Apparatus, system and method for plunger stopper depth measurement in pre-filled syringes

Abstract

An automated pre-filled syringe inspection system, apparatus and method are provided that can determine the depth of a plunger in a syringe pre-filled with a medicament, the depth of the plunger can be based on digital image data representing a silhouette of at least a portion of a tubular container and at least a portion of the plunger within the tubular container.

Description

[Technical field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 249,849, filed September 29, 2021, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates generally to automated inspection of pre-filled syringes and, more particularly, to automated inspection of pre-filled syringes based on image data representing a silhouette of at least a portion of a syringe flange and at least a portion of a plunger within a syringe barrel. [Background technology]

[0003] Various pharmaceutical products are manufactured and stored in syringes. The associated pre-filled syringes may be manufactured to high quality standards. Pre-filled syringes often include a plunger that fits snugly within a cylindrical tube called a barrel. The proximal end of the syringe may be fitted with, for example, a hypodermic needle, a nozzle or a tube for directing the flow of pharmaceutical product into and / or out of the barrel. As often used in the field of drug delivery, "distal" generally means herein the side of the pre-filled syringe that is away from the patient and "proximal" means the side that faces the patient during use of the pre-filled syringe. Summary of the Invention [Problem to be solved by the invention]

[0004] Pre-filled syringes often have specific requirements for plunger depth after capping. For example, the plunger depth may be based on the physical characteristics of the syringe, the pharmaceutical agent in the pre-filled syringe, the fill volume, etc. Thus, for any given pre-filled syringe, the associated plunger may be located at a predetermined depth within the syringe barrel. Because plunger depth may be a variable controlled by the associated process, post-capping pre-filled syringe inspection may include using a machine vision system to determine the actual plunger depth within each syringe barrel. Syringe-to-syringe variations (e.g., variations in physical dimensions, variations in light transmission, etc.) and / or plunger-to-plunger variations may cause artifacts in images of multiple pre-filled syringes while the pre-filled syringes are backlit.

[0005] Prefilled syringes are often placed in an associated tray (e.g., a preformed tray, such as those sold by RONDO OF AMERICA, INC., 209 Great Hill Naugatuck, CT 06770) for use in packaging, storage, shipping, etc. The tray may, for example, be vacuum formed from an at least partially opaque plastic material. Although trays are typically not 100% opaque, an image of the prefilled syringes illuminated by multiple backlights in the tray may appear as if the tray were a neutral density optical filter that includes optical filter material that is not uniformly distributed in the tray material. Thus, an image of the tray of prefilled syringes in the tray while the prefilled syringes are backlit may include artifacts due to the tray, for example. Image artifacts due to the tray are a frequent cause of erroneous determination of plunger depth in known digital image-based syringe inspection systems.

[0006] What is needed is an apparatus, system, and method for generating digital image data that represents a silhouette of at least a portion of a syringe and at least a portion of a plunger within a barrel of the syringe. What is also needed is an apparatus, system, and method for performing automated inspection of pre-filled syringes based on the digital image data. [Means for solving the problem]

[0007] A method for measuring plunger depth of prefilled syringes can include providing a plurality of prefilled syringes at least partially enclosed by packaging that blocks inspection lighting. The method also includes providing lighting conditions that overcome or avoid the blocking by the packaging.

[0008] In another embodiment, a system for inspecting a tubular container after capping may include a digital image data acquisition device and a digital image processing engine. At least a portion of the tubular container may be at least partially transparent. The digital image data acquisition device may include an image sensor and a backlight. The digital image data acquisition device may be configured to cause the backlight to emit light of a predetermined intensity. The digital image data acquisition device may also be configured to acquire image data from the image sensor while at least a portion of the tubular container and at least a portion of the plunger are disposed between the image sensor and the backlight while the backlight is emitting light. The image data may represent a silhouette of at least a portion of the tubular container and at least a portion of the plunger within the tubular container. The system may also include a digital image processing engine configured to determine a depth of the plunger within the tubular container based on the image data.

[0009] In a further embodiment, a method for inspecting tubular containers may include providing a plurality of tubular containers in a tray and an intermediate holder. The method may also include aligning the intermediate holder to the tray and transferring the plurality of tubular containers from the tray to the intermediate holder. The method may further include disposing the plurality of tubular containers and the intermediate holder between an image sensor and a backlight. The method may further include disposing at least a portion of the tubular container and at least a portion of the plunger between the image sensor and the backlight while the backlight is emitting light at a predetermined intensity, and acquiring image data from the image sensor. The image data may represent a silhouette of at least a portion of the tubular container and at least a portion of the plunger within the tubular container.

[0010] In yet a further embodiment, a non-transitory computer readable medium may include computer readable instructions stored thereon that, when executed by a processor, cause the processor to perform a post-stoppering tubular container inspection. At least a portion of the tubular container may be at least partially transparent. The computer readable medium may include a backlight control module that, when executed by the processor, causes the processor to illuminate a backlight with a predetermined intensity of light. The computer readable medium may also include a digital image data acquisition module that, when executed by the processor, causes the processor to acquire image data from an image sensor while at least a portion of the tubular container and at least a portion of a plunger within the tubular container are positioned between the image sensor and the backlight while the backlight is illuminated. The image data may represent a silhouette of at least a portion of the tubular container and at least a portion of the plunger.

