Method and system for coating, cleaning, and checking the presence of particles and defects of a medicine container

Abstract

The present disclosure relates to methods and systems for coating a pharmaceutical vessel, for example, applying a coating set comprising an oxygen barrier layer to a pharmaceutical vessel, which reduces the amount of particles present on the coated vessel. The present disclosure also relates to methods and systems for removing particles from a vessel, such as after a coating is applied to an interior surface of a vessel. The present disclosure also relates to methods and systems for checking the presence of particles in a drug vessel prior to filling using machine-based visual analysis. Each of the foregoing may be controlled and executed by one or more processors, thereby enabling fully automated coating, cleaning, and / or inspection operations for drug vessels.

Description

Technical Field

[0001] The field of the invention is the preparation of pharmaceutical containers, optionally ready-to-use containers, and in particular containers such as vials, cartridges and syringes configured to be filled with injectable drugs with few or no visible particles. The field of the invention is also the detection of visible particles and defects on ready-to-use pharmaceutical containers, and in particular containers such as vials, cartridges and syringes configured to be filled with injectable drugs. Background Art

[0002] The use of ready-to-use (RTU) containers in the pharmaceutical industry is increasing because they provide a simplified filling process. However, RTU containers must be substantially free of visible defects, and in particular removable particles.

[0003] The presence of particles in injectable drug products can pose a serious risk to patients. Therefore, USP requires certain guidelines regarding the presence of visible particles in injectable drug products. See USP <790> (“Visible Particles in Injectables”), and certain product quality tests for injectable drug products, see <1> ("Injectable and Implantable Drug Products (Parenteral) - Product Quality Testing"). According to USP <790> All products intended for parenteral administration must be visually inspected for the presence of injectable and implantable drug products. <1> The product must be “substantially free” of visible particles, as defined by USP <790> and USP <788> (“Particulate Matter in Injectables”) or USP <789> (“Particulate Matter in Ophthalmic Solutions”). USP <790> Sampling and inspection guidelines are established in ANSI / ASQ Z1.4 or SIO 2859-1, and an AQL of 0.65% is established, noting that alternative sampling plans with equivalent or better protection are acceptable. In practice, a pharmaceutical company or contract development and manufacturing organization (CDMO) may require a more stringent sampling plan and / or AQL.

[0004] Typically, the inspected unit is manually inspected against a black background and against a white background, and no magnification is required (other than the optical corrections required to establish normal vision). Figure 1 An example of a workstation for manual visual inspection is shown in FIG. Figure 1), a trained visual inspector will inspect the container against both a black background 1 and a white background 2 under a light source 3 of 2,000 to 3,750 lux, and observe for at least five seconds against each background. Another exemplary workstation for manual inspection is described in U.S. Pat. No. 5,940,176. The system utilizes opposing illumination sources above and below the vial, with the vial positioned at the midpoint between the illumination sources. The background can be changed between a black background and a white background, so that the vial can be inspected without moving the vial from the midpoint of the illumination.

[0005] Even when performed correctly, manual visual inspection is limited by the ability of the human eye to discern particles. Typically, for an empty container, the human eye is able to see particles that are about 80 microns in size or larger. According to some reports, during manual visual inspection, although the probability of detection for particles that are 200 microns in size or larger may be very high (e.g., close to 100%), for particles that are about 100 microns in size, the probability decreases significantly (e.g., to 50% or less), and for particles that are less than 80 microns in size, the probability approaches 0%.

[0006] However, automated visual inspection of empty containers is limited by the difficulty of the automated visual inspection system in accurately checking the transition area of ​​the container and / or accounting for differences in the thickness of the container wall. Due to these problems, conventional automated visual inspection systems cannot achieve the level of effectiveness required for RTU containers for injectable drugs.

[0007] Automated visual inspection systems have found some commercial use in detecting particles in filled containers (i.e., after the container has been filled with an injectable drug product). In those systems, the filled container is spun so that any loose particles migrate to the centerline of the container. Thus, the automated visual inspection system need only inspect the container along that centerline. Such systems are not feasible for visual inspection of empty containers (such as RTU containers) because of their reliance on the presence of fluid within the container. Such systems also cannot inspect for visible particles that may remain adhered to the container wall or defects in the container wall.

[0008] When manufacturing pharmaceutical packaging or other vessels (such as vials and prefilled syringes) for storing or otherwise contacting fluids, an important consideration is that the contents of the pharmaceutical packaging or other vessels are expected to have a relatively long shelf life. During this shelf life, it is important to isolate the material filling the pharmaceutical packaging or other vessels from the vessel walls containing the material, or from the barrier layer or other functional layer applied to the pharmaceutical packaging or other vessel walls to avoid leaching of material from the pharmaceutical packaging or other vessel walls, barrier layers or other functional layers into the prefilled contents, or vice versa.

[0009] Traditional glass pharmaceutical packaging or other containers are susceptible to breakage or degradation during manufacturing, filling operations, transportation, 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 packaging or other containers, which offer greater dimensional tolerances and less breakage than glass, but their use for primary pharmaceutical packaging is limited due to their gas permeability: plastics allow small molecules of gas, such as oxygen, to permeate (or permeate out) of the article. In addition to oxygen, many plastic materials also allow moisture (i.e., water vapor) to permeate (or permeate out) of the article. The permeability of plastics to gases such as oxygen and water vapor is significantly greater than that of glass, and in many cases (such as in the case of oxygen-sensitive drugs such as epinephrine), plastics were not acceptable in the past for this reason.

[0011] The problem of gas permeability has been addressed by adding oxygen barrier coatings or layers to plastic pharmaceutical packaging. One such oxygen barrier layer is a very thin SiOx coating (applied, for example, by plasma enhanced chemical vapor deposition, as defined below). Additional layers (such as a bonding layer and / or a pH protective layer, for example as described and defined in U.S. Pat. No. 9,554,968, the entire contents of which are incorporated herein by reference) may also be applied as part of a coating set applied to the inner surface of the vessel sidewall.

[0012] However, the coating of the vessel with such an oxygen barrier coating or layer and / or with an additional layer that can be used to improve the adhesion of the oxygen barrier coating or layer to the vessel wall to protect the oxygen barrier coating or layer from being dissolved by the fluid stored in the inner cavity of the vessel or both can result in the presence of particles on the vessel wall. In particular, when one or more coatings or layers are deposited using PECVD, the coating can be deposited not only on the vessel wall as expected, but also on various components of the coating system. Then, flakes of the coating can fall off from the coating system components and can reach the surface of the vessel, where they adhere as particles.

[0013] In a coating system of the type described herein, for example, a thin sheet of one or more PECVD coating materials deposited on a source gas inlet probe used during a PECVD coating process may flake off and adhere to an inner wall of a vessel and / or one or more surfaces of the vessel that are in direct contact with the system, which is typically an upper end surface of the vessel surrounding an opening to an inner cavity and a portion of an outer surface of a side wall of the vessel, for example, an upper surface and an outer surface of a flange surrounding an opening to an inner cavity. Summary of the invention

[0014] One aspect of the present invention is an automated system and method for visually inspecting drug containers, such as ready-to-use (RTU) drug containers, for particles and defects.

[0015] Embodiments of the present systems and methods may be configured to inspect all or substantially all of an RTU vessel (which includes all transition zones). Embodiments of the present systems and methods may also be configured to account for variations in wall thickness and distinguish particles or defects from thickness variations.

[0016] Embodiments of the present systems and methods may be configured to inspect an RTU container, such as a vial, syringe barrel, or cartridge, configured for storing an injectable medication.

[0017] Embodiments of the present systems and methods may be configured to detect particles and defects as small as 25 microns in size.

[0018] Embodiments of the present systems and methods may be configured to detect particles within a range of sizes (e.g., between 25 and 500 microns, alternatively between 30 and 500 microns, alternatively between 40 and 500 microns, alternatively between 50 and 500 microns, alternatively between 60 and 500 microns, alternatively between 70 and 500 microns, alternatively between 80 and 500 microns, alternatively between 25 and 400 microns, alternatively between 30 and 400 microns, alternatively between 40 and 400 microns). Between, alternatively between 50 and 400 microns, alternatively between 60 and 400 microns, alternatively between 70 and 400 microns, alternatively between 80 and 400 microns, alternatively between 25 and 300 microns, alternatively between 30 and 300 microns, alternatively between 40 and 300 microns, alternatively between 50 and 300 microns, alternatively between 60 and 300 microns, alternatively between 70 and 300 microns, alternatively between 80 and 300 microns).

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

[0020] Embodiments of the present system and method utilize multiple cameras, multiple light sources, and at least one processor. The system also includes multiple vessel holders configured to rotate the container in a controlled manner. The processor is configured to receive input from the multiple cameras and process the information into output, i.e., particle detection information.

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

[0022] In order to enable embodiments of the present system and method to inspect the inner surface of a container, the container wall should be made of a transparent material, but it has been found that slight coloring can exist in the container wall and still obtain acceptable inspection results. 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 polycarbonate, polystyrene, polyethylene terephthalate (PET), polypropylene, polyethylene, polyamide, cycloolefin polymer (COP), cycloolefin copolymer (COC) or cyclic block copolymer (CBC). In some embodiments, the container wall can be made of a plastic selected from cycloolefin polymer (COP) or cycloolefin copolymer (COC).

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

[0024] In some embodiments, for example, at least one of the container walls may include an oxygen barrier coating or layer that effectively reduces the ingress of oxygen into the interior cavity compared to a container without the oxygen barrier coating or layer. For example, at least one of the container walls may include a SiO x or essentially SiO xThe oxygen barrier coating or layer is composed of an oxygen barrier coating or layer, wherein x is 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 may have a thickness of 1 to 1000nm, optionally 2 to 1000nm, optionally 10 to 1000nm, optionally 10 to 500nm, optionally 10 to 200nm, optionally 20 to 100nm. In particular, in the case where the oxygen barrier coating or layer can be applied by ALD, the oxygen barrier coating or thickness can be 1 to 15nm thick, alternatively 2 to 12nm thick, alternatively 3 to 10nm thick, alternatively 4 to 8nm thick, alternatively 5 to 7nm thick. In some embodiments, the oxygen barrier coating or layer can be positioned between the inner surface of one or more vessel walls and the inner cavity.

[0025] In addition to the oxygen barrier coating or layer, at least one of the container walls may also include a pH protective coating positioned between the oxygen barrier coating or layer and the inner cavity, the pH protective coating effectively reducing the dissolution of the oxygen barrier coating or layer by the fluid in the inner cavity. The pH protective coating may comprise SiOxCy or SiNxCy, wherein x is from about 0.5 to about 2.4, and y is from about 0.6 to about 3. The pH protective coating may be applied by plasma enhanced chemical vapor deposition (PECVD). The pH protective coating may be 10 to 1000 nm thick. In some embodiments, the pH protective coating is at least coextensive with the oxygen barrier coating. In some embodiments, the pH protective coating may have an FTIR absorption spectrum having a ratio greater than 0.75 and optionally greater than 0.9 between the following:

[0026] The maximum amplitude of the Si-O-Si symmetric stretching peak between about 1000 and 1040 cm-1 is

[0027] • The maximum amplitude of the Si-O-Si asymmetric stretching peak between about 1060 and about 1100 cm-1.

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

[0029] For example, in some embodiments, at least one of the container walls may include a three-layer coating, such as the three-layer coating described in U.S. Patent No. 9,554,968, the entire contents of which are incorporated herein by reference. For example, in some embodiments, the interior surface of the container wall may include:

[0030] An optional bonding coating or layer comprising SiOxCy or SiNxCy, wherein x is from about 0.5 to about 2.4, and y is from about 0.6 to about 3, the bonding coating or layer having an inner surface facing the lumen and an outer surface facing the inner surface of the wall;

[0031] a gas barrier coating or layer, optionally comprising SiOx, wherein x is from 1.5 to 2.9, the gas barrier coating or layer having an inner surface facing the inner cavity and an outer surface facing the inner surface of the bond coating or layer, the barrier coating or layer being effective to reduce the ingress of atmospheric gases into the inner cavity compared to a vessel without the barrier coating or layer; and

[0032] A pH protective coating or layer comprising SiOxCy or SiNxCy, wherein 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 having an inner surface facing the lumen and an outer surface facing the inner surface of the barrier coating or layer.

[0033] In some embodiments, at least one of the container walls may include a lubricity coating, such as that described in U.S. Pat. No. 7,985,188, the entire contents of which are incorporated herein by reference. The lubricity coating or layer may consist essentially of SiOxCy, wherein x is from about 0.5 to about 2.4, and y is from about 0.6 to about 3. The lubricity coating may be applied by plasma enhanced chemical vapor deposition (PECVD). The lubricity coating or layer may have a thickness between 10 and 1000 nm, optionally between 10 and 500 nm. In some embodiments, the lubricity coating or layer may have an FTIR absorption spectrum with a ratio of at most 0.75 between the following:

[0034] The maximum amplitude of the Si-O-Si symmetric stretching peak between about 1000 and 1040 cm-1 is

[0035] • The maximum amplitude of the Si-O-Si asymmetric stretching peak between about 1060 and about 1100 cm-1.

[0036] In some embodiments, at least one of the container walls may include an anti-scratch and anti-static coating, such as the anti-scratch and anti-static coating described in U.S. Published Patent Application No. 2018 / 049945, the entire contents of which are incorporated herein by reference.

[0037] In some embodiments, the present systems and methods may be adjustable and / or configurable based on the light transmission and refraction properties of one or more specific materials comprising the vessel walls.

[0038] Another aspect of the invention is an RTU container, such as a vial, syringe, or cartridge, wherein the container has been inspected and found to be free of particles between 80 and 500 microns, optionally between 70 and 500 microns, optionally between 60 and 500 microns, optionally between 50 and 500 microns, optionally between 40 and 500 microns, optionally between 30 and 500 microns, optionally between 25 and 500 microns in size. The inspection may be performed using any of the systems and methods of the present disclosure.

[0039] Another aspect of the invention is a batch or lot of RTU containers, such as vials, syringes, or cartridges, wherein the containers have been inspected for particles between 80 and 500 microns, optionally between 70 and 500 microns, optionally between 60 and 500 microns, optionally between 50 and 500 microns, optionally between 40 and 500 microns, optionally between 30 and 500 microns, optionally between 25 and 500 microns in size, and wherein the 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 may be performed using any of the systems and methods of the present disclosure.

[0040] 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 vessel. The improved system and method described herein reduce the amount of particles (e.g., undesirable flakes of coating) that may be present on one or more vessels after a coating cycle. In some embodiments, for example, the system can be configured to reduce the contact area between the system and the vessel, thereby reducing the probability that particles (e.g., flakes of coating) will eventually be present on the portion of the system that contacts the vessel and thereby become adhered to the vessel or embedded in the vessel. In some embodiments, the system can also be configured to provide improved cleaning of system components, particularly system components that contact the vessel.

[0041] Another aspect of the present invention is a system and method for removing particles from an apparatus for depositing one or more coatings on the inner wall of a vessel, and in particular for removing particles from components of a coating system that cause the vessel to be potentially contaminated by particles (e.g., portions of a vessel holder that directly contact the vessel and / or a source gas inlet probe). In some embodiments, for example, a coating system may include an electrode cavity cleaning unit configured to generate a vacuum within the electrode cavity that is suitable for removing particles (e.g., flakes of a coating) from the electrode cavity. The cleaning unit may operate as a routine element of a coating process, for example, cleaning of the electrode cavity may be performed after a defined number of coating cycles.

[0042] Another aspect of the present invention is a system and method for performing machine-based visual inspection of equipment for depositing one or more coatings on the inner wall of a vessel, and in particular, performing machine-based visual inspection of components of the coating system that cause the vessel to be potentially contaminated by particles (e.g., portions of the vessel holder that directly contact the vessel and / or source gas inlet probes). 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 electrode.

[0043] One or more cameras can be operably connected to one or more processors so that images captured by one or more cameras are sent to one or more processors. One or more processors can be configured to receive images and analyze relevant portions of the images to detect the presence of particles, such as using machine-based visual analysis similar to machine-based visual analysis described elsewhere herein (e.g., defining one or more inspection areas for each image and visually analyzing each defined area for particles). One or more processors can also be configured to determine the number of particles present in one or more electrode cavities and more specifically on the vessel holder / sealing element of the one or more electrode cavities, determine the size of one or more detected particles, or both.

[0044] In some embodiments, an electrode cleaning operation may be initiated in response to the results of a visual inspection system / method. For example, in some embodiments, detection of particles above a certain threshold by one or more processors may cause the one or more processors to automatically initiate an electrode cleaning process. In some embodiments, a visual inspection of the electrode may be performed immediately after the electrode cleaning process, and if particles above a certain threshold are still detected (which may be any particles), the one or more processors may automatically initiate another cleaning operation cycle.

[0045] Another aspect of the present invention is a system and method for removing particles from a vessel after a coating has been applied. In some embodiments, the system and method may include a cleaning station in which the inner surface of the vessel (i.e., the surface that defines the inner cavity and has been provided with one or more coatings or layers using the PECVD coating process and system) is contacted with pressurized air, and desirably with pressurized ionized air, to remove particles that may adhere thereto (e.g., flakes of coating). In some embodiments, the system and method may include a cleaning station in which one or more outer surfaces of the vessel (e.g., outer surfaces that are in direct contact with the coating system during the coating step) are contacted with pressurized air, and desirably with pressurized ionized air, to remove particles that may adhere thereto (e.g., flakes of coating). Either or both of these coating stations may also include a vacuum line and an optional particle collection chamber for removing any particles that fall off the vessel during the cleaning step without damaging the clean room environment.

[0046] Removing particles from the vessel may be performed without washing (eg, without contacting the vessel surface with water).

[0047] Embodiments of the present invention can be fully automated. For example, a series of vessels can be coated, cleaned and inspected (e.g., in a clean room environment), where the entire operation is continuous and controlled by one or more processors. The result is a system and method for producing PECVD-coated pharmaceutical vessels (e.g., RTU containers) that are free of or substantially free of particles (e.g., particles greater than 20 microns, alternatively particles greater than 25 microns, alternatively particles greater than 30 microns, alternatively particles greater than 40 microns, alternatively particles greater than 50 microns), and the system and method make the number of vessels that must be scraped due to the presence of particles or defects extremely low.

[0048] In some embodiments, the RTU container may be filled with a pharmaceutical formulation of any of the following and sealed after coating, cleaning, and / or inspection:

[0049] Biologic drugs

[0050] abatacept; abciximab; abobotulinumtoxinA; adalimumab; adalimumab-adaz; adalimumab-adbm; adalimumab-afzb; adalimumab-atto; adalimumab-bwwd; ado-enmet trastuzumab emtansine; aflibercept; agalsidase beta; albiglutide; albumin chromate CR-51; aldesleukin; alefacept; alemtuzumab; alglucosidase alfa; alirocumab; alteplase; anakinra; aprotinin; asfotas alfa; asparaginase; Erwinia chrysanthemi asparaginase; atezolizumab; avelumab; basiliximab; becaplermin; belatacept; belimumab; benralizumab; beractant; bevacizumab; bevacizumab-awwb; bevacizumab-bvzr; bezlotoxumab; blinatumomab; brentuximab vedotin; brodalumab; brolucizumab-dbll; burosumab-twza; calaspargase pegol-mknl; calfactant; canakinumab; caplucizumab-yhdp; caproumab pendetide; cemiplimab-rwlc; cenegermin-bkbj; cerliponase alfa; certolizumab pegol; cetuximab; choriogonadotropin alfa; chorionic gonadotropin; chymopapain; collagenase; collagenase clostridium histolyticum; corticorelin ovine triflutate;crizanlizumab-tmca; daclizumab; daratumumab; daratumumab and hyaluronidase-fihj; darbepoetin alpha; denileukin diftitox; denosumab; desirudin; dinutuximab; dornase alfa; drotrecogin alfa; dulaglutide; dupilumab; durvalumab; ecallantide; eculizumab; efalizumab; elapegademase-lvlr; elosulfase alfa alfa; elotuzumab; emapalumab-lzsg; emicizumab-kxwh; enfortumab vedotin-ejfv; epoetin alfa; epoetin alfa-epbx; erenumab-aooe; etanercept; etanercept-szzs; etanercept-ykro; evolocumab; fam-trastuzumab deruxetecan-nxki); fibrinolytic enzyme and deoxyribonuclease combined with [bovine] chloramphenicol; filgrastim; filgrastim-aafi; filgrastim-sndz; follitropin alfa; follitropin beta; fremanezumab-vfrm; galcanezumab-gnlm; galsulfase; gemtuzumab ozogamicin; glucarpidase; golimumab; guselkumab; hyaluronidase; human hyaluronidase; ibalizumab-uiyk; ibritumomab tiuxetan tiuxetan; idarucizumab; idursulfatase; imiglucerase; incobotulinumtoxinA; inebilizumab-cdon; infliximab; infliximab-abda; infliximab-axxq; infliximab-dyyb; infliximab-qbtx; oecitabine; insulin aspart;Insulin aspart protamine and insulin aspart; insulin degludec; insulin degludec-aspart; insulin degludec-liraglutide; insulin detemir; insulin glargine; insulin glargine-lixisenatide; insulin glulisine; human insulin; human insulin oligoprotamine zinc insulin human); human oligoprotamine insulin and human insulin; insulin lispro; insulin lispro protamine and insulin lispro; insulin lispro-aabc; interferon alpha-2a; interferon alpha-2b; interferon alfacon-1; interferon alpha-n3 (human leukocyte-derived); interferon beta-1a; interferon beta-1b; interferon gamma-1b; ipilimumab; isatuximab-irfc; ixekizumab; lanadelumab-flyo; laronidase; lixisenatide; luspatercept-aamt; mecasermin; mecasermin-linfipe; urogonadotropin; mepolizumab; methoxypolyethylene glycol-epoetin beta; metreleptin; mogamulizumab-kpkc; moxetumomab pasudotox)-tdfk; moromona-CD3; natalizumab; necitumumab; nivolumab; nofetumomab; obiltoxaximab; obinutuzumab; ocrelizumab; ocrelizumab; ofatumumab; olaratumab; omalizumab; onabotulinumtoxinA; oprelleukin; palifurmin; palivizumab; pancrelipase; panitumumab; parathyroid hormone; pegademase bovine); pegaspargase; pegfilgrastim; pegfilgrastim-apgf; pegfilgrastim-bmez; pegfilgrastim-cbqv; pegfilgrastim-jmdb; peginterferon alfa-2a; peginterferon alfa-2a and ribavirin; peginterferon alfa-2b; peginterferon alfa-2b and ribavirin; peginterferon beta-1a; pegvaliase; pqpz; pegvisomant; pembrolizumab; pertuzumab; polatuzumab vedotin-piiq; porcine alfa alfa); Botulinum toxin type A (prabotulinumtoxinA)-xvfs; Radiolabeled albumin technetium Tc-99m albumin colloid kit; Ramucirumab;ranibizumab; rasburicase; ravulizumab-cwvz; raxicumab; reslizumab; reteplase; rilonacept; rimabotulinumtoxinB; risankizumab-rzaa; rituximab; rituximab and human hyaluronidase; rituximab-abbs; rituximab-pvvr; romiplostim; romosozumab-aqqg; sacituzumab govitecan-hziy; sacrosidase; sargramostim; sarilumab; sebelipase alfa alfa; secukinumab; siltuximab; somatotropin; tagraxofusp-erzs; taliglucerase alfa; tbo-filgrastim; technetium-99m tc fanolesomab; tenecteplase; tetumumab-trbw; tesamorelin acetate acetate); thyrotropin alfa; tildrakizumab-ASMN; tocilizumab; tositumomab and iodine I-131 tositumomab; trastuzumab; trastuzumab and hyaluronidase-OYSK; trastuzumab-ANN; trastuzumab-DKST; trastuzumab-DTTB; trastuzumab-PKRB; trastuzumab-QYYP; urofollicle-stimulating hormone; urokinase; ustekinumab; vedolizumab; velaglucerase alfa alfa; Vestronidase alfa (vjbk); Ziv (Aflibercept); Amjevita (adalimumab - atto); Dabitor (duplimab); Fulphila (pegfilgrastim - jmdb); Ilaris (canakinumab); Ixifi (infliximab - qbtx); Lyumje v (insulin lispro-aabc); Nyvepria (pegfilgrastim-apgf); Ogivri (trastuzumab-dkst); Semglee (insulin glargine); Uplizna (inbilizumab-cdon); APL (chorionic gonadotropin); Abrilada (adalimumab-afzb); Accretropin (somatropin); Actemra (tocilizumab);Acthrel (cortirellin ovine trifluoroacetate); Actimmune (interferon gamma-1b); Activase (alteplase); Adagan (pegastatin in cattle); Adakveo (crizanlizumab-tmca); Ansiri (brentuximab vedotin); Adlyxin (lixisenatide); Admelog (insulin lispro); Afrezza (human insulin); Aimovig (eisenumab-aooe); Ajovy (remanezumab-vfrm); Aldurazyme (laronidase); Alferon N injection (interferon alpha-n3 (human leukocyte-derived)); Amevive (alefacept); Amphadase (hyaluronidase); Anthim (obiltoxaximab); Abid (insulin glulisine); Aranesp (darbepoetin alfa); Arcalyst (rilanacept); Arzerra (ofatumumab); Asparlas (pegylated asparaginase); Avastin (bevacizumab); Avo Nex (interferon beta-1a); Avsola (infliximab-AxxQ); Basaglar (insulin glargine); Bavencio (avelumab); Belytem (belimumab); Beovu (bricizumab-dbll); Bebosa (ogaituzumab); Betaseron (interferon beta-1b); Bexxar (tositumomab and iodine I-131 tositumomab); Beritux (blinatumomab); Botox (botulinumtoxin A (onabotulinumtoxin A) Botox Cosmetic (botulinumtoxinA); Bravelle (urofollicle-stimulating hormone); Brineura (serripadase alfa); Cablivi (caprolactam-yhdp); Campath (alemtuzumab); Cathflo (alteplase); Cerzebin (imiglucerase); hCG (chorionic gonadotropin); Chromalbin (serum albumin chromate C R-51; Chymodiactin (chymopapain); Cimicifuga (pegylated certolizumab); Cinqair (reslizumab); Cosentyx (secukinumab); Cotazym (pancreatic lipase); Demetrin (pancreatic lipase); Crysvita (brosouzumab-twza); Gulsu (porcine alfa); Cyltezo (adalimumab-adbm); Cyramza (ramucirumab); and Zolpidem (daratumumab);Draximage (daratumumab and hyaluronidase-fihj); Draximage MAA (a kit for preparing aggregated technetium Tc-99m albumin); Dysport (abobotulinumtoxinA); Egrifta (tesmorelin acetate); Egrifta SV (tesmorelin acetate); Elaprase (idursulfatase); Elase-chloramphenicol (fibrinolytic enzyme and deoxyribonuclease combined with [bovine] chloramphenicol); Elelyso (tagraxofusp-erzs); Elitek (rasburicase); Elspar (asparaginase); Elzonris (tagraxofusp-erzs); Emgality (ganelizumab-gnlm); Empliciti (etanercept); Enbrel Mini (etanercept); Enhertu (trastuzumab dexmedetomidine); Angione (vedolizumab); Epogen / Procrit (epoetin alfa); Erbitux (cetuximab); Erelzi (etanercept-szzs); Erelzi Sensoready (etanercept-szzs); Erwinaze (Erwinia chrysanthemi asparaginase); Eticovo (etanercept-ykro); Evenity (lomosozumab-aqqg); Extavia (interferon beta-1b); Eylea (aflibercept); Fabrazyme (agalsidase beta); Fasenra (benralizumab); Fiasp (insulin aspart); Follistim (follitropin beta); Follistim AQ (follicle-stimulating hormone beta); Follistim AQ Cartridge (follicle-stimulating hormone beta); Gamifant (emalimumab-lzsg); Gazyva (otuzumab); Genotropin (growth hormone); Gonal-f (follicle-stimulating hormone alfa); Gonal-f RFF (follicle-stimulating hormone alfa); Gonal-f RFF RediJect (follicle-stimulating hormone alfa); Granix (tbo-filgrastim); Hadlima (adalimumab-bwwd); Hemlibra (emicizumab-kxwh); Herceptin (trastuzumab); Herceptin subcutaneous injection (Herceptin Hylecta (trastuzumab and hyaluronidase-oysk); Herzuma (trastuzumab-pkrb); Humalog (insulin lispro); Humalog Mix 50 / 50 (insulin lispro protamine and insulin lispro); Humalog Mix 75 / 25 (insulin lispro protamine and insulin lispro);Humatrope (somatropin); Humegon (urogonadotropin); Humira (adalimumab); Humulin 70 / 30 (human insulin and human insulin); Humulin N (human insulin); Humulin R U-100 (human insulin); Humulin RU-500 (human insulin); Hydase (hyaluronidase); Hylenex recombinant (human hyaluronidase); Hyrimoz (adalimumab-adaz); Ilumya (tirekizumab-asmn); Imfinzi (durvalumab); Increlex (mecasermin); Infasurf (carfaxan); Infergen (interferon alfacon-1); Inflectra (infliximab-dyyb); Intron A) (interferon alpha-2b); Iplex (mecasermin-linfibe); Iprivask (desirudin); Jeanatope (iodinated I-125 albumin kit); Jetrea (octoplasmin); Jeuveau (botulinumtoxinA-XVFS); Kadcyla (ado-enmetazocortuzumab); Kalbitor (ecallote); Kanjin ti (trastuzumab-ANNS); Kanuma (serbelipase alfa); Kepivance (palifermin); Kevzara (salinelumab); Keytruda (pembrolizumab); Kineret (anakinra); Kinlytic (urokinase); Krystexxa (pegroloase); Lantus (insulin glargine); Lartruvo (olarumab); Lemt rada (alemtuzumab); Leukine (sargramostim); Levemir (insulin detemir); Libtayo (cimiprilimab-rwlc); Lucentis (ranibizumab); Lumizyme (alglucosidase alfa); Lumoxiti (pasitumomab-tdfk); Macrotec (kit for preparing aggregated technetium Tc-99m albumin); Megatope ( Iodinated I-131 albumin kit); Menopur (urogonadotropin); Mepsevii (vestronidase alpha-vjbk); Microlite (radiolabeled albumin technetium Tc-99m albumin colloid kit); Mexinluo (methoxypolyethylene glycol-epoetin beta); Mvasi (bevacizumab-awwb); Myalept (metreleptin); Mylotarg (gemtuzumab ozogamicin);Myobloc (botulinumtoxin B); Merezan (alglucosidase alfa); Myxredlin (human insulin); N / A (raxicumab); Naglazyme (gasulfase); Natpara (parathyroid hormone); Neulasta (pegfilgrastim); Neulasta Onpro (pegfilgrastim); Neumega (oprelvekin); Neupogen (filgrastim); NeutroSpec (technetium-99m tc-fasomab); Nivestym (filgrastim-aafi); Norditropin (somatropin); Novarel (chorionic gonadotropin); Novolin 70 / 30 (human protamine insulin and human insulin); Novolin N (human protamine insulin); Novolin R (human insulin); Novolog (insulin aspart); Novolog Mix 50 / 50 (insulin aspart protamine and insulin aspart); Novolog Mix 70 / 30 (insulin aspart protamine and insulin aspart); Nplate (romiplostim); Nucala (mepolizumab); Nulojix (belatacept); Nutropin (somatropin); Nutropin AQ (somatropin); Ocrevus (ocrelizumab); Omnitrope (somatropin); Oncaspar (pegaspargase); Ontak (denileukin 2); Ontruzant (trastuzumab-dttb); Opdivo (nivolumab); Orencia (abatacept); Orthoclone OKT3 (moromona-CD3); Ovidrel (chorionic gonadotropin alfa); Oxervate (cenezumab-bkbj); Padcev (veentuzumab-ejfv); Palynziq (pevalizumab-pqpz); Pancreaze (pancrelipase); Pegasys (pegylated interferon alfa-2a); Pegasys-Copegus combination pack (pegylated stem cell transplant); interferon alfa-2a and ribavirin); PegIntron (peginterferon alfa-2b); PegIntron / Rebetol combination pack (peginterferon alfa-2b and ribavirin); Pugna (uronoceptin); Perjeta (pertuzumab); Pertzye (pancrelipase); Plegridy (peginterferon beta-1a); Polivy (vepotuzumab-piiq); Portrazza (necituzumab);Poteligeo (moglizumab-kpkc); Praluent (alirocumab); Praxbind (idarucizumab); Pregnyl (chorionic gonadotropin); Procrit (epoetin alfa); Proleukin (aldesleukin); Prolia (denosumab); ProstaScint (caprolizumab pendetide); Pulmolite (kit for preparing aggregated technetium Tc-99m albumin); Pulmotech MAA (a kit for preparing aggregated technetium Tc-99m albumin); Pulmozyme (dornase alfa); Raptiva (efalizumab); Rebif (interferon beta-1a); Reblozyl (rotesip-aamt); Regranex (becaplermin); Remicade (infliximab); Renflexis (infliximab-abda); Reopro (abciximab); Rebiotin (evolocumab); Repronex (urogonadotropin); Retacrit (epoetin alfa-epbx); Retavase (reteplase); Re Vcovi (erabesidase-LVLR); Rituxan (rituximab); RituxanHycela (rituximab and human hyaluronidase); Roferon-A (interferon alpha-2a); Ruxience (rituximab-PVVR); Ryzodeg 70 / 30 (insulin degludec and insulin aspart); Sapogenin (somatropin); Santyl (collagenase); Sarclisa (isatuximab-IRFC); Serostim (somatropin); Siliq (berdalumab); Simponi (golimumab); Simponi Aria (golimumab); Simulect (basiliximab); Skyrizi (risankizumab-rzaa); Soliqua 100 / 33 (insulin glargine and lixisenatide); Soliris (eculizumab); Somavert (pegvisomant); Sedano (ustekinumab); Strensiq (asforase alfa); Sucraid (sucrasidase); Survanta (belactan); Sylvant (siltuximab); Synagis (palivizumab); Takhzyro (lanarumab-flyo); Taltz (evizumab); Tanzeum (albiglutide); Tecentriq (atezolizumab);Tepezza (trbw); Thyrogen (thyrotropin alfa); TNKase (tenecteplase); Toujeo (insulin glargine); Trasylol (aprotinin); Trazimera (trastuzumab qyyp); Tremfya (guserkizumab); Tresiba (insulin degludec); Trodelvy (gosartuzumab hziy); Trogarzo (ibalizumab uiyk); Turbomax (Trembryant) rulicity (dulaglutide); Truxima (rituximab-abbs); Tysabri (natalizumab); Udenyca (pegfilgrastim-cbqv); Ultomiris (ravulizumab-cwvz); Unituxin (dalutuximab); Vectibix (panitumumab); Verluma (nofetumomab); Vimizim (elosulfatase alfa); Viokace (pancreatic lipase); Vi The following are the products of the Company: trase (hyaluronidase); Voraxaze (glutaric acidase); VPRIV (velaglucerase alfa); Xeomin (incobotulinumtoxinA); Xgeva (denosumab); Xiaflex (collagenase clostridium histolyticum); Xigris (drotrecogin alfa); Xolair (omalizumab); Xultophy 100 / 3.6 (insulin degludec and liraglutide); Yervoy (ipilimumab); monoclonal antibody); Zaltrap (Ziv-aflibercept); Zarxio (filgrastim-sndz); Zenapax (daclizumab); Zenpep (pancrelipase); Zevalin (ibritumomab tiuxetan); Ziextenzo (pegfilgrastim-bmez); Zinbryta (daclizumab); Zinplava (belotosumab); Zirabev (bevacizumab-bvzr); Zomacton (somatropin); Zorbtive / Serostim (somatropin);

