the gas components.

[0216] The pH protective coating or layer may comprise SiOxCy or Si(NH)xCy, where x is from about 0.5 to about 2.4 and y is from about 0.6 to about 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. The SiOx barrier layer or coating is eroded or dissolved by some fluids, such as aqueous compositions having a pH greater than about 5. Coatings applied by chemical vapor deposition can be very thin, on the order of tens to hundreds of nanometers in thickness, so that even relatively slow erosion rates can remove or reduce the effectiveness of the barrier layer in less time than the desired shelf life of the product packaging. This is particularly a problem for fluid pharmaceutical compositions because 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 body fluids. The higher the pH of the pharmaceutical preparation, the faster the erosion or dissolution of the SiOx coating. The SiO formed from a polysiloxane precursor x C y or Si(NH) x C y Certain pH protective coatings or layers of C are those in which the pH protective coating or layer has a substantial organic component, but which do not erode immediately when exposed to fluid, and in fact erode or dissolve more slowly when the fluid has an elevated pH in the range of 5 to 9. Thus, these pH protective coatings or layers of SiOxCy or Si(NH) x C y can be used to cover the SiOx barrier layer and retain the benefits of the barrier layer by protecting it from the fluid within the pharmaceutical package. The protective layer is applied over the SiOx layer to protect the SiOx layer from the contents stored in the container, which would otherwise come into contact with the SiOx layer. That is, the pH protective coating or layer can be effective in isolating the fluid from the barrier coating or layer for at least as long as is sufficient for the barrier coating to act as a barrier during the shelf life of the pharmaceutical package or other container.

[0217] If the pH protective coating is the final layer, the vacuum can then be broken and the coated container can be recovered. On the other hand, when applying another layer such as a lubricating layer, while maintaining without breaking the partial vacuum within the inner cavity, a lubricating coating or layer of SiO x C y can be applied by a pulsed RF PECVD lubricating coating step. The lubricating PECVD step preferably includes applying pulsed RF power sufficient to generate a plasma within the inner cavity while supplying a precursor gas comprising a siloxane precursor which is preferably a linear siloxane precursor, optionally oxygen, and optionally an inert gas diluent. After applying the lubricating coating, the plasma can be extinguished while maintaining without breaking the partial vacuum within the inner cavity, which has the effect of stopping the application of the lubricating coating or layer.

[0218] Optionally, in any embodiment, each linear siloxane precursor used to deposit any tie coating or tie layer, barrier coating or layer, and optionally pH protective coating or layer can be hexamethyldisiloxane (HMDSO) or tetramethyldisiloxane (TMDSO), preferably HMDSO. Optionally, in any embodiment, the same linear siloxane precursor is used in each coating process, and each coating process can be, for example, a tie PECVD coating process, a barrier PECVD coating process, and a pH protective PECVD coating process. By using the same siloxane, it becomes possible to use the same coating apparatus without the need for a valve arrangement for supplying different siloxanes, and the throughput of the coating process is increased (by eliminating the time required to switch gases). Optionally, in any embodiment, this technique can be further generalized to the use of any plasma-enhanced chemical vapor deposition process using any precursor to generate any number of coatings using the processes described herein.

[0219] Optionally, in any embodiment, at least 12 containers, or at least 16 containers, can be coated simultaneously (e.g., in a 12-Up coater, 16-Up coater, 24-Up coater, 32-Up coater, etc.) using the same RF power source, the same vacuum source, the same precursor gas source, or any combination thereof. Optionally, during each coating step, the precursor gas can be evenly distributed to all containers by a gas manifold. Optionally, during each coating step, the vacuum can be evenly distributed to all containers by a vacuum manifold.

[0220] Cleaning of the sealing unit As described above, during repeated coating cycles, various components of the system 600, such as the source gas injection probe 1101 and the seal unit 700, can accumulate coating flakes or other particles. Thus, after a certain number of coating cycles, the source gas injection probe 1101 and the pack 701 can be retrieved, cleaned, and replaced. This, of course, requires that the coating apparatus be out of service for a period of time. One aspect of the present disclosure is a system and method for cleaning the source gas injection probe 1101 and / or the seal unit 700, where the cleaning can be a step of the coating process, e.g., the cleaning can be performed during the coating of individual (or a defined number of) containers without the need to stop the coating system 600 or otherwise interrupt the coating operation. In some embodiments, the source gas injection probes 1101 and / or the seal units 700 of one or more cavities 605, and desirably, multiple source gas injection probes and / or seal units within multiple cavities, can be cleaned using automated equipment controlled by one or more processors as part of the coating cycle.

[0221] Embodiments of system 800 for cleaning the sealing unit 700 of system 600, and more specifically for cleaning a plurality of sealing units 700 of system 600, are shown in FIGS. 24-25. System 800 can be configured to remove particles, such as flakes of coating, from the raw gas injection probe 1101 and / or the sealing unit 700, and more specifically from the surface of the sealing unit 700 that comes into contact with the container during the coating cycle (although other surfaces, such as the plasma screen 1107, will also have particles removed from the sealing unit).

[0222] System 800 includes one or more inserts 801, each of which is configured to fit into one of the container cavities 605. Each insert 801 includes an inner surface and an outer surface and a wall 802 extending from the proximal end 801a of the insert to the distal end 801b of the insert. Both the proximal and distal ends of the insert may be open. The inner surface of the wall 801 defines a central passage 803 that extends from the proximal end to the distal end of the insert 801. Each insert 801 is operably connected to a vacuum line 810 so as to create a vacuum within the central passage 803. For example, the open proximal end of the insert 801 may be operably connected to the vacuum line 810.

[0223] Preferably, as shown, system 800 includes a plurality of inserts 801. A plurality of inserts 801 or a subset of the plurality of inserts may be operably connected to a single vacuum line 810. In the illustrated embodiment, for example, system 800 includes two sets of inserts 801, each set consisting of four inserts. Each of the four inserts 810 within each set is operably connected to a single vacuum line 810. However, other configurations are contemplated without departing from the scope of the present disclosure / invention, regardless of the illustrated embodiment.

[0224] System 800 may also include a framework 820 that holds each of the plurality of insertion portions 801 and connects each of the plurality of insertion portions so as to be movable as a single unit. However, in other embodiments, a plurality of frameworks 820 may be provided, each of which holds a subset of the plurality of insertion portions 801 and connects the subset of insertion portions so as to be movable as a single unit. For example, although not shown, each subset of four insertion portions 801 may have its own independent framework 820.

[0225] Furthermore, although the illustrated embodiment shows a total of eight insertion portions 801 that branch into two subsets of four, any number and / or arrangement of insertion portions 801 may be provided without departing from the scope of the present disclosure / invention. For example, in other embodiments, the number of insertion portions 801 may be the same as the number of container cavities 605, such that the system 600 can be cleaned in a single pass.

[0226] The cleaning system 800, more specifically one or more frameworks 820, may be movable between a first cleaning position in which each of the one or more insertion portions 801 is at least partially located within one of the one or more cavities 605 and a second coating position in which the cleaning system is located at a distance from the electrode 603 to enable a container loading and coating cycle. The movement of the cleaning system 800 may be controlled by one or more processors and may be, for example, part of a fully automated coating operation.

[0227] During operation, the cleaning system 800 is moved to the cleaning position, and each of the one or more insertion portions 801 is at least partially located within one of the cavities 605 of the electrode 603. One or more vacuum pumps then operate to draw a vacuum within the central passage 803 of the one or more insertion portions 801.

[0228] To obtain a desired vacuum flow within each range of the cavities 605, the outer diameter of the wall 802 of the insertion portion 801 should be close to the diameter of the cavity 605 so that little vacuum is lost due to ambient air entering through the space between the wall of the electrode defining the cavity and the insertion portion. In some embodiments, for example, the outer diameter of the wall 801 of each insertion portion 801 can be within the range of 1 inch, or 3 / 4 inch, or 1 / 2 inch, or 1 / 4 inch, or 1 / 8 inch of each diameter of the cavity 605.

[0229] By drawing a vacuum of appropriate strength within the central passage 803 of each of the one or more insertion portions 801, particles present within the cavity, such as particles present on the surface of the sealed unit 700 and / or the raw gas injection probe 1101, are carried through the central passage 803 and out of the cavity 605. To achieve this removal of particles, it is desirable that one or more vacuum pumps can be configured to create a vacuum of at least 0.3 atm (pressure below 0.3 atm), or at least 0.2 atm, or at least 0.1 atm within the central passage 803 of each of the one or more insertion portions 801.

[0230] Although not shown, the system 800 can further include one or more particle recovery units, such as one or more screens or filters, to recover the particles removed from the cavity 605 and ensure that they do not enter the one or more vacuum pumps. The particle recovery unit can be placed at any suitable location between the insertion portion 801 and the vacuum pump.

[0231] To improve the cleaning step, it is now understood that it is beneficial to position the insertion portion 801 at a plurality of different depths within the cavity 605 while a vacuum is being drawn. By doing so, different flow profiles are created within the cavity 605, which helps ensure that particles from various surfaces are subjected to a vacuum of appropriate strength and are suctioned into the insertion portion 801. It may also be beneficial to hold the insertion portion 801 at each of a plurality of different depths within the cavity 605 for a period of time before the insertion portion moves to the next depth so that a particular vacuum flow profile time can be developed within the cavity.

[0232] In the illustrated embodiment, the cleaning system 800 moves from a first set of cavities 605 to a second set of cavities and cleans each set in series. In some embodiments, the cleaning system 800 may move between the first and second sets of cavities 605 more than once during the cleaning process, i.e., there may be more than one pass through each set of cavities. Of course, configurations where all the cavities can be cleaned in one step (e.g., the system 800 has the same number of insertion portions 801 as there are cavities 605, i.e., a 1:1 ratio), as well as configurations where the ratio of insertion portions 801 to cavities 605 is greater than or less than the 1:2 shown in the illustrated embodiment, are contemplated.

[0233] Once the cleaning of each of the one or more cavities 605 is complete, the vacuum can be stopped and the cleaning system 800 can be moved away from the electrodes 603 so that the container can be loaded into the one or more cavities 605 and the coating cycle can be started.

[0234] The cleaning of the cavity 605 can be carried out in a normal manner or in a manner determined to be necessary. In some embodiments, for example, a cleaning cycle may follow the coating of one or more containers in one cycle, i.e., each time a new set of containers is retrieved from the system 600, the cavity 605 may be cleaned. In other embodiments, the cavity may be cleaned after a defined number of coating cycles. The exact number of coating cycles performed between each cleaning can be determined based on the acquired historical data or, more preferably, by the visual inspection step described herein.