[0011] The present disclosure will be more fully understood from the following description taken in conjunction with the accompanying drawings, in which: Some of the drawings may be simplified by the omission of selected elements for the purpose of more clearly showing other elements. Such omission of elements in some of the drawings does not necessarily indicate the presence or absence of a particular element in any of the exemplary embodiments, unless expressly specified in the corresponding written description. Additionally, none of the drawings are necessarily drawn to scale. [Brief description of the drawings]

[0012] [Figure 1] 1 illustrates an example of a pre-filled syringe inspection system. [Diagram 2] 1 shows an example of a pre-filled syringe. [Diagram 3] 1 shows an example of a silhouette of a portion of two pre-filled syringes in a tray. [Figure 4A] Various examples of pre-filled syringe inspection devices, systems, and methods are presented. [Figure 4B] Various examples of pre-filled syringe inspection devices, systems, and methods are presented. [Figure 4C] Various examples of pre-filled syringe inspection devices, systems, and methods are presented. [Figure 4D] Various examples of pre-filled syringe inspection devices, systems, and methods are presented. [Figure 4E] Various examples of pre-filled syringe inspection devices, systems, and methods are presented. [Figure 4F] Various examples of pre-filled syringe inspection devices, systems, and methods are presented. [Figure 5A] 1 shows an example of a tray of pre-filled syringes, an intermediate holder, a removal tool, and a method for transferring the pre-filled syringes from the tray to the intermediate holder. [Figure 5B] 1 shows an example of a tray of pre-filled syringes, an intermediate holder, a removal tool, and a method for transferring the pre-filled syringes from the tray to the intermediate holder. [Figure 5C]1 shows an example of a tray of pre-filled syringes, an intermediate holder, a removal tool, and a method for transferring the pre-filled syringes from the tray to the intermediate holder. [Figure 5D] 1 shows an example of a tray of pre-filled syringes, an intermediate holder, a removal tool, and a method for transferring the pre-filled syringes from the tray to the intermediate holder. [Figure 5E] 1 shows an example of a tray of pre-filled syringes, an intermediate holder, a removal tool, and a method for transferring the pre-filled syringes from the tray to the intermediate holder. [Figure 5F] 1 shows an example of a tray of pre-filled syringes, an intermediate holder, a removal tool, and a method for transferring the pre-filled syringes from the tray to the intermediate holder. [Figure 5G] 1 shows an example of a tray of pre-filled syringes, an intermediate holder, a removal tool, and a method for transferring the pre-filled syringes from the tray to the intermediate holder. [Figure 5H] 1 shows an example of a tray of pre-filled syringes, an intermediate holder, a removal tool, and a method for transferring the pre-filled syringes from the tray to the intermediate holder. [Figure 5J] 1 shows an example of a tray of pre-filled syringes, an intermediate holder, a removal tool, and a method for transferring the pre-filled syringes from the tray to the intermediate holder. [Figure 5K] 1 shows an example of a tray of pre-filled syringes, an intermediate holder, a removal tool, and a method for transferring the pre-filled syringes from the tray to the intermediate holder. [Figure 6A] 1 shows an example of a syringe return tool. [Figure 6B] 1 shows an example of a syringe return tool. [Figure 6C] 1 shows an example of a syringe return tool. [Figure 6D] 1 shows an example of a syringe return tool. [Figure 7] 1 shows an example of a silhouette representation of multiple pre-filled syringes secured within a gripper. [Figure 8] 1 is a graph showing an example of absorption and transmission of a light sensor. [Figure 9] 1 is a graph illustrating an example of a normalized spectral response of a light sensor. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0013] Those skilled in the art will appreciate that the elements in the figures are depicted for simplicity and clarity and are not necessarily drawn to scale. For example, the dimensions and / or relative positions of some of the elements in the figures may be exaggerated relative to other elements to help improve understanding of the various embodiments of the present invention. Also, common but well-understood elements that are useful or necessary in commercially feasible embodiments are often not shown in order to lessen the clutter of the drawings of these various embodiments. Furthermore, although certain acts and / or things may be described or depicted in a particular order of occurrence, it will be understood that such a particular order is not actually required by those skilled in the art. Furthermore, although certain acts and / or things may be described or depicted in a particular order of occurrence, it will be understood that such a particular order is not actually required by those skilled in the art. It will also be understood that the terms and expressions used herein have the ordinary technical meaning that those skilled in the art would recognize for such terms and expressions, unless a different specific meaning is otherwise expressly set forth herein.

[0014] For example, devices, systems, and methods are provided that can generate digital image data that represents a silhouette of at least a portion of a syringe and at least a portion of a plunger within a barrel of the syringe. Also provided are devices, systems, and methods that can perform automated pre-filled syringe inspection (e.g., determining plunger depth in a pre-filled syringe, determining void height in a pre-filled syringe, etc.) based on the digital image data.