[0051] Inhalation anesthetics

[0052] Aleflurane; chloroform; cyclopropane; desflurane (Uning); diethyl ether; enflurane (Easyning); ethyl chloride; ethylene; trifluorochlorobromide (Halothane); isoflurane (Huo Ning, Isoflurane); isopropenyl vinyl ether; methoxyflurane; methoxyflurane; methoxypropane; nitrous oxide; roflurane; sevoflurane (Xibaofuning, Yuetan, Sevoflurane); teflonane; trichloroethylene; vinyl ether; xenon;

[0053] Injectable drugs

[0054] Ablavar (gadofosvesic trisodium injection); Abarelix Depot; Abobotulinumtoxin type A 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 trifluoroacetate injection) Triflutate); Actummune; Activase; Acyclovir for injection (Zovirax injection); Pertussis vaccine (Adacel); Adalimumab; Adenoscan (adenosine injection); Adenosine injection (Adenoscan); Epinephrine injection (Adrenaclick); AdreView (iobenzylguanidine I123 injection for intravenous use); Influenza virus vaccine (Afluria); Ak-Fluor (fluorescein injection); Aldurazyme (Laronidase); Arabinose cerebrosidase injection (Arabinose cerebrosidase); Alkeran injection (Melphalan hydrochloride injection); Allopurinol sodium for injection (Aloprim); Aloprim (allopurinol sodium for injection); Alprostadil; Alsuma (Sumatriptan injection); ALTU-238; Amino acid injection; Aminosyn; Apidra; Apremilast; Alprostadil injection dual chamber system (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 Injection (Amytal Sodium Sodium); Amytal sodium (ammobarbital sodium injection); Anakinra; Anti-Amyloid (Anti-Abeta); Anti-Beta7 (Anti-Beta7); Anti-Beta20; Anti-CD4; Anti-CD20; Anti-CD40; Anti-IFNα; Anti-IL13; Anti-OX40L; Anti-oxLDS; Anti-NGF; Anti-NRP1; Arixtra sodium; Amphadase (Hyaluronidase injection); Ammonul (sodium phenylacetate and sodium benzoate injection); Anaprox sodium; Atenolol injection (dolasetron mesylate injection); Apidra (insulin glulisine [rDNA source] injection); Apomab; Aranesp (darbepoetin alfa) alfa); Argatroban (Argatroban Injection); Arginine Hydrochloride Injection (R-Gene 10); Aristocort; Aristospan; Arsenic Trioxide Injection (Trisenox); Articane HCl and Septocaine Injection (Septocaine); Arzerra (Ofatumumab Injection); Asclera (Poliodocanol Injection); Ataluren; Ataluren-DMD; Aticane Lorre 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 Injection); Antibacterial Water (Antibacterial Water for Injection); Baclofen Injection (Lioresal Intrathecal Injection); Bal in Oil Ampoule (Bal in Oil Ampules)(Dimercarprol Injection); BayHepB; BayTet; Diphenhydramine; Bendamustine Hydrochloride Injection (Treanda); Benztropine Mesylate Injection (Cogentin); Betamethasone Injectable Suspension (Celestone Soluspan); Tosimol (Bexxar);Bicillin CR 900 / 300 (Bicillin G Benzathine Penicillin and Penicillin G Procaine Injection); Blenoxane (Bleomycin Sulfate Injection); Bleomycin Sulfate Injection (Bleomycin); Ibandronate Sodium (Boniva) Injection (Ibandronate Sodium Injection); Botox Cosmetic (Botulinum Toxin A for Injection); BR3-FC; Bravelle (Follitropin Injection); Tocilamine (Tocilamine Bromide Injection); Brevital Sodium (Methohexital Sodium for Injection); Terbutaline (Brethine); Briobacept; BTT-1023; Butex (Brethine Bromide Injection); Bivacaine HCl; Byetta; Ca-DTPA (calcium trisodium triamine pentaacetate injection); Cabazitaxel injection (Jevtana); Caffeine alkaloids (caffeine and sodium benzoate injection); Calcijex injection (calcitriol); Calcijex (calcitriol); Calcium chloride (calcium chloride injection 10%); Calcium disodium versatate (calcium disodium edetate injection); Campath (alemtuzumab); Camptosar injection (irinotecan hydrochloride); Hydrochloride); Canakinumab injection (Ilaris); Capreomycin sulfate (capreomycin for injection); Capreomycin for injection (capreomycin sulfate); Cardiolite (a kit for the preparation of technetium Tc99 methoxyisocyanate for injection); Autologous chondrocytes (Carticel); Alteplase (Cathflo); Cefazolin and dextrose for injection (cefazolin injection); Cefepime hydrochloride; Acetoclax; Ceftriaxone; Imiglucerase; L-carnitine (Carnitor) injection; Caverject; Betamethasone sodium phosphate (Celestone Soluspan; Celsior; Cerebyx (fosphenytoin sodium injection); Cerebrosidase (cerebrosidase arabinoside injection); Ceretec (technetium Tc99m examoxime injection); Certolizumab; CF-101; Chloramphenicol sodium succinate (chloramphenicol sodium succinate injection); Chloramphenicol sodium succinate injection (chloramphenicol sodium succinate); Cholestagel (colesevelam HCL); Chorionic gonadotropin alfa injection (Ovidrel); Certolizumab (Cimzia); Cisplatin (cisplatin injection); Clolar (clofarabine injection); Clomiphine citrate; Clonidine injection (clonidine hydrochloride injection (Duraclon));Cogentin (benztropine mesylate injection); colistin mesylate injection (polymyxin M); polymyxin M (colistin mesylate injection); Compath; conivaptan hydrochloride injection (Vaprisol); conjugated estrogens for injection (premarin injection); Copaxone; cortisol trifluoroacetate injection (Acthrel); Corvert (ibutilide fumarate injection); Cubicin (daptomycin injection); CF-101; Hydroxocobalamin Cyanokit (hydroxycobalamin for injection); cytarabine liposome injection (DepoCyt); cyanocobalamin; Cytovene (ganciclovir); DHE45; daclizumab; Dacogen (decitabine injection); dalteparin; dantrolene sodium IV (dantrolene sodium for injection); dantrolene sodium for injection (dantrolene sodium IV); daptomycin injection (cubicin); darbepoietin alfa (Darbepoietin Alfa); DDAVP injection (desmopressin acetate injection); Decavax; decitabine injection (Dackin); anhydrous ethanol (anhydrous ethanol injection); denosumab injection (Prolia); testosterone enanthate (Delatestryl); estradiol valerate (Delestrogen); dalteparin sodium; sodium valproate injection (Depacon); Depomet (Depo Medrol (methylprednisolone acetate injectable suspension); DepoCet (cytarabine liposome injection); DepoDur (morphine sulfate XR liposome injection); Desmopressin acetate injection (DDAVP injection); Estradiol cypionate (Depo-Estradiol); Depo-Provera 104 mg / ml; Depo-Provera 150 mg / ml; Depo-Testosterone; Dexrazoxane (Totect) for injection, intravenous infusion only; Dextrose / electrolytes; Dextrose and Sodium Chloride Injection (5% dextrose in 0.9% sodium chloride); Dextrose; Diazepam injection (Diazepam Injection)(Dialex Injection); Digoxin Injection(Lanoxin Injection); Hydromorphone Hydrochloride-HP(Hydromorphone Hydrochloride Injection); Dimercaprol Injection(Bal in Oil Ampules); Diphenhydramine Injection(Benadryl Injection);Dipyridamole injection (Dipyridamole Injection); DMOAD; Docetaxel for injection (Taxotere); Dolasetron mesylate injection (Atenolol injection); Doribax (Doripenem for injection); Doripenem for injection (Doripenem injection); Doxercalciferol injection (Hectorol injection); Doxil (Doxorubicin liposome injection); Doxorubicin liposome injection (Doxorubicin liposome injection); Clonidine hydrochloride injection (Clonidine injection); Morphine injection (Duramor ph) (morphine injection); botulinum toxin (botulinum toxin type A injection); ecallantide injection (Kalbitor); EC-Naprosyn (naproxen); edetate calcium disodium injection (vilcosyl calcium disodium); Edex (alprostadil for injection); hepatitis B vaccine (Engerix); edrophonium injection (Enlon); Eliglustat tartrate; Eloxatin (oxaliplatin injection); Emond injection (fosaprepitant dimeglumine); Dimeglumine injection); Enalaprilat injection (enalaprilat injection); Enlon (edrophonium injection); Enoxaparin sodium injection (enoxaparin); Gadoxetate disodium (Eovist) (gadoxetate disodium injection); Enbrel (etanercept); Enoxaparin (Enoxaparin); Arabinose injection (Epicel); Epinepherine injection (Epinepherine); Epinephrine injection (Epipen); Epinephrine injection (epratuzumab); Erbitux; Ertapenem injection (Invanz); Erythropoietin injection (Erythropoietin) ieten); Essential Amino Acid Injection (Nephramine); Estradiol Cypionate; Estradiol Valerate; Etanercept; Exenatide Injection (Byetta); Clofarabine Injection (Evlotra); Fabrazyme (β-galactosidase); Famotidine Injection; FDG (Fluorodeoxyglucose F18 Injection); Nano-Iron Oxide Injection (Feraheme) (Ferumoxytol Injection); Ferumoxides Intravenous Injection (Ferumoxides Injection Solution); Urotropin (Fertinex); Ferumoxide Injectable Solution (Ferumoxide Intravenous Injection);Felimod Injection (Nano Iron Oxide Injection); Flagyl Injection (Metronidazole Injection); Fluarix; Fludara (Fludarabine Phosphate); Fluodeoxyglucose F18 Injection (FDG); Luciferin Injection (Ak-Fluor); Follistim AQ Cartridge (Follistin β Injection); Follistin α Injection (Gonal-f RFF); Follistin β Injection (Follistim AQ cartridge); Folotyn (Pralatrexate solution for intravenous injection); Fondaparinux; Forteo (Teriparatide (rDNA origin) injection); Fostamatinib; Fosaprepitant dimeglumine injection (Emond injection); Foscarnet injection (foscarnet sodium); Foscarnet sodium (foscarnet injection); Fosphenytoin sodium injection (Cerebyx); Fosprofolate sodium injection (Lusedra); Fragmin; Fuzeon (enfuvirtide); GA101; Gadobenate dimeglumine injection (Multihance); Gadofosvesic trisodium injection (Ablavar); gadoteridol injection solution (ProHance); gadoversetamide injection (OptiMARK); gadoxetate disodium injection (Eovist); Ganirelix (ganirelix acetate injection); Gardasil; GC1008; GDFD; gemtuzumab ozogamicin for injection (Mylotarg); Genotropin; gentamicin injection; GENZ-112638; golimumab injection (Simponi injection); GONAL-F RFF (follicle-stimulating factor alfa injection); granisetron hydrochloride (Kytril injection); gentamicin sulfate; Glatiramer acetate (Glatiramer acetate) Acetate; Glucagon injection (Glucagen); Glucagon; HAE1; Haldol (haloperidol injection); Havrix; Doxcalciferol injection (docecalciferol injection); Hedgehog pathway inhibitors; Heparin; Herceptin; hG-CSF; Humalog; Human growth hormone; Humatrope; HuMax; Humegon;Humira; Humulin; Ibandronate Sodium Injection (Boniva Injection); Ibuprofen Lysine Injection (NeoProfen); Ibutilide Fumarate Injection (Corvert); Idarubicin PFS (Idarubicin Hydrochloride Injection); Idarubicin Hydrochloride Injection (Idarubicin PFS); Ilaris (Canakinumab Injection); Imipenem-cilastatin for Injection (Primaxin IV); Sumatriptan Injection (Imitrex); Incobotulinumtoxin A for Injection (Xeomin); Increlex (Mecasermin [rDNA Origin] Injection); Indocin Injection (Indocin IV) (indomethacin injection); indomethacin injection (intravenous indomethacin); Infanrix; dihydroergotamine sodium injection (Innohep); insulin; insulin aspart [rDNA source] injection (NovoLog); insulin glargine [rDNA source] injection (Lantus); insulin glulisine [rDNA source] injection (Abid); recombinant interferon alpha-2b for injection (Intron A); Intron A (recombinant interferon alpha-2b for injection); Ertapenem injection; InvegaSustenna (paliperidone palmitate extended-release injectable suspension); Invirase (saquinavir mesylate); iobenzylguanidine I for intravenous use 123 injection (AdreView); iopromide injection (Ultravist); ioversetol injection (Optiray injection); Iplex (Rinfabate [rDNA source] injection); desirudin injection (Iprivask); irinotecan hydrochloride (Camptosar injection); iron sucrose injection (Venofer); Istodax injection ( Romidepsin for injection); itraconazole injection (Sporanox injection); Jeftana (cabazitaxel injection); Jonexa; Kalbitor (ecallatide injection); KCL in D5NS (potassium chloride in 5% dextrose and sodium chloride injection); KCL in D5W; KCL in NS; Triamcinolone acetonide 10 injection (triamcinolone acetonide injectable suspension); Kepivance (palifermin);Keppra injection (levetiracetam); Keratin; KFG; Kinase inhibitors; Kineret (anakinra); Kinlytic (urokinase injection); Kinrix; Klonopin (clonazepam); Ketril injection (granisetron hydrochloride); Lacosamide tablets and injection (Vimpat); Lactated Ringer's; Lanoxin injection (digoxin injection); Lansoprazole for injection (Prevacid); Lantus; Calcium folinate (leucovorin injection); Lente(L); Levulin; Insulin detemir (Levemir); Sargramostim (Leukine Sargramostim; Leuprorelin acetate; Levothyroxine; Levetiracetam injection (Kepran injection); Enoxaparin (Lovenox); L-carnitine injection (Carnitor injection); Lexiscan (Regadenoson injection); Lioresal intrathecal injection (Lioresal Intrathecal (baclofen injection); Liraglutide [rDNA] injection (Victoza); Enoxaparin (enoxaparin sodium injection); Lucentis (ranibizumab injection); Lumizyme; Lupron (leuprorelin acetate injection); Lusedra (fospropofol sodium injection); Maci; Magnesium sulfate (magnesium sulfate injection); Mannitol injection (mannitol intravenous injection); Macacaine (bupivacaine hydrochloride and epinephrine injection); Maxipime (cefepime hydrochloride for injection); MDP Multidose Kit for Technetium Injection (technetium Tc99m meprobamate injection liquid); mecasermin [rDNA source] injection (Increas injection); mecasermin linfipa [rDNA source] injection (Iplex); melphalan hydrochloride injection (Iplex injection); methotrexate; meningococcal vaccine (Menactra); Menopur (Menopur injection); Repronex for injection; methohexital sodium for injection (methylhexybarbital sodium); methyldopa hydrochloride injection solution (methyldopa hydrochloride); methylene blue (methylene blue injection); methylprednisolone acetate injectable suspension (Dibomet); MetMab; metoclopramide injection (Reglan injection); Metrodin (urofollicle-stimulating hormone for injection);Metronidazole injection (Metronidazole injection); Miacalcin (Miacalcin); Midazolam (Midazolam injection); Mimpara (Cinacalet hydrochloride); Minocycline injection (Minocycline injection); Minocycline injection (Minocycline injection); Mipomersen; Mitoxantrone concentrate for injection (Novantrone); Morphine injection (Duramorph); Morphine sulfate XR liposomal injection (extended-release morphine sulfate injection); Sodium morrhuate (Sodium morrhuate injection); Motesanib (Motesanib hydrochloride injection); ); Mozobipro (plerixafor injection); Modis (gadobenate dimeglumine injection); Polyelectrolyte and Dextrose Injection; Polyelectrolyte Injection; Milotet (gemtuzumab ozogamicin for injection); Myozyme (alglucosidase alpha); Ethofen injection (ethoxynaphthalene sodium); Ethofen sodium (ethoxynaphthalene injection); Naltrexone XR injection (Vivitrol); Naprosyn (naproxen); NeoProfen (ibuprofen lysine injection); Nandrolone decanoate (Nandrol Decanoate); Neostigmine methylsulfate (neostigmine methylsulfate injection); NEO-GAA; NeoTect (technetium Tc 99m Depreotide injection); Shenbi Amin (essential amino acid injection); Neulasta (pegfilgrastim); Neulasta (filgrastim); Novolin; Novo; NeoRecormon; Neutrexin (trimetrexin glucuronide injection); NPH (N); Amiodarone (Nexterone) (amiodarone HCl injection injection); Norditropin (somatropin injection); Normal saline (sodium chloride injection); Noantol (mitoxantrone concentrate for injection); Innolet 70 / 30 (70% NPH, human low-protamine insulin suspension and 30% regular human insulin injection); Novolet (insulin aspart [rDNA source] injection); Nipute (romiplostim); Nutropin (somatropin injection (rDNA source)); Nutropin AQ; Nutropin Depot (somatropin injection (rDNA source)); Octreotide acetate injection (Sandostatin LAR); Orelizumab; Ofalizumab injection (Arzerra); Olanzapine extended-release injectable suspension (Zyprexa Relprevv);Omnitarg; Omnitrope (somatropin [rDNA source] injection); Ondansetron hydrochloride injection (Zofran injection); OptiMARK (gadofrostamide injection); Ampel injection (ioversetol injection); Orencia; Aviva's Osmitrol injection (mannitol injection in Aviva plasticware); Viagra's Osmitrol injection (mannitol injection in Baxter plasticware); osteoprotegerin (Osteoprotegrin); Ovidrel (chorionic gonadotropin alfa injection); Neopenicillin (Neopenicillin for injection); Oxaliplatin injection (Eloxatin); Oxytocin injection (Oxytocin); Paliperidone palmitate extended-release injectable suspension (Sustastat); Pamidronate disodium injection (Pamidronate injection); Panitumumab injection for intravenous use (Vectibix) ectibix); papaverine hydrochloride injection (papaverine injection); papaverine injection (pavoline hydrochloride injection); parathyroid hormone; paricalcitol injection fliptop vial (Zemplar injection); PARP inhibitors; combination vaccine (Pediarix); PegIntron; pegylated interferon injection (Peginterferon); filgrastim; penicillin G benzathine and penicillin G procaine; calcium trisodium triamine pentaacetate injection (Ca-DTPA); Trisodium zinc triamine pentaacetate injection (Zn-DTPA); Pepcid injection (famotidine injection); Pergonal; Pertuzumab; Phentolamine mesylate (Phentolamine mesylate for injection); Physostigmine salicylate (Physostigmine salicylate injection); Physostigmine salicylate (Physostigmine salicylate injection); Piperacillin and tazobactam injection (Zosyn); Oxytocin (Oxytocin injection); Plasma-Lyte 148 (Plasma-Lyte 148) (polyelectrolyte injection); Promali 56 and dextrose (polyelectrolyte and dextrose injection in Baxter plastic container); Promali; Plerixafor injection (Mozobi); Polidocanol injection (Asclera); Potassium chloride; Pralatrexate solution for intravenous injection (Flotyl); Pramlintide acetate injection (Pramlintide); Premalin injection (conjugated estrogens for injection); Kit for the preparation of technetium Tc99 methoxyisocyanate for injection (tetrakis(methoxyisobutylisocyanate) chromone(I) fluoroborate); Lansoprazole intravenous injection (Prevacid IV) (lansoprazole for injection);Imipenem and Cilastatin Sodium Intravenous Injection (Imipenem and Cilastatin for Injection); Prochymal; Procrit; Progesterone; Proxanthin (Gadoteridol Injection Solution); Procrit (Denosumab Injection); Promethazine HCl Injection (Promethazine Hydrochloride Injection); Propranolol HCl Injection (Propranolol HCl Injection); Quinidine Gluconate Injection (Quinidine Injection); Quinidine Injection (Quinidine Gluconate Injection); R-Gene 10 (arginine hydrochloride injection); Lucentis injection; Ranitidine hydrochloride injection (Zantac injection); Raptiva injection; Reclast (zoledronic acid injection); Recombivarix HB; Regadenoson injection (Lexiscan); Metoclopramide injection (metoclopramide injection); Remicade; Renagel; Renvela (sevelamer carbonate); Repronex (fertility enhancer for injection); Retrovir intravenous injection (Retrovir IV) (azidothymidine injection); rhApo2L / TRAIL; Ringer's solution and 5% dextrose injection (Ringer's solution in dextrose solution); Ringer's injection (Ringer's injection); Rituxan; Rituximab; Rocephin (ceftriaxone); Rocuronium Bromide Injection (Zemuron); Rocuronium-A (interferon alpha-2a); Flumazenil for Injection (Romazicon); Romidepsin for Injection (Isodax Injection); Saizen (Somatropin Injection); Sandostatin LAR (Octreotide Acetate Injection); Sclerostin Antibody; Sensipar (cinacalcet); Sensorcaine (Bupivacaine HCl Injection); Septocaine (articaine HCl and epinephrine Injection); Serostim LQ (Somatropin (rDNA Derived) Injection); Simponi Injection (golimumab Injection); Sodium Acetate (Sodium Acetate Injection); Sodium Bicarbonate (Sodium Bicarbonate 5% Injection); Sodium Lactate (Sodium Lactate Injection from Aviva);Sodium phenylacetate and sodium benzoate injection (Ammonul); somatotropin injection (rDNA source) (Nutropin); Sporanox injection (itraconazole injection); Stelara injection (ustekinumab); Stemgen; Sufenta (sufentanil citrate injection); sufentanil citrate injection (Sufenta); Sumavel; sumatriptan injection (Aluma); Symlin; Symlin pen injection (Symlin Pen); systemic hedgehog antagonist; Synvisc-One (Hylan GF 20 single intra-articular injection); Tasiva; Taxotere (docetaxel for injection); Technetium Tc99m; Telavancin for injection (Vibativ); Sirolimus injection (Tolisai); Tenormin intravenous injection (atenolol injection); Teriparatide (rDNA-derived) injection (Bone Stabilizer); Testosterone cypionate; Testosterone enanthate; Testosterone propionate; Tev-Tropin (rDNA-derived growth hormone for injection); tgAAC94; Thallium chloride; Theophylline; Thiotepa (thiotepa injection); Anti-thymocyte globulin injection (Thymoglobulin) (Anti-Thymocyte globulin Globulin (rabbit); Thyrogen (thyroid stimulating hormone alpha for injection); Timentin injection (timentin injection); Tigan injection (trimethoxazole hydrochloride injection); Timentin injection (timentin injection); Tenecteplase; Tobramycin injection (tobramycin injection); Tocilizumab injection (Acmero); Tolisai (sirolimus injection); Totec (dexrazoxane for injection, intravenous infusion only); Trastuzumab-DM1 (Trastuzumab-DM1); Travasol (amino acid (injection)); Triamurt (bendamustine hydrochloride injection); Trelstar (triptorelin pamoate for injectable suspension); Triamcinolone acetonide; Triamcinolone diacetate; Triamcinolone hexanoate injectable suspension (triamcinolone hexanoate injection 20 mg); Triamcinolone injectable suspension (triamcinolone acetonide injectable suspension); Trimethoxazole hydrochloride injectable (Tigan injection); Trimetrexate glucuronide injection (trimetrexate glucuronide injection); Triptorelin pamoate for injectable suspension (Trelstar); Epinephrine injection; Trivaris (triamcinolone acetonide injectable suspension);Trisenlo (arsenic trioxide injection); Sulfolisine; Typhoid Vi; Uvisen (iopromide injection); Urofollicle-stimulating hormone for injection (follicle-stimulating hormone); Urokinase injection (Kinlytic); Ustekinumab (Sidano injection); Ultra-long-acting agent (U); Diazepam; Sodium valproate injection (Depacon); Valtropin (somatropin injection); Vancomycin hydrochloride (Vancomycin hydrochloride injection); Vancomycin hydrochloride injection (Vancomycin hydrochloride injection hydrochloride); Vaprisol (conivaptan hydrochloride injection); VAQTA; Vasovist (gadofosvesant trisodium injection for intravenous use); Vectibix (panitumumab injection for intravenous use); Vilafort (iron sucrose injection); Verteporfin injection (Visudal); Telavancin injection (telavancin for injection); Victoza (liraglutide [rDNA] injection); Vimpat (lacosamide tablets and injection); Vinblastine sulfate (vinblastine sulfate injection); Vicasa PFS (sulfuron vincristine sulfate injection); Victoza; vincristine sulfate (vincristine sulfate injection); Visudyne (verteporfin injection); vitamin B-12; Vivitrol (naltrexone XR injection); Voluven (hydroxyethyl starch sodium chloride injection); Xeloda; Xenical (orlistat); Xeomin (botulinum toxin A for injection); Xolair; Mefosfolate injection (ranitidine hydrochloride injection); Zemplar injection (paricalcitol injection Fliptop vial); Rocuronium (rocuronium injection); Zenipax (daclizumab); Zevalin; Azidothymidine injection (Rituvik intravenous injection); Zithromax injection (azithromycin); Zn-DTPA (zinc trisodium triamine pentaacetic acid injection); Zofran injection (ondansetron hydrochloride injection); Lidocaine; Zoledronic acid for injection (Zometa); Zoledronic acid injection (Aclasta); Zometa (zoledronic acid for injection); Zocine (piperacillin and tazobactam injection); Zyprexa Relprevv (olanzapine extended-release injectable suspension);

[0055] Liquid medication (non-injectable)