[0235] In some embodiments, for example, the container holder 1105 of each cavity 605, more specifically the sealing unit 700, can be visually inspected for the presence of particles, and this visual inspection is controlled and performed by one or more processors. In some embodiments, the visual inspection can be performed after each coating step, and if it is determined that the cavity 605 contains particles exceeding a defined threshold (e.g., some particles including zero), the cleaning step can be initiated. Additionally, or alternatively, the visual inspection can be performed after each cleaning step, and if it is determined that the cavity 605 contains particles exceeding a defined threshold, the cleaning step can be repeated. This process may be repeated multiple times, and then the continued presence of particles exceeding the defined threshold may cause one or more processors to stop the coating operation, warn the operator, etc.

[0236] Visual inspection may include obtaining images of one or more cavities 605, particularly images of the sealing unit 700 at the base of each of the one or more cavities, and then transmitting the images to a processor configured to analyze the images to detect whether there are particles exceeding a specific minimum size (e.g., 10 microns, or 20 microns, or 30 microns, or 40 microns, or 50 microns), i.e., the detection limit. The processor may also be configured to determine the number of particles exceeding the minimum size, the size of each detected particle, or a combination thereof. If the processor determines that there are particles present in an amount, size, or combination thereof that exceeds a predefined / stored threshold value, the processor may initiate a cleaning step.

[0237] A system for visually inspecting one or more cavities 605, more specifically the sealing unit 700 at the base of each of the one or more cavities, may comprise one or more cameras 850, each of which is configured to obtain an image of the sealing unit of the one or more cavities. The one or more cameras are desirably located above the electrodes, preferably directly above the electrodes. The system may also comprise one or more lights 851 configured to irradiate the interior, particularly the sealing unit 700 at the base of each cavity 605. In some embodiments, for example, the system may include one or more isotropic linear lights. The one or more lights are also desirably located above the electrodes, preferably directly above the electrodes. An example of a visual inspection system is shown in FIG. 21A.

[0238] In some embodiments, the system may comprise an assembly, optionally a movable assembly, including one or more cameras and one or more lights. Thus, this movable assembly can be moved to a location above the electrode 603 for performing an appearance inspection, and when an image is captured, the assembly can be moved a certain distance away from the electrode 603 so as not to interfere with subsequent container loading or cavity cleaning. In other embodiments, the assembly may be in a fixed position above the electrode 603, but at a sufficient distance so as not to interfere with the container loading or cleaning system 800. When the assembly is movable, its movement can be controlled by one or more processors and can form part of, for example, a fully automated continuous coating operation.

[0239] The system further comprises one or more processors, which are configured to receive an image from one or more cameras and analyze the image to detect particles, for example as described above.

[0240] An example of the type of image that can be captured by the above-described assembly and received by one or more processors for analysis is shown in FIG. 21B.

[0241] Although described above in connection with the system 800 and method for cleaning the cavity 605 of the electrode 603 of the coating system 600 described herein, in some embodiments, the appearance inspection system and method described herein can be implemented as part of the coating system 600 and coating operation, regardless of whether the coating system and operation utilize a cavity cleaning step. For example, in some embodiments, an appearance inspection can be performed and the results can determine when to replace any one or more of the feed gas injection probe 1101, the pack 701, the flexible seal 702, or any combination thereof.

[0242] Typically, the feed gas injection probe 1101 is replaced after a defined number of coating cycles. During the repetition of the coating cycle, the temperature of the injection probe rises. Thus, during the replacement of the feed gas injection probe 1101, the used probe is cooled before removal. However, when the injection probe is cooled, it often begins to shed flakes or particles of the coating that have come off. In some embodiments, a vacuum can be applied during the cooling process. For example, the cavity cleaning system described herein can be utilized to provide a vacuum during the cooling step of the gas injection probe. By applying a vacuum during the cooling step, the cooling step can be significantly accelerated. The vacuum can also prevent the shed material from landing in areas of concern, such as the sealing unit, and remove the shed flakes and particles before they can acquire an electric charge.

[0243] Method and system for removing particles from a container Another aspect of the present disclosure / invention is directed to a method and system for removing particles from a container, particularly a container having a coating prepared using the systems and / or methods described herein.

[0244] As described herein, the process of coating the inner surface of one or more containers can result in particles being present on various parts of the container, particularly including the inner surface of the container and parts of the container that will come into contact with the sealing unit 700. The container can also collect particles during the molding process and / or during transportation or other process steps. The present disclosure provides a two-step method for removing particles from the surfaces of the container, particularly including the surfaces of the container where particle collection is most likely during the coating process.

[0245] Embodiments of the present disclosure are directed to a method and system for treating one or more containers, such as one or more containers coated according to the above process, to remove particles from the inner surface of the container. The method may include placing the container within a cleaning station 950, and more specifically within a cavity 951 of the cleaning station, such as that illustrated in FIGS. 26-27. Similar to the case in the coating system 600, the opening of the container into its lumen is positioned within the cavity 951. The lumen of the container may be sealed from the ambient environment by one or more seals between the station 950 and the outer surface of the container. As shown in the illustrated embodiment, for example, the sealing of the container may be performed by a sealing unit including a flexible seal 952, which may be similar or identical to that shown and described above with reference to the coating system 600.

[0246] A blowing probe 953 may be inserted into the lumen of the container for use in spraying high-pressure air. In some embodiments, for example, the high-pressure air may be sprayed at a pressure of at least 50 psi, or at least 55 psi, or at least 60 psi, or at least 70 psi, or at least 80 psi. In some embodiments, the surface of the container may be contacted with, for example, sprayed with ionized air, because many particles may have an electrostatic charge associated with them. The ionized air makes it possible to remove the charge and makes it easier to remove the particles. The blowing probe may be moved up and down, for example, along the longitudinal axis of the container, and / or rotated, for example, about the longitudinal axis of the container, to ensure that the entire inner surface of the container is in contact with the pressurized air.

[0247] During spraying, a vacuum may be drawn within the container lumen, for example, by a vacuum line 954, to ensure that the removed particles can be removed from the cleaning station 950 without contaminating the surrounding cleanroom environment.

[0248] When the cleaning step is complete, the vacuum may be stopped and the container may be retrieved.

[0249] One or more containers can be loaded into the cleaning station 950 and retrieved from the cleaning station 950 by a container conveyor. The movement of one or more container conveyors can be controlled by one or more processors and can be, for example, part of a fully automated coating and cleaning operation.

[0250] Containers exiting the cleaning station 950 desirably contain no or substantially no particles, such as flakes of coating, that are, for example, particles having a dimension of 50 microns or greater, or particles having a dimension of 40 microns or greater, or particles having a dimension of 30 microns or greater, or particles having a dimension of 20 microns or greater. For example, the inner surface of the container, when exiting the cleaning station 950 after a cleaning process has been performed, desirably contains no or substantially no particles that are, for example, particles having a dimension of 50 microns or greater, or particles having a dimension of 40 microns or greater, or particles having a dimension of 30 microns or greater, or particles having a dimension of 20 microns or greater.

[0251] An embodiment of a system for removing particles from the inner surface of one or more containers, i.e., the cleaning station 950, is shown in FIGS. 26 - 27. As shown, the cleaning station can include one or more cavities 951, one or more sealing elements 952 disposed at the base of each cavity and configured to form an airtight or substantially airtight seal with the container, a pressurized air delivery probe 953 that extends into the lumen of the container when the container is placed within the cavity, and a vacuum line 954 operably connected to the cavity and configured to evacuate the lumen of the container.

[0252] Although not shown, the cleaning station 950 can further include one or more particle recovery units, such as one or more screens or filters, to recover particles removed from one or more containers and ensure that they do not enter one or more vacuum pumps. The particle recovery unit can be placed at any suitable location between the cavity 951 and the vacuum pump.

[0253] The cleaning station may further include one or more container conveyors (not shown) that can move the container into and out of the cleaning station 950. The operation of the cleaning station 950 and the movement of the one or more container conveyors can be controlled by one or more processors. In this way, the cleaning station may be part of a fully automated coating and cleaning operation.

[0254] Embodiments of the present disclosure are directed to a method and system for processing one or more containers, such as one or more containers coated according to the above process, to remove particles from a portion of the container that will come into contact with the sealing unit 700. The method may include inserting the container into the chamber 901 of the cleaning station 900, spraying air, optionally ionized air, onto at least a portion of the outside of the container, and applying a vacuum within the chamber 901 to remove any particles removed from the chamber. The portion of the container that is sprayed may include the portion of the container that will come into contact with the sealing unit 700 during the coating process. For example, the portion of the container that is sprayed may include the portion of the container that surrounds the opening into the lumen. If the container includes a flange, the portion of the container that is sprayed may include the top and outer surfaces of the flange.

[0255] A system for removing particles from at least a portion of the outer surface of a container, namely the cleaning station 900, is shown in FIGS. 28 - 30. The system 900 may include a chamber 901 configured to receive each of the one or more containers, one or more nozzles 902 configured to spray air, optionally ionized air, towards the container disposed within the chamber, and one or more vacuum lines 903 configured to apply a vacuum within the chamber. Each of the one or more nozzles may be associated with one or more pressurized air supply manifolds.

[0256] In some embodiments, including the illustrated embodiment, system 900 may include at least a first nozzle or nozzle set 902a and a second nozzle or nozzle set 902b, each of which is positioned and oriented to spray different (but possibly overlapping) portions of the outer surface of the container.

[0257] As shown in FIG. 30, the first nozzle or nozzle set 902a may be configured to be substantially aligned with a portion of the outer surface of the container sidewall adjacent to the opening into the lumen and, for example, the outer surface of the flange, and may be oriented substantially perpendicular to the longitudinal axis of the container when the container is received within the chamber 901. Thus, the first nozzle or nozzle set 902a may be configured to remove particles from a portion of the container that will come into contact with the flexible seal 702 during the coating process. The first nozzle is illustrated as a single nozzle 902a, but may comprise, for example, a set of nozzles that may be positioned around the circumference of the container when the container is within the chamber 901. A plurality of nozzles 902a may be substantially evenly spaced around the circumference of the container when positioned around the circumference of the container. Adjacent nozzles within the nozzle set 902a may provide overlapping sprays to ensure contact around the entire circumference of the container.

[0258] The second nozzle or nozzle assembly 902b is positioned below the container (or above if the chamber is inverted), and when the container is received within chamber 901, it can be configured to be directed, for example, toward the end face of the flange of the container that surrounds and approaches the opening into the lumen. In some embodiments, for example, the second nozzle of nozzle assembly 902b can be oriented at an angle of about 20 degrees to about 70 degrees, optionally about 30 degrees to about 60 degrees, optionally about 40 degrees to about 50 degrees, optionally about 45 degrees, relative to the longitudinal axis of the container when the container is received within the chamber. Thus, the second nozzle or nozzle assembly 902b can be configured to remove particles from a portion of the container that will come into contact with the upper surface 703 of the pack 701 during the coating process. The second nozzle is shown as a single nozzle 902b, but may comprise, for example, a set of nozzles that can be positioned around the circumference of the container when the container is within chamber 901. The plurality of nozzles 902b, when positioned around the circumference of the container, can be spaced substantially evenly around the circumference of the container. Adjacent nozzles within nozzle assembly 902b can provide overlapping sprays to ensure contact around the entire circumference of the container.