[0015] Post-stoppering inspection of a pre-filled syringe (e.g., a pre-filled 1 mL syringe, a pre-filled 0.5 mL (Terumo) syringe, a pre-filled 2.25 mL syringe, a 5 mL cartridge, etc.) may include measuring the depth to which an associated plunger is inserted into the syringe barrel. The depth of the plunger within the syringe barrel may be unique for a given pharmaceutical product based on physical variables of the syringe, optical properties of the syringe, physical properties of the plunger, the fill volume of the syringe, etc. If an associated inspection system determines that the plunger is located at an improper depth within the pre-filled syringe, the inspection system may determine that the pre-filled syringe fails inspection.

[0016] An automated syringe measurement system may, for example, be more precise and accurate than manual measurement methods. Also, quality data and batch numbers may be automatically and securely recorded using an automated prefilled syringe inspection system. Furthermore, an automated prefilled syringe inspection system may process more syringes per minute than manual measurement techniques. An automated inspection system according to the present disclosure may require fewer operating personnel compared to manual inspection. As a result, the automated syringe inspection system of the present disclosure may improve quality control procedures for prefilled syringes.

[0017] 1, a tubular container (e.g., pre-filled syringe, etc.) inspection system 100 may include a digital image data acquisition device 105 (e.g., Keyence IM-7030; PID TRPT-031206 Vision System; DASI Vision System, etc., available from Keyence Corporation of America, 500 Park Boulevard, Suite 200, Itasca, Ill. 60143). In addition to acquiring digital image data, the digital image data acquisition device 105 may be configured to, for example, determine the depth of a plunger in an associated pre-filled syringe based on the digital image data. Commonly assigned U.S. Pat. No. 9,881,367 discloses details of an exemplary option for determining the depth of a plunger in an associated pre-filled syringe based on digital image data, the disclosure of which is incorporated herein by reference in its entirety.

[0018] The digital image data acquisition device 105 includes a digital camera 110 (e.g., a camera including a CMOS image sensor, a 1″ 6.6 megapixel monochrome CMOS image sensor, a CCD imaging sensor, etc.), a backlight 111 (e.g., an infrared emitting backlight, a backlight emitting light at a wavelength of 850 nm, etc.), a stage 112, a user interface display 115, a user control panel 116, a manual image plane / camera orientation / focus control 117, a mouse 118, a keyboard 119, and a display device 109 having a printer 135 communicatively connected via a link 133. The digital camera 110 may include, for example, a field of view of 11.81″×7.87″ (4×R50) or a high precision mode field of view of 8.86″×4.92″.

[0019] As described in detail herein, the digital image capture device 105 may be configured, for example, to cause the backlight 111 to emit light of a predetermined wavelength and / or intensity, and to capture image data from the image sensor 110 while at least a portion of the tubular container 140 and at least a portion of the plunger 150 are positioned between the image sensor 110 and the backlight 111 while the backlight 111 is emitting light.

[0020] As described in detail herein, the plurality of pre-filled syringes 140 may be held in a tray 170 or an intermediate holder 180. When the pre-filled syringes 140 are held in the tray 170, at least a portion of the tray 170 may be between the pre-filled syringes 140 and the associated backlight 110. When the pre-filled syringes 140 are held in the intermediate holder 180, at least a portion of the space between the pre-filled syringes 140 and the associated backlight 110 may be optically unobstructed. In this regard, the backlight 111 may emit a lower intensity of light when using the intermediate holder 180 as compared to the intensity when using the tray 170.

[0021] The tubular container inspection system 100 may also include a remote device 120 communicatively coupled to the digital image data acquisition device 105 via a network 130. The remote device 120 may include a display device 124 having a user interface 129, a keyboard 128, a mouse 127, and a printer 136 communicatively coupled via a link 134. As described in detail herein, the remote device 120 may be configured, for example, to receive the digital image data and / or the prefilled syringe inspection data and may analyze and / or store the digital image data. For example, the tubular container inspection system 100 may be configured to determine the depth of the plunger within the tubular container based on the image data.

[0022] Returning to FIG. 2 , a view 200 of an “optically uniform” pre-filled syringe (PFS) 240 is shown after plunger insertion. The PFS 240 may include a needle 255 and a needle cap 256. As shown in FIG. 200, the optically uniform PFS 240 may include a flange 241 that defines an open distal end 242. The flange 241 may include optically uniform portions 246, 247. Similarly, the optically uniform PFS 240 may include a syringe barrel 245 having an optically uniform wall 248.

[0023] Plunger depth 260 can be, for example, the difference between distal edge 243 of syringe flange 241 and distal edge 251 of plunger 250. Gap 261 can be, for example, the difference between proximal end 252 of plunger 250 and distal end 257 of associated medication 258 within syringe 245 with proximal end 244 of syringe 245 pointing downward toward the ground.