[0056] Alimta; AccuNeb (salbutamol sulfate inhalation solution); Activated charcoal suspension in water (activated charcoal suspension); Activated charcoal suspension (activated charcoal suspension in water); Seretide; Agenerase oral solution (amprenavir oral solution); Akten (lidocaine hydrochloride ophthalmic gel); Alamast (pemilast potassium ophthalmic solution); Albumin (human) 5% solution (human serum albumin 5%); Salbutamol sulfate inhalation solution; Nitazoxanide oral suspension (Alinia); Nedocril sodium (Alocril); Alphagan (Alphagan); Alrex; Avisco; amprenavir oral solution; hydrocortisone acetate and pramoxine hydrochloride cream (Analpram-HC); formoterol tartrate inhalation solution (Bulova); triamcinolone hexanoate injection 20 mg (triamcinolone hexanoate injectable suspension); mesalamine (Asacol); mometasone furoate (Asmanex); azelastine hydrochloride (Astepro); azelastine hydrochloride (azelastine hydrochloride nasal spray); atrovent nasal spray (ipratropium bromide nasal spray); atrovent nasal spray .06; Augmentin ES-600 (Augmentin ES-600); Azasite (azithromycin ophthalmic solution); Azelaic Acid (Finacea gel); Azelastine hydrochloride nasal spray (azelastine hydrochloride); Azelex (azelaic acid cream); Perimin (brinzolamide ophthalmic suspension); Antibacterial saline; Balanced salt; Bepotastine; Bactroban Nasal; Beclovent; Betimol W; Timolol solution (Betimol); Betoptic S; Bepreve; Bimatoprost ophthalmic solution; Bleph 10 (sodium acesulfame ophthalmic solution 10%); brinzolamide ophthalmic suspension (Pailimin); bromfenac ophthalmic solution (Xibrom); Bromhist; Bulova (formoterol tartrate inhalation solution); budesonide inhalation suspension (Pulmicort Respules); Cambia (diclofenac potassium for oral solution); Capex; Carac; Carboxin-PSE; Kanting; Cayston (aztreonam for inhalation solution); mycophenolate mofetil; Centany; Cerumenex; Ciloxan ophthalmic solution (ciprofloxacin HCl ophthalmic solution); Ciprofloxacin dexamethasone ear drops (Ciprodex); Ciprofloxacin HCl ophthalmic solution (Ciprodex ophthalmic solution); Clemastine fumarate syrup (clemastine fumarate syrup); CoLyte (PEG electrolyte solution); Combiven;Comtan; Condylox; Cordran; Cortisporin ophthalmic suspension; Cortisporin ear suspension; Cromolyn sodium inhalation solution (Intal spray solution); Cromolyn sodium ophthalmic solution (Opticrom); Crystalline amino acid solution with electrolytes (Aminosyn electrolytes); Cuvposa; Glycopyrrolate (Cuvposa oral solution); Cyanocobalamin (CaloMist nasal spray); Cyclosporine oral solution (Jingefu oral solution); Cyclogyl; Cysview (5-aminolevulinic acid hexyl ester hydrochloride intravesical solution); DermOtic oil (Fluocinolone Acetonide Oil Ear drops) 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); Differin; Dilantin 125 (phenytoin oral suspension); Oxybutynin (Ditropan); Dorzolamide hydrochloride ophthalmic solution (Shujinglu); Dorzolamide hydrochloride timolol maleate ophthalmic solution (Cosopt); Dovonex Scalp (calcipotriol solution); Doxycycline calcium (Doxycycline Calcium) Calcium oral suspension (oral doxycycline); Efudex; Elaprase (idosulfatase solution); Elestat (epinastat ophthalmic solution); Mometasone; Epinastine hydrochloride ophthalmic solution (elestat); Lamivudine (Epivir HBV); Epoetin (epoetin alfa); Erythromycin topical solution 1.5% (kalinamide); Ethiodol (Ethiodized Oil); Ethosuximide oral solution (Zarontin oral solution); Ulis; Extraneal (icodextrin peritoneal dialysis solution); Fimad; Felecithin intravenous injection (felecithin injectable solution); Flovent; Ofloxacin otic (Floxin Otic) (ofloxacin otic solution); Flo-Pred (prednisolone acetate oral suspension); Fluoroplex; Flunisolide nasal solution (flunisolide nasal spray. 025%);Fluorometholone Ophthalmic Suspension (FML); Flurbiprofen Sodium Ophthalmic Solution (Ocofen); FML; Foradil; Formoterol Fumarate Inhalation Solution (Perforomist); Fosamax; Furadantin (Nitrofurantoin Oral Suspension); Furoxone; Gammagard Liquid (Immune Globulin Intravenous (Human) 10%); Gantrisin (Sulfadimethoxazole Pediatric Suspension); Gatifloxacin Ophthalmic Solution (Zymar); Jingefu Oral Solution (Cyclosporin Oral Solution); Weichangning Oral Solution (Glycopyrrolate); Haclofosone Topical Solution (Halog Solution); Haclofosone Solution (Haclofosone Topical Solution); HEP-LOCK U / P (Preservative-Free Heparin Lock Flush Solution); Heparin Lock Flush Solution (Hepflush 10); 5-aminolevulinic acid hexyl ester hydrochloride intravesical solution (Cysview); Hydrocodone bitartrate and acetaminophen oral solution (Lortab elixir); Hydroquinone 3% topical solution (Melquin-3 topical solution); IAP antagonists; Pilocarpine eye drops (Isopto); Ipratropium bromide nasal spray (Atrovent nasal spray); Itraconazole oral solution (Sporanox oral solution); Ketorolac tromethamine ophthalmic solution (Acular LS); Kaletra; Lanoxin; Fosamprenavir oral solution (Lexiva); Leuprorelin acetate for depot suspension (Lupron Depot Depot) 11.25 mg); Betaxon; Levocarnitine Tablets, Oral Solution, Sugar-Free (Kangting); Levofloxacin Ophthalmic Solution 0.5% (Quixin); Lidocaine Hydrochloride Sterile Solution (Xylocaine MPF Sterile Solution); Lok Pak (Locke's heparin flushing solution); lorazepam concentrate oral solution; Lortab elixir (hydrocodone bitartrate and acetaminophen oral solution); Ludasol (loteprednol etabonate ophthalmic suspension); loteprednol etabonate ophthalmic suspension (Alrex); low calcium peritoneal dialysis solution (low calcium Dianeol); Lumigan (bimatoprost ophthalmic solution 0.03% for glaucoma); Lipron Depot 11.25 mg (leuprolide acetate for depot suspension); megestrol acetate oral suspension (megestrol acetate oral suspension); MEK inhibitors; Mepron;Mesnex; pyridostigmine bromide; aminosalicylic acid rectal suspension enema (Rowasa); Melquin-3 topical solution (hydroquinone 3% topical solution); MetMab; methyldopa hydrochloride (methyldopa hydrochloride injection, solution); polyol methyl ether oral solution (methylphenidate hydrochloride oral solution 5mg / 5mL and 10mg / 5mL); methylprednisolone acetate injectable suspension (Dibomet); methylphenidate hydrochloride oral solution 5mg / 5mL and 10mg / 5mL (polyol methyl ether oral solution); methylprednisolone sodium succinate (SoluMedrol); metipranolol ophthalmic solution liquid (Optipranolol); dihydroergotamine (Migranal); Miochol-E (acetylcholine chloride intraocular solution); Micro-K for liquid suspension (potassium chloride extended-release formulation for liquid suspension); Minocycline (minocycline hydrochloride oral suspension); Nasacort (Nasacort); Neomycin with polymyxin B sulfate and hydrocortisone; Nepafenac ophthalmic suspension (Nevanac); Nevanac (nepafenac ophthalmic suspension); Nitrofurantoin oral suspension (nitrofurantoin); Noxafil (posaconazole oral suspension); Nystatin (oral) (nystatin oral suspension); Nystatin oral suspension (nystatin (oral)); Ocofen (flurbiprofen sodium ophthalmic solution); ofloxacin ophthalmic solution (ofloxacin ophthalmic solution); ofloxacin otic solution (ofloxacin otic); olopatadine hydrochloride ophthalmic solution (Pataday); Opticrom (cromolyn sodium ophthalmic solution); Optipranolol (metipranolol ophthalmic solution); Patanol (Patanol); prednisone (Pediapred); PerioGard; phenytoin oral suspension (Dilantin 125); Phisohex; posaconazole oral suspension (Noxafil); potassium chloride extended release for liquid suspension release formulations (Micro-K for liquid suspension); Patanide (olopatadine hydrochloride ophthalmic solution); Patanase nasal spray (olopatadine hydrochloride nasal spray); PEG electrolyte solution (CoLyte); Pemirolast potassium ophthalmic solution (Alamast); Penlac (ciclopirox topical solution); PENNSAID (diclofenac sodium topical solution); Perforomist (formoterol fumarate inhalation solution); Peritoneal dialysis solution; Phenylephrine hydrochloride ophthalmic solution (Neo-Synephrine); Phospholine Iodide (phospholine iodide for ophthalmic solution); Podofilox (podofilox topical solution);Pred Forte (prednisolone acetate ophthalmic suspension); Pralatrexate solution for intravenous injection (Flotate); Prednisolone acetate eye drops (Pred Mild); Prednisone concentrate oral solution; Pred Forte; lansoprazole (Prevacid); PrismaSol solution (sterile hemofiltration hemodiafiltration solution); ProAir; diazoxide (Proglycem); Procran (gadoteridol injection solution); proparacaine hydrochloride ophthalmic solution (Alcaine); Propiridine; Pulmicort; Pulmozyme; Quixin (levofloxacin ophthalmic solution 0.5%); QVAR; Rapamune; Ribavirin; Relacon-HC; Rotavirus (live rotavirus vaccine oral suspension); Rotavirus live rotavirus vaccine oral suspension (Rotavirus); Rowasa (aminosalicylic acid rectal suspension enema); Vigabatrin (vigabatrin oral solution); Sacrosidase oral solution (Sucraid); Santiamin; Sepra; Serevent Diskus; Solu Cortef (hydrocortisone sodium succinate); methylprednisolone sodium succinate; Spiriva; Sporanox oral solution (itraconazole oral solution); Carlinamide (erythromycin topical solution 1.5%); Stalevo; Nateglinide (Starlix); Sterile hemofiltration hemodiafiltration solution (PrismaSol solution); Stimate; Sucralfate (Carafate suspension); Sulfamethoxazole sodium ophthalmic solution 10% (Bleph 10); Synarel nasal solution (nafarelin acetate nasal solution for endometriosis); Taclonex Scalp (calcipotriol and betamethasone dipropionate topical suspension); Tamiflu; Tobiprofen; Tobramycin; Tobramycin ST (tobramycin / dexamethasone ophthalmic suspension 0.3% / 0.05%); Tobramycin / dexamethasone ophthalmic suspension 0.3% / 0.05% (Tobramycin ST); Timolol; Timoptic; Travatan Z ( Z); treprostinil inhalation solution (Tyvaso); Sono-Sol (dorzolamide hydrochloride ophthalmic solution); Tyvaso (treprostinil inhalation solution); Ventolin; Vivan; doxycycline oral solution (doxycycline calcium oral suspension); Vitosine (didanosine pediatric powder for oral solution); vigabatrin oral solution (Vibond); pancreatin; nelfinavir (Viracept); Viagra; vitamin K1 (vitamin K1 fluid colloidal solution); Voltaren ophthalmic solution (diclofenac sodium ophthalmic solution);Chailandin oral solution (ethosuximide oral solution); Cygwin; Linezolid; Zymar (gatifloxacin ophthalmic solution); Zymaxid (gatifloxacin ophthalmic solution);

[0057] Drug Class

[0058] 5-α-reductase inhibitors; 5-aminosalicylate; 5HT3 receptor antagonists; adamantane antiviral agents; adrenocortical steroids; adrenocortical steroid inhibitors; adrenergic bronchodilators; agents for hypertensive emergencies; agents for pulmonary hypertension; aldosterone receptor antagonists; alkylating agents; α-adrenergic receptor antagonists; α-glucosidase inhibitors; alternative medicines; amebicides; aminoglycosides; aminopenicillins; aminosalicylates; amylin analogs; analgesic combinations; analgesics; androgens and anabolic steroids; angiotensin converting enzyme inhibitors; angiotensin II inhibitors; anorectal preparations; anorectics; antacids; anthelmintics; antiangiogenic ophthalmic agents; anti-CTLA-4 monoclonal antibodies; anti-infectives; centrally acting antiadrenergic agents; peripherally acting antiadrenergic agents; antiandrogens; antianginal agents; antiarrhythmic agents; antiasthmatic combinations; antibiotics / antineoplastics; anticholinergic antiemetics; anticholinergic antiparkinsonian agents; anticholinergic bronchodilators; anticholinergic chronotropics anticholinergic / spasmodic; anticoagulant; anticonvulsant; antidepressant; antidiabetic; antidiabetic combination; antidiabetic agent; antidiabetic agent combination; antidiarrheal; antidiuretic hormone; antidote; antiemetic / antivertigo agent; antifungal agent; antigonadotropin agent; antigout agent; antihistamine; antihyperlipidemic agent; antihyperlipidemic combination; antihypertensive combination; antihyperuricemic agent; antimalarial agent; antimalarial combination; antimalarial quinoline; antimetabolite; antimigraine agent; antitumor detoxification agent; antitumor interferon; antitumor monoclonal antibody; antineoplastic agent; antiparkinsonian agent; anti Platelet-lowering agents; antipseudomonal penicillins; antipsoriatic agents; antipsychotics; antirheumatic agents; antiseptics and antiseptics; antithyroid agents; antitoxins and antivenoms; antituberculosis agents; antituberculosis combinations; cough suppressants; antivirals; antiviral combinations; antiviral interferons; anxiolytics, sedatives and hypnotics; aromatase inhibitors; atypical antipsychotics; azole antifungals; bacterial vaccines; barbiturate anticonvulsants; barbiturates; BCR-ABL tyrosine kinase inhibitors; benzodiazepine anticonvulsants; benzodiazepines beta-adrenergic blockers; beta-lactamase inhibitors; bile acid sequestrants; biologics; bisphosphonates; bone resorption inhibitors; bronchodilator combinations; bronchodilators; calcitonin; calcium channel blockers; carbamate anticonvulsants; carbapenems; carbonic anhydrase inhibitor anticonvulsants; carbonic anhydrase inhibitors; cardiac stress agents; cardioselective beta blockers; cardiovascular agents; catecholamines; CD20 monoclonal antibody; CD33 monoclonal antibody; CD52 monoclonal antibody; Central nervous system agents; cephalosporins; cerumen lytics; chelating agents; chemokine receptor antagonists; chloride channel activators; cholesterol absorption inhibitors; cholinergic agonists; cholinergic muscle stimulants; cholinesterase inhibitors; CNS stimulants; coagulation modulators; colony stimulating factors; contraceptives; adrenocorticotropic hormone; coumarins and indanediones; cyclooxygenase-2 inhibitors (cox-2inhibitors); decongestants; dermatologic agents; diagnostic radiopharmaceuticals; dibenzazepines Anticonvulsants; digestive enzymes; dipeptidyl peptidase 4 inhibitors; diuretics; dopaminergic antiparkinsonian agents; drugs for alcohol dependence; echinocandins; EGFR inhibitors; estrogen receptor antagonists; estrogens; expectorants; factor Xa inhibitors; fatty acid derivative anticonvulsants; fibric acid derivatives; first-generation cephalosporins; fourth-generation cephalosporins; agents for functional bowel disorders; gallstone solubilizers; gamma-aminobutyric acid analogs; gamma-aminobutyric acid reuptake inhibitors; gamma-aminobutyric acid transaminase inhibitors; gastrointestinal agents; general anesthetics; genitourinary agents; GI stimulants; glucocorticoids; glucose-raising agents; glycopeptide antibiotics; glycoprotein platelet inhibitors; glycylcyclines; gonadotropin-releasing hormone; gonadotropin-releasing Hormone antagonists; gonadotropins; group I antiarrhythmics; group II antiarrhythmics; group III antiarrhythmics; group IV antiarrhythmics; group V antiarrhythmics; growth hormone receptor blockers; growth hormones; Helicobacter pylori eradicants; H2 antagonists; hematopoietic stem cell mobilization agents; heparin antagonists; heparin; HER2 inhibitors; herbal products; histone deacetylase inhibitors; hormone replacement therapy; hormones; hormone / antineoplastic agents; hydantoin anticonvulsants; illegal (street) drugs; immunoglobulins; immunological agents; immunosuppressants; impotence drugs; in vivo diagnostic biologics; incretin mimetics; inhaled anti-infectives; inhaled corticosteroids; inotropes; insulin; insulin-like growth factor; integrase strand transfer inhibitors; interferons; intravenous nutrition products; iodinated contrast media; ionized iodinated contrast media; iron products; ketolides; laxatives; antileprosy agents; leukotriene modifiers; lincomycin derivatives; lipoglycopeptides; local injectable anesthetics; loop diuretics; pulmonary surfactants; lymph stains; lysosomal enzymes; macrolide derivatives; macrolides; magnetic resonance imaging contrast agents; mast cell stabilizers; medical gases; meglitinides; metabolic agents; methylxanthines; mineralocorticoids; minerals and electrolytes; miscellaneous agents; miscellaneous analgesics; miscellaneous antibiotics; miscellaneous anticonvulsants; miscellaneous antidepressants; miscellaneous antidiabetic agents; miscellaneous antiemetics; miscellaneous antifungals; miscellaneous antihyperlipidemic agents; miscellaneous antimalarials; miscellaneous antineoplastics; miscellaneous antiparkins Mori agents; miscellaneous antipsychotic agents; miscellaneous antituberculosis agents; miscellaneous antiviral agents; miscellaneous anxiolytics, sedatives and hypnotics; miscellaneous biologics; miscellaneous bone resorption inhibitors; miscellaneous cardiovascular agents; miscellaneous central nervous system agents; miscellaneous coagulation regulators; miscellaneous diuretics; miscellaneous genitourinary agents; miscellaneous GI agents; miscellaneous hormones; miscellaneous metabolic agents; miscellaneous ophthalmic agents; miscellaneous otic agents; miscellaneous respiratory agents; miscellaneous sex hormones; miscellaneous topical agents; miscellaneous unclassified agents; miscellaneous vaginal agents; mitotic inhibitors; monoamine oxidase inhibitors; monoclonal antibodies; oral and throat products; mTOR inhibitors; mTOR kinase inhibitors; mucolytics; multikinase inhibitors; muscle relaxants; mydriatics; narcotic analgesic combinations;Narcotic analgesics; Nasal anti-infectives; Nasal antihistamines and decongestants; Nasal lubricants and irrigants; Nasal preparations; Nasal steroids; Natural penicillins; Neuraminidase inhibitors; Neuromuscular blockers; Next generation cephalosporins; Nicotinic acid derivatives; Nitrates; NNRTIs; Non-cardioselective beta blockers; Non-iodinated contrast media; Non-ionic iodinated contrast media; Non-sulfonylureas; Non-steroidal anti-inflammatory agents; Norepinephrine reuptake inhibitors; Norepinephrine dopamine reuptake inhibitors; Nucleoside reverse transcriptase inhibitors (NRTIs); Nutritional drug products; Nutritional products; Ophthalmic anesthetics; Ophthalmic anti-infectives; Ophthalmic anti-inflammatory agents; Ophthalmic antihistamines and decongestants; Ophthalmic diagnostic agents; Ophthalmic glaucoma agents; Ophthalmic lubricants and irrigants; Ophthalmic preparations; ophthalmic steroids; ophthalmic steroids with anti-infectives; ophthalmic surgical agents; oral nutritional supplements; otic anesthetics; otic anti-infectives; otic preparations; otic steroids; otic steroids with anti-infectives; oxazolidinedione anticonvulsants; parathyroid hormone and analogs; penicillinase-resistant penicillins; penicillins; peripheral opioid receptor antagonists; peripheral vasodilators; peripherally acting antiobesity agents; phenothiazine antiemetics; phenothiazine antipsychotics; phenylpiperazine antidepressants; plasma expanders; platelet aggregation inhibitors; platelet stimulators; polyenes; potassium-sparing diuretics; probiotics; progesterone receptor modulators; progestogens; prolactin inhibitors; prostaglandin D2 antagonists; protease inhibitors; proton pump inhibitors; psoralens; psychotherapeutic agents; neurotherapeutic combinations; purine nucleosides; pyrrolidine anticonvulsants; quinolones; radiographic contrast agents; radiographic adjuvants; radiopharmaceuticals; radioconjugates; radiopharmaceuticals; RANK ligand inhibitors; recombinant human erythropoietin; renin inhibitors; respiratory agents; respiratory inhalation products; rifamycin derivatives; salicylates; sclerosing agents; second-generation cephalosporins; selective estrogen receptor modulators; selective serotonin reuptake inhibitors; serotonin-norepinephrine reuptake inhibitors; serotonergic enterocyte modulators; sex hormone combinations; sex hormones; skeletal muscle relaxant combinations; skeletal muscle relaxants; smoking cessation agents; somatostatin and somatostatin analogs; spermicides; statins; sterile irrigation 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; tocolytics; topical acne agents; topical agents; topical anesthetics; topical anti-infectives; topical antibiotics; topical antifungals; topical antihistamines; topical antipsoriatics; topical antivirals; topical astringents; topical debridements; topical depigmenting agents; topical emollients; topical keratolytics; topical steroids; topical steroids with anti-infectives; toxoids; triazine anticonvulsants; tricyclic antidepressants; trifunctional monoclonal antibodies; tumor necrosis factor (TNF) inhibitors;Tyrosine kinase inhibitors; ultrasound contrast agents; upper respiratory tract disease drug combinations; urea anticonvulsants; urethral anti-infectives; urethral antispasmodics; urethral pH regulators; uterotonics; vaccines; vaccine combinations; vaginal anti-infectives; vaginal preparations; vasodilators; vasopressin antagonists; vasopressors; VEGF / VEGFR inhibitors; viral vaccines; viscosupplementation agents; vitamin and mineral combinations; vitamins; protein-based vaccines; DNA-based vaccines; mRNA-based vaccines;

[0059] Diagnostic tests

[0060] 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); alpha 1-antitrypsin; alpha-fetoprotein; alpha-fetoprotein; ammonia level; amylase; ANA (antinuclear antibody); ANA (antinuclear antibody); angiotensin converting enzyme (ACE); anion gap; antiphospholipid antibodies; antiphospholipid antibodies (ACA); anticentromere antibodies; antidiuretic hormone; anti-DNA; anti-DNase-B; anti-gliadin Protein antibodies; anti-glomerular basement membrane antibodies; anti-HBc (hepatitis B core antibody); anti-HBs (hepatitis B surface antibody); antiphospholipid antibodies; anti-RNA polymerase; anti-Smith (Sm) antibodies; anti-smooth muscle antibodies; anti-streptolysin O (ASO); antithrombin III; anti-Xa activity; anti-Xa assay; apolipoprotein; arsenic; aspartate aminotransferase (AST); B12; basophils; beta-2-microglobulin; beta-hydroxybutyrate; B-HCG; bilirubin; direct bilirubin; indirect bilirubin; total bilirubin; bleeding time; blood gases (arterial); blood urea nitrogen (BUN); BUN; BUN (blood urea nitrogen); CA 125; CA 15-3; CA 19-9; calcitonin; calcium; calcium (ionized); carbon monoxide (CO); carcinoembryonic antigen (CEA); CBC; CEA; CEA (carcinoembryonic antigen); ceruloplasmin; CH50Chloride; cholesterol; cholesterol, HDL; clot lysis time; clot retraction time; CMP; CO2; cold agglutinin; complement C3; copper; corticotropin-releasing hormone (CRH) stimulation test; cortisol; synthetic corticotropin (Cortrosyn) stimulation test; C-peptide; CPK (total); CPK-MB; C-reactive protein; creatinine; creatinine kinase (CK); cryoglobulins; DAT (direct antiglobulin test); D-dimer; dexamethasone suppression test; DHEA-S; diluted Russell's viper venom; oval cell; eosinophil; erythrocyte sedimentation rate (ESR); estradiol; estriol; ethanol; ethylene glycol; euglobulin lysis; factor V Leiden; factor VIII inhibitor; factor VIII level; ferritin; fibrin split products; fibrinogen; folate; folate (serum); fractional excretion of sodium (FENA); FSH (follicle stimulating factor); FTA-ABS; gamma glutamyl transferase (GGT); gastrin; GGTP (gamma glutamyl transferase); glucose; growth hormone; haptoglobin; HBeAg (hepatitis Be 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; Lymphocytes; Magnesium; MCH (mean corpuscular hemoglobin); MCHC (mean corpuscular hemoglobin concentration); MCV (mean corpuscular volume); Methylmalonate; Monocytes; MPV (mean platelet volume); Myoglobin; Neutrophils; Parathyroid hormone (PTH); Phosphorus; Platelets (plt); Potassium; Prealbumin; Prolactin; Prostate specific antigen (PSA); Protein C; Protein S; PSA (prostate specific antigen); PT (prothrombin time); PTT (partial thromboplastin time); RDW (red cell distribution width); renin; chymosin; reticulocyte count; reticulocyte; rheumatoid factor (RF); sedimentation rate; serum glutamate pyruvate transaminase (SGPT); serum protein electrophoresis (SPEP); sodium; T3-resin absorbance (T3RU); free T4; thrombin time; thyroid stimulating hormone (TSH); thyroxine (T4); total iron binding capacity (TIBC); total protein; transferrin; transferrin saturation; triglycerides (TG); troponin; uric acid; vitamin B12; white blood cells (WBC); Widal test. ; BRIEF DESCRIPTION OF THE DRAWINGS

[0061] Figure 1 is a perspective view of a conventional prior art workstation for manual visual inspection.

[0062] Figure 2 is an exploded perspective view of a conventional nest and box packaging of ready-to-use (RTU) vials.

[0063] Figure 3 is a cross-sectional view of a first exemplary vial showing the bottom wall, sidewalls, top opening, shoulder area, neck, top flange, and transition between the sidewalls and bottom wall.

[0064] Figure 4 is a cross-sectional view of a second exemplary vial, showing the bottom wall, side walls, top opening, shoulder area, neck, top flange, and transition between the side walls and bottom wall; and also including a cover (a combination of stopper 411 and cap 412).

[0065] Figure 5 is a cross-sectional view of a first exemplary syringe barrel, showing the sidewall, rear opening, rear flange, shoulder region, and needle hub; and also including a plunger 509 and a rigid needle shield 511 .

[0066] Figure 6is a cross-sectional view of a second exemplary syringe barrel, showing the sidewall, rear opening, rear flange, shoulder area, and Luer hub; and also including a plunger and tip cap.

[0067] Figure 7 is a perspective view of an exemplary blood collection tube, showing the side walls, the bottom wall, the transition area between the side walls and the bottom wall; and also including a cap 270.

[0068] Fig. 8A is an exemplary image of a vial acquired by a side body camera according to an embodiment of the vessel inspection system / method of the present disclosure.

[0069] Figure 8B yes Fig. 8A An image is provided which is modified by a processor to identify an inspection region to be applied to the image.

[0070] Fig.9A is an exemplary image of a vial acquired by an angled shoulder camera according to an embodiment of the vessel inspection system / method of the present disclosure.

[0071] Fig. 9B yes Fig.9A An image is provided which is modified by a processor to identify an inspection region to be applied to the image.

[0072] Fig. 10A is an exemplary image of a vial acquired by an angled top camera according to an embodiment of the vessel inspection system / method of the present disclosure.

[0073] Fig. 10B yes Fig. 10A An image is provided which is modified by a processor to identify an inspection region to be applied to the image.

[0074] Fig.11A is an exemplary image of a vial acquired by an angled bottom camera according to an embodiment of the vessel inspection system / method of the present disclosure.

[0075] Fig. 11B yes Fig. 8A An image is provided which is modified by a processor to identify an inspection region to be applied to the image.

[0076] Fig. 12A is an exemplary image of a vial acquired by a bottom camera according to an embodiment of the vessel inspection system / method of the present disclosure.

[0077] Fig. 12B yes Fig.9A An image is provided which is modified by a processor to identify an inspection region to be applied to the image.

[0078] Fig.13A is a front perspective view of an embodiment of a side body inspection station of the vessel inspection system / method of the present disclosure.

[0079] Fig. 13B yes Fig.13A A rear perspective view of an embodiment of a side body inspection station is shown in FIG.

[0080] Fig.14 is a rear top perspective view of an embodiment of a shoulder inspection station of the vessel inspection system / method of the present disclosure.

[0081] Fig.15 is a rear perspective view of an embodiment of a top inspection station of the vessel inspection system / method of the present disclosure.

[0082] Fig.16 is a perspective view of an embodiment of a rotatable vessel holder for use in a top inspection station of the vessel inspection system / method of the present disclosure.

[0083] Fig.17 is a perspective view of an embodiment of an inspection station for both the bottom wall and the transition between the sidewall and the bottom wall of the vessel inspection system / method of the present disclosure.

[0084] Fig.18 is a perspective view of an embodiment of a vessel coating system.

[0085] Fig.19 is a cross-sectional view of an embodiment of a vessel coating system configured to coat an interior surface of a vial and including a source gas inlet probe.

[0086] Fig. 20 is a cross-sectional view of an embodiment of a vessel coating system configured to coat the interior surface of a vial and excluding a source gas inlet probe.

[0087] Fig.21A is a perspective view of an embodiment of a vessel coating system including a visual inspection system configured to capture an image of an electrode cavity and analyze the image of the electrode cavity for the presence of particles.

[0088] Fig. 21B Is Fig.21A An exemplary image of an electrode cavity captured by a camera of a visual inspection system is shown in FIG.

[0089] Fig. 22 is a cross-sectional view of a first embodiment of a vessel holder of a coating system of the present disclosure.

[0090] Fig.23 is a cross-sectional view of a second embodiment of a vessel holder of the coating system of the present disclosure.

[0091] Fig.24 is a top perspective view of an embodiment of an electrode cleaning system of the present disclosure.

[0092] Fig.25 yes Fig.24 A cross-sectional view of an embodiment of an electrode cleaning system is shown in FIG.

[0093] Fig.26 is a top perspective view of an embodiment of a cleaning system configured to remove particles from an interior surface of a vessel.

[0094] Fig. 27 yes Fig.26 A cross-sectional view of an embodiment of a cleaning system is shown in FIG.

[0095] Fig.28 is a top perspective view of an embodiment of a cleaning system configured to remove particles from at least a portion of an exterior surface of a vessel.

[0096] Fig.29 yes Fig.28 An embodiment of a cleaning system shown in FIG. 4 is a cross-sectional view taken along the length of the system.

[0097] Fig.30 yes Figure 28-29 An embodiment of a cleaning system shown in FIG. 1 is a cross-sectional view taken along the width of the system.

[0098] Fig.31 is a graph showing particle counts for vials coated using a vessel coating system according to the present disclosure in which the vials and coating system were cleaned compared to particle counts for vials coated using the same vessel coating system but without a cleaning step. DETAILED DESCRIPTION

[0099] In the context of the present invention, the following definitions and abbreviations are used:

[0100] In the context of the present invention, the term "at least" means "equal to or more than" the integer following the term. The word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality / multiples unless otherwise indicated. Whenever a parameter range is indicated, it is intended to disclose the parameter values ​​given as the limits of the range as well as all parameter values ​​falling within the range.

[0101] For example, references to "first" and "second" or similar references to a processing station or processing device refer to the minimum number of processing stations or processing devices that exist, but do not necessarily represent the order or total number of processing stations and processing devices, nor do they necessarily require additional processing stations and processing devices beyond the stated number. These terms do not limit the number of processing stations or the specific processing performed at the corresponding station. For example, a "first" station in the context of this specification can be the only station or any one of a plurality of stations without limitation. In other words, the description of the "first" station allows but does not require that the embodiment also has a second station or additional stations.

[0102] The word "comprising" does not exclude other elements or steps.