[0259] In the illustrated embodiment, system 900 is oriented such that the container is placed within chamber 901 with the end of the container that includes the opening into the lumen inserted first and facing downward. However, other orientations are contemplated without departing from the scope / disclosure of the present invention.

[0260] One or more containers can be held within one or more chambers 901 by a container holder 904. The container holder 904 can be configured to contact the end of the container opposite the end having the opening into the lumen. For example, in the illustrated embodiment, the container holder 904 is shown contacting the bottom of the vial. When configured for a syringe barrel, the container holder 904 can contact the front end of the barrel (since the opening into the lumen is at the rear of the syringe barrel).

[0261] In some embodiments, the container holder 904 can be configured to rotate the container during the cleaning process. Rotation of the container may be desirable to ensure that the outer surface of the vial contacts the air from the nebulizer over the entire circumference of the container. In other embodiments, it may not be necessary to rotate the container.

[0262] As shown in the illustrated embodiment, the container holder 904 can be configured to place the container within the chamber 901 and remove the container from the chamber. For example, the system 900 may also include a framework 905 that operably connects each of the plurality of container holders 904 so as to be movable as a single unit. However, in other embodiments, a plurality of frameworks 905 may be provided, each holding a subset of the plurality of container holders 904 and connecting the subset of container holders so as to be movable as a single unit. The container holder 904, and more specifically the framework 905, can be movable toward and away from a unit that houses one or more chambers 901 so as to place the container within the chamber and remove the container from the chamber when the cleaning step is complete. Movement of one or more container holders 904, and more specifically movement of the framework 905, can be controlled by one or more processors. Because the operation of the cleaning station 900 and the movement of one or more container holders 904 can be controlled by one or more processes, the cleaning station 900 can be part of a fully automated coating operation.

[0263] Although not shown, the system 900 can further include one or more particle collection units to collect the particles removed from one or more containers and ensure that they do not enter one or more vacuum pumps, which can include, for example, one or more screens or filters. The particle collection unit can be placed at any suitable location between the chamber 901 and the vacuum pump.

[0264] To remove particles from the outer surface of one or more containers, the one or more containers are inserted into chamber 901 of cleaning system 900. The one or more containers can be held in place by a container holder 904 including, but not limited to, the types shown in FIGS. 28 - 30. Upon entering chamber 901, at least a portion of the outer surface of the container desirably includes at least a portion of the container that will contact sealing unit 700 during the coating operation, such as a portion of the container surrounding an opening into the inner cavity (which can include the upper and outer surfaces of the flange), and this is sprayed with pressurized air, desirably ionized air.

[0265] The pressurized air desirably removes any particles present on the surface of the contacting container. In some embodiments, for example, the pressurized air can be sprayed at a pressure of at least 50 psi, or at least 60 psi, or at least 70 psi, or at least 80 psi, or at least 90 psi, or at least 100 psi, or at least 110 psi, or at least 120 psi, or at least 130 psi. In some embodiments, the surface of the container is contacted with, for example, sprayed with, ionized air because many particles can have an associated electrostatic charge. The ionized air can remove the charge and enable the pressurized air to more easily remove the particles.

[0266] In some embodiments, the container can move within the chamber during spraying. For example, in some embodiments, the container can be moved up and down (along the longitudinal axis of the container) within the chamber during spraying to ensure that the pressurized air contacts a larger surface area of the container. In some embodiments, the container can rotate about its longitudinal axis during spraying to ensure that the pressurized air contacts the entire circumference of the container. In some embodiments, both movements can be performed. The one or more movements can be performed by container holder 904. The movement of container holder 904, more specifically framework 905, can be controlled by one or more processors and can, for example, be part of a fully automated container coating and cleaning operation.

[0267] During the spraying, a vacuum is drawn in the chamber so that all particles removed from the container are discharged from the chamber without contaminating the clean room environment. As shown in the illustrated embodiment, a single vacuum line 903 can be operably connected to a plurality of chambers 901 and / or the plurality of chambers may be coupled to be open to each other.

[0268] In some embodiments, at least a portion of the sidewall of the container is sprayed with pressurized air to remove any particles present thereon. As shown in FIG. 30, for example, the spraying can be performed by one or more nozzles 902a positioned substantially in alignment with a portion of the outer surface of the sidewall adjacent to the opening into the lumen and, for example, the outer surface of the flange, and directed substantially perpendicular to the longitudinal axis of the container.

[0269] In some embodiments, at least a portion of the end wall of the container is sprayed with pressurized air to remove any particles present thereon. As shown in FIG. 30, for example, the spraying can be performed by one or more nozzles 902b positioned below the container and directed toward the end face of the container, such as the upper surface of the flange, surrounding and approaching the opening into the lumen. The one or more nozzles 902b can be directed, for example, at an angle of from about 20 degrees to about 70 degrees, optionally from about 30 degrees to about 60 degrees, optionally from about 40 degrees to about 50 degrees, relative to the longitudinal axis of the container.

[0270] When the cleaning process is executed, one or more containers are removed from the chamber 901. Placing the container within the chamber 901 and removing the container from the chamber can be performed by a container holder 904, which can be controlled by one or more processors. Thus, the step of cleaning at least a portion of the outer surface of the container may be part of a fully automated container coating and cleaning operation.

[0271] The container exiting the chamber 901 desirably contains no or substantially no particles such as particles having a dimension of 50 microns or more, or particles having a dimension of 40 microns or more, or particles having a dimension of 30 microns or more, or particles having a dimension of 20 microns or more, such as flakes of coating. For example, a portion of the outer surface of the container surrounding the opening to the lumen, such as a portion of the end wall and / or side wall of the container that comes into contact with the sealing unit 700 of the coating system 600, desirably contains no or substantially no particles having a dimension of 50 microns or more, or particles having a dimension of 40 microns or more, or particles having a dimension of 30 microns or more, or particles having a dimension of 20 microns or more when exiting the chamber 901 after the cleaning process has been performed.

[0272] In some embodiments, the container can be transported between an inner surface cleaning station 950 and an outer surface cleaning station 900, for example, in a cleanroom environment.

[0273] When both the inner surface and the outer surface of the container are cleaned according to the present disclosure, the container desirably contains no or substantially no particles such as particles having a dimension of 50 microns or more, or particles having a dimension of 40 microns or more, or particles having a dimension of 30 microns or more, or particles having a dimension of 20 microns or more, such as flakes of coating. Further, by using the cleaning operations described herein, there is no need to perform washing or rinsing with water.

[0274] Embodiments of the present disclosure may provide a fully automated system for coating, cleaning, and / or inspecting containers. For example, a cleanroom environment may include a coating station 600, an inner container surface cleaning station 950, and an outer container surface cleaning station 900, and a plurality of containers may be transported from the coating station to each of the cleaning stations by one or more transport lines. Similarly, a cleanroom environment may include the container cleaning stations 950, 900 described herein and a plurality of inspection stations 101, 102, 103, 104, 105, and a plurality of containers may be transported between the cleaning stations and the inspection stations by one or more transport lines. The overall coating, cleaning, and / or inspection operations may be controlled by one or more processors.

[0275] Although much of the description of coating system 600 and systems 900, 950 shows that they are configured to coat the surface of a vial and then remove particles from the surface of the vial, the systems may also be configured to coat and remove particles from the surface of other containers, such as syringe (and cartridge) barrels, blood collection tubes, etc., using the same techniques shown in the illustrated embodiments. Unless otherwise specified, the present disclosure is in no way limited to the particular container 210 shown in the illustrated embodiments.

[0276] In a further embodiment, a fully automated system for coating, cleaning, and / or inspecting the containers may be configured to store information related to the operating parameters during the manufacture of the containers (including but not limited to the batch numbers of all components for forming polymer or glass containers, the batch numbers of all components used in the coating process, the forming parameters used, the coating parameters used, the specific operator on duty, the maintenance status of all elements of the clean room and manufacturing machinery), the resulting particulate load on the raw gas injection probe 1101, the sealing unit 700, or other components, the resulting particulate load on the coated containers, and / or defects. This information may be stored in a conventional database known in the art. Further, the system may be configured to analyze the data to identify process parameters that result in an increase in the particulate load or an increase in the number of defects at any point in the process. In yet a further embodiment, this analysis may identify components, settings, environmental conditions, or personnel that early on adversely affect the particulate load or the number of defects so that mitigation can be employed. In yet a further embodiment, this analysis may allow for testing permutations of the forming and coating parameters to optimize process efficiency while maintaining an acceptably low particulate load and number of defects in the manufactured containers.

Example

[0277] Example 1 Using an automated coating, cleaning, and inspection system according to the present disclosure, a plurality of 10 mL vials were prepared and inspected. Each vial, after coating, was cleaned (internal blow-off) of its inner surface defining the lumen and (2) the outer surface of the vial that comes into direct contact with the coating system during the coating step (surface blow-off) as described herein. Specifically, in the cleaning station described and shown herein, each surface was contacted with pressurized ionized air to remove particles. Further, after each coating cycle, the coating system was cleaned using the hermetic unit cleaning system described and shown herein to remove particles from the surfaces of the hermetic unit that contact the vial during coating.

[0278] Each vial was inspected using both the automated inspection system described and shown herein and light obscuration test technology for measuring non-visible particles after the cleaning processes of internal blow-off and surface blow-off. Extensive information including cleaning group number, pre- and post-cleaning correlations, timestamps, time since final cleaning, cavity number, particle count (for various particle sizes), and total particle area was saved. Data was generated and saved in a computer-accessible database.

[0279] As a comparison, a second plurality of vials were coated using the same coating system. However, for this control sample, neither the vials nor the coating system were cleaned to remove particles after each cycle. The control vials were also inspected using both the automated inspection system described and shown herein and light obscuration test technology for measuring non-visible particles. The results were compared to the test samples. The comparison results are shown in Figure 31. As shown in Figure 31, the implementation of the cleaning system significantly reduced the total particle count to less than 25 particles per 10 mL vial in all uptake counts (out of 150 cycles) and the test vials (here 142).

[0280] Provide Table 1 with the average size distribution of the particles in the vials that have been subjected to the cleaning step (and that have been coated after the sealing unit of the coating system has been cleaned). Table 1 shows that by using the cleaning system described herein, particles larger than 50 μm have been completely removed from the vials. [Table 1]

[0281] The particle size distribution within the vial after the implementation of the automated cleaning technique, which indicates that the automated system has successfully excluded particles larger than 50 μm (average over 3 runs).