[0024] 3, an image 300 of a portion of two pre-filled syringes 340a,b in a tray 370 may include syringe artifacts 346, 347 that may reflect, for example, optical variations between the flanges 341a,b of the two pre-filled syringes 340a,b. The image 300 may also include a tray artifact 379 that may reflect, for example, optical variations within the tray 370. In either case, the image 300 may be based on image data that represents, for example, a silhouette of at least a portion of the plurality of pre-filled syringes 340a,b. As described in more detail elsewhere herein, the image data may be acquired from the image sensor 110 while at least a portion of the pre-filled syringes 340a,b and at least a portion of the plunger 350 are positioned between the image sensor 110 and an associated backlight 111 while the backlight 111 emits light of a predetermined wavelength and / or intensity. Additionally or alternatively, an integration period of the image sensor 110 may include a predetermined integration period.

[0025] As shown in FIG. 3, a silhouette image 300 may be obtained by having the intensity of the backlight 111 and / or the integration period of the image sensor 110 based on the optical characteristics of the syringe flanges 341 a,b. For example, an associated digital image data acquisition device 105 may include a digital camera 110 with a predetermined integration period and a backlight 111 with a predetermined intensity such that the silhouette image 300 of any given syringe flange 341 a,b includes each successive distal edge 343. As reflected in image 300, the light intensity associated with the edge of the artifact 379 is greater than the light intensity of both the distal edge of the syringe flange and the distal edge of the plunger. As described herein, edge detection parameters and / or associated digital image processing filters may be incorporated into an associated tubular container inspection device to, for example, cause the device to ignore edges of the tray artifact 379 that may otherwise trigger erroneous distal syringe flange edge and / or distal plunger edge detection.

[0026] 4A-F, tubular container inspection systems 400a-f may include digital image data acquisition devices 405a,b,c in communication with remote devices (e.g., servers) 420b,e via network 430b. Digital image data acquisition devices 405a,b,c may be similar to, for example, digital image data acquisition device 105 of FIG 1. Remote devices 420b,e may be similar to, for example, remote device 120 of FIG 1.

[0027] The tubular container inspection systems 400a-f may, for example, facilitate communication between digital image data acquisition devices 405a, b, c and remote devices 420b, e (e.g., remote servers, cloud-based resources, etc.) to provide prefilled syringe inspection data and / or image data to a digital image-based measurement database 420b.

[0028] For example, the tubular container inspection systems 400a-f may acquire prefilled syringe data (e.g., prefilled syringe physical dimension data, prefilled syringe optical transmission data, prefilled syringe manufacturing data, etc.) from, for example, a user of the digital image data acquisition devices 405a,b,c. Alternatively, or additionally, although not shown in FIGS. 4A-F, the syringe data and / or desired inspection data may be acquired automatically from a third party data source (e.g., a syringe manufacturer, a pharmaceutical manufacturer, etc.). The desired inspection data may include, for example, backlight intensity, signal response backlight, image sensor integration period, plunger depth threshold, etc. As described in detail herein, the tubular container inspection systems 400a-f may automatically determine the depth of a plunger in at least one syringe based on image data (e.g., image data as visually represented in FIG. 3 ) that represents a silhouette of at least a portion of a syringe flange and a portion of an associated plunger.

[0029] For clarity, only one digital image data collection device 405a, b, c is shown in FIG. 4B. Although only one digital image data acquisition device 405a, b, c is shown in FIG. 4B, it should be understood that any number of digital image data acquisition devices 405a, b, c can be supported, and each digital image data acquisition device 405a, b, c can be any suitable digital image-based measurement device. Each digital image data acquisition device 405a, b, c can include a memory 406b and a processor 408b for storing and executing a module 407b. The module 407b stored in the memory 406b as a set of computer readable instructions can relate to an application for automatically determining a plunger depth in at least one syringe based on image data representing a silhouette of at least a portion of the pre-filled syringe.

[0030] As described in more detail herein, the module 407b may facilitate interaction between the associated digital image data collection devices 405a,b,c and the remote devices 420b,e. For example, the processor 408b executing the module 407b may further facilitate communication between the remote devices 420b,e and the digital image data collection devices 405a,b,c via the digital image data collection device network interface 413b, the digital image data collection device communication link 431b, the network 430b, the remote device communication link 432b and the remote device network interface 425b.

[0031] The digital image data acquisition devices 405a,b,c may include user interfaces 409a,b, which may be any type of electronic display device, such as a touch screen display, a liquid crystal display (LCD), a light emitting diode (LED) display, a plasma display, a cathode ray tube (CRT) display, or any other type of known or suitable electronic display, along with user input devices. The user interfaces 409a,b may represent a user interface (e.g., any of the user interfaces 115, 129, 415a, etc.) that present a user interface for configuring the digital image data acquisition devices 405a,b,c to communicate with remote devices 420b,e.

[0032] The network interface 413b may be configured to facilitate communication between the digital image data collection devices 405a,b,c and the remote devices 420b,e via any wireless communication network 430b, including, for example, wireless LAN, MAN or WAN, WiFi, the Internet, or any combination thereof. Furthermore, the digital image data acquisition devices 405a,b,c may be communicatively coupled to the remote devices 420b,e via any suitable communication system, for example, any publicly available or privately owned communication network, including those using wireless communication structures such as wireless LAN and WAN, wireless communication networks including satellite and cellular communication systems, etc. The digital image data acquisition devices 405a,b,c may transmit and store, for example, prefilled syringe inspection data and / or image data to, for example, the remote devices 420b,e, memory 421b, and / or remote digital image-based measurement database 426b.