[0103] The term "ready-to-use" or "ready to use" or "RTU" refers to containers, such as vials, syringe barrels, cartridges, etc., that are empty, clean, and sterile so that they are configured to be filled without any additional processing. RTU containers are typically cleaned (e.g., washed) and then packaged in a nest and box configuration, where the trays and boxes are packed with The seal is sealed. The nest and box construction of the container is then sterilized. Figure 2 An example of a nest and box configuration for RTU vials is shown in . As shown in the illustrated example, a typical nest and box configuration for RTU vials may include a nest 4 holding a plurality of vials 400, a box 5 enclosing the nest and vials, an inlay 6, and a seal 7.

[0104] exist Figure 3 An exemplary vial 400 is shown in FIG. 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 403 connecting the bottom wall and the side wall, a radially inwardly extending shoulder 404 formed at the top of the side wall, and a neck 405 extending upward from the shoulder, the neck terminating at a neck flange 405a that defines an opening 406 to the interior of the vial (i.e., the inner cavity 212). Figure 3 As shown in , the bottom wall 401 may have a flat or substantially flat lower surface 407. Alternatively, as in a conventional vial (e.g. Figure 4 As in the case of the conventional vial shown in FIG. 4 ), the bottom wall 401 may have an outer resting ring and a central curved push-up area. Vials with 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).

[0105] exist Figure 5 and 6 An exemplary syringe is shown in FIG. In particular, Figure 5 A syringe is shown having a needle hub 506 and a needle (which is shown covered and protected by a rigid needle shield 511). Figure 6A syringe having a Luer hub 507 (shown as covered by a tip cap) in place of a needle is shown. In both cases, the syringe barrel 500 includes a sidewall portion 501 spanning between a rear end including an opening to the lumen and a front end including a needle hub 506 or a Luer hub 507. The rear end of the syringe barrel includes a flange 508 having an upper surface surrounding the opening to the lumen and an outer surface extending beyond a major portion of the sidewall 501. At the front end of the syringe barrel, the sidewall portion 501 includes a shoulder 510 where the sidewall transitions from the main sidewall portion to the needle hub 506 or Luer hub 507 portion. Both syringes are also shown to include a plunger 509, but the plunger is not part of the syringe barrel 500.

[0106] For the purposes of the coating, cleaning, and vessel inspection techniques described herein, the rear end of the syringe barrel should be considered equivalent to the top portion of the vial, as both contain an opening to the lumen. In addition, although the shoulder 510 of the syringe barrel is positioned toward the front end, it is contemplated that the same or substantially the same inspection techniques described with respect to the shoulder portion 404 of the vial 400 can be applied to the shoulder portion 510 of the syringe barrel. In general, although such embodiments are not shown, it is contemplated that the same or substantially the same inspection techniques shown and described with respect to the vial can be applied to various portions of the syringe barrel.

[0107] exist Figure 7 274 is shown in FIG. The blood collection tube includes a side wall 268 spanning between a closed bottom end and an open top end. The open top end including an opening to a central lumen is shown covered by a cap 270. The open top end may or may not include a small flange. The closed bottom end includes a small bottom wall 269. The blood collection tube also includes a transition area 271 between the side wall 268 and the bottom wall 269.

[0108] For 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 both include a sidewall portion 268, an opening to the lumen at the top end of the vessel, and a closed bottom end. Like the vial, the blood collection tube 274 also has a transition zone 271 between the sidewall 268 and the bottom wall 269. Unlike the vial 400, the blood collection tube 274 generally does not include a shoulder. Although such an embodiment is not shown, 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 portions of the blood collection tube 274.

[0109] The RTU container is supplied to a pharmaceutical company or a contract development and manufacturing organization (CDMO) for filling. In a sterile environment, the pharmaceutical company or CDMO unseals the tray and box, fills the container, and seals the container (e.g., by inserting a rubber stopper 411 into the opening of the vial and optionally applying an additional cap 412, typically made of a metal such as aluminum and crimped onto the top of the stopper and the neck flange 405a of the vial, by inserting a plunger 509 into a syringe barrel or cartridge, or by a blood collection tube cap 270). The RTU container eliminates the need for the pharmaceutical company to handle the container (e.g., by washing or sterilizing) prior to filling.

[0110] The term "syringe" is meant to include syringes with an embedded needle (such as a staked needle syringe), and alternatively syringes with a Luer lock or Luer cone fluid outlet. The term "syringe barrel" is meant to represent the barrel of the syringe, including (if present) any embedded needle and / or any removable cap or needle shield, but excluding the plunger, which is inserted after filling.

[0111] The term "Acceptable Quality Level" 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 defects per 100 units. AQL specifies the maximum number of defective containers, above which a batch or lot is rejected.

[0112] The present invention will now be described more fully with reference to the accompanying drawings, in which several embodiments are shown. However, the present invention may be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are examples of the present invention, which have a full scope as indicated by the language of the claims. Throughout the text, like numbers refer to like or corresponding elements.

[0113] use FIG. 13A to FIG. 17 The system shown in and described herein is used to inspect a plurality of vials 400 .

[0114] The vials 400 are moved between various inspection stations, including the side body inspection station 101, the angled shoulder inspection station 102, the angled top inspection station 103, the angled bottom inspection station 104, and the bottom inspection station 105, but in some embodiments including the illustrated embodiment, the angled bottom inspection station and the bottom inspection station can be combined in a single station 104, 105. The transportation of multiple vials 400 between each station 101, 102, 103, 104, 105 can be automated, and the placement and positioning of the vials in each inspection station can also be automated. In some embodiments, the multiple vials 400 can be transported along one or more transport routes until a predetermined point is reached, at which predetermined point, at least one of the vials is removed from the transport route by one of the vessel holder or vessel transport unit (depending on which inspection station it is). Then, the vessel holder or vessel transport unit can transport the vessel to the inspection station 101, 102, 103, 104, 105, or some components of the inspection station (such as bottom lights and side lights) can be located adjacent to the vessel holder so as to partially form the vessel compartment of the inspection station in close proximity to the transport line (such as directly above the transport line). In the case of using a vessel transport unit, the vessel transport unit can also position the vial on the vessel holder of the inspection station for inspection. Once the image has been captured, the vessel holder or vessel transport unit can return the vial to the transport unit, and the vial can be transported to a subsequent inspection station until each inspection has been performed.

[0115] Furthermore, in any embodiment, a number of identical inspection stations may be arranged alongside one another so that multiple vials 400 are inspected at a given time.

[0116] Side body inspection

[0117] Fig.13A and 13B A side body inspection station 101 , also called a side wall inspection station, is shown. The side body inspection station 101 includes a body side camera 110 , a bottom light 111 , a side light 112 , and a vessel holder 113 .

[0118] The bottom light 111 is configured and positioned so that the bottom light is below the vial 400 and the light shines upward, e.g., through the bottom of the vial and around all sides of the vial. In some embodiments, the bottom light 111 can be a direct-down backlight (e.g., a 63 mm x 60 mm direct-down backlight, blue LED, M12, or similar light). The use of blue light is optional but desirable because it enhances the color of plasma sheet particles, such as the color of plasma sheet particles that may be present in one or more coatings on the sidewalls of the vial 400. The side lights 112 are positioned so that the side lights are behind the vial 400 from the perspective of the camera 110 (i.e., on the side of the vial opposite the camera), and the light shines through the sidewalls of the vial and over the sides of the vial as viewed from the camera. In some embodiments, the side lights 112 can be a direct-down backlight (e.g., a 100 mm x 100 mm high output planar light, blue, M12, or similar light). Again, the use of blue light is optional but desirable because it enhances the color of plasma sheet particles, such as those that may be present in one or more coatings on the sidewalls of vial 400. Because in this embodiment, body-side camera 110 includes telecentric lens 114, it is desirable to use a high-output planar light instead of a direct-type backlight of the type used as bottom light 111.

[0119] In the illustrated embodiment, the bottom light 111 and the side light 112 define the bottom and rear surfaces of the vessel compartment 115, in which the vial 400 is held. Here, the sides and front of the vessel compartment 115 are completely open. However, in other embodiments, one or both of the sides and / or front may be partially or completely closed.

[0120] The main body side camera 110 is positioned in front of the vessel compartment 115, and the lens is aligned with the vessel compartment. The main body side camera 110 is desirably an area scan camera. Preferably, the main body side camera 110 is an area scan camera that captures at least 60° of the arc of the vial side wall, so that the entire vial side wall 402 can be inspected using six or less image captures. For example, the main body side camera 110 can be an area scan camera that captures at least 65° of the arc of the vessel side wall (which provides overlap with adjacent arcs, and therefore ensures that the entire side wall is captured and inspected). In some embodiments, the main body side camera 110 can be a Cognex In-Sight9912M, 12.0M camera.

[0121] The body side camera 110 may also include a high resolution telecentric lens 114 (and associated lens holder and bandpass filter). Due to the relatively large area of ​​the vial sidewall 402 captured at this inspection station 101, it is desirable to use a telecentric lens 114. If a standard lens is used, the captured image may be susceptible to a slight fisheye effect (which interferes with accurate measurement of particle size), i.e., particles present at the top and bottom portions of the sidewall 402 will appear different than particles present at the middle portion of the sidewall. By using a telecentric lens 114, the system may be calibrated to measure particle size consistently across the entire sidewall 402 of the vial 400. In other (not shown) embodiments, it is contemplated that multiple cameras with standard lenses may be used in place of a single camera 110 with a telecentric lens 114, or even a single camera with a standard lens may be used and the system calibrated to account for the resulting fisheye effect. If a telecentric lens 114 is not used, the sidelight 112 may not need to be as bright as the sidelight used in the illustrated embodiment.

[0122] The vessel holder 113 is configured to hold the vial 400 from above without contacting the side wall 402 of the vial or otherwise interfering with the view around the side wall of the vial (which includes the side of the neck 405 and the side of the neck flange 405a). In the illustrated embodiment, for example, the vessel holder 113 interacts with the top of the neck flange 405a of the vial, such as by clamping, suction, etc., so that the vial 400 is suspended on the vessel holder within the vessel compartment 115. Thus, the vessel holder 113 forms at least a portion of the top surface of the vessel compartment 115.

[0123] The vessel holder 113 is also configured to rotate the vial so that the entire 360° of the side wall 402 can be captured and inspected by images. In some embodiments, the vessel holder 113 is configured to rotate continuously, which allows a high-throughput inspection process. For example, the vessel holder 116 of the illustrated embodiment is configured to rotate at a speed of up to about 120rpm. Of course, continuous rotation requires the camera 110 to open the shutter very briefly. For example, the camera 110 can be selected, and the lights 111, 112 can be configured and positioned so that the shutter remains open for less than one millisecond when the image is captured. In other embodiments, the vial 400 can be rotated discontinuously, that is, the vial can remain stable in a single image capture and rotate between image captures.

[0124] In the illustrated embodiment, the vessel holder 113 is movable relative to the camera 110 and the lights 111, 112. In this way, the vessel holder 113 can pick up the vial 400 (e.g., from a transport line or a different inspection station) and position the vial in the vessel compartment 115 for inspection. In other embodiments, certain components such as the lights 111, 112 may alternatively be moved to a suitable position beside the vessel holder 113, for example, the vessel holder may remove the vial 400 from the transport line, and then the lights 111, 112 may be located in a position adjacent to the transport line (e.g., directly above the transport line) to form the vessel compartment 115 of the inspection station 101.

[0125] Although the inspection station 101 is described as oriented in the drawings, in other embodiments not shown, the vessel compartment 115 can be flipped 180 degrees so that the bottom light 111 forms the top of the vessel compartment and the vessel holder 113 forms at least a portion of the bottom of the vessel compartment. In fact, the components can be oriented in any desired manner as long as the relationship between the camera 110, lights 111, 112 and vials 400 that allows accurate image capture is maintained.

[0126] It is also contemplated that in other embodiments not shown, the side body inspection station 101 and the angled shoulder inspection station 102 may be combined such that the angled shoulder camera 120 may capture images during the same rotation of the vial 400 as the side body camera 110. This may be accomplished by, for example, temporally offsetting the image capture of the two cameras 110, 120 from one another, and varying the characteristics of the light (e.g., intensity) as may be desired between the light characteristics for image capture by the side body camera 110 and the light characteristics for image capture by the angled shoulder camera 120. This may also be accomplished by using one or more cameras with standard lenses for side body inspection (or cameras with telemetry lenses for angled shoulder cameras, but this may be undesirable for other reasons).

[0127] In order to inspect the side wall 402 of the vial, the vial 400 is picked up by the vessel holder 113 and positioned in the vessel compartment 115 of the side wall inspection station 101. When the bottom light 111 and the side light 112 are turned on, the vial 400 rotates 360° around its longitudinal axis. During this rotation, the camera 110 captures many images of the side body portion of the vial, such as six images. The captured images together show the entire 360° surface of the side body portion of the vial. The captured images are processed by one or more system processors to identify (i) the presence of particles in the specified side body inspection area and (ii) the size of any identified particles.

[0128] exist Fig. 8A An example of image capture taken by the side body camera 110 during the inspection process is shown in FIG. Figure 8B The same image is shown as it is processed by the system and in particular by one or more processors. The processor identifies one or more independent examination regions, examples of which are shown in FIG. Figure 8B 201, 202, and 203. To ensure that the inspection areas 201, 202, 203 are correctly identified, the system cannot rely solely on the center of the image (which would require the vessel holder 113 to position the vial 400 to be perfectly aligned with the center of the camera lens). Figure 8B As shown in FIG. 2 as blocks 204, 205, and 206, the system can be configured to identify image elements corresponding to certain portions of the vial 400, such as the side of the vial in the captured image (block 204), the top of the vial in the captured image (block 205), and / or a shadow in the captured image representing a shoulder portion of the vial (block 206). The system can then determine the precise location of one or more inspection regions 201, 202, 203 based on the locations of those image elements.

[0129] like Figure 8B As shown in , the side body portion of the vial 400 can be divided into three side body inspection areas: the body portion 201, the neck portion 202, and the neck flange side portion 203. The system can be calibrated separately for each inspection area 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 that they are not mistaken for particles or defects. The presence of similar image elements in the body portion 201 can be correctly identified as particles or defects.

[0130] like Figure 8B , the shoulder portion 404 of the vial is subject to significant shadowing effects and, therefore, cannot be inspected using the camera and light configuration of the side body inspection station 101. Similarly, the transition area 403 between the body of the side wall 402 and the bottom wall 401 of the vial is susceptible to distortion and cannot be inspected using the camera and light configuration of the side body inspection station 101. Therefore, the vial 400 is transported to another inspection station.

[0131] In other embodiments of the vessel inspection systems and methods disclosed herein, for example, where the system is configured to inspect a syringe barrel, the one or more inspection areas defined by one or more processors may be different, for example, a different number of inspection areas may be defined by one or more processors, the inspection areas may have different sizes, etc. For example, since the sidewalls of a blood collection tube typically have few, if any, geometric features (such as a shoulder portion or a neck portion), only a single inspection area (with a relatively high aspect ratio) may be applied to each image. In addition, small modifications may be made to system components to accommodate different geometries of the particular vessel / container being inspected. However, regardless of those differences, the inspection systems and methods disclosed herein may be applied to any of a variety of containers including syringe barrels (and barrels of cartridges) and blood collection tubes.

[0132] Shoulder examination

[0133] Fig.14 A shoulder inspection station 102 , also referred to as an angled shoulder inspection station, is shown. The angled shoulder inspection station 102 includes an angled shoulder camera 120 , a bottom light 121 , a side light 122 , and a vessel holder 123 .

[0134] The bottom light 121 is configured and positioned so that the bottom light is below the vial 400 and the light shines upward, e.g., through the bottom of the vial and around all sides of the vial. In some embodiments, the bottom light 121 can be a direct-down backlight (e.g., a 63 mm x 60 mm direct-down backlight, a blue LED, an M12, or similar light). The use of blue light is optional but desirable because it enhances the color of plasma sheet particles, such as the color of plasma sheet particles that may be present in one or more coatings on the sidewalls of the vial. The side lights 122 are positioned so that the side lights are behind the vial 400 from the perspective of the camera 120 (i.e., the side lights and the camera are on opposite sides of the vial), and the light shines through the sidewalls of the vial and over the sides of the vial as viewed from the camera. In some embodiments, the side lights 122 can be a direct-down backlight (e.g., an 83 mm x 75 mm direct-down backlight, a blue LED, an M12, or similar light). Again, the use of blue light is optional but desirable because it enhances the color of the plasma sheet particles, such as may be present in one or more coatings on the sidewalls of the vial.

[0135] In the illustrated embodiment, the bottom light 121 and the side light 122 define the bottom and rear surfaces of the vessel compartment 125 in which the vial 400 is held. Here, the sides and front of the vessel compartment 125 are completely open. However, in other embodiments, one or both of the sides and / or front may be partially or completely closed.

[0136] The angled shoulder camera 120 is positioned in front of and above the vial 400 and the vessel compartment 125, and the lens is aligned toward the vial and more generally toward the vessel compartment. More specifically, the angled shoulder camera 120 is positioned and aligned at the vessel compartment 125 in such a way as to capture an image of the vial shoulder 404 without shadows or other interferences. 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 60° of arc of the vial shoulder, so 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 65° of 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 or similar camera. The angled shoulder camera 120 may also include a 50 mm lens (and associated lens spacer (20 mm) and bandpass filter).

[0137] The vessel holder 123 is configured to hold the vial 400 from above without contacting the side wall of the vial or otherwise interfering with the view around the side wall of the vial. In the illustrated embodiment, for example, the vessel holder 123 interacts with the top of the neck flange 405a of the vial 400, such as by clamping, suction, etc., so that the vial is suspended on the vessel holder in the vessel compartment 125. Thus, the vessel holder 123 forms at least a portion of the top surface of the vessel compartment 125.

[0138] The vessel holder 123 is also configured to rotate the vial so that the entire 360° of the shoulder 404 can be captured and inspected by the image. In some embodiments, the vessel holder 123 is configured to rotate continuously, which allows a high-throughput inspection process. For example, the vessel holder 123 can be configured to rotate at a speed of up to about 120rpm. Of course, continuous rotation requires the camera 120 to open the shutter very briefly. For example, the camera 120 can be selected, and the lights 121, 122 can be configured and positioned so that the shutter remains open for less than one millisecond when the image is captured. In other embodiments, the vial 400 can be rotated discontinuously, that is, the vial can remain stable in a single image capture and rotate between image captures.

[0139] In the illustrated embodiment, the vessel holder 123 is movable relative to the camera 120 and the lights 121, 122. In this way, the vessel holder 123 can pick up the vial 400 (e.g., from a transport line or a different inspection station) and position the vial in the vessel compartment 125 for inspection. In other embodiments, certain components such as the lights 121, 122 may alternatively be moved to a suitable position beside the vessel holder 123, for example, the vessel holder may remove the vial 400 from the transport line, and then the lights 121, 122 may be located in a position adjacent to the transport line (e.g., directly above the transport line) to form the vessel compartment 125 of the inspection station 102.

[0140] Although the inspection station 102 is described as being oriented in the drawings, in other embodiments not shown, the vessel compartment 125 can be flipped 180 degrees so that the bottom light 121 forms the top of the vessel compartment and the vessel holder 123 forms at least part of the bottom of the vessel compartment. In such an embodiment, the angled shoulder camera 120 will of course be located in front of and below the vial 400, and more generally in front of and below the vessel 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 vial 400 that allows accurate image capture is maintained.

[0141] It is also contemplated that in other embodiments not shown, the side body inspection station 101 and the angled shoulder inspection station 102 may be combined so that the angled shoulder camera 120 may capture images during the same rotation of the vial as the side body camera 110. This may be accomplished by, for example, temporally offsetting the image capture of the two cameras 110, 120 from one another and varying the characteristics of the light (e.g., intensity) between the characteristics of the light used for image capture by the side body camera and the characteristics of the light used for image capture by the angled shoulder camera as may be desired. This may also be accomplished by using one or more cameras with standard lenses for side body inspection (or cameras with telemetry lenses for angled shoulder cameras, but this may be undesirable for other reasons).

[0142] In order to check the shoulder 404 of the vial, the vial 400 is picked up by the vessel holder 123 and positioned in the vessel compartment 125 of the shoulder inspection station 102. When the bottom light 121 and the side light 122 are turned on, the vial 400 rotates 360 ° around its longitudinal axis. During this rotation, the angled shoulder camera 120 captures many images of the shoulder portion 404 of the vial, such as six images. The captured images show the entire 360 ​​° surface of the vial shoulder portion 404 together. The captured images are processed by one or more system processors to identify the presence of particles in one or more specified shoulder inspection areas and (ii) the size of any identified particles.

[0143] exist Fig.9A An example of image capture taken by the angled shoulder camera 120 during this inspection process is shown in FIG. Fig. 9B The same image processed by the system is shown. The processor identifies one or more independent inspection regions, examples of which are shown in FIG. Fig. 9B 213). To ensure that the inspection areas 211, 212 are correctly identified, the system cannot rely solely on the center of the image (which would require the vessel holder 123 to position the vial 400 to be perfectly aligned with the center of the camera lens). More specifically, Fig. 9B As shown in FIG. 2 as box 214 and line 215, the system can be configured to identify image elements corresponding to certain portions of the vial 400, such as the sides of the vial in the captured image, and more specifically the sides of the bottle neck flange 405a (e.g., as determined by line 215) and / or the bottom of the bottle neck flange 405a in the captured image (e.g., as shown in box 214). The system can then determine the precise location of one or more inspection regions 211, 212 based on the locations of those image elements.

[0144] like Fig. 9B As shown in FIG. 4 , the shoulder 404 of the vial can be divided into multiple inspection areas 211, 212 to account for shadow effects or other interference. For example, Fig. 9B The box 212 shown in FIG. 2 has a smaller width than the box 211 due to the shadows immediately to the left and right of the box 212. If necessary, the system can also be calibrated separately for each inspection area 211, 212 in order to take into account surface features and the like.

[0145] In other embodiments of the vessel inspection system and method disclosed herein, for example, in the case where the system is configured to inspect a syringe barrel, one or more inspection areas defined by one or more processors may be different. In addition, small modifications may be made to the system components to accommodate the different geometries of the specific vessel / container being inspected. For example, since the shoulder of the syringe barrel is positioned toward the front end and the opening to the lumen is located at the rear end, the vessel holder may hold the syringe barrel by a needle shield or a tip cap, i.e., wherein the opening to the lumen is the lower hanging end. However, regardless of those differences, the inspection system and method disclosed herein may be applied to any of the various containers including syringe barrels (and barrels of cartridges) and blood collection tubes.

[0146] Top inspection

[0147] Fig.15A top inspection station 103 , also referred to as an angled top inspection station, is shown. The angled top inspection station 103 includes an angled top camera 130 , a bottom light 131 , a side light 132 , a vessel holder 133 , and a reflective wall 134 .

[0148] The bottom light 131 is configured and positioned so that the bottom light is below the vial 400, and the light shines upward, for example, through the bottom of the vial and around all sides of the vial. The bottom light 131 can be a direct-down backlight (e.g., a 63mm x 60mm direct-down backlight, a blue LED, an M12, or similar light). The use of blue light is optional but desirable because it enhances the color of the plasma sheet particles, such as the color of the plasma sheet particles that may be present in one or more coatings on the side walls of the vial. The side lights 132 are positioned so that the side lights are behind the vial 400 from the perspective of the camera 130 (i.e., the side lights and the camera are on opposite sides of the vial), and as viewed from the camera, the light shines through the side walls of the vial and over the sides of the vial. The side lights 132 can be a direct-down backlight (e.g., a 51mm x 51mm direct-down backlight, a blue LED, an M12, or similar light). Again, the use of blue light is optional but desirable because it enhances the color of the plasma sheet particles, such as may be present in one or more coatings on the sidewalls of the vial.

[0149] In the illustrated embodiment, the bottom light 131 and the side light 132 define the bottom surface and the rear surface of the vessel compartment 135 in which the vial 400 is held. The top inspection station 103 also includes a reflective wall 134 positioned on a side of the vessel holder 133 and the vial 400 opposite the side light 132. Thus, the reflective wall 134 forms at least a portion of the front surface of the vessel compartment 135. Fig.15 As shown in , the reflective wall 134 may also include a concave surface 136 configured to extend at least partially around the vial 400. Thus, the reflective wall 134 forms at least a portion of the left and right side surfaces of the vessel compartment 135. The reflective wall 134 reflects light irradiated from the side lights 132 and the bottom lights 131, and is configured to eliminate shadows appearing on the top surface of the vial (i.e., the upper surface of the neck flange 405a) in image capture.

[0150] The angled top camera 130 is positioned in front of and above the vial 400, and more generally in front of and above the vessel compartment 135, and the lens is aligned toward the vial and more generally toward the vessel compartment. More specifically, the angled top camera 130 is positioned and aligned in such a way at the vessel compartment 135 to capture an image of the vial top surface without shadows or other interferences. The angled top camera 130 is desirably an area scan camera. Preferably, the angled top camera 130 is an area scan camera that captures at least 60° of the vial top surface, so that six image captures can be used to inspect the entire vial top surface. For example, the angled top camera 130 can be an area scan camera that captures at least 65° of the vial top surface (which provides overlap with adjacent arcs, and therefore ensures that the entire top surface is captured and inspected). For example, the angled top camera 130 can be a Cognex In-Sight 9912M, 12.0MP or similar camera. The angled top camera 130 of this embodiment may also include a 50 mm lens (and associated lens spacer (20 mm) and bandpass filter).

[0151] The vessel holder 133 is configured to rotate the vial 400 so that the entire 360° of the top can be captured and inspected by the image. In some embodiments, the vessel holder 133 is configured to rotate continuously, which allows a high-throughput inspection process. For example, the vessel holder 133 can be configured to rotate at a speed of up to about 120rpm. Of course, continuous rotation requires the camera 130 to open the shutter very briefly. For example, the camera 130 can be selected, and the lights 131, 132 can be configured and positioned so that the shutter remains open for less than one millisecond when the image is captured. In other embodiments, the vial 400 can be rotated discontinuously, that is, the vial can remain stable in a single image capture and rotate between image captures.

[0152] like Fig.16 As shown in , the vessel holder 133 may include a rotatable platform 137 that supports the bottom surface or base 401 of the vial. The rotatable platform 137 is preferably configured so that it does not interfere with or distort the bottom light 131. For example, the rotatable platform 137 can be made of a material that causes the bottom light 131 to fluoresce without significant distortion that would produce shadows, etc. in the image capture. Alternatively, the rotatable vessel holder 133 (e.g., the platform 137) itself may include at least a portion of the bottom light 131. In some embodiments, for example, the bottom light 131 or a portion thereof can be used as the rotatable vessel holder 133.

[0153] Compared to the side body inspection station 101 and the shoulder inspection station 102, the vessel holder 133 of the top surface inspection station 103 of the illustrated embodiment is not movable to transport the vial 400 into and out of the inspection station, but may do so in other (not shown) embodiments. More specifically, the top surface inspection station 103 may also include a vessel transport element 138 configured to pick up the vial 400 (e.g., from a transport line or a different inspection station) and position the vial in the vessel compartment 135, and more specifically on the vessel holder 133. Once the image has been obtained, the vessel transport element 138 may pick up the vial 400 and return it to the transport line or transport it directly to a different inspection station.

[0154] Although the inspection station 103 is described as being oriented as in the drawings, in other embodiments not shown, the vessel compartment 135 may be flipped 180 degrees so that the bottom light 131 forms the top of the vessel compartment. In such an embodiment, the angled top camera 130 will of course be located in front of and below the vial 400, and more generally in front of and below the vessel 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 vial 400 that allows accurate image capture is maintained.

[0155] In order to check the top of the vial, the vial 400 is positioned upright on the vessel holder 133 (that is, wherein the base 401 of the vial rests on the vessel holder), and is positioned in the vessel compartment 135 of the top inspection station 103. When the bottom light 131 and the side light 132 are turned on, the vial 400 is rotated 360 ° around its longitudinal axis, for example, by the operation of the rotatable vessel holder 133 (such as platform 137). During this rotation, the angled top camera 130 captures many images of the top portion of the vial (i.e., the upper surface of the bottle neck flange 405a), for example, six images. The captured images show the entire 360 ​​° surface of the top portion of the vial together. The captured images are processed by one or more system processors to identify the presence of particles in one or more specified top surface inspection areas and (ii) the size of any identified particles.

[0156] exist Fig. 10A An example of image capture taken by the angled top camera 130 during this inspection process is shown in FIG. Fig. 10B The same image processed by the system is shown. The processor identifies one or more independent inspection regions, examples of which are shown in FIG. Fig. 10B221, 222. To ensure that the inspection area is correctly identified, the system cannot rely solely on the center of the image (which would require the vessel holder 133 and / or vessel transport element 138 to position the vial 400 to be perfectly aligned with the center of the camera lens). Fig. 10B As shown in the figure as line 223 and / or box 224, 225, the system can be configured to identify image elements corresponding to certain parts of the vial, such as the outer edge of the vial in the captured image, and more specifically the outer edge of the bottle neck flange 405a (shown by line 223 and box 224) and / or a portion of the inner surface of the vial in the captured image (e.g., the hatching shown by box 225). The system can then determine the precise location of one or more inspection areas 221, 222 based on the location of those image elements.

[0157] like Fig. 10B As shown in , the top surface of the vial can be divided into multiple inspection areas 221, 222 to account for shadow effects or other interference. Fig. 10B The inspection region identified by block 222 shown in FIG. 1 may need to be calibrated separately from the inspection region identified by block 221 in order to account for surface features, shadows, etc.

[0158] In other embodiments of the vessel inspection systems and methods disclosed herein, for example, where the system is configured to inspect a syringe barrel or a blood collection tube, one or more inspection areas defined by one or more processors may be different. In addition, small modifications may be made to the system components to accommodate the different geometries of the specific vessel / container being inspected (note that for the purposes of this inspection process, the rear end of the syringe barrel should be considered equivalent to the top of the vial, both of which define an opening to the lumen and typically have a flange). However, regardless of those differences, the inspection systems and methods disclosed herein may be applied to any of a variety of containers including syringe barrels (and barrels of cartridges) and blood collection tubes.

[0159] Bottom transition zone inspection

[0160] Fig.17 A combined bottom transition zone inspection station 104 and bottom surface inspection station 105 are shown. However, in other embodiments, the bottom surface inspection station 105 may be separate from the bottom transition zone inspection station 104. The combined bottom transition zone inspection station 104 and bottom surface inspection station 105 (or, if separate, the bottom transition zone inspection station 104) includes an angled bottom camera 140, a bottom light 141, a side light 412, and a vessel holder 143.