[0282] The cleaning system and method also consistently and repeatedly produce vials that meet the exclusion requirement for particle sizes of ≧ 0.0019 mm 2 which means that even if there are some particles remaining in the vial, their surface area should be less than 0.0019 mm 2

[0283] Specific embodiments: Container inspection method 1. A method for inspecting a pharmaceutical container, which may be a ready-to-use pharmaceutical container, with respect to particles, the container having generally cylindrical side walls, an upper part defining an opening, a shoulder connecting the side walls and the neck, and optionally a transition region connecting the bottom wall and the side walls, Capturing a plurality of images of the side wall portion of the container with a body side camera, Optionally, capturing a plurality of images of the shoulder of the container with an angled shoulder camera, Optionally, capturing a plurality of images of the upper part of the container with an angled upper camera, Optionally, capturing a plurality of images of the transition region portion of the container with an angled bottom camera, and Optionally, capturing one or more images of the bottom wall portion of the container with a bottom camera. ​Defining one or more inspection regions for each image, and Determining whether there are particles or defects within the one or more inspection regions, the number of particles or defects within the one or more inspection regions, the size of at least one identified particle or defect, or any combination thereof, a method comprising. 2. A method for inspecting a pharmaceutical container, which may be an immediately usable pharmaceutical container, with respect to particles, a. Any one or more of the following combinations, For a container having a side wall, capturing a plurality of images of the side wall portion of the container with a body side camera, For a container having a shoulder, capturing a plurality of images of the shoulder of the container with an angled shoulder camera, For a container having an upper portion, capturing a plurality of images of the upper portion of the container with an angled upper camera, For a container having a side wall, a bottom wall, and a transition region between the side wall and the bottom wall, capturing a plurality of images of the transition region portion of the container with an angled bottom camera, and For a container having a bottom wall, capturing one or more images of the bottom wall of the container with a bottom camera, b. Defining one or more inspection regions for each image, and c. Determining whether there are particles or defects within the one or more inspection regions, the number of particles or defects within the one or more inspection regions, the size of at least one identified particle or defect, or any combination thereof, a method comprising. 3. The step of determining whether there are particles or defects within the one or more inspection regions, the number of particles or defects within the one or more inspection regions, the size of any identified particle or defect, or any combination thereof is performed by at least one processor, the method according to any of the preceding embodiments. 4. The step of applying one or more inspection regions to each image is performed by at least one processor, the method according to any of the preceding embodiments. 5. A method for inspecting a pharmaceutical container, which is a pharmaceutical container that can be used immediately, for example, with respect to particles, a. Any one or more of the following combinations, With respect to a container having a side wall, capturing a plurality of images of the side wall portion of the container with a main body side camera, With respect to a container having a shoulder, capturing a plurality of images of the shoulder of the container with an angled shoulder camera, With respect to a container having an upper part, capturing a plurality of images of the upper part of the container with an angled upper camera, With respect to a container having a side wall, a bottom wall, and a transition region between the side wall and the bottom wall, capturing a plurality of images of the transition region portion of the container with an angled bottom camera, and With respect to a container having a bottom wall, capturing one or more images of the bottom wall of the container with a bottom camera, b. Defining one or more inspection regions for each image by at least one processor, and c. Determining by at least one processor whether there are particles or defects in one or more inspection regions, the number of particles or defects in one or more inspection regions, the size of at least one identified particle or defect, or any combination thereof, a method comprising. 6. The step of capturing a plurality of images of the side wall portion of the container is Supporting the container above a bottom light and between a side light and a main body side camera, Rotating the container about its central axis, optionally continuously rotating the container about its central axis, Using the main body side camera to capture a plurality of images of the container side wall while rotating the container, such that the images match or overlap such that the plurality of images span a 360° arc of the container side wall, capturing, a method according to any of the preceding embodiments. 7. The bottom light is a direct type backlight, optionally a blue direct type backlight, a method according to any of the preceding embodiments. 8. The body side camera is the method according to any of the preceding embodiments, including an ultra-high resolution area scan camera with a telecentric lens. 9. The side light is the method according to any of the preceding embodiments, including a high-power planar light, optionally a high-power planar blue light. 10. The step of capturing a plurality of images of the side wall portion of the container is the method according to any of the preceding embodiments, which is carried out at a station on the transport line of the plurality of containers. 11. a. Providing a container holder, b. Operating the container holder to remove the container from the transport line, c. At least one of (i) operating the container holder to move the container to the station, or (ii) moving the bottom light and the side light to an operating position adjacent to the container to form a station, d. After capturing a plurality of images, at least one of (i) operating the container holder to move the container away from the station, or (ii) moving the bottom light and the side light to a standby position away from the container, and e. Further including operating the container holder to relocate the container onto the transport line, which is the method according to any of the preceding embodiments. 12. The step of capturing a plurality of images of the shoulder of the container is Supporting the container between the shoulder camera angled with the side light above the bottom light, Rotating the container about its central axis, optionally continuously rotating the container about its central axis, Using the angled shoulder camera to capture a plurality of images of the container while rotating the container, where the images match or overlap such that the plurality of images span a 360° arc of the shoulder of the container, which is the method according to any of the preceding embodiments. 13. The bottom light is the method according to any of the preceding embodiments, which is a direct-type backlight, optionally a blue direct-type backlight. 14. The angled shoulder camera is the method according to any of the preceding embodiments, which includes an ultra-high-resolution area scan camera. 15. The side light is the method according to any of the preceding embodiments, which includes a direct-type backlight, optionally a blue direct-type backlight. 16. The step of capturing a plurality of images of the shoulder of the container is the method according to any of the preceding embodiments, which is performed at a station on a transport line of a plurality of containers. 17. a. Providing a container holder; b. Operating the container holder to remove the container from the transport line; c. At least one of (i) operating the container holder to move the container to the station, or (ii) moving the bottom light and the side light to an operating position adjacent to the container to form the station; d. After capturing a plurality of images, at least one of (i) operating the container holder to move the container away from the station, or (ii) moving the bottom light and the side light to a standby position away from the container; and e. Further including operating the container holder to relocate the container on the transport line, the method according to any of the preceding embodiments. 18. The step of capturing a plurality of images of the upper part of the container is Supporting the bottom surface of the container above or on the bottom light such that the container is between the side light and an upper camera at an angle; Rotating the container about its central axis, optionally continuously rotating the container about its central axis; Capturing a plurality of images of a container while rotating the container using an angled upper camera, wherein the images match such that the plurality of images span a 360° arc at the top of the container, and the method according to any of the preceding embodiments, including: 19. The bottom light is a direct-type backlight, optionally a blue direct-type backlight, and the method according to any of the preceding embodiments. 20. The angled upper camera includes an ultra-high resolution area scan camera, and the method according to any of the preceding embodiments. 21. The side lights include a direct-type backlight, optionally a blue direct-type backlight, and the method according to any of the preceding embodiments. 22. The container is supported above the bottom light by a rotatable platform, and the method according to any of the preceding embodiments. 23. The rotatable platform is configured to substantially not distort the bottom light, and the method according to any of the preceding embodiments. 24. The bottom light is rotatable, and the method according to any of the preceding embodiments. 25. The method according to any of the preceding embodiments, further comprising reducing or removing shadows by providing a reflective wall on the side of the container opposite the side lights. 26. The step of capturing a plurality of images of the top of the container is performed at a station on a plurality of container transport lines, and the method according to any of the preceding embodiments. 27. a. Providing a container holder; b. Operating the container holder to remove the container from the transport line; c. (i) Operating the container holder to move the container to the station, or (ii) moving the bottom light and the side lights to an operating position adjacent to the container to form the station, at least one of these. d. After capturing a plurality of images, (i) operating the container holder to move the container away from the station, or (ii) moving the bottom light and the side lights to a standby position away from the container, at least one of these, and e. Further including operating the container holder to relocate the container on the transport line, the method according to any of the preceding embodiments. 28. The step of capturing a plurality of images of the transition region between the side wall and the bottom wall of the container comprises supporting the upper surface of the container above or over the bottom light such that the container is inverted and between the angled bottom camera and the side light, rotating the container about its central axis, optionally continuously rotating the container about its central axis, and capturing a plurality of images of the container while rotating the container using the angled bottom camera, the images being such that the plurality of images match over a 360° arc of the transition region of the container, the method according to any of the preceding embodiments. 29. The bottom light is a direct-type backlight, optionally a blue direct-type backlight, the method according to any of the preceding embodiments. 30. The angled bottom camera includes an ultra-high resolution area scan camera, the method according to any of the preceding embodiments. 31. The side lights include a direct-type backlight, optionally a blue direct-type backlight, the method according to any of the preceding embodiments. 32. The container is supported above the bottom light by a rotatable platform, the method according to any of the preceding embodiments. 33. The method according to any of the preceding embodiments, wherein the rotatable platform is configured to substantially not distort the bottom light. 34. The method according to any of the preceding embodiments, wherein the bottom light is rotatable. 35. The method according to any of the preceding embodiments, wherein the step of capturing a plurality of images of the transfer area of the container is performed at a station of a plurality of container transport lines. 36. a. Providing a container holder, b. Operating the container holder to remove the container from the transport line, c. At least one of (i) operating the container holder to move the container to the station, or (ii) moving the bottom light and the side lights to an operating position adjacent to the container to form the station, d. After capturing a plurality of images, at least one of (i) operating the container holder to move the container away from the station, or (ii) moving the bottom light and the side lights to a standby position away from the container, and e. Further comprising operating the container holder to relocate the container onto the transport line, the method according to any of the preceding embodiments. 37. The step of capturing one or more images of the bottom wall of the container comprises supporting the upper surface of the container above or on the bottom light such that the container is inverted and between the bottom light and the bottom camera, and capturing one or more images of the bottom wall of the container using the bottom camera, the method according to any of the preceding embodiments. 38. The method according to any of the preceding embodiments, wherein the bottom light is a direct type backlight, optionally a blue direct type backlight. 39. The method according to any of the preceding embodiments, wherein the step of capturing one or more images of the bottom wall of the container further includes supporting the container adjacent to a side light. 40. The method according to any of the preceding embodiments, wherein the side light includes a direct backlight, optionally a blue direct backlight. 41. The method according to any of the preceding embodiments, wherein the step of capturing one or more images of the bottom wall of the container is performed at a station on a transport line of a plurality of containers. 42. The method according to any of the preceding embodiments, wherein the step of capturing one or more images of the bottom wall of the container is performed at the same station as the step of capturing a plurality of images of the transfer area of the container. 43. a. Providing a container holder; b. Operating the container holder to remove the container from the transport line; c. At least one of (i) operating the container holder to move the container to the station, or (ii) moving the bottom light and the side light to an operating position adjacent to the container to form a station; d. After capturing a plurality of images, at least one of (i) operating the container holder to move the container away from the station, or (ii) moving the bottom light and the side light to a standby position away from the container; and e. Operating the container holder to relocate the container onto the transport line, which is the method according to any of the preceding embodiments. 44. One or more of the body side camera, angled shoulder camera, angled upper camera, and angled bottom camera are configured to capture an image having an inspection area extending over an arc of at least 50°, optionally at least 55°, optionally at least 60°, optionally at least 65°, optionally at least 70°, which is the method according to any of the preceding embodiments. 45. Each of the body side camera, angled shoulder camera, angled top camera, and angled bottom camera is configured to capture an inspection area extending over an arc of at least 50°, optionally at least 55°, optionally at least 60°, optionally at least 65°, optionally at least 70°, according to the method described in any of the preceding embodiments. 46. One or more of the body side camera, angled shoulder camera, angled top camera, and angled bottom camera capture at least six images of the container, according to the method described in any of the preceding embodiments. 47. Each of the body side camera, angled shoulder camera, angled top camera, and angled bottom camera captures at least six images of the container, according to the method described in any of the preceding embodiments. 