[0033] The digital image data acquisition devices 405a,b,c may include a camera 410b, a backlight control 411b, and a stage control 412b. As described in more detail herein, the digital image acquisition devices 405a,b,c may be configured, for example, to cause the backlight 411b to emit light of a predetermined wavelength and / or intensity and to acquire image data from the image sensor 410b while at least a portion of the tubular vessel 140 and at least a portion of the plunger 150 are positioned between the image sensor 410b and the backlight 411b while the backlight 411b is emitting light.

[0034] The remote devices 450b,e may include a user interface 424b, a memory 421b,e, and a processor 423b for storing and executing a module 422b, respectively. The module 422b, stored in the memory 421b as a set of computer readable instructions, may implement an application relating to the automated determination of plunger depth in at least one pre-filled syringe. The module 422b may also implement communication between the remote devices 420b,e and the digital image data acquisition devices 405a,b,c, and other functions and instructions, via a network interface 425b and a network 430b.

[0035] The remote devices 420b,e may be communicatively coupled to the digital image-based metrology database 426b. Although the digital image-based metrology database 426b is shown in FIG. 4B as communicatively coupled to the remote devices 420b,e, it should be understood that the digital image-based metrology database 426b may be located in a separate remote server (or any other suitable computing device) communicatively coupled to the remote devices 420b,e. Optionally, portions of the digital image-based metrology database 426b may be associated with separate memory modules, such as memories 406b,c of the digital image data acquisition devices 405a,b,c.

[0036] The digital image data acquisition devices 405a,b,c may include, for example, a user interface generation module 407c, a prefilled syringe data receiving module 408c, a measurement device configuration data receiving module 409c, a camera control module 410c, a backlight control module 411c, a stage control module 412c, a printer control module 414c, an inspection data storage module 415c, and an inspection data transmission module 416c, which may be stored in memory 406c as a set of computer readable instructions. In any case, modules 407c-416c may be similar to, for example, module 407b of FIG. 4B.

[0037] The method for operating the digital image data acquisition devices 405a,b,c may be performed, for example, by a first processor (e.g., processor 408b) executing at least a portion of modules 407c-416c. In particular, processor 408b may execute user interface generation module 407c causing processor 408b to generate (block 407d), for example, user interfaces 115, 129, 415a, 615. The user interfaces may enable a user to input, for example, prefilled syringe data.

[0038] The processor 408b may execute a syringe data receiving module 408c, causing the processor 408b to receive pre-filled syringe data, for example, from a pre-filled syringe manufacturer, a pharmaceutical manufacturer, etc. (block 408d). The processor 408b may execute a measurement device configuration data receiving module 409c, causing the processor 408b to receive measurement device configuration data, for example, from a remote device (block 409d). The processor 408b may execute a camera control module 410c, causing the processor 408b to control, for example, the camera 110 (e.g., receive real-time image data) (block 410d). The processor 408b may execute a backlight control module 412c, causing the processor 408b to control, for example, the wavelength and / or intensity of light emitted from the backlight 111 (block 411d). The processor 408b may execute a stage control module 412c, causing the processor 408b to control, for example, the stage 112 (block 412d).

[0039] The processor 408b may execute the test data generation module 413c, causing the processor 408b to determine, for example, plunger position data and / or digital image data representing a silhouette of at least a portion of a prefilled syringe (block 413d). The processor 408b may execute the printer control module 414c, causing the processor 408b to print, for example, the prefilled syringe test data and / or image data (block 414d). The processor 408b may execute the test data storage module 415c, causing the processor 408b to store, for example, the prefilled syringe test data and / or image data (block 415d). The processor 408b may execute the test data transmission module 416c, causing the processor 408b to transmit, for example, the prefilled syringe test data and / or image data (block 416d).

[0040] The remote devices 420b,e may include, for example, a user interface generation module 422e, a syringe data receiving module 423e, a measurement device data generation module 424e, a measurement device data transmission module 425e, a test data receiving module 426e, a test data analysis module 427e, and a test data storage module 428e stored in memory 421b,e as a set of computer readable instructions. In any case, the modules 422e-428e may be similar to, for example, module 422b of FIG. 4B.

[0041] The method for operating the remote device 400f may be performed, for example, by a processor (e.g., processor 423b) executing at least a portion of modules 422e-428e. In particular, processor 423b may execute user interface generation module 422e, causing processor 423b to generate, for example, user interfaces 115, 129, 415a, 615, etc. (block 422f).

[0042] The processor 423b may execute a syringe data receiving module 423e, causing the processor 423b to receive pre-filled syringe data, for example, from a user via a user interface and / or from a third-party pre-filled syringe database (block 423f). The processor 423b may execute a measurement device data generating module 424e, causing the processor 423b to generate, for example, digital image data acquisition device configuration data (block 424f). The digital image data acquisition device configuration data may represent backlight wavelength, backlight intensity, image sensor integration period, etc.