[0161] The bottom light 141 is configured and positioned so that the bottom light is below the vial 400 and the light shines upward, for example, through the top of the vial (the vial is oriented upside down, where the top of the vial is closer to the bottom light than the bottom of the vial) and around all sides of the vial. The bottom light 141 can be a direct-down backlight (e.g., a 63mm x 60mm direct-down backlight, a blue LED, an M12, or similar light). The use of blue light is optional but desirable because it enhances the color of the plasma sheet particles, such as the color of the plasma sheet particles in one or more coatings that may be present on the side walls and / or bottom wall of the vial. The side lights 142 are positioned so that the side lights are behind the vial 400 from the perspective of the camera 140 (i.e., the side lights and the camera are on opposite sides of the vial), and as viewed from the camera, the light shines through the side walls of the vial and over the sides of the vial. The side lights 142 can be a direct-down backlight (e.g., a 51mm x51mm direct-down backlight, a blue LED, an M12, or similar light). Again, the use of blue light is optional but desirable because it enhances the color of the plasma sheet particles, such as may be present in one or more coatings on the sidewalls and / or bottom wall of the vial.

[0162] In the illustrated embodiment, the bottom light 141 and the side light 142 define the bottom and rear surfaces of the vessel compartment 145 in which the vial 400 is held. Here, the sides and front of the vessel compartment 145 are completely open. However, in other embodiments, one or both of the sides and / or front may be partially or completely closed.

[0163] The angled bottom camera 140 is positioned in front of and above the vial 400, and more generally in front of and above the vessel compartment 145, and the lens is aimed at the vial and more generally at the vessel compartment. More specifically, the angled bottom camera 140 is positioned and aimed at the vessel compartment 145 in such a way as to capture an image of the transition zone 403 between the side wall body 402 and the bottom wall 401 of the vial without shadows or other interferences. 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 60° of arc of the transition zone 403, so that six image captures can be used to inspect the entire vial transition zone. For example, the angled bottom camera 140 can be an area scan camera that captures at least 65° of arc of the transition zone 403, which provides overlap with adjacent arcs, and therefore ensures that the entire transition zone is captured and inspected. For example, the angled bottom camera 140 may be a Cognex In-Sight 9912M, 12.0MP or similar camera. The angled bottom camera 140 of this embodiment may also include a 50 mm lens (and associated lens spacer (20 mm) and bandpass filter).

[0164] Vessel holder 143 is configured to rotate vial 400 so that the entire 360° of transition zone 403 can be captured and inspected by image. In some embodiments, vessel holder 143 is configured to rotate continuously, which allows a high-throughput inspection process. For example, vessel holder 143 can be configured to rotate at a speed of up to about 120rpm. Of course, continuous rotation requires camera 140 to open the shutter very briefly. For example, camera 140 can be selected, and lights 141, 142 can be configured and positioned so that the shutter remains open for less than one millisecond when capturing an image. In other embodiments, vial 400 can be rotated discontinuously, that is, the vial can remain stable in a single image capture and rotate between image captures.

[0165] The vessel holder 143 may include a rotatable platform 147 that supports the top surface of the vial, such as the upper surface of the vial neck flange 405a (the vial is placed upside down on the vessel holder, as shown in Figure 13). The rotatable platform 147 is preferably configured so that it does not interfere with or distort the bottom light 141. For example, the rotatable platform 147 can be made of a material that causes the bottom light to fluoresce without significant distortion that would produce shadows, etc. in image capture. Alternatively, the rotatable platform 147 itself may include at least a portion of the bottom light 141. In some (not shown) embodiments, for example, the bottom light 141 or a portion thereof can be used as a vessel holder 143, such as a rotatable platform 147.

[0166] Compared to the side body inspection station 101 and the shoulder inspection station 102, the vessel holder 143 in the illustrated embodiment of the angled bottom inspection station 104 is not movable to allow the vial 400 to enter and leave the inspection station, but in other (not shown) embodiments, this can be done. More specifically, the angled bottom surface inspection station 104 can also include a vessel conveying element 148 that is configured to pick up the vial 400 (e.g., from a transport line or a different inspection station) and position the vial in the vessel compartment 145, and more specifically on the vessel holder 143. Once the image has been obtained, the vessel conveying element 148 can pick up the vial 400 and return it to the transport line or transport it directly to a different inspection station.

[0167] Although the inspection station 104 is described as being oriented as in the drawings, in other embodiments not shown, the vessel compartment 145 can be flipped 180 degrees so that the bottom light 141 forms the top of the vessel compartment. In such an embodiment, the angled bottom camera 140 will of course be located in front of and below the vial 400, and more generally in front of and below the vessel compartment 145, and the vial 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 140, lights 141, 142 and the vial 400 that allows accurate image capture is maintained.

[0168] In order to check the transition zone 403 of the vial, the vial 400 is positioned on the vessel holder 143 and positioned in the vessel compartment 145 of the angled bottom inspection station 104. When the bottom light 141 and the side light 142 are turned on, the vial 400 is rotated 360 ° around its longitudinal axis, for example, by the operation of the rotatable vessel holder 143 (for example, platform 147). During this rotation, the angled bottom camera 140 captures many images of the transition zone 403 of the vial, for example, six images. The captured images together show the entire 360 ​​° surface of the transition zone 403 of the vial. The captured images are processed by one or more system processors to identify the presence of particles in one or more specified transition zone inspection areas and (ii) the size of any identified particles.

[0169] exist Fig.11A An example of image capture taken by the angled bottom camera 140 during this inspection process is shown in FIG. Fig. 11B The same image processed by the system is shown. The processor identifies one or more examination regions, which in this example are, for example, Fig. 11B 231 (minus the portion shown in cross-hatching 232). To ensure that the one or more inspection regions 231 are correctly identified, the system cannot rely solely on the center of the image (which would require the vessel holder 143 and / or vessel transport element 148 to position the vial 400 to be perfectly aligned with the center of the camera lens). More specifically, as shown in FIG. Fig. 11B As shown in the figure as box 233 and lines 234, 235, the system can be configured to identify image elements corresponding to certain portions of the vial, such as the side edge of the vial sidewall in the captured image (e.g., shown by line 234), the side edge of the vial base in the captured image (e.g., shown by line 235), and / or the center of the base of the vial (e.g., as shown in box 233). The system can then determine the precise location of one or more inspection regions 231 based on the locations of those image elements.

[0170] In other embodiments not shown, the transition zone 403 of the vial can be divided into multiple inspection areas to take into account shadow effects or other interference. If necessary, the system can also be calibrated separately for each inspection area to take into account surface features, etc.

[0171] In other embodiments of the vessel inspection systems and methods disclosed herein, for example, where the system is configured to inspect a blood collection tube, one or more inspection areas defined by one or more processors may be different. In addition, small modifications may be made to the system components to accommodate the different geometries of the specific vessels / containers being inspected. However, regardless of those differences, the inspection systems and methods disclosed herein may be applied to any of a variety of containers including syringe barrels (and barrels of cartridges) and blood collection tubes.

[0172] Bottom surface inspection

[0173] As mentioned above, Fig.17 A combined bottom transition zone station 104 and bottom surface inspection station 105 is shown. However, in other embodiments, the bottom surface inspection station 105 may be separate from the bottom transition zone inspection station 104. The combined bottom transition zone inspection station 104 and bottom surface inspection station 105 (or, if separate, the bottom surface inspection station 105) includes a bottom camera 150, a bottom light 141, optional side lights 142, and a vessel holder 143.

[0174] The bottom light 141 is configured and positioned so that the bottom light is below the vial 400 and the light shines upward, for example, through the top of the vial (the vial is placed upside down so that the top of the vial is closer to the bottom light than the base of the vial) and around all sides of the vial. The bottom light 141 can be a direct-down backlight (e.g., a 63mm x 60mm direct-down backlight, a blue LED, an M12, or similar light). The use of blue light is optional but desirable because it enhances the color of the plasma sheet particles, such as the color of the plasma sheet particles that may be present in one or more coatings on the side walls and / or bottom walls of the vial. The side lights 142 are optional. Here, the side lights 142 are direct-down backlights (particularly 51mm x 51mm direct-down backlights, blue LEDs, an M12). Again, the use of blue light is optional but desirable because it enhances the color of the plasma sheet particles, such as the color of the plasma sheet particles that may be present in one or more coatings on the side walls and / or bottom walls of the vial.

[0175] In the illustrated embodiment, the bottom lamp 141 and optional side lamps 142 used during the inspection of the vial bottom wall 401 define the bottom surface and rear surface of the vessel compartment 145, in which the vial is kept. Here, the side and front of the vessel compartment are fully open. However, in other embodiments, one or both of the side and / or front can be partially or completely closed. Alternatively, when the bottom surface inspection station 105 is independent of the bottom transition zone inspection station 104, the side lamps 142 may not exist, and all sides of the vessel compartment 145 may be open.

[0176] Bottom camera 150 is positioned above vessel compartment 145, and lens is aimed at vessel compartment.More specifically, bottom camera 150 is positioned and aimed at vessel compartment in such a way to capture the image of the bottom wall 401 of the vial without shadow or other interferences.Desirably, bottom camera 150 is an area scan camera.For example, bottom camera 150 can be Cognex In-Sight 9912M, 12.0MP or similar camera. Bottom camera 150 can also include 50mm lens (and associated lens spacer (15mm) and bandpass filter).Compared with other cameras 110,120,130,140 described herein, bottom camera 150 can be able to capture the whole bottom wall 401 of the vial in a single image capture.

[0177] The bottom wall inspection station 105 may also include a vessel holder 143. For example, where the bottom wall inspection station 105 is combined with the transition zone inspection station 104, the bottom wall inspection station may include a rotatable vessel holder 143 as described above. In other embodiments where the bottom wall inspection station 105 is independent of the transition zone inspection station 104, the vessel holder 143 does not need to be rotatable (because the entire bottom wall can be captured in a single image capture, and therefore the vial does not need to be rotated). For example, the vial 400 may be placed directly on the bottom light 141, which may be used as a vessel holder, or directly on a fixed (non-rotatable) platform that does not interfere with the bottom light.

[0178] In some embodiments, the bottom wall inspection station 105 also includes a vessel 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 in a vessel compartment and, if present, on a vessel holder 143. Once the image has been acquired, the vessel transport element 148 can pick up the vial 400 and return it to the transport line or transport it directly to a different inspection station.

[0179] Although the inspection station 105 is described as being oriented in the accompanying drawings, in other embodiments not shown, the vessel compartment 145 can be flipped 180 degrees so that the bottom light 141 forms the top of the vessel compartment. In such an embodiment, the bottom camera 150 will of course be located below the vessel 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 accurate image capture is maintained.

[0180] To inspect the bottom wall 401 of the vial, the vial 400 is positioned in the vessel compartment 145 and positioned on the vessel holder 143 (if present) of the bottom wall inspection station 105. When the bottom light 141 and the optional side light 142 are turned on, the bottom camera 150 captures at least one image of the bottom wall 401 of the vial, the at least one image showing the entire bottom wall of the vial individually (e.g., if one image) or together (e.g., if more than one image). The captured one or more images are processed by one or more system processors to identify (i) the presence of particles within one or more designated bottom wall inspection areas and (ii) the size of any identified particles.

[0181] exist Fig. 12A An example of image capture taken by bottom camera 150 during this inspection process is shown in FIG. Fig. 12B The same image processed by the system is shown in FIG. The processor identifies one or more examination regions, which in this example are Fig. 12B 241. To ensure that the inspection area or areas are correctly identified, the system cannot rely solely on the center of the image (which would require the vial 400 to be positioned perfectly aligned with the center of the camera lens). Fig. 12B , the system can be configured to identify image elements corresponding to certain portions of a vial, such as a side edge of a vial in a captured image (shown by line 242) and / or the center of a bottom wall of a vial in a captured image. The system can then determine the precise location of one or more inspection regions based on the locations of those image elements.

[0182] In other embodiments not shown, the bottom wall 401 of the vial can be divided into multiple inspection areas to take into account shadow effects or other interference. If necessary, the system can also be calibrated separately for each inspection area to take into account surface features, etc.

[0183] In other embodiments of the vessel inspection systems and methods disclosed herein, for example, where the system is configured to inspect a blood collection tube, one or more inspection areas defined by one or more processors may be different. In addition, small modifications may be made to the system components to accommodate the different geometries of the specific vessels / containers being inspected. However, regardless of those differences, the inspection systems and methods disclosed herein may be applied to any of a variety of containers including syringe barrels (and barrels of cartridges) and blood collection tubes.

[0184] Each vial rotates continuously, with each camera 110, 120, 130, 140 capturing an image of the vial during rotation, except for the bottom camera 150 which captures a single image of the vial's bottom wall 401 when the vial 400 is stationary.

[0185] Although in all of the above embodiments, it has been described that the vial (or other container) is rotated during the image capture process, it is also contemplated that in alternative embodiments, the camera and / or sidelights can rotate around the vial to capture images across the entire circumference of the vial. In other embodiments, multiple cameras can be present at different locations around the vessel compartment of a given inspection station, and (i) multiple sidelights can be provided and activated at different times to provide a desired light distribution to each of the cameras, or (ii) one or more sidelights can rotate around the vial to provide a desired light distribution to each of the cameras.

[0186] Applying the one or more inspection regions to each image may be performed by the one or more processors. Determining whether any particles or defects are present within the one or more inspection regions, the number of particles or defects within the one or more inspection regions, the size of any particles or defects identified, or any combination thereof may also be performed by the one or more processors. For example, the one or more processors may be configured to receive one or more images from each camera, apply the one or more inspection regions to each image, and determine whether particles and / or defects are present within each of the one or more inspection regions.

[0187] In some embodiments, the one or more processors may be configured to determine whether there are any particles of 25 microns or greater, alternatively 30 microns or greater, alternatively 40 microns or greater, alternatively 50 microns or greater, alternatively 60 microns or greater, alternatively 70 microns or greater, alternatively between 25 and 500 microns, alternatively between 30 and 500 microns, alternatively between 40 and 500 microns, alternatively between 50 and 500 microns, alternatively between 60 and 500 microns, alternatively between 70 and 500 microns, alternatively between 80 and 500 microns, or alternatively between 100 and 150 microns in each of the one or more inspection regions. Alternatively, between 25 and 400 microns, alternatively between 30 and 400 microns, alternatively between 40 and 400 microns, alternatively between 50 and 400 microns, alternatively between 60 and 400 microns, alternatively between 70 and 400 microns, alternatively between 80 and 400 microns, alternatively between 25 and 300 microns, alternatively between 30 and 300 microns, alternatively between 40 and 300 microns, alternatively between 50 and 300 microns, alternatively between 60 and 300 microns, alternatively between 70 and 300 microns, alternatively between 80 and 300 microns.

[0188] The surface area of ​​a particle can be an important criterion for determining whether a vessel meets quality standards in terms of the presence of particles. In some embodiments, one or more processors can be configured (e.g., equipped with an image analysis tool) to determine (e.g., quantify) the surface area of ​​the identified particles. The one or more processors can then compare the surface area of ​​the identified particles to a threshold. If the surface area of ​​the identified particles exceeds the threshold, the vessel, such as a vial, can be removed from the transport line. In some embodiments, a particle surface area exceeding a threshold will require the rejection of the vessel (e.g., a vial), which threshold particle surface area can be 0.0019 mm 2 .

[0189] In some embodiments, a vial (or other container) may be removed from a transport line if the vial is found to contain particles and / or defects within one or more inspection regions. In other embodiments, a vial may be removed from a transport line if the vial is found to contain particles and / or defects that are determined to be above a threshold value (the threshold value may be, for example, zero particles or defects, or zero minimum size particles or defects). For example, the threshold value may be related to the number of particles or defects, the threshold value may be related to the size of the particles or defects, or the threshold value may be related to a combination of the number of particles or defects and the size of each particle or defect. One or more processors may be configured to determine whether a vial exceeds the threshold value for particles and / or defects based on an analysis of one or more images.

[0190] In some embodiments, one or more processors can be configured to determine whether a detected defect is a cosmetic 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 by at least one processor whether a defect is a cosmetic defect or a critical defect can include analyzing the shape of the defect, the depth of the defect, or a combination thereof.

[0191] In some embodiments, one or more of the inspection stations can compensate for changes in ambient lighting of one or more of the following. For example, one or more of the side body camera, the angled shoulder camera, the angled top camera, the angled bottom camera, and the bottom camera, and optionally each, can be configured to compensate for changes in ambient lighting. One way (in which this is accomplished) is for one or more of the cameras, and optionally each camera, to include a bandpass filter, such as a bandpass filter that only passes light having the wavelengths required to detect particles and / or defects.

[0192] In addition, in some embodiments, the intensity of one or more backlights, the intensity of one or more sidelights, or both can be monitored to ensure that one / more intensities remain within a defined range. This monitoring can also be performed by one or more processors. In order to ensure that each vial has appropriate lighting during inspection, if the intensity of one or more backlights, one or more sidelights, or both falls outside the defined range, the inspection can be stopped.

[0193] System and method for applying a coating set to a vessel

[0194] Another aspect of the present invention is an improved method and system for producing a vessel having a coating group consisting of one or more coatings on its inner surface and having reduced particles (e.g., free of or substantially free of particles), the vessel being, for example, an RTU drug container, such as a vial, a syringe (or cartridge) barrel, a blood collection tube, etc. One or more coatings may be applied in any of a variety of ways, such as plasma enhanced chemical vapor deposition (PECVD) and atomic layer deposition (ALD). For many embodiments described herein, at least one of the coatings is applied by PECVD. In some embodiments, for example, at least a gas barrier layer and a pH protective layer may be applied by PECVD. However, in other embodiments, a gas barrier layer (e.g., SiO2, Al2O3, or a combination thereof) may be applied by atomic layer deposition, and a pH protective layer may be applied by PECVD. Additional details on depositing a gas barrier layer onto the inner surface of a drug vessel by ALD may be found in PCT / US2021 / 038548, the entire contents of which are incorporated by reference. Additional details regarding depositing one or more layers onto the inner surface of a drug vessel by PECVD can be found in PCT / US2021 / 045819, the entire contents of which are incorporated herein by reference.

[0195] Fig.18 A pulsed RF PECVD reactor according to an exemplary embodiment of the present disclosure is shown. Fig.18 , shows a pulsed RF PECVD reactor 600, which includes an RF power supply 601, an electrode 603, a vessel chamber 605, a camera 607, an exhaust manifold 609, a gas inlet manifold 611, and a vacuum line 613. At the bottom of each vessel chamber 605 is a vessel holder 1105, 1107, against which the opening of the vessel is placed and through which precursor gas flows into the vessel (from the gas inlet manifold 611) and exhaust gas flows out of the vessel (to the exhaust manifold 609). Reference will be made to Figure 22-23 The vessel holder is described in more detail.

[0196] The RF power supply 601 may include suitable circuits for providing an RF signal at a desired power level, duty cycle, pulse duration, and frequency (e.g., to the electrode 603). The RF power supply 601 may include an adjustable matching impedance network for tuning its output impedance to match the output impedance of the electrode 603. The RF power supply 601 may provide an RF voltage with a resolution of 100 mV to achieve optimal control of the plasma. In addition, the generated RF signal may have a pulse high power of 250 W to 1000 W, but depending on other parameters, the power may be increased to several kW. For example, the pulse low power may be 0 W, and the power frequency may be 13.65 MHz. The duty cycle may vary between 1% and 99%, preferably between 50% and 99%. The pulse train frequency may be in the range of 250 Hz to 5000 Hz, which may be extended to 10000 Hz. Although the coating system described herein utilizes pulsed RF power, in other embodiments, different power supplies may be utilized. In other words, the power supply is not necessarily an RF power supply, but may be a different power supply, such as a microwave power supply.

[0197] Electrode 603 may include metal components for transmitting signals from a power source to a separate PECVD chamber defined by vessel cavity 605 and the vessel itself. Electrode 603 includes a plurality of apertures in the top surface into which the vessel to be coated is placed into the separate vessel cavity 605.

[0198] The vessel chamber 605 includes portions of the electrode 603 within which the portion of the vessel to be coated is placed, and each of which substantially surrounds the vessel wall. The potential between the electrode 603 and a ground plane (not shown) is configured to generate a plasma using an input gas provided by a gas inlet manifold 611. In this example, there are sixteen vessel chambers 605, in two rows of eight, but the present disclosure is not limited thereto.

[0199] In some embodiments, the vessel cavities 605 may have "window" openings in the walls of the electrodes 603 defining the vessel cavities, thereby enabling the camera 607 to have a view of the plasma generated by the applied RF signal in each vessel.

[0200] Camera 607 may include, for example, a CCD or CMOS imaging sensor for monitoring deposition. Camera 607 may be used to monitor plasma intensity, uniformity, and / or color, for example, to ensure that plasma conditions have been properly configured for deposition and / or maintained during deposition of a coating. In some embodiments (such as Fig.18In the embodiment shown in ), more than one camera may be needed to monitor deposition in all (e.g., sixteen) chambers. In the embodiment shown, for example, camera 607 can be placed on each side of electrode 603. In other embodiments, vessel chambers 605 can be arranged and configured so that a single camera 607 can be used to monitor plasma in all vessels of the coated vessels. By staggering the vessel chambers 605 in the first row with the vessel chambers in the second row, each chamber can include a single window, wherein all of the windows face the same direction. Thus, one or more cameras 607, and preferably one camera, can be placed on a single side of electrode 603 and used to monitor plasma conditions within vessels contained in two rows of chambers during the PECVD coating process.

[0201] In one embodiment, the camera 607 can capture and interrogate images of the plasma in the visible range. In another embodiment, the camera 607 can capture and interrogate images of the plasma in the infrared range. In another embodiment, the camera 607 can capture and interrogate images of the plasma in the ultraviolet (UV) range. Light in any one or more of these wavelength ranges can be captured and interrogated to assess the quality of the plasma process.

[0202] Interrogation of the captured images may be performed by a processor operably linked to the camera 607 and optionally further operably linked to a display and / or user interface. If, by interrogating the images captured by the camera 607, it is determined that the plasma within one or more vessels is not within a predetermined acceptable range for one or more characteristics (e.g., intensity, uniformity, or color), an operator may be alerted, one or more of the PECVD variables (e.g., gas flow rates, vacuum levels, RF power levels, pulsation rates, etc.) may be adjusted, and / or the process may be stopped for system maintenance. The vessel(s) whose plasma is deemed unacceptable may be discarded.

[0203] The exhaust manifold 609 includes a network of gas flow lines that enable multiple exhaust outputs to be combined into one exhaust output, thereby enabling a single vacuum system / pump to evacuate multiple chambers equally, thus providing a uniform and consistently reproducible vacuum within each of the multiple vessel cavities. In this example, each of the two sides of the exhaust manifold 609 combines the outputs from eight vessel cavities into one output line, where each output line is coupled together at vacuum line 613.

[0204] Vacuum line 613 may provide vacuum to the vessel chamber via exhaust manifold 609, and the vacuum may be achieved by one or more pumps (not shown). By providing the same pressure at each vessel, vessel-to-vessel uniformity during deposition may be ensured.

[0205] The gas inlet manifold 611 includes a network of gas flow lines that enable a single input gas line to be split into multiple input lines for supplying gas to the vessels to be coated, thereby enabling a single input port 611A to provide gas equally to each vessel, thus providing a uniform and consistently reproducible precursor gas flow in each of the multiple vessel cavities. In this example, the gas inlet manifold splits the output of the gas input port 611A equally between sixteen vessels.

[0206] Fig.19 FIG. 1 shows a pulsed RF PECVD vessel deposition apparatus according to an exemplary embodiment of the present disclosure. Fig.19 , a cross-sectional view and an enlarged cross-sectional view of a vessel 210 (here a vial) placed in a vessel chamber 605 are shown, wherein the opening of the vessel 210 is oriented downward in 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. In addition, the gas delivery probe 1101 can act as an internal electrode (e.g., can include metal and can be grounded) so that when an RF signal is provided by the electrode 603, an electric field is generated, thereby igniting a plasma within the vessel 210 during the deposition process.

[0207] Fig.19 Also shown is a plasma barrier 1107 that extends across the opening of the vacuum port 1103 and ensures that the plasma is confined above the barrier 1107 and within the vessel 210. In any embodiment, the plasma barrier 1107 can take any of a variety of forms. In some embodiments, for example, the plasma barrier 1107 can include a perforated grid, such as a perforated metal disk or plate, as shown in the illustrated embodiment. In other embodiments, the plasma barrier 1107 can include a metal mesh.

[0208] During the pulsed plasma PECVD coating process, one or more precursor gases flow from the gas inlet manifold 611 into the gas delivery probe 1101 and into the vessel 210, where a plasma may be generated by a pulsed RF signal, thereby causing deposition of the desired coating on the interior surface of the wall of the vessel 210. The desired vacuum level is maintained by the flow of gas through the vacuum port 1103 to the exhaust manifold 609 described previously. Because the outlet of the gas delivery probe 1101 is positioned near the end of the vessel opposite the opening through which the vacuum is drawn, the precursor gas flows along the length of the vessel to provide a substantially uniform gas distribution, and the coating can be applied substantially uniformly along the wall of the vessel.

[0209] Although the gas delivery probe 1101 can provide uniform gas distribution within the vessel 210, in other embodiments, pulsing the RF field that generates the plasma can allow the probe 1101 to be eliminated because the pulsing (and the precursor gas flow) can be controlled to provide sufficient time between pulses to allow the precursor gas to be distributed in the vessel before each pulse. Fig. 20 An example of such an embodiment is shown in .

[0210] Fig. 20 A pulsed RF PECVD vessel coating system without a gas delivery probe is shown according to an exemplary embodiment of the present disclosure. Fig. 20 , showing a vessel 210 (here a vial, similar to Fig.19 210, but without a gas delivery probe within the vessel 210. In this example, the precursor gas inlet line 1201 is present but does not extend into the lumen of the vessel 210. Instead, the gas inlet line 1201 is separated from the lumen of the vessel by a plasma barrier 1107 that extends across the opening of the gas inlet line and ensures that the plasma is confined above the barrier 1107 and within the vessel 210.

[0211] and Fig.19 , the opening of the vessel 210 is oriented downward in the vessel holder 1105. In this example, with the electrode 603 providing an RF signal, an electric field is generated between the electrode 603 and the plasma barrier 1107, thereby igniting the plasma within the vessel 210 during the deposition process, and the plasma barrier can act as an "internal" (but in this example, not inside the vessel) electrode (e.g., it can include metal and can be grounded). In the illustrated embodiment, the plasma barrier 1107 extends across both the outlet of the gas inlet line 1201 and the inlet of the vacuum port 1103. However, in other embodiments, the first plasma barrier 1107 can be associated with the gas inlet line 1201, and the second plasma barrier 1107 can be associated with the vacuum port 1103.

[0212] Fig. 22 A detailed view of a first embodiment of a vessel holder 1105 as described above is shown. Although the illustrated embodiment is sized and configured for coating of syringe barrels, the same components and arrangements of components are used for coating of any vessel including, for example, vials (although the size of the components may of course be different).

[0213] The vessel holder 1105 positioned at the bottom of the vessel cavity 605 of the electrode 603 includes a sealing unit 700 configured to form a seal with the vessel 210, and more specifically with the portion of the vessel surrounding the opening to the inner cavity. The seal is important because it allows evacuation of the inner cavity and ensures that ambient air does not enter the inner cavity of the vessel during the coating process. The sealing unit includes a puck 701 and a flexible seal 702.

[0214] The puck-shaped nub 701 has an upper surface 703 that contacts against a portion of the vessel surrounding the opening to the lumen when the vessel is positioned within the cavity 605. The portion of the vessel surrounding the opening to the lumen is an end surface of the vessel, such as an upper surface of a vial, a rear surface of a syringe barrel, etc. In some embodiments (such as the illustrated embodiment), the vessel 210 may have a flange (e.g., at an upper end of a vial, at a rear end of a syringe barrel, etc.), and the end surface may be an end surface of the flange.

[0215] The puck-shaped block 701 also has a central orifice 704 defined by an inner wall 705. The inner cavity of the vessel passes through the central orifice 704 through which the vacuum port 1103 is evacuated. Similarly, as shown, the source gas inlet probe 1101 can pass through the central orifice 704. In an alternative embodiment that excludes the source gas inlet probe 1101, such as the embodiment shown in Figure 12, the precursor gas inlet line 1201 can extend into the central orifice 704 but not through the central orifice. Finally, the plasma barrier 1107 can be positioned within the central orifice 704 of the puck-shaped block 701. For example, the puck-shaped block 701 can include a smaller thickness portion near the upper end, thereby providing a boss for the inner wall 705, and the plasma barrier 1107 can be supported on the boss.

[0216] The puck-shaped block 701 may be made of any heat-resistant, non-conductive material including, 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 puck-shaped block 701 .

[0217] The sealing unit 700 also includes a flexible seal 702. The flexible seal 702 is vertically positioned above the puck-shaped nugget 701 and is configured to contact a portion of the vessel side wall when the vessel is positioned within the electrode cavity 605. In some embodiments (such as the illustrated embodiment), a portion of the vessel side wall may be a flange, and more specifically, the outer surface of the flange. The seal is configured and positioned so that when the vessel 210 is inserted into the cavity 605 and contacts the puck-shaped nugget 701, the portion of the side wall that contacts the flexible seal 702 (e.g., the outer surface of the flange) will apply pressure to the flexible seal, thereby creating an airtight or substantially airtight seal between the vessel side wall and the sealing unit 700 (meaning that if any gas passes through the seal, it is not sufficient to have a measurable effect on the coating process conditions or the resulting one or more coatings). As shown in the illustrated embodiment, the flexible seal 702 may be an O-ring, such as a silicone or elastomeric polymer O-ring.

[0218] The vessel holder 1105 may also include a housing 706 that at least partially encloses the sealing unit 700, i.e., the puck-shaped dome 701 and the flexible seal 702, and prevents undesired movement of the components and, in particular, the flexible seal. The vessel holder 1105 may also include an intermediate element 707 between the puck-shaped dome 701 and the housing 705. As shown in the illustrated embodiment, the intermediate element 707 and the housing 706 may form a recess that holds the flexible seal 702. In other (not shown) embodiments, the puck-shaped dome 701 may have an increased thickness so that it replaces the intermediate element 707.

[0219] Fig.23 A detailed view of a second embodiment of a vessel holder 1105 as described above is shown. Again, while the illustrated embodiment is sized and configured for coating of syringe barrels, the same components and arrangements of components are used for coating of any vessel including, for example, vials (although the size of the components may of course be different). This embodiment is similar to the first embodiment described above, but unlike the first embodiment, the second embodiment includes a puck-shaped nub 701 configured to prevent accumulated particles from contacting the vessel and / or to achieve more effective cleaning of the vessel contacting area of ​​the sealing unit 700.

[0220] It has been observed that during the application of one or more coatings to the inner surface of the vessel, one or more coatings are also deposited on the source gas inlet probe 1101. Over time, the coating deposited on the source gas inlet probe 1101 flakes off and accumulates on the vessel holder 1105, including on the surfaces of the sealing unit 700 that the vessel 210 contacts (i.e., the upper surface 703 of the puck-shaped block 701 and the flexible seal 702). Similarly, in embodiments that exclude the source gas inlet probe 1101, such as Fig. 20In the embodiment shown in , it is contemplated that flakes of the coating may similarly end up on the vessel holder 1105, including on the surfaces of the sealing unit 700 that contact the vessel 210, or it is contemplated that the coating may be deposited on those portions of the vessel holder 1105. Flakes of coating and other particles present on the surfaces of the sealing unit 700 that contact the vessel 210 may become embedded in the vessel during the coating process (e.g., a subsequent coating process), thereby causing the vessel to have a potentially critical defect that prevents it from being used.