48. Each inspection area of the images overlaps with another inspection area of the images, according to the method described in any of the preceding embodiments. 49. The container is configured to store an injection, according to the method described in any of the preceding embodiments. 50. The container is a vial, syringe barrel, or cartridge, according to the method described in any of the preceding embodiments. 51. The container is a vial, according to the method described in any of the preceding embodiments. 52. The container has a glass wall or a plastic wall, according to the method described in any of the preceding embodiments. 53. The wall of the container is transparent, according to the method described in any of the preceding embodiments. 54. The method includes determining whether there are particles or defects within one or more inspection areas, according to the method described in any of the preceding embodiments. 55. The method is the method according to any of the preceding embodiments, including determining the number of particles or defects in one or more inspection regions. 56. The method is the method according to any of the preceding embodiments, including determining the size of any particle or defect in one or more inspection regions. 57. The method is the method according to any of the preceding embodiments, including determining the surface area of any particle or defect in one or more inspection regions. 58. The step of determining whether there are particles or defects in one or more inspection regions includes determining whether there are particles or defects that are 20 microns or more, or 25 microns or more, or 30 microns or more, or 40 microns or more, or 50 microns or more, or 60 microns or more, or 70 microns or more, or 25 - 500 microns, or 30 - 500 microns, or 40 - 500 microns, or 50 - 500 microns, or 60 - 500 microns, or 70 - 500 microns, or 80 - 500 microns, or 25 - 400 microns, or 30 - 400 microns, or 40 - 400 microns, or 50 - 400 microns, or 60 - 400 microns, or 70 - 400 microns, or 80 - 400 microns, or 25 - 300 microns, or 30 - 300 microns, or 40 - 300 microns, or 50 - 300 microns, or 60 - 300 microns, or 70 - 300 microns, or 80 - 300 microns. The method is the method according to any of the preceding embodiments. 59. The step of determining the surface area of any particle or defect in one or more inspection regions includes determining whether any particle has a surface area that meets or exceeds a threshold value. Optionally, the threshold value is 0.0019 mm 2 The method is the method according to any of the preceding embodiments. 60. The method according to any of the preceding embodiments, further comprising removing the container from the transport line when it is determined that the particles or defects in one or more inspection regions exceed a threshold value. 61. The threshold value is related to the number of particles or defects, the threshold value is related to the size of the particles or defects, the threshold value is related to the surface area of the particles or defects, or the threshold value is related to any combination thereof, the method according to any of the preceding embodiments. 62. One or more of the following, Capturing a plurality of images of the side wall portion of the container with a body side camera, Capturing a plurality of images of the shoulder portion of the container with an angled shoulder camera, Capturing a plurality of images of the upper portion of the container with an angled upper camera, Capturing a plurality of images of the transition region between the side wall and the bottom wall of the container with an angled bottom camera, and Capturing one or more images of the bottom wall of the container with a bottom camera, further comprising compensating for changes in ambient illumination in one or more of these. The method according to any of the preceding embodiments. 63. One or more of a body side camera, an angled shoulder camera, an angled upper camera, an angled bottom camera, and a bottom camera, and optionally each of them is configured to compensate for changes in ambient illumination, the method according to any of the preceding embodiments. 64. One or more of a body side camera, an angled shoulder camera, an angled upper camera, an angled bottom camera, and a bottom camera, and optionally each of them includes a bandpass filter, a bandpass filter that passes only light having wavelengths necessary for the step of determining optionally. The method according to any of the preceding embodiments. 65. The method according to any of the preceding embodiments, further comprising monitoring the intensity of one or more backlights, the intensity of one or more side lights, or both to ensure that the intensity remains within a defined range. 66. The method according to any of the preceding embodiments, further comprising stopping the inspection when the intensity of one or more backlights, one or more side lights, or both is outside a defined range. 67. The method according to any of the preceding embodiments, further comprising determining by at least one processor whether the defect is a surface defect or a critical defect. 68. The method according to any of the preceding embodiments, further comprising removing the container from the transport line when the defect is determined to be a critical defect. 69. Determining by at least one processor whether the defect is a surface defect or a critical defect includes analyzing, by at least one processor, the shape of the defect, the depth of the defect, or a combination thereof, according to any of the preceding embodiments. System 70. A system for inspecting a pharmaceutical container, comprising a plurality of cameras, comprising a body side camera, an angled shoulder camera, an angled top camera, an angled bottom camera, and a bottom camera, the plurality of cameras; one or more container holders, at least one of the one or more container holders being configured to rotate the container; a plurality of lights, comprising at least one or more bottom lights, and one or more side lights, the system comprising the plurality of lights. 71. A system for inspecting a pharmaceutical container, comprising any combination of the following cameras: a body side camera, an angled shoulder camera, Angled upper camera, angled bottom camera, and any combination of cameras of the bottom camera, one or more container holders, wherein optionally at least one of the one or more container holders is configured to rotate the container during inspection, a plurality of lights, wherein at least one or more bottom lights, and one or more side lights, a system comprising a plurality of lights. 72. The system according to any of the preceding embodiments, further comprising at least one processor configured to receive an image captured by each camera, apply one or more inspection regions to the image, and detect whether there are particles or defects within the one or more inspection regions. 73. The system according to any of the preceding embodiments, wherein at least one processor is further configured to determine the size of any detected particles or defects. 74. The system according to any of the preceding embodiments, wherein at least one processor is further configured to determine the number of particles or defects within the one or more inspection regions. 75. The system according to any of the preceding embodiments, wherein at least one processor is further configured to determine the surface area of any detected particles. 76. The system according to any of the preceding embodiments, wherein the processor is configured to determine whether the container is not perfectly aligned with the camera and adjust the inspection region based on that determination. 77. The system according to any of the preceding embodiments, wherein the system is configured to remove the container from the transport line if it is determined that the particles or defects within the one or more inspection regions exceed a threshold. 78. The threshold value is related to the number of particles or defects, the threshold value is related to the size of the particles or defects, or the threshold value is related to a combination of the number of particles or defects and the size of the particles or defects, the system according to any of the preceding embodiments. 79. The processor is configured to determine whether the defect is a surface defect or a critical defect, the system according to any of the preceding embodiments. 80. The system is configured to remove the container from the transport line if it is determined that the defect is a critical defect, the system according to any of the preceding embodiments. 81. To determine whether the defect is a surface defect or a critical defect, the processor is configured to analyze the shape of the defect, the depth of the defect, or a combination thereof, the system according to any of the preceding embodiments. 82. At least one of the lights is a blue backlight, optionally a blue LED backlight, the system according to any of the preceding embodiments. 83. One or more of the cameras are ultra-high resolution area scan cameras, the system according to any of the preceding embodiments. 84. At least one of the cameras comprises a telecentric lens, and optionally the body side camera comprises a telecentric lens, the system according to any of the preceding embodiments. 85. One or more of the body side camera, angled shoulder camera, angled upper camera, angled bottom camera, and bottom camera, and optionally each of them is configured to compensate for changes in ambient lighting, the system according to any of the preceding embodiments. 86. One or more of the body side camera, angled shoulder camera, angled top camera, angled bottom camera, and bottom camera, and optionally each of them, includes a bandpass filter, optionally a bandpass filter that passes only light having wavelengths necessary for determination of particles or defects, of the systems described in any of the preceding embodiments. 87. At least one of the container holders is configured to continuously rotate the container during inspection to which the container is related, of the systems described in any of the preceding embodiments. 88. At least one of the cameras is configured to capture an inspection area while the container is rotating, and optionally, the shutter of the camera is open for less than one millisecond, of the systems described in any of the preceding embodiments. 89. At least one of the body side camera, angled shoulder camera, angled top camera, and angled bottom camera, and optionally each of them, is configured to capture an image having an inspection area that extends over at least an arc of 50° of the circumference of the range of the inspected container, optionally at least an arc of 55°, optionally at least an arc of 60°, optionally at least an arc of 65°, optionally at least an arc of 70°, of the systems described in any of the preceding embodiments. 90. At least one of the body side camera, angled shoulder camera, angled top camera, and angled bottom camera, and optionally each of them, captures at least six images of the container, of the systems described in any of the preceding embodiments. 91. Each inspection area of the images taken by the camera overlaps with another inspection area of the images taken by the camera, of the systems described in any of the preceding embodiments. 92. At least one of the container holders holds the upper part of the container so that the bottom of the container does not contact any surface, of the systems described in any of the preceding embodiments. 93. The system according to any of the preceding embodiments, wherein at least one of the container holders is a rotating platform for supporting the container. 94. The system according to any of the preceding embodiments, wherein the rotating platform is attached above the bottom light and is configured so as not to substantially distort the bottom light. 95. The system according to any of the preceding embodiments, wherein the rotating platform is provided with gears and the gears are configured so as not to substantially distort the bottom light. 96. The system according to any of the preceding embodiments, comprising a plurality of inspection stations. 97. The system has a body side inspection station, a body side camera, a bottom light, optionally a direct type backlight, optionally a blue direct type backlight, a container holder configured to hold the upper part of the container such that the container is suspended above the bottom light and is configured to rotate the container about its central axis, and a side light located on the side opposite to the container holder from the body side camera, and comprises a body side inspection station according to any of the preceding embodiments. 98. The system according to any of the preceding embodiments, wherein the body side camera includes an ultra-high resolution area scan camera with a telecentric lens. 99. The system according to any of the preceding embodiments, wherein the side light includes a high-power planar light, optionally a high-power planar blue light. 100. The system according to any of the preceding embodiments, wherein the body side inspection station is part of a transport line for a plurality of containers. 101. The system is a. The container holder removes the container from the transport line, b. Either (i) the container holder moves the container to the body side inspection station or (ii) a component including a bottom light and a side light moves to a position adjacent to the container to at least partially form the body side inspection station, c. Either (i) the container holder moves the container back to the transport line or (ii) a component including a bottom light and a side light moves away from the container, and d. The system according to any of the preceding embodiments, wherein the container holder is configured to relocate the container to the transport line. 102. The system according to any of the preceding embodiments, wherein the movement of the container holder and / or the component is controlled by at least one processor and optionally the movement is fully automated. 103. The system is an angled shoulder inspection station, including an angled shoulder camera, a bottom light, optionally a direct type backlight, optionally a blue direct type backlight, a container holder configured to hold the upper part of the container such that the container is suspended above the bottom light and is configured to rotate the container about its central axis, and a side light located on the opposite side of the container holder from the angled shoulder camera. The system according to any of the preceding embodiments includes an angled shoulder inspection station. 104. The system according to any of the preceding embodiments, wherein the angled shoulder camera includes an ultra-high resolution area scan camera. 105. The system according to any of the preceding embodiments, wherein the side light is a direct type backlight, optionally a blue direct type backlight. 106. The shoulder inspection station is a system according to any of the preceding embodiments that is part of a transport line for a plurality of containers. 107. The system is a. where a container holder removes the container from the transport line, b. either (i) the container holder moves the container to the shoulder inspection station or (ii) a component including a bottom light and side lights moves to a position adjacent to the container to at least partially form the shoulder inspection station, c. either (i) the container holder moves the container back to the transport line or (ii) a component including a bottom light and side lights moves away from the container, and d. the container holder is configured to relocate the container to the transport line, a system according to any of the preceding embodiments. 108. The movement of the container holder and / or the component is controlled by at least one processor and optionally the movement is fully automated, a system according to any of the preceding embodiments. 109. The system is an angled upper inspection station, an angled upper camera, a bottom light, optionally a direct type backlight, optionally a blue direct type backlight, a rotatable container holder that supports the bottom wall of the container, optionally a rotatable platform, where the rotatable platform is configured to not substantially distort the bottom light, a side light located on the opposite side of the container holder from the angled upper camera, and optionally, a reflective wall located on the opposite side of the container holder from the side light, configured to reduce or remove shadows, optionally the reflective wall has a concave surface, a system according to any of the preceding embodiments comprising an angled upper inspection station comprising the reflective wall. 110. The angled upper camera is a system according to any of the preceding embodiments, including an ultra-high resolution area scan camera. 