[0043] The processor 423b may execute a measurement device data transmission module 425e, causing the processor 423b to transmit, for example, digital image data acquisition device configuration data to the digital image data acquisition devices 405a-c (block 425f). The processor 423b may execute a test data reception module 426e, causing the processor 423b to receive, for example, prefilled syringe test data and / or image data from the digital image data acquisition devices 405a-c (block 426f). The processor 423b may execute a test data analysis module 427e, causing the processor 423b to analyze, for example, the prefilled syringe test data and / or image data (block 427f). The processor 423b may execute a test data storage module 428e, causing the processor 423b to store, for example, the prefilled syringe test data and / or image data (block 428f).

[0044] 5A-H, J, K, prefilled syringe inspection systems 500a-h, j, k may include a tray 570a of prefilled syringes. Tray 570a of prefilled syringes 540a may be similar to tray 170 of prefilled syringes 140 of FIG. 1, for example. Tray 570a may include a plurality of prefilled syringe receptacles, each having a distal end 571a, a proximal end 576a, and a prefilled syringe holder 579a. Each prefilled syringe 540a may include a plunger 550a and a proximal end 541a. Proximal end 541a of each prefilled syringe 540a may be oriented toward proximal end 576a.

[0045] The tray 570a may be vacuum molded from opaque white plastic, for example. The tray 570a may not block 100% of the light. Instead, the tray 570a may tend to appear as a neutral density optical filter made of non-homogenously distributed filter material. A higher intensity backlight may transmit more light into the tray and illuminate multiple PFS through the tray. This effect may form a silhouette of the PFS against which the plunger depth is measured.

[0046] Inspection of prefilled syringes is often performed by technicians. Therefore, it may not be desirable to use strong lighting in the visible spectrum. Also, the light passing through the prefilled syringe (PFS) must not damage or generally disturb the active product contained within the syringe. Therefore, the wavelength of the backlight may be in the infrared (IR) spectrum. Operators cannot see IR with the naked eye, and IR wavelengths are longer (lower energy) than visible or UV wavelengths. Therefore, light in the IR spectrum generally poses less risk of damaging pharmaceutical products. The "invisible" nature of the backlight to the operator may improve the experience and provide an additional visual safety measure not available with conventional systems. 850 nm infrared lighting was selected due to its commercial availability and Keyence's ability to operate in this field.

[0047] Inspection of pre-filled syringes in tray 570a may include detection of syringe distal flange edge and distal plunger edge and determination of plunger depth as an off-tray method described in U.S. Pat. No. 9,881,367 (e.g., pre-filled syringes in intermediate holder 580j, pre-filled syringes in gripper 600, etc.). Because optical artifacts 379, 579a in tray 370, 570a may generate false edges (e.g., edges of artifacts 379, 579a, etc.) in determining flange and stopper location, edge detection boxes (or regions of interest (ROIs) as described in U.S. Pat. No. 9,881,367, etc.) of distal plunger edge and / or distal syringe flange edge may be incorporated. Any given region of interest may be based, for example, on the particular pre-filled syringe being inspected (e.g., the ROI may be large enough to measure the syringe within the product specification range, etc.). The tubular container inspection system may receive configuration data based on, for example, products (tubular containers, pre-filled syringes, etc.) that may exhibit certain measurement parameters. Edge detection parameters and / or associated digital image processing filters may be incorporated within the associated tubular container inspection device to, for example, ignore edges of tray artifacts 379, 579a that may otherwise trigger spurious distal syringe flange edge and / or distal plunger edge detection that may result in erroneous plunger depth determinations, tubular container inspection results, etc.

[0048] The intermediate holder 580b may include a plurality of V-block pre-filled syringe receptacles 583b. The V-blocks 583b are known mounts for holding cylindrically shaped objects and may be self-centered within the V-blocks. The pitch 584b between adjacent V-blocks 583b may be the pitch of the corresponding tray receptacles to facilitate transfer and placement of syringes into the intermediate holder 580b. The strips 585b located in the center of the V-blocks 583b directly below each PFS may be removed (i.e., optically unobstructed) to allow transmission of light through the PFS when placed in the V-blocks 583b. The intermediate holder 580b may include outer tabs 582b that align the sides and bottom of the tray to the intermediate holder, ultimately aligning the V-block slots with the tray's syringe receptacles and therefore the PFS.

[0049] The intermediate holder 580b may include, for example, 20 adjacent V-block shaped slots on the same 14.9 mm pitch as a 1 ml PFS tray. Alignment tabs 582b on the sides and bottom of the intermediate holder 580c may allow the tray 570c to fit inside the tabs 582b, which may align the PFS in the tray with the corresponding slots in the intermediate holder. The intermediate holder 580b may include a number of needle cap receptacles 588b at the proximal end 581b, a number of pre-filled syringe alignment features 587b, and a distal end 586b. When a pre-filled syringe 540j is received within each V-block 583b, each alignment feature 587b is positioned between the proximal end 244 of the pre-filled syringe 540j and the distal end of the needle cap 256.