[0221] like Fig.23 As shown in , the puck-shaped nugget 701 includes an upper surface 703, at least a portion of which is inclined from the inner wall 705 (and the central aperture 704) at an angle greater than 10 degrees, alternatively greater than 15 degrees, alternatively greater than 20 degrees, alternatively greater than 25 degrees, alternatively greater than 30 degrees, alternatively greater than 35 degrees, alternatively greater than 40 degrees, alternatively 45 degrees or more. In contrast, Fig. 22 The corresponding portion of the upper surface 703 of the puck-shaped nub 701 of the embodiment shown in FIG. 7 has a slope of only about 10 degrees.

[0222] By providing an increased angle of inclination for a portion of the upper surface 703, the puck-shaped nub 701 is configured to reduce the surface area in contact with the vessel 210. The increased angle of inclination of the portion of the upper surface 703 can also direct flakes or other particles toward the central orifice and away from the vessel contact surface. Thus, particles that fall onto the puck-shaped nub 701 accumulate on surfaces that are not in contact with the vessel and are therefore less likely to become embedded in the vessel 210 during the coating process.

[0223] The puck-shaped nub 701 may also facilitate more efficient cleaning of the sealing unit 700 (e.g., using methods such as described elsewhere herein) by providing an increased angle of inclination for a portion of the upper surface 703. In particular, the increased angle of inclination of at least a portion of the upper surface 703 may create a stronger flow profile (e.g., vacuum flow) near the flexible seal 702 during the cleaning process. The increased angle of inclination may also direct particles toward the center of the puck-shaped nub 701, which may be subjected to the strongest flow profile (e.g., vacuum flow) during the cleaning process.

[0224] The following is an exemplary process for coating a vessel using the system described above, and in particular, an exemplary process for providing a three-layer coating to the interior surface of a vessel.

[0225] A vessel 210 is provided, the vessel comprising a wall 214 substantially consisting of a thermoplastic polymer material defining an inner 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 vessel inner cavity has a capacity of 2 to 12 mL, optionally 3 to 5 mL, optionally 8 to 10 mL. The wall 214 has an inner surface 303 facing the inner cavity, and an outer surface 305.

[0226] The vessel is placed into one of the cavities 605 in the electrode 603 with the opening to the vessel lumen oriented downward and a portion of the side wall of the vessel (eg, the outer surface of the flange) in sealing contact with the flexible seal 702 .

[0227] A partial vacuum is formed in the inner cavity. In some embodiments, for example, the partial vacuum can be between about 20 and about 60 mTorr, alternatively between about 30 and about 50 mTorr.

[0228] While maintaining the partial vacuum in the inner cavity, SiO is optionally applied by a pulsed PECVD bonding layer coating step. x C y The bonding coating or layer 289 of the inner cavity is formed by applying sufficient pulsed RF power (alternatively, the same concept is referred to as "energy" in this specification) to generate a plasma in the inner cavity, while feeding a precursor gas containing a siloxane precursor (preferably a linear siloxane precursor), optionally oxygen, and optionally an inert gas diluent to stabilize the plasma. In some embodiments, the precursor gas can be introduced and the ratio of the gas components can be stabilized before igniting the plasma. Then, while maintaining the partial vacuum in the inner cavity, the plasma can be extinguished, which has the effect of stopping the application of SiO x C y The effect of the bonding coating or layer.

[0229] If present, the bonding coating or layer may comprise SiOxCy or Si(NH)xCy. In either formulation, x is from about 0.5 to about 2.4, and y is from about 0.6 to about 3. The bonding coating or layer has an inner surface facing the lumen and an outer surface facing the inner surface of the wall.

[0230] After extinguishing the plasma used in the bonding PECVD coating process and before commencing the barrier PECVD coating process, the feed of the gas employed in the bonding PECVD coating process may be stopped and replaced or simply changed to a gas feed more suitable for depositing the barrier coating or layer, such as by increasing the ratio of oxygen to siloxane precursor and, optionally, reducing or eliminating an inert gas (e.g., argon) from the gas feed.

[0231] While still maintaining the partial vacuum in the inner cavity unbroken, a barrier coating or layer 288 is applied by a pulsed PECVD barrier coating step that includes applying sufficient pulsed RF power to generate a plasma within the inner cavity while feeding a precursor gas comprising a siloxane (preferably a linear siloxane) and oxygen. In some embodiments, the precursor gas may be introduced and the ratio of the gas components stabilized before igniting the plasma. After applying the barrier coating or layer, while maintaining the partial vacuum in the inner cavity unbroken, the plasma may be extinguished, which has the effect of stopping the application of the barrier coating or layer. As a result of the barrier coating step, a SiO bond coat is generated between the bond coat or layer and the inner cavity. x A barrier coating or layer of , wherein x is 1.5 to 2.9, as determined by XPS. The barrier layer can be 2 to 1000 nm thick. It can have an inner surface facing the inner cavity and an outer surface facing the inner surface of the bonding coating or layer. The barrier coating or layer effectively reduces the entry of atmospheric gases into the inner cavity compared to a vessel without a barrier coating or layer.

[0232] After extinguishing the plasma used in the barrier PECVD coating process and before starting the pH protective PECVD coating process, the feed of the gas employed in the barrier PECVD coating process can be stopped and replaced or simply changed to a gas feed more suitable for depositing the pH protective coating or layer, for example by reducing the ratio of oxygen to siloxane precursor and optionally adding or introducing an inert gas (e.g., argon) to the gas feed.

[0233] Then, while maintaining the partial vacuum in the inner cavity, the SiO2 can be applied by a pulsed RF PECVD pH protective coating step. x C y A pH protective coating or layer 286 is provided. The pH protective coating or layer is applied between the barrier coating or layer and the inner cavity. The pH protective PECVD step includes applying sufficient pulsed RF power to generate a plasma within the inner cavity while feeding a precursor gas comprising a siloxane precursor (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 and the ratio of the gas components stabilized before igniting the plasma.

[0234] The pH protective coating or layer may comprise SiOxCy or Si(NH)xCy, wherein 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 corroded or dissolved by some fluids (e.g., aqueous compositions having a pH greater than about 5). Since the coating applied by chemical vapor deposition can be very thin—ten to hundreds of nanometers thick, even a relatively slow erosion rate can eliminate or reduce the effectiveness of the barrier layer in a time shorter than the expected shelf life of the product packaging. This is particularly a problem for fluid pharmaceutical compositions, since many fluid pharmaceutical compositions have a pH of about 7, or more broadly in the range of 5 to 9, similar to the pH of blood and other human or animal fluids. The higher the pH of the pharmaceutical formulation, the faster it corrodes or dissolves the SiOx coating. The SiOx formed from a polysiloxane precursor may be formed into a thin film of the SiOx coating. The SiOx coating may be formed into a thin film of the SiOx coating. The SiOx coating may be formed into a thin film of the SiOx coating. The SiOx coating may be formed into a thin film of the SiOx coating. The SiOx coating may be formed into a thin film of the SiOx coating. The SiOx coating may be formed into a thin film of the SiOx coating. The SiOx coating may be formed into a thin film of the SiOx coating. x C y or Si(NH) x C y Certain pH protective coatings or layers of SiOxCy or Si(NH) do not corrode rapidly when exposed to fluids, and in fact corrode or dissolve more slowly when the fluids have a higher pH in the range of 5 to 9. x C y A pH protective coating or layer can be used to cover the barrier layer of SiOx, preserving the benefits of the barrier layer by protecting it from the fluid in the pharmaceutical package. The protective layer is applied over the SiOx layer to protect the SiOx layer from the contents stored in the vessel, which would otherwise come into contact with the SiOx layer in the vessel. The pH protective coating or layer can thus effectively isolate the fluid from the barrier coating or layer, at least long enough to allow the barrier coating to act as a barrier during the storage period of the pharmaceutical package or other vessel.

[0235] If the pH protective coating is the last layer, the vacuum can be broken and the coated vessel removed. On the other hand, if another layer is to be applied, such as a lubricity layer, the SiO2 can be applied by a pulsed RF PECVD lubricity coating step while maintaining the partial vacuum in the lumen. x C y The lubricious PECVD step comprises applying sufficient pulsed RF power to generate a plasma within the lumen while feeding a precursor gas comprising a siloxane precursor (preferably a linear siloxane precursor), optionally oxygen, and optionally an inert gas diluent. After the lubricious coating is applied, while maintaining the partial vacuum in the lumen unbroken, the plasma may be extinguished, which has the effect of stopping the application of the lubricious coating or layer.

[0236] Optionally in any embodiment, each linear siloxane precursor for depositing optional bonding coating or layer, barrier coating or layer and optional pH protective coating or layer can be hexamethylene disiloxane (HMDSO) or tetramethylene disiloxane (TMDSO), preferably HMDSO. Optionally, in any embodiment, the same linear siloxane precursor is used in each coating process, and the coating process can be, for example, bonding PECVD coating process, barrier PECVD coating process and pH protective PECVD coating process. Using the same siloxane allows the use of the same coating equipment without the need for valve arrangement to feed different siloxanes, and increases the throughput of the coating process (by eliminating the time required for switching between gases). Optionally, in any embodiment, the technology can be further extended to the use of any plasma enhanced chemical vapor deposition process using any precursor to generate any number of coatings using the process as described herein.

[0237] Optionally, in any embodiment, at least 12 vessels, alternatively at least 16 vessels, can be coated simultaneously using the same RF power source, the same vacuum source, the same precursor gas source, or any combination thereof (e.g., in a 12-Up coater, a 16-Up coater, a 24-Up coater, a 32-Up coater, etc.). Optionally, during each coating step, the precursor gas can be distributed equally to all vessels by a gas manifold. Optionally, during each coating step, the vacuum can be distributed equally to all vessels by a vacuum manifold.

[0238] Cleaning of sealing units

[0239] As previously described, during repeated coating cycles, various parts of the system 600, including, for example, the source gas inlet probe 1101 and the sealing unit 700, may accumulate flakes or other particles of the coating. Therefore, after a certain number of coating cycles, the source gas inlet probe 1101 and the ice hockey block 701 may be removed, cleaned, and replaced. This of course requires that the coating equipment be stopped for a period of time. One aspect of the present disclosure is a system and method for cleaning the source gas inlet probe 1101 and / or the sealing unit 700, wherein the cleaning may be a step of the coating process, for example, the cleaning may be performed between coating of a single (or a limited number of) vessels without shutting down the coating system 600 or otherwise interrupting the coating operation. In some embodiments, as part of the coating cycle, an automated device controlled by one or more processors may be used to clean the source gas inlet probe 1101 and / or the sealing unit 700 of one or more chambers 605, and desirably, multiple source gas inlet probes and / or sealing units in multiple chambers may be cleaned.

[0240] exist Figure 24-251 and 2. An embodiment of a system 800 for cleaning a sealing unit 700 of a system 600, and more specifically for cleaning multiple sealing units 700 of a system 600, is shown in FIG. The system 800 can be configured to remove particles (e.g., flakes of coating) from the source gas inlet probe 1101 and / or the sealing unit 700, and more specifically to remove particles from surfaces of the sealing unit 700 that come in contact with the vessel during a coating cycle (although other surfaces such as the plasma barrier 1107 will also have particles removed therefrom).

[0241] System 800 includes one or more inserts 801, each of which is configured to enter a vessel cavity in vessel cavity 605. Each insert 801 includes a wall 802 having an inner surface and an outer surface, and the wall spans from the proximal end 801a of the insert to the distal end 801b of the insert. Both the proximal end and the distal end of the insert can be open. The inner surface of the wall 801 defines a central passage 803 extending from the proximal end of the insert 801 to the distal end. Each insert 801 is operably connected to a vacuum line 810 so as to generate a vacuum in the central passage 803. For example, the open proximal end of the insert 801 can be operably connected to the vacuum line 810.

[0242] Preferably and as shown, the system 800 includes a plurality of inserts 801. The plurality of inserts 801 or a subset of the plurality of inserts can be operably connected to a single vacuum line 810. In the illustrated embodiment, for example, the system 800 includes two groups of inserts 801, each group consisting of four inserts. Each of the four inserts 810 within each group can be operably connected to a single vacuum line 810. However, regardless of the illustrated embodiment, other configurations are contemplated without departing from the scope of the present disclosure / invention.

[0243] The system 800 may also include a frame 820 that holds each of the plurality of inserts 801 and connects each of the plurality of inserts so that they can move as a single unit. However, in other embodiments, multiple frames 820 may be provided, each holding a subset of the plurality of inserts 801 and connecting the subset of the inserts so that they can move as a single unit. For example, although not shown, each subset of four inserts 801 may have its own independent frame 820.

[0244] In addition, although the illustrated embodiment shows a total of eight inserts 801, which are divided into two subsets of four inserts each, any number and / or arrangement of inserts 801 may be provided without departing from the scope of the present disclosure / invention. For example, in other embodiments, the number of inserts 801 may be the same as the number of vessel chambers 605, so that the system 600 may be cleaned in a single pass.

[0245] The cleaning system 800, and more specifically one or more frames 820, may be movable between a first cleaning position, in which each of the one or more inserts 801 is at least partially positioned within one of the one or more cavities 605, and a second coating position, in which the cleaning system is positioned a distance away from the electrode 603 to allow vessel loading and coating cycles. 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.

[0246] During operation, the cleaning system 800 is moved to a cleaning position, wherein each of the one or more inserts 801 is at least partially positioned within one of the cavities 605 of the electrode 603. The one or more vacuum pumps are then operated to draw a vacuum within the central passageway(s) 803 of the one or more inserts 801.

[0247] In order to obtain the desired vacuum flow within each of the cavities 605, the outer diameter of the wall 802 of the insert 801 should be close to the diameter of the cavity 605 so that there is little vacuum loss due to the entry of ambient air through the space between the wall of the electrode defining the cavity and the insert. In some embodiments, for example, the outer diameter of the wall 801 of each insert 801 can be within one inch, alternatively 3 / 4 inch, alternatively 1 / 2 inch, alternatively 1 / 4 inch, alternatively 1 / 8 inch of the diameter of each of the cavities 605.

[0248] By drawing a vacuum of suitable strength within the central passage 803 of each of the one or more inserts 801, particles present in the chamber (e.g., on the surface of the sealing unit 700 and / or the source gas inlet probe 1101) are carried through the central passage 803 and out of the chamber 605. To achieve such removal of particles, the one or more vacuum pumps may desirably be configured to generate a vacuum of at least 0.3 atm (0.3 atm or less pressure), alternatively at least 0.2 atm, alternatively at least 0.1 atm, within the central passage 803 of each of the one or more inserts 801.

[0249] Although not shown, the system 800 may also include one or more particle collection units (which include, for example, one or more screens or filters) to collect particles removed from the cavity 605 and ensure that the particles do not enter the one or more vacuum pumps. The particle collection unit can be positioned at any suitable location between the insert 801 and the vacuum pump.

[0250] To improve the cleaning step, it has been found to be beneficial to position the insert 801 at a plurality of different depths in the cavity 605 while the vacuum is being drawn. Doing so creates different flow profiles within the cavity 605, which helps ensure that particles from various surfaces experience a vacuum of appropriate strength and are drawn into the insert 801. It is also beneficial to maintain the insert 801 at each of the plurality of different depths in the cavity 605 for a period of time before moving the insert to the next depth, in order to allow a particular vacuum flow profile time to develop within the cavity.

[0251] In the illustrated embodiment, the cleaning system 800 moves from the first group of cavities 605 to the second group of cavities, thereby cleaning each group of cavities one by one. In some embodiments, the cleaning system 800 can move between the first group of cavities and the second group of cavities 605 more than once during the cleaning process, that is, it can make two or more passes at each group of cavities. Of course, other configurations are contemplated, including configurations in which all cavities in the cavity can be cleaned in a single step (e.g., the system 800 includes the same number of inserts 801 as there are cavities 605, i.e., a 1:1 ratio) and configurations in which the ratio of inserts 801 to cavities 605 is greater or less than the 1:2 shown in the illustrated embodiment.

[0252] Once cleaning of each of the one or more cavities 605 has been completed, the vacuum may be deactivated and the cleaning system 800 moved away from the electrode 603 so that vessels may be loaded into the one or more cavities 605 and a coating cycle initiated.

[0253] The cleaning of the chamber 605 can be performed in a routine manner or as determined to be needed. In some embodiments, for example, the coating of one or more vessels in a single cycle can be followed by a cleaning cycle, i.e., the chamber 605 can be cleaned each time a new set of vessels is removed from the system 600. In other embodiments, the chamber can be cleaned after a defined number of coating cycles. The exact number of coating cycles to be performed between cleanings can be determined based on collected historical data, or more desirably by a visual inspection step as described herein.

[0254] In some embodiments, for example, the vessel holder 1105 of each cavity 605, and more specifically the sealing unit 700, can be visually inspected for the presence of particles, which is controlled and performed by one or more processors. In some embodiments, a visual inspection can be performed after each coating step, and if it is determined that the cavity 605 contains particles above a defined threshold (the defined threshold can be, for example, the number of particles, including zero), a cleaning step can be started. Additionally or alternatively, a visual inspection can be performed after each cleaning step, and if it is determined that the cavity 605 contains particles above a defined threshold, the cleaning step can be repeated. This process can be repeated multiple times, after which the continued presence of particles above the defined threshold can cause one or more processors to stop the coating operation, remind the operator, etc.

[0255] The visual inspection may include obtaining an image of the one or more cavities 605, and in particular an image of the sealing unit 700 at the base of each of the one or more cavities, and then sending the image to a processor configured to analyze the image to detect the presence of particles above a certain minimum size (i.e., detection limit) (e.g., 10 microns, alternatively 20 microns, alternatively 30 microns, alternatively 40 microns, alternatively 50 microns). The processor may also be configured to determine how many particles above the minimum size there are, the size of each detected particle, or a combination thereof. If the processor determines that particles of an amount, size, or combination thereof that exceed a defined and programmed / stored threshold are present, the processor may initiate a cleaning step.

[0256] A system for visually inspecting one or more cavities 605 and more specifically for visually inspecting a sealing unit 700 at the base of each of the one or more cavities may include one or more cameras 850, each camera configured to obtain an image of the sealing unit of the one or more cavities. The one or more cameras are desirably positioned above the electrode, preferably directly above the electrode. The system may also include one or more lights 851, which are configured to illuminate the interior at the base of each cavity 605, and in particular illuminate the sealing unit 700. In some embodiments, for example, the system may include one or more isotropic linear lights. The one or more lights are also desirably positioned above the electrode, preferably directly above the electrode. In Fig.21A An example of a visual inspection system is shown in .

[0257] In some embodiments, the system may include an assembly, optionally a movable assembly, comprising one or more cameras and one or more lights. Therefore, the movable assembly can be moved to a suitable position above the electrode 603 to perform a visual inspection, and once one or more images are captured, the assembly can move a certain distance away from the electrode 603 so as not to interfere with the subsequent loading of the vessel or the cleaning of the cavity. In other embodiments, the assembly can be in a fixed position above the electrode 603, but at a sufficient distance so as not to interfere with the loading of the vessel or the cleaning system 800. In the case where the assembly is movable, its movement can be controlled by one or more processors, for example, its movement can form a part of a fully automated and continuous coating operation.

[0258] For example, as described above, the system also includes one or more processors configured to receive images from the one or more cameras and analyze the images to detect particles.

[0259] exist Fig. 21B Examples of the types of images that may be captured by the above-described components and received by one or more processors for analysis are shown in FIG.

[0260] Although described above in conjunction 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 visual inspection system and method described herein can be performed as part of the coating system 600 and coating operation, regardless of whether the coating system and operation utilizes a cavity cleaning step. For example, in some embodiments, a visual inspection can be performed and the results can determine when to replace any one or more of the source gas inlet probe 1101, the puck-shaped nub 701, the flexible seal 702, or any combination thereof.

[0261] Typically, the source gas inlet probe 1101 is replaced after a defined number of coating cycles. During repeated coating cycles, the temperature of the inlet probe increases. Therefore, during replacement of the source gas inlet probe 1101, the used probe is cooled before removal. However, as the inlet probe cools, it typically begins to shed loose flakes or particles of the coating. In some embodiments, a vacuum can be applied during the cooling process. For example, the cavity cleaning system described herein can be used to provide a vacuum during the gas inlet probe cooling step. By applying a vacuum during the cooling step, the cooling step can be significantly accelerated. The vacuum can also prevent shed material from falling into areas of concern (e.g., sealing units) and remove shed flakes and particles before they can acquire an electrical charge.

[0262] Method and system for removing particles from a vessel

[0263]

[0013] Another aspect of the present disclosure / invention relates to methods and systems for removing particles from vessel, and in particular from vessel having a coating prepared using the systems and / or methods described herein.

[0264] As described herein, the process of coating the inner surface of one or more vessels can result in particles being present on various portions of the vessel (particularly including the inner surface of the vessel and / or the portion of the vessel in contact with the sealing unit 700). The vessel 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 surface of the vessel (particularly including the surface of the vessel that is most likely to collect particles during the coating process).

[0265] Embodiments of the present disclosure relate to methods and systems for treating one or more vessels (e.g., one or more vessels coated according to the above process) to remove particles from the inner surface of the vessel. The method may include positioning the vessel in a cleaning station 950, and more specifically, in a cavity 951 of the cleaning station (such as Figure 26-27 950) in the cavity shown in the coating system 600. As in the coating system 600, the vessel is positioned in the cavity 951 so as to open to the inner cavity of the vessel. The inner cavity of the vessel can be sealed from the surrounding environment by one or more seals between the station 950 and the outer surface of the vessel. As shown in the illustrated embodiment, for example, the sealing of the vessel can be performed by a sealing unit including a flexible seal 952, and the sealing unit can be similar or identical to the sealing unit shown and described above with reference to the coating system 600.

[0266] Blower probe 953 can be inserted into the inner cavity of the vessel and used to spray high-pressure air. In some embodiments, for example, air can be sprayed at a pressure of at least 50psi, alternatively at least 55psi, alternatively at least 60psi, alternatively at least 70psi, alternatively at least 80psi. Since many particles in the particles can have static charges associated therewith, in some embodiments, the surface of the vessel can be contacted with ionized air, such as sprayed with ionized air. Ionized air removes charge, thereby allowing particles to fall off more easily. The blower probe can move up and down (e.g., along the longitudinal axis of the vessel), and / or can rotate (e.g., around the longitudinal axis of the vessel) to ensure that the entire inner surface of the vessel has been in contact with pressurized air.

[0267] During blasting, a vacuum may be drawn within the vessel cavity (eg, via vacuum line 954) to ensure that dislodged particles may be removed from cleaning station 950 without contaminating the surrounding cleanroom environment.

[0268] Once the cleaning step has been completed, the vacuum can be deactivated and the vessel can be removed.

[0269] One or more vessels may be loaded into and removed from the cleaning station 950 by a vessel conveyor. The movement of the one or more vessel conveyors may be controlled by one or more processors and may, for example, be part of a fully automated coating and cleaning operation.

[0270] The vessels exiting the cleaning station 950 are desirably free of or substantially free of particles (such as flakes of coatings), for example, particles of 50 microns or greater in size, alternatively, particles of 40 microns or greater in size, alternatively, particles of 30 microns or greater in size, alternatively, particles of 20 microns or greater in size. For example, upon exiting the cleaning station 950 after a cleaning process has been performed, the interior surfaces of the vessels are desirably free of or substantially free of particles, for example, particles of 50 microns or greater in size, alternatively, particles of 40 microns or greater in size, alternatively, particles of 30 microns or greater in size, alternatively, particles of 20 microns or greater in size.

[0271] exist Figure 26-27 9 shows an embodiment of a system for removing particles from the interior surface of one or more vessels, i.e., a cleaning station 950. As shown, the cleaning station may include one or more chambers 951, one or more sealing elements 952 located at the base of each chamber and configured to form an airtight or substantially airtight seal with the vessel, a pressurized air delivery probe 953 extending into the interior of the vessel when the vessel is positioned in the chamber, and a vacuum line 954 operably connected to the chamber and configured to evacuate the interior of the vessel.

[0272] Although not shown, the cleaning station 950 may also include one or more particle collection units (which, for example, include one or more screens or filters) to collect particles removed from one or more vessels and ensure that the particles do not enter one or more vacuum pumps. The particle collection unit can be positioned at any suitable location between the cavity 951 and the vacuum pump.

[0273] The cleaning station may also include one or more vessel conveyors (not shown) that can move vessels into and out of the cleaning station 950. The operation of the cleaning station 950 and the movement of the one or more vessel conveyors may be controlled by one or more processors. Thus, the cleaning station may be part of a fully automated coating and cleaning operation.

[0274] Embodiments of the present disclosure relate to methods and systems for treating one or more vessels (e.g., one or more vessels coated according to the above-described process) to remove particles from a portion of the vessel that is in contact with a sealing unit 700. The method may include inserting the vessel into a chamber 901 of a cleaning station 900; spraying air, optionally ionized air, onto at least a portion of the exterior of the vessel; and applying a vacuum within the chamber 901 to remove any dislodged particles from the chamber. The sprayed portion of the vessel may include the portion of the vessel that is in contact with the sealing unit 700 during the coating process. For example, the sprayed portion of the vessel may include a portion of the vessel surrounding an opening to an inner cavity. In the case where the vessel includes a flange, the sprayed portion of the vessel may include an upper surface and an outer surface of the flange.

[0275] exist Figure 28-30 900 for removing particles from at least a portion of the outer surface of a vessel. The system 900 may include a chamber 901 configured to receive each of one or more vessels; one or more nozzles 902 configured to spray air, optionally ionized air, toward the vessel positioned in the chamber; and one or more vacuum lines 903 configured to apply a vacuum in the chamber. Each of the one or more nozzles may be associated with one or more pressurized air supply manifolds.

[0276] In some embodiments, including the embodiment shown, system 900 may include at least a first nozzle or set of nozzles 902a and a second nozzle or set of nozzles 902b, each positioned and oriented to spray a different (although possibly overlapping) portion of the vessel exterior surface.

[0277] like Fig.30 As shown in, the first nozzle or group of nozzles 902a can be configured to be substantially aligned with the portion of the outer surface of the opening adjacent to the inner cavity of the vessel side wall (e.g., the outer surface of the flange) when the vessel is received in the chamber 901, and can be substantially aligned perpendicular to the longitudinal axis of the vessel. Therefore, the first nozzle or group of nozzles 902a can be configured to remove particles from the portion of the vessel that contacts with the flexible seal 702 during the coating process. Although shown as a single nozzle 902a, the first nozzle may include a group of nozzles, which can be positioned around the circumference of the vessel, such as when the vessel is in the chamber 901. When positioned around the circumference of the vessel, a plurality of nozzles 902a can be substantially evenly spaced around the circumference of the vessel. Adjacent nozzles in the group of nozzles 902a can provide overlapping sprays to ensure that the entire circumference of the vessel has been contacted.

[0278] The second nozzle or group of nozzles 902b can be configured to be positioned below the vessel (or above if the orientation of the chamber is flipped) when the vessel is received in the chamber 901, and aligned toward the end surface of the vessel that is closely around the opening to the inner cavity (e.g., the end surface of the flange). In some embodiments, for example, when the vessel is received in the chamber, the second nozzle in the group of nozzles 902b can be aligned at an angle of between about 20 degrees to about 70 degrees, optionally between about 30 degrees to about 60 degrees, optionally between about 40 degrees to about 50 degrees, and optionally about 45 degrees relative to the longitudinal axis of the vessel. Therefore, the second nozzle or group of nozzles 902b can be configured to remove particles from the portion of the vessel that contacts the upper surface 703 of the ice hockey nugget 701 during the coating process. Although shown as a single nozzle 902b, the second nozzle may include a group of nozzles that can be positioned around the circumference of the vessel, for example, when the vessel is in the chamber 901. When positioned around the circumference of the vessel, the plurality of nozzles 902b can be substantially evenly spaced around the circumference of the vessel. Adjacent nozzles in the group of nozzles 902b can provide overlapping sprays to ensure that the entire circumference of the vessel has been contacted.

[0279] In the illustrated embodiment, the system 900 is oriented so that a vessel is placed into the chamber 901 with the end of the vessel containing the opening to the lumen inserted first and facing downward. However, other orientations are contemplated without departing from the scope of the invention / disclosure.

[0280] One or more vessels can be held in one or more chambers 901 by vessel holder 904. Vessel holder 904 can be configured to contact the end of the vessel opposite to the end having an opening to the lumen. For example, in the illustrated embodiment, vessel holder 904 is shown as contacting the bottom of a vial. When configured for a syringe barrel, vessel holder 904 can contact the front end of the barrel (because the opening to the lumen is located at the rear of the syringe barrel).

[0281] In some embodiments, vessel holder 904 can be configured to rotate the vessel during the cleaning process. The rotation of the vessel may be desired to ensure that the (one or more) outer surfaces of the vial are contacted by the air from the ejector across the entire circumference of the vessel. In other embodiments, the vessel may not need to rotate.

[0282] As shown in the illustrated embodiment, the vessel holder 904 can be configured to place the vessel in the chamber 901 and remove the vessel from the chamber. For example, the system 900 can also include a framework 905, which is operably connected to each vessel holder in a plurality of vessel holders 904 so that they can be moved as a single unit. However, in other embodiments, a plurality of frameworks 905 can be provided, each framework keeps a subset of a plurality of vessel holders 904 and a subset of the connector vessel holder so that they can be moved as a single unit. The vessel holder 904, and more specifically the framework 905, can be moved toward and away from the unit containing one or more chambers 901, so that the vessel is placed in the chamber and the vessel is removed from the chamber when the cleaning step has been completed. The movement of one or more vessel holders 904, and more specifically the 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 vessel holders 904 can be controlled by one or more processors, the cleaning station 900 can be a part of a fully automated coating operation.

[0283] Although not shown, the system 900 may also include one or more particle collection units (which include, for example, one or more screens or filters) to collect particles removed from one or more vessels and ensure that the particles do not enter one or more vacuum pumps. The particle collection unit can be positioned at any suitable location between the chamber 901 and the vacuum pump.

[0284] To remove particles from the outer surface of one or more vessels, one or more vessels are inserted into chamber 901 of cleaning system 900. One or more vessels may be held in place by vessel holders 904, including but not limited to Figure 28-30 Once in chamber 901, pressurized air, and desirably ionized air, is sprayed toward at least a portion of the outer surface of the vessel, desirably including at least the portion of the vessel that contacts the sealing unit 700 during the coating operation, such as the portion of the vessel surrounding the opening to the inner cavity (which may include the upper surface and the outer surface of the flange).