111. The side light is a system according to any of the preceding embodiments, which is a direct type backlight, optionally a blue direct type backlight. 112. The angled upper inspection station is a system according to any of the preceding embodiments, which is part of a transport line for a plurality of containers. 113. The system is a. The container transport unit removes the container from the transport line, b. Either (i) the container transport unit moves the container to the angled upper inspection station, or (ii) the components including the bottom light and the side light move to a position adjacent to the container to at least partially form the angled upper inspection station, c. Either (i) the container transport unit moves the container back to the transport line, or (ii) the components including the bottom light and the side light move away from the container, and d. The container transport unit is configured to relocate the container to the transport line, a system according to any of the preceding embodiments. 114. The movement of the container transport unit and / or the components is controlled by at least one processor, and optionally the movement is fully automated, a system according to any of the preceding embodiments. 115. The system is an angled bottom inspection station, an angled bottom camera, a bottom light, which is optionally a direct type backlight, optionally a blue direct type backlight, a rotatable container holder for supporting the upper surface of the container, optionally a rotatable platform, and the rotatable platform is configured so as not to distort the bottom light, a rotatable container holder, The system according to any of the preceding embodiments, comprising a angled bottom inspection station with a side light located on the opposite side of the container holder from the angled bottom camera. 116. The system according to any of the preceding embodiments, wherein the angled bottom camera comprises an ultra-high resolution area scan camera. 117. The system according to any of the preceding embodiments, wherein the side light is a direct type backlight, optionally a blue direct type backlight. 118. The system according to any of the preceding embodiments, wherein the angled bottom inspection station further comprises a bottom camera. 119. The system according to any of the preceding embodiments, wherein the bottom camera is mounted directly above the container holder. 120. The system according to any of the preceding embodiments, wherein the angled bottom inspection station is part of a transport line for a plurality of containers. 121. The system comprises a. a container transport unit removes a container from the transport line, b. either (i) the container transport unit moves the container to the angled bottom inspection station or (ii) components including the bottom light and the side light move to a position adjacent to the container to at least partially form the angled bottom inspection station, c. either (i) the container transport unit moves the container back to the transport line or (ii) the components including the bottom light and the side light move away from the container, and d. the container transport unit is configured to relocate the container to the transport line, 122. The movement of the container handling unit and / or components is controlled by at least one processor, and optionally the movement is fully automated, for the system described in any of the preceding embodiments. 123. The system is a bottom inspection station, a bottom camera, and a bottom light, optionally a direct-type backlight, optionally a blue direct-type backlight, for the system described in any of the preceding embodiments, which includes a bottom inspection station with a bottom light. 124. The bottom camera includes an ultra-high resolution area scan camera, for the system described in any of the preceding embodiments. 125. The bottom inspection station is part of a transport line for a plurality of containers, for the system described in any of the preceding embodiments. 126. The system is a. the container handling unit takes the container out of the transport line, b. (i) the container handling unit moves the container to the bottom inspection station, or (ii) components including the bottom light and optionally side lights move to a position adjacent to the container to at least partially form the bottom inspection station, c. (i) the container handling unit moves the container back to the transport line, or (ii) components including the bottom light and optionally side lights move away from the container, and d. the container handling unit is configured to relocate the container to the transport line, for the system described in any of the preceding embodiments. 127. The movement of the container handling unit and / or components is controlled by at least one processor, and optionally the movement is fully automated, for the system described in any of the preceding embodiments. 128. The movement of containers between each of the inspection stations and the transport line is controlled by at least one processor and is optionally configured to be fully automated, a system according to any of the preceding embodiments. 129. A system according to any of the preceding embodiments, further comprising a plurality of containers. 130. A system according to any of the preceding embodiments, wherein each container is configured to store an injection. 131. A system according to any of the preceding embodiments, wherein the container is a vial, a syringe barrel, or a cartridge. 132. A system according to any of the preceding embodiments, wherein the container is a vial. 133. A system according to any of the preceding embodiments, wherein the system processes at least about 20,000 containers per day, at least about 30,000 containers per day, at least about 35,000 containers per day, or at least about 40,000 containers per day. 134. A system according to any of the preceding embodiments, wherein the system processes at least about 30,000 containers per day. 135. A system according to any of the preceding embodiments, comprising one or more image analysis tools, whereby one or more processors are configured to determine the size of particles, the surface area of particles, or both. 136. A method of inspecting a container for particles, defects, or both, using a system according to any of the preceding embodiments. Application of the coating set 137. A system for preparing a coating set for a container, optionally a container according to any of the preceding embodiments, A power supply, optionally a radio frequency (RF) power supply, and An electrode having one or more cavities operable to receive a container, and A source gas line configured to provide one or more source gases into the interior cavity of a container disposed within one of the cavities, and A vacuum line configured to evacuate the interior cavity of a container disposed within one of the cavities, and A sealing unit positioned at the bottom of at least one of the cavities, the sealing unit comprising A pack defining a central opening and having an upper surface that contacts, when the container is disposed within the cavity, a portion of the container surrounding the opening to the interior cavity and optionally the end face of a flange, and A flexible seal that contacts, when the container is disposed within the cavity, a portion of the container sidewall and optionally the outer surface of a flange, The system is configured to Receive one or more containers within one or more cavities of the electrode, Evacuate the internal volume of each of the one or more containers, Introduce one or more source gases into each of the one or more containers, Generate a plasma within each of the one or more containers using the one or more source gases and a signal applied to the electrode by the power supply, optionally an RF signal applied to the electrode by an RF power supply, and Deposit a coating on the inner surface of each of the one or more containers using the plasma. 138. The system according to any of the preceding embodiments, further comprising a source gas injection probe extending into the interior cavity of a container positioned within the opening. New pack 139. The system according to any of the preceding embodiments, wherein at least a portion of the upper surface of the pack is configured to prevent particles, optionally flakes of the coating, optionally flakes of the coating from the source gas injection probe, from contacting the portion of the container surrounding the opening to the interior cavity and optionally the flange. 140. The system according to any of the preceding embodiments, wherein at least a portion of the upper surface of the pack is configured to reduce the surface area of the pack that contacts or is proximate to the container when the container is placed within the cavity. 141. The system according to any of the preceding embodiments, wherein at least a portion of the upper surface of the pack is inclined from a central opening at an angle greater than 10 degrees, optionally greater than 15 degrees, optionally greater than 20 degrees, optionally greater than 25 degrees, optionally greater than 30 degrees, optionally greater than 35 degrees, optionally greater than 40 degrees, optionally greater than 45 degrees. 142. The system according to any of the preceding embodiments, wherein the upper surface of the pack is inclined from a central opening at an angle greater than 10 degrees, optionally greater than 15 degrees, optionally greater than 20 degrees, optionally greater than 25 degrees, optionally greater than 30 degrees, optionally greater than 35 degrees, optionally greater than 40 degrees, optionally greater than 45 degrees. 143. The system according to any of the preceding embodiments, wherein the sealing unit further comprises a plasma screen disposed within the central opening of the pack. 144. The system according to any of the preceding embodiments, wherein the inner wall of the pack comprises a ledge configured to support the plasma screen. 145. The system according to any of the preceding embodiments, wherein the system is configured to receive a container selected from a syringe barrel, a vial, or a blood collection tube, optionally a syringe barrel, optionally a vial, optionally a blood collection tube. 146. The system according to any of the preceding embodiments, wherein the pack is made of a heat-resistant non-conductive material, optionally a ceramic or a thermoplastic material, such as a polyetheretherketone (PEEK) material. 147. The system according to any of the preceding embodiments, wherein the flexible seal is an O-ring, optionally a silicone O-ring. Cleaning of the sealing unit (including those with appearance inspection) 148. The system according to any of the preceding embodiments, further comprising a sealed unit cleaning system, the sealed unit cleaning system being configured to remove particles from the surface of the sealed unit that contacts the container. 149. The sealed unit cleaning system comprises one or more insertion parts, each of the one or more insertion parts being configured to enter one or more cavities, and each of the one or more insertion parts defining a central passage, the one or more insertion parts; one or more vacuum lines configured to create a vacuum within the central passage of each of the one or more insertion parts, the system according to any of the preceding embodiments. 150. Each of the one or more insertion parts has an outer surface, the diameter of the outer surface being within 1 / 2 inch of the diameter of each of the one or more cavities, the system according to any of the preceding embodiments. 151. The sealed unit cleaning system is configured to position each of the one or more insertion parts at a plurality of depths within the one or more cavities, the system according to any of the preceding embodiments. 152. The sealed unit cleaning system is configured to hold each of the one or more insertion parts at each of a plurality of depths within the one or more cavities, the system according to any of the preceding embodiments. 153. Each of the one or more vacuum lines has an air flow of at least 400 cfm and a pumping head of at least 35 inches, the system according to any of the preceding embodiments. 154. The sealed unit cleaning system is movable between at least (i) a first cleaning position in which each of the one or more insertion parts is at least partially located within one of the one or more cavities and (ii) a second coating position in which the sealed unit cleaning system is positioned away from the coating system, the system according to any of the preceding embodiments. 155. The movement of the sealing unit cleaning system is controlled by one or more processors, the system according to any of the preceding embodiments. 156. A method comprising the step of removing particles from a sealing unit of a system according to any of the preceding embodiments, the step comprising: a. positioning one or more insertion portions into one or more cavities, each of the one or more insertion portions being operably connected to a vacuum line and a vacuum pump; b. operating the vacuum pump to thereby create a vacuum within each of the one or more insertion portions. 157. c. further comprising moving each of the one or more insertion portions to a plurality of depths within the one or more cavities during operation of the vacuum pump, the method according to any of the preceding embodiments. 158. d. further comprising holding each of the one or more insertion portions at each of the plurality of depths for a period of time during operation of the vacuum pump, the method according to any of the preceding embodiments. 159. Further comprising stopping the vacuum, removing the one or more insertion portions from the one or more cavities, and positioning the one or more insertion portions at a distance from an electrode that permits placing one or more containers within the one or more cavities, the method according to any of the preceding embodiments. 160. The outer diameter of each of the one or more insertion portions is within 1 / 2 inch of the diameter of each of the one or more cavities, the method according to any of the preceding embodiments. 161. Creating a pressure of 0.3 atm or less, optionally 0.2 atm or less, optionally 0.1 atm or less within a portion of each of the one or more cavities by operation of the vacuum, the method according to any of the preceding embodiments. 162. The movement of the one or more insertion portions is controlled by one or more processors, the method according to any of the preceding embodiments. 163. A coating step, comprising: a. placing one or more containers within one or more cavities of the electrode; b. evacuating the internal volume of each of the one or more containers; c. introducing one or more source gases into each of the one or more containers; d. generating plasma within each of the one or more containers using the one or more source gases and a signal applied to the electrode by a power supply, optionally an RF signal applied to the electrode by an RF power supply; e. depositing a coating on the inner surface of each of the one or more containers using the plasma; f. removing the one or more containers from the one or more cavities of the electrode, the coating step further comprising the method according to any of the preceding embodiments. 164. Before placing the one or more containers within the one or more cavities of the electrode, further comprising cleaning the inner surface, outer surface, or both the inner and outer surfaces of the one or more containers with a pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, optionally pressurized CO2, the method according to any of the preceding embodiments. 165. After removing the one or more containers from the one or more cavities of the electrode, further comprising cleaning the inner surface, outer surface, or both the inner and outer surfaces of the one or more containers with a pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, optionally pressurized CO2, the method according to any of the preceding embodiments. 166. Further comprising applying a vacuum during cleaning of the one or more containers to trap any particles removed by the pressurized gas, the method according to any of the preceding embodiments. 167. Further comprising alternately performing the coating step and a step of removing particles from the sealing unit, the method according to any of the preceding embodiments. 168. The method according to any of the preceding embodiments, further comprising performing a step of removing particles from the sealing unit after a defined number of coating steps. 169. The method according to any of the preceding embodiments, wherein the defined number of coating steps is determined by visual inspection of each sealing unit of one or more cavities. 170. The method according to any of the preceding embodiments, further comprising a step of visually inspecting each sealing unit of one or more cavities. 