[0050] The tray 570c of prefilled syringes 540c can be aligned with the intermediate holder 580c with the V-blocks 583c aligned with each prefilled syringe 540c as viewed from the proximal end 576c. The aligned tray 570c and intermediate holder 570c can be inverted with the proximal end 570d of the tray 570d facing away from the proximal end 570c and the bottom side of the prefilled syringe receptacle 579c facing up.

[0051] The pre-filled syringe removal tool 590e-h may include multiple thick "fingers" 591e located on the central axis of each PFS 540f-h, which are then used to remove the PFS one at a time, but in rapid succession, so that the PFS may pop out of the tray receptacle and drop into a corresponding V-block in the intermediate holder. The "fingers" may be only a few millimeters long, for example, and may be aligned and inserted into each PFS syringe tube during an alignment process. When the tray is lifted, the fingers may apply downward pressure to the PFS, causing it to pop out of the tray receptacle. The tray 570g may be lifted asymmetrically, alternating one side and the other, so that the pre-filled syringes 540g may pop out of the tray one at a time.

[0052] A method 500k of transferring prefilled syringes from a tray to an intermediate holder may include providing a tray of prefilled syringes (block 501k), an intermediate holder (block 502k), a syringe removal tool (block 503k), and a syringe return tool (block 504k). The method 500k may also include aligning the intermediate holder to the tray of prefilled syringes (block 505k), aligning the syringe removal tool to the tray of prefilled syringes (block 506k), and transferring the prefilled syringes from the tray to the intermediate holder (block 507k). Following inspection, the syringes may be returned from the intermediate holder 180 to the tray 170 using, for example, the syringe return tools 600a-d (block 508k).

[0053] The principle of the fast transfer method is to quickly move the syringe from the tray to an intermediate holder that is more suitable for measurement by the image processing system. There are several criteria that the intermediate holder must meet, which ultimately define the intermediate holder design. Pre-filled syringes can be quickly and easily transferred from the tray to the intermediate holder without damage. The syringe barrel is not optically obstructed by illumination and imaging.

[0054] The syringe removal tool 590e may include left and right alignment slots 593e into which the combined tray / intermediate holders 570c, 580c may be positioned, allowing a point or "finger" 591e to be slowly inserted into the distal end 242 of each syringe barrel 245. The syringes 540g, 540h may be transferred by lifting the tray 570g from one corner and pulling toward the opposite corner. This asymmetric lifting action allows the pre-filled syringes to pop out of the tray 570g one at a time, and the pre-filled syringe 540j then rests in the corresponding V-blocks 583b,c in the intermediate holder 580j.

[0055] Once the prefilled syringe 540j is transferred to the intermediate holder 580j, the flange 541j may extend beyond the distal end 586b of the intermediate holder 580j. When the intermediate holder 580j with the prefilled syringe 540j is positioned between the image sensor 110 and the backlight 111, at least a portion of the flange 541j and at least a portion of the plunger 550a are not optically obstructed by the intermediate holder 580j. Thus, the intensity of the backlight 111 may be lower than when the prefilled syringe 540a is in the tray 570a, thereby reducing artifacts in the associated image data.

[0056] The prefilled syringes are measured immediately after being transferred to the intermediate holder. Briefly, the vision engine identifies clear reference points in the image. From these reference points measurement boxes of the PFS flange and stopper are derived. The measurement boxes are designed to identify the top of the flange and the top of the stopper. The distance between these two points is calculated at the axis of the PFS barrel, i.e. along the barrel axis.

[0057] 6A-D, the prefilled syringe inspection system 600a-d may include syringe return tools 695a-d. The syringe return tools 695a-d may include, for example, pads 696a (e.g., rubber pads, soft materials, etc.) configured to form contact points for pushing the syringe into the tray 670a. The syringe return tools 695a-d may also include, for example, chamfered inner surfaces 697a that may match the design of the tray 670a to ensure continuous alignment. The syringe return tools 695a-d may also further include, for example, an arc shape 698a based on the tray 670a. The arc shape 698a allows for ergonomic and efficient hand, wrist, and arm movements while an operator reorients the syringe return tools 695b-d, as shown, for example, in FIGS. 6B-D. An operator can roll syringe return tools 695a-d across trays 670a-d to safely and sequentially push the syringes into place in one motion.

[0058] For example, after inspection of the tubular container, the syringes can be returned to the trays 670a-d while the tubular container is in the intermediate holder to integrate inspection of the tubular container with an associated manufacturing process. The syringe return tools 695a-d can reduce risks to associated products, safety risks to operators, etc. The syringe return tools 695a-d may also serve to increase the efficiency of the syringe return portion of the inspection process.

[0059] 7, a pre-filled syringe inspection system 700 can include a user interface 709 having a silhouette display 715 of multiple pre-filled syringes secured within a gripper. As can be seen in the figure, light from the backlight is optically unobstructed to the pre-filled syringes, and light through the PFS is optically unobstructed from the pre-filled syringes to the image sensor.