[0285] Pressurized air is expected to remove any particles present on the contacted surface of the vessel. In some embodiments, for example, air can be sprayed at a pressure of at least 50psi, alternatively at least 60psi, alternatively at least 70psi, alternatively at least 80psi, alternatively at least 90psi, alternatively at least 100psi, alternatively at least 110psi, alternatively at least 120psi, alternatively at least 130psi. Since many of the particles can have an electrostatic charge associated with them, in some embodiments, the surface of the vessel is contacted with ionized air, such as sprayed with ionized air. Ionized air can remove the charge, thereby allowing pressurized air to more easily dislodge particles.

[0286] In some embodiments, the vessel can be moved in the chamber during spraying. For example, in some embodiments, the vessel can be moved up and down in the chamber (along the longitudinal axis of the vessel) during spraying to ensure that a larger surface area of ​​the vessel is contacted by pressurized air. In some embodiments, the vessel can be rotated around its longitudinal axis during spraying to ensure that the entire circumference of the vessel is contacted by pressurized air. In some embodiments, both movements can occur. One or more movements can be performed by the vessel holder 904. The movement of the vessel holder 904, and more specifically the movement of the frame 905, can be controlled by one or more processors and can, for example, be part of a fully automated vessel coating and cleaning operation.

[0287] During spraying, a vacuum is drawn in the chamber so that all particles that fall off the vessel are evacuated from the chamber without contaminating the clean room environment. As shown in the illustrated embodiment, a single vacuum line 903 may be operably connected to multiple chambers 901 and / or multiple chambers may be associated so as to lead to each other.

[0288] In some embodiments, pressurized air is sprayed toward at least a portion of the sidewall of the vessel and any particles present thereon are removed. Fig.30 As shown in , the spraying can be performed by one or more nozzles 902a, which are positioned to be substantially aligned with a portion of the outer surface of the side wall adjacent to the opening to the inner cavity (e.g., the outer surface of the flange) and substantially perpendicular to the longitudinal axis of the vessel.

[0289] In some embodiments, pressurized air is sprayed toward at least a portion of the vessel end wall and any particles present thereon are removed. Fig.30As shown in , the spraying can be performed by one or more nozzles 902b, which are positioned below the vessel and are aimed toward the end surface of the vessel that closely surrounds the opening to the inner cavity (e.g., the upper surface of the flange). One or more nozzles 902b can be aimed at an angle of, for example, between about 20 degrees and about 70 degrees, optionally between about 30 degrees and about 60 degrees, optionally between about 40 degrees and about 50 degrees relative to the longitudinal axis of the vessel.

[0290] Once the cleaning process has been performed, one or more vessels are removed from chamber(s) 901. Placing vessels in chamber 901 and removing vessels from chambers may be performed by vessel holder 904, which may be controlled by one or more processors. Thus, the step of cleaning at least a portion of the outer surface of a vessel may be part of a fully automated vessel coating and cleaning operation.

[0291] The vessel leaving the chamber 901 is desirably free of or substantially free of particles (such as flakes of coating), for example, particles of 50 microns or more in size, alternatively, particles of 40 microns or more in size, alternatively, particles of 30 microns or more in size, alternatively, particles of 20 microns or more in size. For example, upon leaving the chamber 901 after the cleaning process has been performed, the portion of the outer surface of the vessel surrounding the opening to the inner cavity (which includes, for example, the portion of the vessel end wall and / or side wall that contacts the sealing unit 700 of the coating system 600) is desirably free of or substantially free of particles, for example, particles of 50 microns or more in size, alternatively, particles of 40 microns or more in size, alternatively, particles of 30 microns or more in size, alternatively, particles of 20 microns or more in size.

[0292] In some embodiments, vessels may be transported between interior surface cleaning station 950 and exterior surface cleaning station 900 (eg, in a clean room environment).

[0293] When both the inner and outer surfaces of the vessel have been cleaned according to the present disclosure, the vessel is desirably free of or substantially free of particles (such as flakes of a coating), for example particles of 50 microns or greater in size, alternatively particles of 40 microns or greater in size, alternatively particles of 30 microns or greater in size, alternatively particles of 20 microns or greater in size. In addition, by using the cleaning operations described herein, no washing or water rinsing is required.

[0294] Embodiments of the present disclosure can provide a kind of fully automated system for coating, cleaning and / or checking vessels.For example, a clean room environment can include a coating station 600, a vessel inner surface cleaning station 950 and a vessel outer surface cleaning station 900, and a plurality of vessels can be transported to each cleaning station in the cleaning station from the coating station by one or more transport lines.Similarly, a clean room environment can include a vessel cleaning station 950,900 and a plurality of inspection stations 101,102,103,104,105 as described herein, and a plurality of vessels can be transported between the cleaning station and the inspection station by one or more transport lines.The whole coating, cleaning and / or inspection operation can be controlled by one or more processors.

[0295] Although many illustrations of coating system 600 and systems 900, 950 are shown as being configured to coat the surface of a vial and then remove particles from the surface of the vial, the same system can also be configured to coat the surface of other containers (e.g., syringe (and cartridge) barrels, blood collection tubes, etc.) and remove particles from the surface of other containers using the same techniques shown in the illustrated embodiments. Unless otherwise specified, the present disclosure is in no way limited to the specific vessel 210 shown in the illustrated embodiments.

[0296] In a further embodiment, a fully automated system for coating, cleaning and / or inspecting vessels can be configured to store information related to: operating parameters during the manufacture of vessels (which include, but are not limited to, batch numbers of all parts used to mold polymer or glass vessels, batch numbers of all parts used in the coating process, molding parameters used, coating parameters used, specific operators on duty, and maintenance status of all elements of the clean room and manufacturing machinery); the resulting particle load on the source gas inlet probe 1101, the sealing unit 700 or other components; and the resulting particle load and / or defects on the coated vessel. This information can be stored in a conventional database known in the art. In addition, the system can be configured to analyze the data to identify process parameters that cause an increase in particle load or an increase in the number of defects at any point in time in the process. In a further embodiment, the analysis can identify components, settings, environmental conditions, or personnel that have a negative impact on particle load or defect count earlier, so that mitigation measures can be taken. In a further embodiment, the analysis can allow testing of permutations of molding and coating parameters in order to optimize process efficiency while maintaining an acceptable low particle load and defect count on the produced vessels.

[0297] Example 1

[0298] The automated coating, cleaning and inspection system according to the present disclosure is used to prepare and inspect multiple 10mL vials. As described herein, after coating, each vial is treated to (1) clean the inner surface defining the inner cavity (internal blowing), and (2) clean the outer surface of the vial that is in direct contact with the coating system during the coating step (face blowing). Specifically, each surface is contacted with pressurized ionized air in the cleaning station described and shown herein to remove particles. In addition, after each coating cycle, the coating system is cleaned using the sealing unit cleaning system described and shown herein to remove particles from the surface of the sealing unit that contacts the vial during coating.

[0299] After the internal and face puff cleaning treatments, each vial is inspected using both the automated inspection system described and shown herein and the light obscuration testing technique for measuring sub-visible particles. A large amount of information is stored, including the cleaning group number, pre-cleaning / post-cleaning association, time stamp, time since last cleaning, cavity number, particle count (for various particle sizes), and total area of ​​particles. Data is generated and stored in a database that can be accessed by a computer.

[0300] 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 after each cycle to remove particles. The control vials were also inspected using both the automated inspection system described and illustrated herein and the light obscuration testing technique for measuring sub-visible particles. The results were compared to the test samples. Fig.31 The comparison results are shown in Fig.31 As shown in , implementation of the cleaning system drastically reduced the total particle count to less than 25 particles per 10 mL vial across all numbers of inlets (out of 150 cycles) and vials tested (here 142).

[0301] The average size distribution of particles for vials subjected to the cleaning step (and coated after cleaning the sealing unit of the coating system) is provided in Table 1. Table 1 demonstrates that particles above 50 μm are completely eliminated from the vials by using the cleaning system described herein.

[0302] Table 1

[0303]

[0304] The particle size distribution in the vials after implementation of the automated cleaning technique showed that the automated system successfully eliminated particles above 50 μm (values ​​averaged over 3 runs).

[0305] The cleaning system and method also consistently and repeatably produces a pass of ≥ 0.0019 mm 2The particle size required to reject the vial means that if there are any particles remaining in the vial, their surface area should be less than 0.0019mm 2 . Specific embodiment:

[0307] Vessel inspection method

[0308] 1. A method of inspecting a pharmaceutical container, optionally a ready-to-use pharmaceutical container, for particles, the container having a generally cylindrical side wall, a top portion including a neck defining an opening, a shoulder connecting the side wall to the neck, and optionally a bottom wall and a transition region connecting the bottom wall to the side wall, the method comprising:

[0309] capturing a plurality of images of a side wall portion of the container with a side body camera,

[0310] Optionally, capturing a plurality of images of a shoulder portion of the container using an angled shoulder camera,

[0311] Optionally, capturing multiple images of the top portion of the container using an angled top camera,

[0312] Optionally, capturing multiple images of the transition zone portion of the container using an angled bottom camera, and

[0313] Optionally, capturing one or more images of a bottom wall portion of the container using a bottom camera;

[0314] defining one or more inspection regions with respect to each image; and

[0315] A determination is made as to whether any particles or defects are present 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.

[0316] 2. A method for inspecting a drug container, optionally a ready-to-use drug container, for particles, the method comprising

[0317] a. Any combination of one or more of the following:

[0318] For a container having a side wall, a plurality of images of a side wall portion of the container are captured using a side body camera,

[0319] For containers having shoulders, a plurality of images of the shoulder portion of the container are captured using an angled shoulder camera,

[0320] For containers having a top, multiple images of the top portion of the container are captured using an angled top camera.

[0321] for a container having a sidewall, a bottom wall, and a transition region between the sidewall and the bottom wall, capturing a plurality of images of a portion of the transition region of the container using an angled bottom camera, and

[0322] For a container having a bottom wall, capturing one or more images of the bottom wall of the container using a bottom camera;

[0323] b. defining one or more inspection regions with respect to each image; and

[0324] c. Determining whether there are any 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.

[0325] 3. A method according to any of the preceding embodiments, wherein the step of determining whether there are any particles or defects within the one or more inspection areas, the number of particles or defects within the one or more inspection areas, the size of any particles or defects identified, or any combination thereof is performed by at least one processor.

[0326] 4. The method according to any preceding embodiment, wherein the step of applying one or more inspection regions to each image is performed by at least one processor.

[0327] 5. A method for inspecting a drug container, such as a ready-to-use drug container, for particles, the method comprising

[0328] a. Any combination of one or more of the following:

[0329] For a container having a side wall, a plurality of images of a side wall portion of the container are captured using a side body camera,

[0330] For containers having shoulders, a plurality of images of the shoulder portion of the container are captured using an angled shoulder camera,

[0331] For containers having a top, multiple images of the top portion of the container are captured using an angled top camera.

[0332] for a container having a sidewall, a bottom wall, and a transition region between the sidewall and the bottom wall, capturing a plurality of images of a portion of the transition region of the container using an angled bottom camera, and

[0333] For a container having a bottom wall, capturing one or more images of the bottom wall of the container using a bottom camera;

[0334] b. defining, by at least one processor, one or more inspection regions with respect to each image; and

[0335] c. Determining, by at least one processor, whether there are any 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.

[0336] 6. The method according to any preceding embodiment, wherein the step of capturing a plurality of images of the sidewall portion of the container comprises:

[0337] supporting the container above the bottom light and between the side light and the side subject camera;

[0338] rotating the container about its central axis, optionally continuously rotating the container about its central axis;

[0339] The side body camera is used to capture multiple images of the container sidewall as the container sidewall rotates, the images coinciding or overlapping so that the multiple images cover a 360° arc of the container sidewall.

[0340] 7. The method according to any preceding embodiment, wherein the bottom light is a direct backlight, optionally a blue direct backlight.

[0341] 8. The method of any preceding embodiment, wherein the side body camera comprises an ultra-high resolution area scan camera equipped with a telecentric lens.

[0342] 9. The method according to any preceding embodiment, wherein the sidelight comprises high output planar light, optionally high output planar blue light.

[0343] 10. The method according to any preceding embodiment, wherein the step of capturing a plurality of images of the sidewall portion of the container is performed at a station of a transport line for a plurality of containers.

[0344] 11. The method according to any preceding embodiment, further comprising:

[0345] a. Provide a vessel holder

[0346] b. operating the vessel holder to remove a container from the transport line;

[0347] c. performing at least one of: (i) operating the vessel 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;

[0348] d. after capturing the plurality of images, performing at least one of: (i) operating the vessel holder to move the container away from the station, or (ii) moving the bottom light and the side light away from the container to a standby position; and

[0349] e. Operating the vessel holder to place the container back on the transport line.

[0350] 12. The method according to any preceding embodiment, wherein the step of capturing a plurality of images of the shoulder portion of the container comprises

[0351] supporting the container above the bottom light and between the side light and the angled shoulder camera;

[0352] rotating the container about its central axis, optionally continuously rotating the container about its central axis;

[0353] The angled shoulder camera is used to capture multiple images of the container as the container is rotated, the images coinciding or overlapping such that the multiple images cover a 360° arc of the container shoulder.

[0354] 13. The method according to any preceding embodiment, wherein the bottom light is a direct backlight, optionally a blue direct backlight.

[0355] 14. The method of any preceding embodiment, wherein the angled shoulder camera comprises an ultra-high resolution area scan camera.

[0356] 15. The method according to any preceding embodiment, wherein the sidelight comprises a direct backlight, optionally a blue direct backlight.

[0357] 16. The method according to any preceding embodiment, wherein the step of capturing a plurality of images of the shoulder portion of the container is performed at a station of a transport line for a plurality of containers.

[0358] 17. The method according to any preceding embodiment, further comprising:

[0359] a. Provide a vessel holder

[0360] b. operating the vessel holder to remove a container from the transport line;

[0361] c. performing at least one of: (i) operating the vessel 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;

[0362] d. after capturing the plurality of images, performing at least one of: (i) operating the vessel holder to move the container away from the station, or (ii) moving the bottom light and the side light away from the container to a standby position; and

[0363] e. Operating the vessel holder to place the container back on the transport line.

[0364] 18. The method according to any preceding embodiment, wherein the step of capturing a plurality of images of the top portion of the container comprises

[0365] supporting a bottom surface of the container on or over a bottom light so that the container is between the side light and the angled top camera;

[0366] rotating the container about its central axis, optionally continuously rotating the container about its central axis;

[0367] The angled top camera is used to capture multiple images of the container as the container is rotated, the images coinciding such that the multiple images cover a 360° arc of the top of the container.

[0368] 19. The method according to any preceding embodiment, wherein the bottom light is a direct backlight, optionally a blue direct backlight.

[0369] 20. The method of any preceding embodiment, wherein the angled top camera comprises an ultra-high resolution area scan camera.

[0370] 21. The method according to any preceding embodiment, wherein the sidelight comprises a direct backlight, optionally a blue direct backlight.

[0371] 22. The method of any preceding embodiment, wherein the container is supported above the bottom light by a rotatable platform.

[0372] 23. The method of any preceding embodiment, wherein the rotatable platform is configured such that it does not substantially distort the bottom light.

[0373] 24. The method according to any preceding embodiment, wherein the bottom light is rotatable.

[0374] 25. The method of any preceding embodiment, further comprising reducing or eliminating shadows by providing a reflective wall on a side of the container opposite the sidelights.

[0375] 26. The method according to any preceding embodiment, wherein the step of capturing a plurality of images of the top portion of the container is performed at a station of a transport line for a plurality of containers.

[0376] 27. The method according to any preceding embodiment, further comprising:

[0377] a. Provide a vessel holder

[0378] b. operating the vessel holder to remove a container from the transport line;

[0379] c. performing at least one of: (i) operating the vessel 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;

[0380] d. after capturing the plurality of images, performing at least one of: (i) operating the vessel holder to move the container away from the station, or (ii) moving the bottom light and the side light away from the container to a standby position; and

[0381] e. Operating the vessel holder to place the container back on the transport line.

[0382] 28. The method according to any preceding embodiment, wherein the step of capturing a plurality of images of a transition area between a side wall and a bottom wall of the container comprises

[0383] supporting a top surface of the container on or over a bottom light so that the container is inverted and between the side light and the angled bottom camera;

[0384] rotating the container about its central axis, optionally continuously rotating the container about its central axis;

[0385] The angled bottom camera is used to capture multiple images of the container as the container is rotated, the images coinciding such that the multiple images cover a 360° arc of the container transition zone.

[0386] 29. The method according to any preceding embodiment, wherein the bottom light is a direct backlight, optionally a blue direct backlight.

[0387] 30. The method of any preceding embodiment, wherein the angled bottom camera comprises an ultra-high resolution area scan camera.

[0388] 31. The method according to any preceding embodiment, wherein the sidelight comprises a direct backlight, optionally a blue direct backlight.

[0389] 32. The method of any preceding embodiment, wherein the container is supported above the bottom light by a rotatable platform.

[0390] 33. The method of any preceding embodiment, wherein the rotatable platform is configured such that it does not substantially distort the bottom light.

[0391] 34. The method according to any preceding embodiment, wherein the bottom light is rotatable.

[0392] 35. The method according to any preceding embodiment, wherein the step of capturing a plurality of images of a transition zone of the container is performed at a station of a transport line for a plurality of containers.

[0393] 36. The method according to any preceding embodiment, further comprising:

[0394] a. Provide a vessel holder

[0395] b. operating the vessel holder to remove a container from the transport line;

[0396] c. performing at least one of: (i) operating the vessel 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;

[0397] d. after capturing the plurality of images, performing at least one of: (i) operating the vessel holder to move the container away from the station, or (ii) moving the bottom light and the side light away from the container to a standby position; and

[0398] e. Operating the vessel holder to place the container back on the transport line.

[0399] 37. The method according to any preceding embodiment, wherein the step of capturing one or more images of the bottom wall of the container comprises

[0400] supporting a top surface of the container on or over a bottom light so that the container is inverted and between the bottom light and the bottom camera;

[0401] One or more images of a bottom wall of the container are captured using the bottom camera.

[0402] 38. The method according to any preceding embodiment, wherein the bottom light is a direct backlight, optionally a blue direct backlight.

[0403] 39. The method of any preceding embodiment, wherein the step of capturing one or more images of a bottom wall of the container further comprises supporting the container adjacent a side light.

[0404] 40. The method according to any preceding embodiment, wherein the sidelight comprises a direct backlight, optionally a blue direct backlight.

[0405] 41. The method according to any preceding embodiment, wherein the step of capturing one or more images of the bottom wall of the container is performed at a station of a transport line for a plurality of containers.

[0406] 42. The method of any preceding embodiment, 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 multiple images of the transition zone of the container.

[0407] 43. The method according to any preceding embodiment, wherein

[0408] a. Provide a vessel holder

[0409] b. operating the vessel holder to remove a container from the transport line;

[0410] c. performing at least one of: (i) operating the vessel 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;

[0411] d. after capturing the plurality of images, performing at least one of: (i) operating the vessel holder to move the container away from the station, or (ii) moving the bottom light and the side light away from the container to a standby position; and

[0412] e. Operating the vessel holder to place the container back on the transport line.

[0413] 44. A method according to any of the preceding embodiments, wherein one or more of the side body camera, the angled shoulder camera, the angled top camera, and the angled bottom camera are configured to capture an image having an inspection area extending across at least a 50° arc, optionally at least a 55° arc, optionally at least a 60° arc, optionally at least a 65° arc, optionally at least a 70° arc.

[0414] 45. A method according to any of the preceding embodiments, wherein each of the side body camera, the angled shoulder camera, the angled top camera, and the angled bottom camera is configured to capture an inspection area extending across at least a 50° arc, optionally at least a 55° arc, optionally at least a 60° arc, optionally at least a 65° arc, optionally at least a 70° arc.

[0415] 46. ​​The method of any preceding embodiment, wherein one or more of the side body camera, the angled shoulder camera, the angled top camera, and the angled bottom camera captures at least six images of the container.

[0416] 47. The method of any preceding embodiment, wherein each of the side body camera, the angled shoulder camera, the angled top camera, and the angled bottom camera captures at least six images of the container.

[0417] 48. The method of any preceding embodiment, wherein the inspection region of each of the images overlaps with the inspection region of another of the images.

[0418] 49. The method according to any preceding embodiment, wherein the container is configured to store an injectable drug.

[0419] 50. The method according to any preceding embodiment, wherein the container is a vial, a syringe barrel, or a cartridge.

[0420] 51. The method according to any preceding embodiment, wherein the container is a vial.

[0421] 52. The method of any preceding embodiment, wherein the container has glass walls or plastic walls.

[0422] 53. The method according to any preceding embodiment, wherein the container wall is transparent.

[0423] 54. The method according to any preceding embodiment, wherein the method includes determining whether there are any particles or defects within the one or more inspection regions.

[0424] 55. The method according to any preceding embodiment, wherein the method comprises determining the number of particles or defects within the one or more inspection regions.

[0425] 56. The method of any preceding embodiment, wherein the method comprises determining the size of any particles or defects within the one or more inspection regions.

[0426] 57. The method of any preceding embodiment, wherein the method comprises determining the surface area of ​​any particles or defects within the one or more inspection regions.

[0427] 58. The method of any preceding embodiment, wherein the step of determining whether any particles or defects are present in the one or more inspection areas comprises determining whether there are particles or defects of 20 microns or greater, alternatively 25 microns or greater, alternatively 30 microns or greater, alternatively 40 microns or greater, alternatively 50 microns or greater, alternatively 60 microns or greater, alternatively 70 microns or greater, alternatively between 25 and 500 microns, alternatively between 30 and 500 microns, alternatively between 40 and 500 microns, alternatively between 50 and 500 microns, alternatively between 60 and 500 microns, alternatively between 70 and 500 microns, alternatively between 80 and 800 microns, alternatively between 100 and 1500 microns, alternatively between 150 and 1500 microns, alternatively between 10 ... Any particle or defect between 0 and 500 microns, alternatively between 25 and 400 microns, alternatively between 30 and 400 microns, alternatively between 40 and 400 microns, alternatively between 50 and 400 microns, alternatively between 60 and 400 microns, alternatively between 70 and 400 microns, alternatively between 80 and 400 microns, alternatively between 25 and 300 microns, alternatively between 30 and 300 microns, alternatively between 40 and 300 microns, alternatively between 50 and 300 microns, alternatively between 60 and 300 microns, alternatively between 70 and 300 microns, alternatively between 80 and 300 microns.

[0428] 59. The method of any preceding embodiment, wherein the step of determining the surface area of ​​any particles or defects within the one or more inspection regions comprises determining whether any particles have a surface area that meets or exceeds a threshold value, optionally wherein the threshold value is 0.0019 mm 2 .

[0429] 60. The method of any preceding embodiment, further comprising removing a container from the transport line if the particles or defects within the one or more inspection regions are determined to be above a threshold.

[0430] 61. A method according to any of the preceding embodiments, wherein the threshold relates to the number of particles or defects, the threshold relates to the size of particles or defects, the threshold relates to the surface area of ​​particles or defects, or the threshold relates to any combination thereof.

[0431] 62. The method of any preceding embodiment, further comprising compensating for changes in ambient lighting of one or more of the following:

[0432] capturing a plurality of images of a side wall portion of the container using a side body camera,

[0433] capturing a plurality of images of a shoulder portion of the container using an angled shoulder camera,

[0434] capturing multiple images of the top portion of the container using an angled top camera,

[0435] capturing a plurality of images of the transition area between the side wall and the bottom wall of the container using an angled bottom camera, and

[0436] One or more images of a bottom wall of the container are captured using a bottom camera.

[0437] 63. A method according to any of the preceding embodiments, wherein one or more of the side body camera, the angled shoulder camera, the angled top camera, the angled bottom camera and the bottom camera, and optionally each, is configured to compensate for changes in ambient lighting.

[0438] 64. A method according to any of the preceding embodiments, wherein one or more of the side body camera, the angled shoulder camera, the angled top camera, the angled bottom camera and the bottom camera, and optionally each, includes a bandpass filter, optionally a bandpass filter that only allows light having a wavelength required for the determination step to pass.

[0439] 65. The method of any preceding embodiment, further comprising monitoring the intensity of the one or more backlights, the intensity of the one or more sidelights, or both, to ensure that one / more intensities remain within a defined range.

[0440] 66. The method of any preceding embodiment, further comprising stopping the checking if the intensity of the one or more backlights, the one or more sidelights, or both falls outside the defined range.

[0441] 67. The method of any preceding embodiment, further comprising determining, by the at least one processor, whether the defect is a cosmetic defect or a critical defect.

[0442] 68. The method of any preceding embodiment, further comprising removing the container from the transport line if the defect is determined to be a critical defect.

[0443] 69. The method of any preceding embodiment, wherein determining by at least one processor whether a defect is a cosmetic defect or a critical defect comprises analyzing by the at least one processor a shape of the defect, a depth of the defect, or a combination thereof.

[0444] system

[0445] 70. A system for inspecting a drug container, the system comprising:

[0446] A plurality of cameras, the plurality of cameras comprising

[0447] Side body camera,

[0448] Angled shoulder camera,

[0449] Angled top camera,

[0450] An angled bottom camera, and

[0451] Bottom camera;

[0452] one or more vessel holders, at least one of the one or more vessel holders being configured to rotate the container;

[0453] A plurality of lamps, the plurality of lamps comprising at least

[0454] One or more bottom lights, and

[0455] One or more side lights.

[0456] 71. A system for inspecting a drug container, the system comprising:

[0457] Any combination of the following cameras:

[0458] Side body camera,

[0459] Angled shoulder camera,

[0460] Angled top camera,

[0461] An angled bottom camera, and

[0462] Bottom camera;

[0463] one or more vessel holders, optionally at least one of the one or more vessel holders is configured to rotate the container during inspection;

[0464] A plurality of lamps, the plurality of lamps comprising at least

[0465] One or more bottom lights, and

[0466] One or more side lights.

[0467] 72. The system according to any of the preceding embodiments further includes at least one processor configured to receive images captured by each camera, apply one or more inspection regions to the images, and detect whether any particles or defects are present within the one or more inspection regions.

[0468] 73. The system according to any preceding embodiment, wherein the at least one processor is further configured to determine the size of any particles or defects detected.

[0469] 74. The system according to any preceding embodiment, wherein the at least one processor is further configured to determine a number of particles or defects within the one or more inspection regions.

[0470] 75. The system of any preceding embodiment, wherein the at least one processor is further configured to determine a surface area of ​​any particles detected.

[0471] 76. The system according to any preceding embodiment, wherein the processor is configured to determine whether the container is not fully aligned with the camera, and adjust the inspection area based on the determination.

[0472] 77. The system according to any preceding embodiment, wherein the system is configured to remove a container from a transport line if the particles or defects in the one or more inspection areas are determined to be above a threshold.

[0473] 78. A system according to any of the preceding embodiments, wherein the threshold relates to the number of particles or defects, the threshold relates to the size of particles or defects, or the threshold relates to a combination of the number of particles or defects and the size of particles or defects.

[0474] 79. The system according to any preceding embodiment, wherein the processor is configured to determine whether the defect is a cosmetic defect or a critical defect.

[0475] 80. The system according to any preceding embodiment, wherein the system is configured to remove the container from the transport line if the defect is determined to be a critical defect.

[0476] 81. The system according to any preceding embodiment, wherein to determine whether a defect is a cosmetic 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.

[0477] 82. The system according to any preceding embodiment, wherein at least one of the lights is a blue backlight, optionally a blue LED backlight.

[0478] 83. The system according to any preceding embodiment, wherein one or more of the cameras are ultra-high resolution area scan cameras.

[0479] 84. The system of any preceding embodiment, wherein at least one of the cameras comprises a telecentric lens, optionally wherein the side body camera comprises a telecentric lens.

[0480] 85. A system according to any of the preceding embodiments, wherein one or more of the side body camera, the angled shoulder camera, the angled top camera, the angled bottom camera and the bottom camera, and optionally each, is configured to compensate for changes in ambient lighting.

[0481] 86. A system according to any of the preceding embodiments, wherein one or more of the side body camera, the angled shoulder camera, the angled top camera, the angled bottom camera and the bottom camera, and optionally each, includes a bandpass filter, optionally a bandpass filter that only allows light having a wavelength required to detect particles or defects to pass.

[0482] 87. The system according to any preceding embodiment, wherein at least one of the vessel holders is configured to continuously rotate the container during an inspection associated with the container.

[0483] 88. The system according to any preceding embodiment, wherein at least one of the cameras is configured to capture an inspection area while the container is rotating, optionally wherein a shutter of the camera is open for less than one millisecond.

[0484] 89. A system according to any of the preceding embodiments, wherein at least one and optionally each of the side body camera, the angled shoulder camera, the angled top camera, and the angled bottom camera is configured to capture images having an inspection area extending across at least a 50° arc, optionally at least a 55° arc, optionally at least a 60° arc, optionally at least a 65° arc, optionally at least a 70° arc of the circumference of the container area being inspected.

[0485] 90. A system according to any of the preceding embodiments, wherein at least one of the side body camera, the angled shoulder camera, the angled top camera, and the angled bottom camera, and optionally each, captures at least six images of the container.

[0486] 91. The system of any preceding embodiment, wherein an inspection area of ​​each of the images captured by the camera overlaps an inspection area of ​​another of the images captured by the camera.

[0487] 92. The system of any preceding embodiment, wherein at least one of the vessel holders holds the top of the container such that the bottom of the container is not in contact with any surface.

[0488] 93. The system according to any preceding embodiment, wherein at least one of the vessel holders is a rotating platform supporting the vessel.

[0489] 94. The system of any preceding embodiment, wherein the rotating platform is mounted on top of a bottom light, and wherein the rotating platform is configured such that it does not substantially distort the bottom light.

[0490] 95. The system of any preceding embodiment, wherein the rotating platform comprises gears, and wherein the gears are configured such that they do not substantially distort the bottom lights.

[0491] 96. The system according to any preceding embodiment, wherein the system comprises a plurality of inspection stations.

[0492] 97. The system of any preceding embodiment, wherein the system comprises a side body inspection station, the side body inspection station comprising:

[0493] the side subject camera;

[0494] Bottom light, optionally direct backlight, optionally blue direct backlight;

[0495] a vessel holder configured to hold a top portion of the container so that the container is suspended above the bottom light and configured to rotate the container about its central axis; and

[0496] A side light is positioned on a side of the vessel holder opposite the side body camera.

[0497] 98. The system of any preceding embodiment, wherein the side body camera comprises an ultra-high resolution area scan camera equipped with a telecentric lens.

[0498] 99. The system of any preceding embodiment, wherein the sidelight comprises a high output planar light, optionally a high output planar blue light.

[0499] 100. The system according to any preceding embodiment, wherein the side body inspection station is part of a transport line for a plurality of containers.

[0500] 101. A system according to any preceding embodiment, wherein the system is configured such that

[0501] a. A vessel holder removes a container from the transport line;

[0502] b. (i) the vessel holder moves the container to the side body inspection station, or (ii) the components including the bottom light and the side light are moved into a position adjacent to the container to at least partially form the side body inspection station;

[0503] c. (i) the vessel holder 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

[0504] d. The vessel holder places the container back into the transport line.