171. The method according to any of the preceding embodiments, wherein the visual inspection is performed after each coating step. 172. The method according to any of the preceding embodiments, wherein the visual inspection is performed after each step of removing particles from the sealing unit. 173. The method according to any of the preceding embodiments, wherein the visual inspection includes acquiring an image of each sealing unit of one or more cavities by one or more cameras located above the electrodes. 174. The method according to any of the preceding embodiments, wherein acquiring an image of each sealing unit of one or more cavities further optionally includes applying light into one or more cavities by one or more isotropic linear lights. 175. The method according to any of the preceding embodiments, wherein acquiring an image of each sealing unit of one or more cavities further includes adjusting the position and spectral power distribution of one or more lights. 176. The method according to any of the preceding embodiments, wherein the one or more lights have wavelengths in the visible spectrum, the IR spectrum, or a combination thereof. 177. The appearance inspection further includes causing one or more processors to analyze each image to determine whether the amount of particles present on the sealed unit, the size of one or more particles present on the sealed unit, or a combination thereof meets or exceeds a threshold value, and starting a step of removing particles from the sealed unit, the method according to any of the preceding embodiments. 178. The method according to any of the preceding embodiments, further including starting a step of removing particles from the sealed unit if the amount of particles present on the sealed unit, the size of one or more particles present on the sealed unit, or a combination thereof meets or exceeds a threshold value. Appearance inspection of the sealing unit (independent of the cleaning step) 179. The system according to any of the preceding embodiments, further comprising a sealed unit inspection station configured to inspect the sealed unit with respect to particles. 180. The sealed unit inspection station comprises one or more cameras configured to acquire images of each sealed unit of one or more cavities, and one or more processors configured to analyze the images taken by the one or more cameras and detect the presence of particles, the system according to any of the preceding embodiments. 181. The system according to any of the preceding embodiments, further comprising one or more lights configured to irradiate one or more cavities, and optionally the one or more lights include one or more isotropic linear lights. 182. The system according to any of the preceding embodiments, wherein the one or more cameras and the one or more lights are on a movable assembly. 183. The system according to any of the preceding embodiments, wherein the one or more lights are movable relative to the one or more cavities and irradiate the one or more cavities at any angle from directly above to obliquely during image acquisition. 184. The system according to any of the preceding embodiments, wherein one or more lights are configured to irradiate one or more cavities from above. 185. The system according to any of the preceding embodiments, wherein various spectral power distributions can be emitted by one or more lights. 186. The system according to any of the preceding embodiments, wherein one or more lights have wavelengths in the visible spectrum, the IR spectrum, or a combination thereof. 187. The system according to any of the preceding embodiments, wherein one or more processors are configured to analyze an image to detect the amount of particles present on the sealed unit, the size of one or more particles present on the sealed unit, or a combination thereof. 188. The system according to any of the preceding embodiments, wherein one or more processors are configured to analyze an image to determine whether the amount of particles present on the sealed unit, the size of one or more particles present on the sealed unit, or a combination thereof meets or exceeds a threshold. 189. A method for visually inspecting a sealed unit of a system according to any of the preceding embodiments, a. obtaining an image of the sealed unit of each of the one or more cavities by one or more cameras positioned above the electrodes; and b. analyzing the image by one or more processors to detect the amount of particles present on the sealed unit, the size of one or more particles present on the sealed unit, or both. 190. The method according to any of the preceding embodiments, wherein obtaining an image of the sealed unit of each of the one or more cavities further optionally includes applying light into the one or more cavities by one or more isotropic linear lights. 191. The method according to any of the preceding embodiments, wherein obtaining an image of each of the sealing units of the one or more cavities further comprises adjusting the position and spectral power distribution of the one or more lights. 192. The method according to any of the preceding embodiments, wherein the one or more lights have wavelengths in the visible spectrum, the IR spectrum, or a combination thereof. 193. The method according to any of the preceding embodiments, further comprising initiating removal of particles from the sealing unit if the amount of particles present on the sealing unit, the size of one or more particles present on the sealing unit, or a combination thereof meets or exceeds a threshold. 194. The method according to any of the preceding embodiments, further comprising repositioning the feed gas injection probe if the amount of particles present on the sealing unit, the size of one or more particles present on the sealing unit, or a combination thereof meets or exceeds a threshold. 195. A coating step comprising: a. placing one or more containers within one or more cavities of the electrode; b. evacuating the internal volume of each of the one or more containers; c. introducing one or more feed gases into each of the one or more containers; d. generating a plasma within each of the one or more containers using the one or more feed gases and a signal applied to the electrode by a power source, optionally an RF signal applied to the electrode by an RF power source; e. depositing a coating on the inner surface of each of the one or more containers using the plasma; f. removing the one or more containers from the one or more cavities of the electrode, the method according to any of the preceding embodiments further comprising the coating step. 196. The method according to any of the preceding embodiments, further comprising cleaning the inner surface, outer surface, or inner and outer surfaces of the one or more containers with a pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, optionally pressurized CO2, before placing the one or more containers within one or more cavities of the electrode. 197. The method according to any of the preceding embodiments, further comprising cleaning the inner surface, outer surface, or inner and outer surfaces of the one or more containers with a pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, optionally pressurized CO2, after removing the one or more containers from the one or more cavities of the electrode. 198. The method according to any of the preceding embodiments, further comprising applying a vacuum during cleaning of the one or more containers to trap any particles removed by the pressurized gas. 199. The method according to any of the preceding embodiments, wherein visual inspection is performed after each coating step. 200. If the amount of particles present on the sealing unit, the size of one or more particles present on the sealing unit, or a combination thereof meets or exceeds a threshold, removing particles from the sealing unit, replacing the pack, the flexible seal, or both, replacing the gas feed probe, or performing any combination thereof, the method according to any of the preceding embodiments. Removal of particles from the container contact surface 201. A method of preparing a container having reduced particles, comprising: a. providing a system for preparing a coating set for the container, the system comprising: a power source, optionally a radio frequency (RF) power source, and an electrode having one or more cavities operable to receive the container. A source gas line configured to provide one or more source gases into the inner cavity of a container placed within one of the cavities, and A vacuum line configured to evacuate the inner cavity of a container placed within one of the cavities, and A sealing unit located at the bottom of at least one of the cavities, the sealing unit comprising A pack defining a central opening, the pack having an upper surface that contacts a portion of the container surrounding the opening to the inner cavity and optionally the end face of a flange when the container is placed within the cavity, and A flexible seal that contacts a portion of the side wall of the container and optionally the outer surface of the flange when the container is placed within the cavity, and a system comprising the sealing unit is provided. b. Coating the inner surface of one or more containers, comprising i. Placing one or more containers within one or more cavities of the electrodes, ii. Evacuating the internal volume of each of the one or more containers, iii. Introducing one or more source gases into each of the one or more containers, iv. Generating plasma within each of the one or more containers using one or more source gases and a signal applied to the electrodes by a power supply, optionally an RF signal applied to the electrodes by an RF power supply, v. Depositing a coating on the inner surface of each of the one or more containers using the plasma, vi. Removing the one or more containers from one or more cavities of the electrodes, thereby coating. c. A method comprising treating one or more containers to remove particles from at least a portion of each container that comes into contact with the sealing unit. 202. The method further comprises treating one or more containers to remove particles from each container prior to placing the one or more containers within one or more cavities of the electrodes, and optionally, treating comprises contacting the inner surface, outer surface, or both the inner and outer surfaces of each container with a pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, optionally pressurized CO2, according to any of the preceding embodiments. 203. A method of processing a container provided with a coating by a system according to any of the preceding embodiments so as to remove particles from at least a portion of the container that comes into contact with a sealing unit. 204. Removing particles from at least a portion of the container that comes into contact with a sealing unit comprises a. inserting the container into a chamber of a cleaning station; and b. spraying at least a portion of the container that comes into contact with the sealing unit, i.e., optionally including the upper and outer surfaces of the flange, a portion of the container surrounding the opening into the lumen, with a pressurized gas, optionally pressurized air, optionally pressurized ionized air, optionally pressurized nitrogen, optionally pressurized CO2; and c. applying a vacuum within the chamber to remove any particles removed from the chamber, the method according to any of the preceding embodiments. 205. A method of removing particles from a container, the container having a lumen at least partially defined by side walls, the side walls having an inner surface and an outer surface facing the lumen, the method comprising a. inserting the container into a chamber of a cleaning station; and b. spraying at least a portion of the container surrounding the opening into the lumen, optionally the upper and outer surfaces of the flange, with a pressurized gas, optionally pressurized air, optionally pressurized ionized air, optionally pressurized nitrogen, optionally pressurized CO2; and c. applying a vacuum within the chamber to remove any particles removed from the chamber. 206. The inner surface of the container comprises a coating set applied at least in part by PECVD, the method according to any of the preceding embodiments. 207. Spraying is carried out by one or more nozzles that are positioned substantially aligned with a part of the outer surface of the side wall adjacent to the opening into the lumen, optionally the outer surface of the flange, and are directed substantially perpendicular to the longitudinal axis of the container, according to any of the preceding embodiments. 208. Spraying is carried out by one or more nozzles that are positioned above or below the container, are directed towards the end face of the container that surrounds and approaches the opening into the lumen, optionally towards the end face of the flange, according to any of the preceding embodiments. 209. The one or more nozzles are directed at an angle of about 20 degrees to about 70 degrees, optionally about 30 degrees to about 60 degrees, optionally about 40 degrees to about 50 degrees, with respect to the longitudinal axis of the container, according to any of the preceding embodiments. 210. A part of the container surrounding the opening into the lumen is sprayed by at least a first nozzle and a second nozzle with pressurized gas, optionally pressurized air, optionally pressurized ionized air, optionally pressurized nitrogen, optionally pressurized CO2, and the first nozzle and the second nozzle have different positions and orientations relative to the container, according to any of the preceding embodiments. 211. The first nozzle is positioned substantially aligned with a part of the outer surface of the side wall adjacent to the opening into the lumen, optionally the outer surface of the flange, and is directed substantially perpendicular to the longitudinal axis of the container, according to any of the preceding embodiments. 212. The second nozzle is positioned above or below the container and is directed towards the end face of the container that surrounds and approaches the opening into the lumen, optionally towards the end face of the flange, according to any of the preceding embodiments. 213. The second nozzle is directed at an angle of about 20 degrees to about 70 degrees, optionally about 30 degrees to about 60 degrees, optionally about 40 degrees to about 50 degrees, with respect to the longitudinal axis of the container, according to any of the preceding embodiments. 214. The method according to any of the preceding embodiments, further comprising rotating the container about its longitudinal axis during spraying. 215. Spraying is carried out by a plurality of nozzles arranged at different points in the circumferential direction around the container, the method according to any of the preceding embodiments. 216. The plurality of nozzles are substantially evenly spaced around the circumference of the container, the method according to any of the preceding embodiments. 217. Spraying is carried out by a plurality of nozzles that are positioned substantially in alignment with a portion of the outer surface of the side wall adjacent to the opening into the lumen and optionally with the outer surface of the flange, and are directed substantially perpendicular to the longitudinal axis of the container, each of the plurality of nozzles being arranged at different points in the circumferential direction around the container, the method according to any of the preceding embodiments. 218. Spraying is carried out by a plurality of nozzles that are positioned above or below the container and surround and approach the end face of the container adjacent to the opening into the lumen and are optionally directed towards the end face of the flange, each of the plurality of nozzles being arranged at different points in the circumferential direction around the container, the method according to any of the preceding embodiments. 219. The plurality of nozzles are substantially evenly spaced around the circumference of the container, the method according to any of the preceding embodiments. 220. The container is held such that the opening into the lumen is positioned downward, the method according to any of the preceding embodiments. 221. The end of the container opposite the opening into the lumen is held by a container holder, the method according to any of the preceding embodiments. 222. Spraying is carried out in the presence of a vacuum, the method according to any of the preceding embodiments. 223. The pressurized gas is sprayed at a pressure of 100 psi or more, the method according to any of the preceding embodiments. 224. The method according to any of the preceding embodiments, further comprising removing the container from the chamber. 225. A portion of the container surrounding the opening into the lumen, upon exiting the chamber, is substantially free of particles having a dimension of 50 microns or more, optionally 40 microns or more, optionally 30 microns or more, optionally 20 microns or more, according to any of the preceding embodiments. 226. A portion of the container that comes into contact with the sealing unit, upon exiting the chamber, does not ...

Claims

1. A method for preparing a coated container that is substantially free of particles, a. To provide a system for preparing a coating set for one or more containers, the system is: A power source, which is optionally a radio frequency (RF) power source, An electrode comprising one or more cavities configured to receive a container, A raw material gas line is configured to supply one or more raw material gases into the lumen of a container placed inside one of the aforementioned cavities, A vacuum line configured to evacuate the lumen of a container placed inside one of the aforementioned cavities, A sealing unit located at the bottom of at least one of the aforementioned cavities, A pack defining a central opening, wherein when the container is placed in the cavity, a portion of the container surrounding the opening to the lumen and an upper surface which optionally comes into contact with the end face of a flange, and To provide a system comprising: a sealing unit having a flexible seal on a portion of the side wall of the container that, when the container is placed in the cavity, is voluntarily made to contact the outer surface of the flange; b. To coat the inner surface of one or more containers, i. Placing one or more containers in one or more cavities of the electrode, ii. Evaporating the internal volume of each of the one or more containers, iii. Introducing one or more raw material gases into each of the one or more containers, iv. Generating plasma in each of the one or more containers using the one or more raw material gases, a signal applied to the electrodes by the power supply, and an RF signal optionally applied to the electrodes by an RF power supply, v. Using the plasma to deposit a coating on the inner surface of each of the one or more containers, vi. Removing one or more covering containers from one or more cavities of the electrode, thereby covering, c. Processing one or more of the coated containers to remove particles from the inner surface of the containers, and d. Processing one or more of the coated containers to remove particles from a portion of each container that comes into contact with the sealing unit, The resulting coated container is (4) Does not contain, or substantially does not contain, particles having dimensions of 50 microns or more, optionally 40 microns or more, optionally 30 microns or more, optionally 25 microns or more, or optionally 20 microns or more. (5) 0.0019mm ２ It does not contain, or substantially does not contain, particles having a surface area greater than or equal to the above. (6) A method that is both (1) and (2).

2. The process further includes, before placing the one or more containers in the one or more cavities of the electrode, treating the one or more containers to remove particles from each container, optionally, using pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, optionally pressurized CO ２ The method according to claim 1, further comprising bringing the inner surface, outer surface, or inner surface and outer surface of each container into contact.

3. Processing one or more of the containers to remove particles from the inner surface of the containers is, a. Placing the container inside the cleaning station, b. Inserting the air blowing probe into the lumen through the opening of the container, c. Pressurized gas, optionally pressurized air, optionally pressurized ionized air, optionally pressurized nitrogen, optionally pressurized CO ２ This is sprayed onto the inner surface of the lumen of the side wall, d. The method according to claim 1, comprising applying a vacuum to the lumen to remove any particles removed through the opening of the container.

4. Removing particles from a portion of the container that comes into contact with the sealing unit is, a. Inserting the container into the chamber of the cleaning station, b. At least a portion of the container that comes into contact with the sealing unit, i.e., a portion of the container surrounding the opening to the lumen, optionally including the upper and outer surfaces of the flange, is filled with pressurized gas, optionally pressurized air, optionally pressurized ionized air, optionally pressurized nitrogen, optionally pressurized CO ２ To spray, c. The method according to claim 1, comprising applying a vacuum to the chamber to remove any particles removed from the chamber.

5. The method according to any one of claims 1 to 4, further comprising processing the sealing unit to remove particles before the coating step.

6. It is a system, a) One or more systems for preparing coating sets for multiple pharmaceutical containers ("coating systems"), a. Optionally, one or more sealed unit inspection stations, b. Optionally, one or more systems ("covering systems") comprising one or more sealed unit cleaning systems, b) One or more systems for removing particles from multiple pharmaceutical containers ("cleaning systems"), and c) A system comprising one or more systems for inspecting multiple pharmaceutical containers ("inspection systems").

7. It is a system, a. One or more coating systems comprising a system for preparing a coating set for a container by the method described in claim 1, b. One or more cleaning systems, i. A system for removing particles from a container, particularly from at least a portion of the container surrounding the opening to the lumen. ii. A system for removing particles from the inner surface of the container, or iii. i. and ii. A cleaning system comprising one or more, and c. One or more inspection systems comprising a system for inspecting pharmaceutical containers A system that includes these features.

8. The system according to claim 7, further comprising one or more transport lines, the transport lines transporting a plurality of pharmaceutical containers between the one or more coating systems, the one or more cleaning systems, and the one or more inspection systems.

9. The system according to claim 8, wherein each of the one or more transport lines, the one or more coating systems, the one or more cleaning systems, and the one or more inspection systems are each controlled by one or more processors and are fully automated at will.

10. The system according to claim 9, wherein the system is configured to store information relating to one or more operating parameters associated with the manufacture of the pharmaceutical container in a database.

11. The system according to claim 10, wherein the system is configured to analyze the stored information to identify one or more operating parameters related to the manufacture of the pharmaceutical container that are associated with an increase in particulate load or an increase in the number of defects.

12. The system according to claim 11, wherein the system is configured to modify one or more operating parameters that are identified as being related to an increase in particulate load or an increase in the number of defects.

13. The system according to claim 12, wherein the system is configured to test the sorting of one or more operating parameters related to the manufacture of the pharmaceutical containers in order to increase the rate at which multiple pharmaceutical containers are manufactured while maintaining particulate loads and / or defective pharmaceutical containers below a set threshold.

14. A pharmaceutical container, optionally a vial, syringe barrel, injection cartridge, or blood collection tube, which is coated, cleaned, and inspected by the method described in claim 1.

15. The container was inspected and found to be 0.0019 mm ２ A pharmaceutical container, optionally a vial, syringe barrel, injection cartridge, or blood collection tube according to claim 14, which is known not to contain particles having the above surface area.

16. It is a vial, A lumen at least partially defined by the lateral and bottom walls, The side wall has an inner surface facing the inner lumen and an outer surface, The bottom wall has an upper surface facing the lumen and a lower surface, and the lumen It comprises an opening to the lumen located on the opposite side of the bottom wall, The aforementioned side wall is body area, A neck region having a diameter that is relatively smaller than that of the main body region, The shoulder region between the main body region and the neck region, and A transitional region is provided between the main body region and the bottom wall, The vials are inspected using an automated system. (1) Particles with sizes of 80-500 microns, optionally 70-500 microns, optionally 60-500 microns, optionally 50-500 microns, optionally 40-500 microns, optionally 30-500 microns, optionally 25-500 microns, (2) 0.0019mm ２ Particles having the above surface area, or (3) A vial that is known not to contain either (1) or (2).

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