[0505] 102. The system according to any preceding embodiment, wherein movement of the vessel holder and / or the component is controlled by at least one processor, optionally wherein the movement is fully automated.

[0506] 103. The system of any preceding embodiment, wherein the system comprises an angled shoulder inspection station, the angled shoulder inspection station comprising:

[0507] said angled shoulder camera;

[0508] Bottom light, optionally direct backlight, optionally blue direct backlight;

[0509] a vessel holder configured to hold a top portion of the container so that the container is suspended above the bottom light and configured to rotate the container about its central axis;

[0510] A side light is positioned on a side of the vessel holder opposite the angled shoulder camera.

[0511] 104. The system of any preceding embodiment, wherein the angled shoulder camera comprises an ultra-high resolution area scan camera.

[0512] 105. The system according to any preceding embodiment, wherein the sidelight is a direct backlight, optionally a blue direct backlight.

[0513] 106. The system of any preceding embodiment, wherein the shoulder inspection station is part of a transport line for a plurality of containers.

[0514] 107. The system according to any preceding embodiment, wherein the system is configured such that

[0515] a. A vessel holder removes a container from the transport line;

[0516] b. (i) the vessel holder moves the container to the shoulder inspection station, or (ii) the components including the bottom light and the side light are moved into a position adjacent to the container to at least partially form the shoulder inspection station;

[0517] c. (i) the vessel holder 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

[0518] d. The vessel holder places the container back into the transport line.

[0519] 108. The system according to any preceding embodiment, wherein movement of the vessel holder and / or the component is controlled by at least one processor, optionally wherein the movement is fully automated.

[0520] 109. The system of any preceding embodiment, wherein the system comprises an angled top inspection station, the angled top inspection station comprising:

[0521] said angled top camera;

[0522] Bottom light, optionally direct backlight, optionally blue direct backlight;

[0523] a rotatable vessel holder, optionally a rotatable platform, supporting a bottom wall of the vessel, the rotatable platform being configured so that it does not substantially distort the bottom light;

[0524] a side light positioned on a side of the vessel holder opposite the angled top camera; and

[0525] Optionally, a reflective wall positioned on a side of the vessel holder opposite the sidelight, the reflective wall configured to reduce or eliminate shadows, optionally wherein the reflective wall has a concave surface.

[0526] 110. The system of any preceding embodiment, wherein the angled top camera comprises an ultra-high resolution area scan camera.

[0527] 111. A system according to any preceding embodiment, wherein the sidelight is a direct backlight, optionally a blue direct backlight.

[0528] 112. The system of any preceding embodiment, wherein the angled top inspection station is part of a transport line for a plurality of containers.

[0529] 113. A system according to any preceding embodiment, wherein the system is configured such that

[0530] a. A vessel transport unit removes the container from the transport line;

[0531] b. (i) the vessel transport unit moves the container to the angled top inspection station, or (ii) the components including the bottom light and the side light are moved into a position adjacent to the container to at least partially form the angled top inspection station;

[0532] c. (i) the vessel 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

[0533] d. The vessel transport unit returns the container to the transport line.

[0534] 114. The system according to any preceding embodiment, wherein the movement of the vessel transport unit and / or the component is controlled by at least one processor, optionally wherein the movement is fully automated.

[0535] 115. The system of any preceding embodiment, wherein the system comprises an angled bottom inspection station, the angled bottom inspection station comprising:

[0536] said angled bottom camera;

[0537] Bottom light, optionally direct backlight, optionally blue direct backlight;

[0538] a rotatable vessel holder, optionally a rotatable platform, supporting a top surface of the vessel, the rotatable platform being configured so that it does not distort the bottom light;

[0539] A side light is positioned on a side of the vessel holder opposite the angled bottom camera.

[0540] 116. The system of any preceding embodiment, wherein the angled bottom camera comprises an ultra-high resolution area scan camera.

[0541] 117. A system according to any preceding embodiment, wherein the sidelight is a direct backlight, optionally a blue direct backlight.

[0542] 118. The system of any preceding embodiment, wherein the angled bottom inspection station further comprises the bottom camera.

[0543] 119. A system according to any preceding embodiment, wherein the bottom camera is mounted directly above the vessel holder.

[0544] 120. The system of any preceding embodiment, wherein the angled bottom inspection station is part of a transport line for a plurality of containers.

[0545] 121. A system according to any preceding embodiment, wherein the system is configured such that

[0546] a. A vessel transport unit removes the container from the transport line;

[0547] b. (i) the vessel transport unit moves the container to the angled bottom inspection station, or (ii) the components including the bottom light and the side light are moved into a position adjacent to the container to at least partially form the angled bottom inspection station;

[0548] c. (i) the vessel 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

[0549] d. The vessel transport unit returns the container to the transport line.

[0550] 122. The system according to any preceding embodiment, wherein the movement of the vessel transport unit and / or the component is controlled by at least one processor, optionally wherein the movement is fully automated.

[0551] 123. The system according to any preceding embodiment, wherein the system comprises a bottom inspection station, the bottom inspection station comprising:

[0552] the bottom camera; and

[0553] Bottom light, optionally direct backlight, optionally blue direct backlight.

[0554] 124. The system of any preceding embodiment, wherein the bottom camera comprises an ultra-high resolution area scan camera.

[0555] 125. The system according to any preceding embodiment, wherein the bottom inspection station is part of a transport line for a plurality of containers.

[0556] 126. A system according to any preceding embodiment, wherein the system is configured such that

[0557] a. A vessel transport unit removes the container from the transport line;

[0558] b. (i) the vessel transport unit moves the container to the bottom inspection station, or (ii) the components including the bottom light and optionally the side light are moved into a position adjacent to the container to at least partially form the bottom inspection station;

[0559] c. (i) the vessel transport unit moves the container back to the transport line, or (ii) the component including the bottom light and optionally the side light moves away from the container; and

[0560] d. The vessel transport unit returns the container to the transport line.

[0561] 127. The system according to any preceding embodiment, wherein the movement of the vessel transport unit and / or the component is controlled by at least one processor, optionally wherein the movement is fully automated.

[0562] 128. The system according to any preceding embodiment, configured such that the transfer of containers between each of the inspection stations and the transport lanes is controlled by at least one processor, optionally fully automated.

[0563] 129. The system according to any preceding embodiment, further comprising a plurality of containers.

[0564] 130. The system according to any preceding embodiment, wherein the containers are each configured to store an injectable drug.

[0565] 131. The system according to any preceding embodiment, wherein the container is a vial, a syringe barrel, or a cartridge.

[0566] 132. The system according to any preceding embodiment, wherein the container is a vial.

[0567] 133. The system of any preceding embodiment, 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.

[0568] 134. The system according to any preceding embodiment, wherein the system processes at least about 30,000 containers per day.

[0569] 135. A system according to any of the preceding embodiments, wherein the system comprises one or more image analysis tools, and the one or more processors are configured to determine the size of the particle, the surface area of ​​the particle, or both through the one or more image analysis tools.

[0570] 136. A method of inspecting a container for particles, defects, or both using the system of any preceding embodiment.

[0571] Application of coating sets

[0572] 137. A system for preparing a coating set on a vessel, optionally a vessel according to any preceding embodiment, comprising:

[0573] a power source, optionally a radio frequency (RF) power source;

[0574] an electrode comprising one or more cavities operable to receive a vessel;

[0575] a source gas line configured to provide one or more source gases into an interior cavity of a vessel positioned within one of the cavities;

[0576] a vacuum line configured to evacuate an interior cavity of a vessel positioned within one of the cavities;

[0577] a sealing unit, the sealing unit being positioned at the bottom of at least one of the cavities, the sealing unit comprising:

[0578] a puck-shaped nub defining a central aperture and having an upper surface against which an end surface of a portion of the vessel surrounding the opening to the interior cavity, optionally a flange, contacts when the vessel is positioned within the cavity; and

[0579] a flexible seal that contacts a portion of the vessel sidewall, optionally an outer surface of the flange, when the vessel is positioned within the cavity;

[0580] The system is operable to:

[0581] receiving one or more vessels in one or more cavities of the electrode;

[0582] evacuating an interior volume of each of the one or more vessels;

[0583] introducing one or more source gases into each of the one or more vessels;

[0584] generating a plasma within each of the one or more vessels using the one or more source gases and a signal applied to the electrodes by the power supply, and optionally an RF signal applied to the electrodes by the RF power supply; and

[0585] A coating is deposited on an interior surface of each of the one or more vessels using the plasma.

[0586] 138. The system of any preceding embodiment, further comprising a source gas inlet probe extending into the interior cavity of the vessel positioned within the opening.

[0587] New ice ball

[0588] 139. A system according to any of the preceding embodiments, wherein at least a portion of the upper surface of the puck-shaped nub is configured to prevent particles, optionally flakes of a coating, optionally flakes of a coating from the source gas inlet probe, from contacting a portion of the vessel surrounding an opening to the inner cavity, optionally a flange.

[0589] 140. The system of any preceding embodiment, wherein at least a portion of the upper surface of the puck is configured to reduce a surface area of ​​the puck that is in contact with or in close proximity to the vessel when the vessel is positioned within the cavity.

[0590] 141. A system according to any of the preceding embodiments, wherein at least a portion of the upper surface of the puck-shaped nugget is inclined from the central orifice 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 45 degrees or more.

[0591] 142. A system according to any of the preceding embodiments, wherein the upper surface of the puck-shaped nugget is inclined from the central orifice 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 45 degrees or more.

[0592] 143. The system of any preceding embodiment, wherein the sealing unit further comprises a plasma barrier positioned within a central aperture of the puck-shaped nub.

[0593] 144. The system of any preceding embodiment, wherein an inner wall of the puck-shaped nub comprises a boss configured to support the plasma barrier.

[0594] 145. A system according to any preceding embodiment, wherein the system is configured to accommodate a vessel selected from the group consisting of: a syringe barrel, a vial, or a blood collection tube; optionally a syringe barrel; optionally a vial; optionally a blood collection tube.

[0595] 146. The system of any preceding embodiment, wherein the puck-shaped nub is made of a heat-resistant, non-conductive material, optionally a ceramic or thermoplastic (eg, polyetheretherketone (PEEK)).

[0596] 147. The system according to any preceding embodiment, wherein the flexible seal is an O-ring, optionally a silicone O-ring.

[0597] Sealing unit cleaning (including by visual inspection)

[0598] 148. The system of any preceding embodiment, further comprising a sealing unit cleaning system configured to remove particles from a surface of the sealing unit that contacts a vessel.

[0599] 149. The system according to any preceding embodiment, wherein the sealing unit cleaning system comprises:

[0600] one or more inserts, each of the one or more inserts being configured to enter the one or more cavities and each of the one or more inserts defining a central passage;

[0601] One or more vacuum lines configured to create a vacuum within the central passageway of each of the one or more inserts.

[0602] 150. The system of any preceding embodiment, wherein each of the one or more inserts has an outer surface having a diameter within 1 / 2 inch of a diameter of each of the one or more cavities.

[0603] 151. The system of any preceding embodiment, wherein the seal unit cleaning system is configured to position each of the one or more inserts at multiple depths in the one or more cavities.

[0604] 152. The system of any preceding embodiment, wherein the seal unit cleaning system is configured to maintain each of the one or more inserts at each of a plurality of depths in the one or more cavities.

[0605] 153. The system of any preceding embodiment, wherein each of the one or more vacuum lines has an air flow of at least 400 cfm and a water lift of at least 35 inches.

[0606] 154. A system according to any of the preceding embodiments, wherein the sealing unit cleaning system is movable between at least (i) a first cleaning position and (ii) a second coating position, wherein each of the one or more inserts is at least partially positioned within one of the one or more cavities, and wherein the sealing unit cleaning system is positioned away from the coating system.

[0607] 155. The system according to any preceding embodiment, wherein movement of the sealing unit cleaning system is controlled by one or more processors.

[0608] 156. A method comprising the step of removing particles from a sealing unit of a system according to any one of the preceding embodiments, the method comprising:

[0609] a. positioning one or more inserts into the one or more cavities, each of the one or more inserts being operably connected to a vacuum line and a vacuum pump; and

[0610] b. Operating the vacuum pump, thereby drawing a vacuum within each of the one or more inserts.

[0611] 157. The method according to any preceding embodiment, further comprising:

[0612] c. moving each of the one or more inserts to a plurality of depths within the one or more cavities during operation of the vacuum pump.

[0613] 158. The method according to any preceding embodiment, further comprising:

[0614] d. maintaining each of the one or more inserts at each of a plurality of depths for a period of time during operation of the vacuum pump.

[0615] 159. The method of any of the preceding embodiments, further comprising deactivating the vacuum, removing the one or more inserts from the one or more cavities, and positioning the one or more inserts a distance away from the electrode that allows one or more vessels to be positioned in the one or more cavities.

[0616] 160. The method of any preceding embodiment, wherein the diameter of the outer surface of each of the one or more inserts is within 1 / 2 inch of the diameter of each of the one or more cavities.

[0617] 161. A method according to any of the preceding embodiments, wherein operation of the vacuum produces 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 chambers.

[0618] 162. The method of any preceding embodiment, wherein movement of the one or more inserts is controlled by one or more processors.

[0619] 163. The method according to any preceding embodiment, further comprising a coating step, wherein the coating step comprises:

[0620] a. positioning one or more vessels in one or more cavities of the electrode;

[0621] b. evacuating the internal volume of each of the one or more vessels;

[0622] c. introducing one or more source gases into each of the one or more vessels;

[0623] d. generating a plasma in each of the one or more vessels using the one or more source gases and a signal applied to the electrodes by the power supply, optionally an RF signal applied to the electrodes by the RF power supply;

[0624] e. depositing a coating on an inner surface of each of the one or more vessels using the plasma; and

[0625] f. Removing the one or more vessels from the one or more cavities of the electrode.

[0626] 164. The method according to any of the preceding embodiments further includes cleaning the inner surface, the outer surface, or both the inner and outer surfaces of the one or more vessels using a pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, or optionally pressurized CO2 before positioning the one or more vessels in one or more cavities of the electrode.

[0627] 165. The method according to any of the preceding embodiments further includes cleaning the inner surface, the outer surface, or both the inner surface and the outer surface of the one or more vessels using a pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, or optionally pressurized CO2 after removing the one or more vessels from one or more cavities of the electrode.

[0628] 166. The method of any preceding embodiment, further comprising applying a vacuum during cleaning of the one or more vessels to capture any particles dislodged by the pressurized gas.

[0629] 167. The method of any preceding embodiment, further comprising alternating between the coating step and the step of removing particles from the sealing unit.

[0630] 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.

[0631] 169. The method according to any preceding embodiment, wherein the defined number of coating steps has been determined by visually inspecting the sealing unit of each of the one or more cavities.

[0632] 170. The method according to any preceding embodiment, further comprising the step of visually inspecting the sealing unit of each of the one or more cavities.

[0633] 171. The method according to any preceding embodiment, wherein the visual inspection is performed after each coating step.

[0634] 172. The method according to any preceding embodiment, wherein the visual inspection is performed after each step of removing particles from the sealing unit.

[0635] 173. The method of any preceding embodiment, wherein the visual inspection comprises obtaining an image of the sealing unit of each of the one or more cavities by one or more cameras positioned above the electrode.

[0636] 174. A 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 comprises applying light to the one or more cavities, optionally by one or more isotropic linear lamps.

[0637] 175. The method of any preceding embodiment, wherein obtaining an image of the sealed unit of each of the one or more cavities further comprises adjusting a position and spectral power distribution of the one or more lamps.

[0638] 176. The method of any preceding embodiment, wherein the one or more lamps have wavelengths in the visible spectrum, the IR spectrum, or a combination thereof.

[0639] 177. A method according to any of the preceding embodiments, wherein the visual inspection further includes causing one or more processors to analyze each image to determine whether 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 reaches or exceeds a threshold to initiate the step of removing particles from the sealing unit.

[0640] 178. The method according to any of the preceding embodiments further includes initiating a step of removing 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 reaches or exceeds the threshold.

[0641] Visual inspection of sealed units (independent of cleaning step)

[0642] 179. The system according to any of the preceding embodiments, further comprising a sealing unit inspection station, wherein the sealing unit inspection station is configured to inspect the sealing unit for particles.

[0643] 180. The system according to any preceding embodiment, wherein the sealing unit inspection station comprises

[0644] one or more cameras configured to obtain an image of the sealing unit of each of the one or more chambers, and

[0645] One or more processors configured to analyze images captured by the one or more cameras and detect the presence of particles.

[0646] 181. The system of any preceding embodiment, further comprising one or more lamps configured to illuminate the one or more cavities, optionally wherein the one or more lamps comprise one or more isotropic linear lamps.

[0647] 182. A system according to any preceding embodiment, wherein the one or more cameras and the one or more lights are on a movable assembly.

[0648] 183. A system according to any of the preceding embodiments, wherein the one or more lights are movable relative to the one or more cavities during image acquisition to illuminate the one or more cavities at any angle from directly above to oblique.

[0649] 184. A system according to any preceding embodiment, wherein the one or more lights are configured to illuminate the one or more cavities from above.

[0650] 185. A system according to any of the preceding embodiments, wherein various spectral power distributions can be emitted by the one or more lamps.

[0651] 186. A system according to any preceding embodiment, wherein the one or more lamps have wavelengths in the visible spectrum, the IR spectrum, or a combination thereof.

[0652] 187. A system according to any of the preceding embodiments, wherein the one or more processors are configured to analyze the image to detect 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.

[0653] 188. A system according to any of the preceding embodiments, wherein the one or more processors are configured to analyze the image to determine whether 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 reaches or exceeds a threshold.

[0654] 189. A method of visually inspecting a sealing unit of a system according to any one of the preceding embodiments, the method comprising:

[0655] a. obtaining an image of a sealed unit of each cavity in the one or more cavities by one or more cameras positioned above the electrode; and

[0656] b. Analyzing the image by one or more processors to detect the amount of particles present on the sealing unit, the size of one or more particles present on the sealing unit, or both.

[0657] 190. A 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 comprises applying light into the one or more cavities, optionally by one or more isotropic linear lamps.

[0658] 191. The method of any preceding embodiment, wherein obtaining an image of the sealed unit of each of the one or more cavities further comprises adjusting a position and spectral power distribution of the one or more lamps.

[0659] 192. The method of any preceding embodiment, wherein the one or more lamps have wavelengths in the visible spectrum, the IR spectrum, or a combination thereof.

[0660] 193. The method according to any of the preceding embodiments further includes initiating a step of removing 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 reaches or exceeds a threshold value.

[0661] 194. The method of any preceding embodiment, further comprising replacing a source gas inlet probe if an amount of particles present on the sealing unit, a size of one or more particles present on the sealing unit, or a combination thereof, reaches or exceeds a threshold.

[0662] 195. The method according to any preceding embodiment, further comprising a coating step, wherein the coating step comprises:

[0663] a. positioning one or more vessels in one or more cavities of the electrode;

[0664] b. evacuating the internal volume of each of the one or more vessels;

[0665] c. introducing one or more source gases into each of the one or more vessels;

[0666] d. generating a plasma in each of the one or more vessels using the one or more source gases and a signal applied to the electrodes by the power supply, optionally an RF signal applied to the electrodes by the RF power supply;

[0667] e. depositing a coating on an inner surface of each of the one or more vessels using the plasma; and

[0668] f. Removing the one or more vessels from the one or more cavities of the electrode.

[0669] 196. The method according to any of the preceding embodiments further includes cleaning the inner surface, outer surface, or inner and outer surface of the one or more vessels using a pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, or optionally pressurized CO2 before positioning the one or more vessels in one or more cavities of the electrode.

[0670] 197. The method according to any of the preceding embodiments further includes cleaning the inner surface, outer surface, or inner and outer surface of the one or more vessels using pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, or optionally pressurized CO2 after removing the one or more vessels from one or more cavities of the electrode.

[0671] 198. The method of any preceding embodiment, further comprising applying a vacuum during cleaning of the one or more vessels to capture any particles dislodged by the pressurized gas.

[0672] 199. The method according to any preceding embodiment, wherein the visual inspection is performed after each coating step.

[0673] 200. The method of any preceding embodiment, further comprising 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 reaches or exceeds the threshold, performing the following:

[0674] removing particles from the sealing unit;

[0675] replacing the puck, the flexible seal, or both;

[0676] Replace the gas source inlet probe; or

[0677] Any combination of them.

[0678] Remove particles from utensil contact surfaces

[0679] 201. A method of preparing a vessel having reduced particles, the method comprising:

[0680] a. Provide a system for preparing a coating set on a vessel, the system comprising

[0681] a power source, optionally a radio frequency (RF) power source;

[0682] an electrode comprising one or more cavities operable to receive a vessel;

[0683] a source gas line configured to provide one or more source gases into an interior cavity of a vessel positioned within one of the cavities;

[0684] a vacuum line configured to evacuate an interior cavity of a vessel positioned within one of the cavities;

[0685] a sealing unit, the sealing unit being positioned at the bottom of at least one of the cavities, the sealing unit comprising:

[0686] a puck-shaped nub defining a central aperture and having an upper surface against which an end surface of a portion of the vessel surrounding the opening to the interior cavity, optionally a flange, contacts when the vessel is positioned within the cavity; and

[0687] a flexible seal that contacts a portion of the vessel sidewall, optionally an outer surface of the flange, when the vessel is positioned within the cavity;

[0688] b. Coating the inner surface of one or more vessels by the following operations

[0689] i. positioning the one or more vessels in one or more cavities of the electrode;

[0690] ii. evacuating the internal volume of each of the one or more vessels;

[0691] iii. introducing one or more source gases into each of the one or more vessels;

[0692] iv. generating a plasma in each of the one or more vessels using the one or more source gases and a signal applied to the electrodes by the power supply, optionally an RF signal applied to the electrodes by the RF power supply;

[0693] v. using the plasma to deposit a coating on the inner surface of each of the one or more vessels; and

[0694] vi. removing the one or more vessels from the one or more cavities of the electrode;

[0695] c. treating the one or more vessels to remove particles from at least the portion of each vessel that is in contact with the sealing unit.

[0696] 202. The method according to any of the preceding embodiments, further comprising treating the one or more vessels to remove particles from each vessel before positioning the one or more vessels in one or more cavities of the electrode, optionally wherein the treating comprises contacting the inner surface, outer surface, or inner and outer surface of each vessel with a pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, optionally pressurized CO2.

[0697] 203. A method of treating a vessel provided with a coating by a system according to any preceding embodiment to remove particles from at least the portion of the vessel in contact with the sealing unit.

[0698] 204. The method according to any preceding embodiment, wherein removing particles from at least a portion of the vessel in contact with the sealing unit comprises:

[0699] a. Inserting the vessel into the chamber of the cleaning station;

[0700] b. spraying pressurized gas, optionally pressurized air, optionally pressurized ionized air, optionally pressurized nitrogen, optionally pressurized CO2, to at least the portion of the vessel in contact with the sealing unit, i.e., the portion of the upper surface and outer surface of the vessel surrounding the opening to the inner cavity, optionally including the flange; and

[0701] c. Apply a vacuum inside the chamber to remove any dislodged particles from the chamber.

[0702] 205. A method of removing particles from a vessel having an interior cavity defined at least in part by a sidewall, the sidewall having an interior surface facing the interior cavity, and an exterior surface, the method comprising:

[0703] a. Inserting the vessel into the chamber of the cleaning station;

[0704] b. spraying pressurized gas, optionally pressurized air, optionally pressurized ionized air, optionally pressurized nitrogen, optionally pressurized CO2, to at least the portion of the vessel surrounding the opening to the inner cavity, optionally the upper surface and outer surface of the flange; and

[0705] c. Apply a vacuum inside the chamber to remove any dislodged particles from the chamber.

[0706] 206. The method of any preceding embodiment, wherein the inner surface of the vessel comprises a coating set that is at least partially applied by PECVD.

[0707] 207. A method according to any of the preceding embodiments, wherein the spraying is performed by one or more nozzles, which are positioned to be substantially aligned with a portion of the outer surface of the side wall adjacent to the opening to the inner cavity, optionally the outer surface of the flange, and are aligned substantially perpendicular to the longitudinal axis of the vessel.

[0708] 208. A method according to any of the preceding embodiments, wherein the spraying is performed by one or more nozzles, which are positioned above or below the vessel and are aligned toward an end surface of the vessel, optionally a flange, that closely surrounds an opening to the inner cavity.

[0709] 209. A method according to any of the preceding embodiments, wherein the one or more nozzles are aligned at an a...

Claims

1. A method of preparing a coated vessel that is substantially free of particles, the method comprising: a. providing a system for preparing a coating set on one or more vessels, the system comprising a power source, optionally a radio frequency (RF) power source; an electrode comprising one or more cavities configured to receive the vessel; a source gas line configured to provide one or more source gases into an interior cavity of a vessel positioned within one of the cavities; a vacuum line configured to evacuate an interior cavity of a vessel positioned within one of the cavities; a sealing unit, the sealing unit being positioned at the bottom of at least one of the cavities, the sealing unit comprising: a puck-shaped nub defining a central aperture and having an upper surface against which an end surface of a portion of the vessel surrounding the opening to the interior cavity, optionally a flange, contacts when the vessel is positioned within the cavity; and a flexible seal that contacts a portion of the vessel sidewall, optionally an outer surface of the flange, when the vessel is positioned within the cavity; b. Coating the inner surface of one or more vessels by the following operations i. positioning the one or more vessels in one or more cavities of the electrode; ii. evacuating the internal volume of each of the one or more vessels; iii. introducing one or more source gases into each of the one or more vessels; iv. generating a plasma in each of the one or more vessels using the one or more source gases and a signal applied to the electrodes by the power supply, optionally an RF signal 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 vessels; and vi. removing one or more coated vessels from one or more cavities of the electrode; c. treating the one or more coated vessels to remove particles from the inner surface of the vessel; and d. treating the one or more coated vessels to remove particles from a portion of each vessel in contact with the sealing unit; The coated vessel obtained (4) contains no or substantially no particles of 50 microns or more, optionally 40 microns or more, optionally 30 microns or more, optionally 25 microns or more, optionally 20 microns or more; (5) No or substantially no surface area of ​​0.0019 mm 2 or larger particles; or (6) Both (1) and (2).

2. The method according to claim 1 further includes treating the one or more vessels to remove particles from each vessel before positioning the one or more vessels in one or more cavities of the electrode, optionally wherein the treating includes contacting the inner surface, outer surface, or inner and outer surface of each vessel with a pressurized gas, optionally pressurized air, optionally ionized and pressurized air, optionally pressurized nitrogen, optionally pressurized CO2.

3. The method of any preceding claim, wherein treating the one or more vessels to remove particles from an interior surface of the vessel comprises: a. Positioning the vessel in a cleaning station; b. inserting the blower probe through the opening of the vessel and into the inner cavity; c. spraying a pressurized gas, optionally pressurized air, optionally pressurized ionized air, optionally pressurized nitrogen, optionally pressurized CO2, onto the inner surface of the side wall cavity; and d. Apply a vacuum within the lumen to remove any dislodged particles through the opening of the vessel.

4. The method of any preceding claim, wherein removing particles from a portion of the vessel in contact with the sealing unit comprises: a. Inserting the vessel into the chamber of the cleaning station; b. spraying pressurized gas, optionally pressurized air, optionally pressurized ionized air, optionally pressurized nitrogen, optionally pressurized CO2, to at least the portion of the vessel in contact with the sealing unit, i.e., the portion of the upper surface and outer surface of the vessel surrounding the opening to the inner cavity, optionally including the flange; and c. Apply a vacuum inside the chamber to remove any dislodged particles from the chamber.

5. The method according to any preceding claim, further comprising treating the sealing unit to remove particles prior to the coating step, optionally wherein the sealing unit is treated to remove particles by the method according to any preceding claim.

6. A system for producing a plurality of drug containers which are coated, cleaned and / or inspected by a method according to any preceding claim.

7. A system, comprising: d) one or more systems for preparing a coating set on a plurality of pharmaceutical containers ("coating system"), comprising: a. Optionally, one or more sealing unit inspection stations, and b. Optionally, one or more sealing units cleaning system; e) one or more systems for removing particles from the plurality of drug containers ("cleaning systems"), and f) One or more systems for inspecting a plurality of drug containers ("inspection systems").

8. A system, comprising: a. one or more coating systems, the one or more coating systems comprising a system for preparing a coating set on a vessel according to any of the preceding claims, the system for preparing a coating set on a vessel optionally comprising a sealing unit cleaning system according to any of the preceding claims and / or a sealing unit inspection station according to any of the preceding claims; b. One or more cleaning systems, the one or more cleaning systems comprising: i. A system for removing particles from a vessel according to any preceding claim, and in particular from at least a portion of the vessel surrounding an opening to the inner cavity; ii. a system for removing particles from the inner surface of the vessel; or iii. both i. and ii.; and c. One or more inspection systems, said one or more inspection systems comprising a system for inspecting a drug container according to any preceding claim.

9. The system of any preceding claim, further comprising one or more transport lines, wherein the transport lines transport the plurality of drug containers between the one or more coating systems, the one or more cleaning systems, and the one or more inspection systems.

10. A system according to any preceding claim, wherein 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, optionally wherein 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 fully automated.

11. A system according to any preceding claim, wherein the system is configured to store information relating to one or more operating parameters associated with the manufacture of the drug container in a database.

12. The system of any preceding claim, wherein the system is configured to analyze the stored information to identify one or more operating parameters associated with the manufacture of the drug container that are associated with an increased particle load or an increased number of defects.

13. A system according to any preceding claim, wherein the system is configured to change one or more operating parameters identified as being associated with an increase in particle loading or an increase in the number of defects.

14. A system according to any preceding claim, wherein the system is configured to test permutations of the one or more operating parameters associated with the manufacture of the drug containers in order to increase the rate at which a plurality of drug containers are produced while maintaining particle loads and / or defective drug containers below set thresholds.

15. A pharmaceutical container, optionally a vial, syringe barrel, injection cartridge or blood collection tube, coated, cleaned and inspected by a method according to any preceding claim.

16. A pharmaceutical container according to claim 15, optionally a vial, syringe barrel, injection cartridge or blood collection tube, wherein the container has been inspected and found to contain no surface area of ​​0.0019 mm 2 or larger particles.

17. A vial comprising: an interior cavity defined at least in part by side walls and a bottom wall, The side wall has an inner surface facing the inner cavity, and an outer surface; The bottom wall has an upper surface facing the inner cavity, and a lower surface; an opening to the inner cavity positioned opposite to the bottom wall; The side wall includes Main area, a neck region having a reduced diameter relative to the body region, a shoulder region between the body region and the neck region, and In the transition area between the main body area and the bottom wall, wherein the vial has been inspected using an automated system and found to contain no (1) particles having a size between 80 and 500 microns, optionally between 70 and 500 microns, optionally between 60 and 500 microns, optionally between 50 and 500 microns, optionally between 40 and 500 microns, optionally between 30 and 500 microns, optionally between 25 and 500 microns; (2) Surface area: 0.0019 mm 2 or larger particles; or (3) Both (1) and (2).

Images