[0060] Referring to FIG. 8, a tube container inspection system 800 may include an image sensor 110 having a photosensor absorption and transmission graph 801. The backlight 111 may emit light having a wavelength of .about.850 nm. The backlight 111 may include individual LED light sources that are 82 W and uniformly distributed. The backlight 111 may be pulse width modulated PWM with a duty cycle of 35%. The efficiency of the LEDs may be .about.70%, so that under normal operation (e.g., 380 W / m for a 150 mm x 350 mm light), the efficiency of the LEDs may be .about.70%. 2 20 W of unmixed light can be provided during illumination (e.g., during illumination of the tube container). As a result, the exposure time of the image sensor 110 can be, for example, 12 seconds. The tube container inspection system can include a balance between the exposure time of the image sensor 110 and the intensity setting of the backlight 111.

[0061] 9, a tube container inspection system 900 can include an image sensor 110 having a photosensor normalized spectral response 901. The intensity of the backlight 111 can be minimized while still achieving good imaging under moderate exposure (e.g., as shown in FIG. 3, etc.). The intensity and number of exposures can be adjusted, for example, to a range with a linear relationship between intensity and exposure time.

[0062] The backlight 111 can emit light having a wavelength of, for example, 400-700 nm. Alternatively, the backlight 111 can emit light having a wavelength in the near infrared spectrum of 700-800 nm. As another alternative, the backlight 111 can emit light having a wavelength in the infrared spectrum of 800-1 nm. In certain applications, the backlight 111 can be configured to emit light having a wavelength of 1.6 nm using, for example, an InGaAs detector. The backlight 111 can include a light source having a lower power (e.g., as low as 15 W with a maximum power based on the illumination area required to perform this measurement, etc.).

[0063] The duty cycle of the illumination source of the backlight 111 and the exposure of the image sensor 110 may be, for example, inversely proportional. A short exposure to light (e.g., a few milliseconds, etc.) may have the advantage, for example, of high light intensity to avoid shot noise. Conversely, lower exposure may be used to reduce light intensity. The overall relationship between the exposure of the image sensor 110 and the intensity of the backlight 111 may be based, for example, on the total amount of light (i.e., time*luminous flux=total amount of light per unit area per image=constant). Exemplary exposure ranges include a few milliseconds to about 20 milliseconds. Extended exposure times with PWM duty cycles of 20-60% may result in overexposure.

[0064] The above description describes various devices, assemblies, components, subsystems, and methods for use in conjunction with drug delivery devices such as pre-filled syringes. The devices, assemblies, components, subsystems, methods, or drug delivery devices (i.e., pre-filled syringes) may further include or be used with drugs, including, but not limited to, the drugs listed below, as well as corresponding generics and biosimilars. As used herein, the term "drug" may be used interchangeably with other synonyms and may refer to any type of pharmaceutical or therapeutic material, including traditional and non-traditional medicines, nutraceuticals, supplements, biologics, bioactive substances and compositions, macromolecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules, and generics. Non-therapeutic injectables are also included. Drugs may be in liquid, lyophilized, or reconstituted from lyophilized form. The following list of exemplary drugs should not be considered exhaustive or limiting.

[0065] The drug is contained in a reservoir, for example, in a pre-filled syringe. In some instances, the reservoir is a primary container that is filled or pre-filled with the drug treatment. The primary container may be a vial, cartridge, or pre-filled syringe.

[0066] In some embodiments, the reservoir of the drug delivery device may be loaded with or used in conjunction with a colony stimulating factor, such as granulocyte colony stimulating factor (G-CSF). Such G-CSF agents include, but are not limited to, Neulasta® (pegfilgrastim, pegylated filgastrim, pegylated G-CSF, pegylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-MetG-CSF), UDENYCA® (pegfilgrastim-cbqv), Ziextenzo® (LA-EP2006; pegfilgrastim-bmez), or FULPHILA (pegfilgrastim-bmez).

[0067] In other embodiments, the drug delivery device may include or be used with an erythropoietin stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoietin. In some embodiments, the ESA is an erythropoietin stimulating protein. As used herein, the term "erythropoietin stimulating protein" refers to any protein that directly or indirectly activates the erythropoietin receptor, for example, by binding to the receptor and causing dimerization. Erythropoietin stimulating proteins include erythropoietin and variants, analogs or derivatives that bind to and activate the erythropoietin receptor, antibodies that bind to and activate the erythropoietin receptor, or peptides that bind to and activate the erythropoietin receptor. Erythropoietin stimulating proteins include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methyoxypolyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), Binocrit® (epoetin alpha), epoetin alfa hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alpha, epoetin beta, epoetin iota, epoetin omega, epoetin delta, epoetin zeta, epoetin theta, and epoetin delta, pegylated erythropoietin, carbamylated erythropoietin, and molecules or variants or analogs thereof.

[0068] Among the specific exemplary proteins are the specific proteins set forth below, including fusions, fragments, analogs, variants or derivatives. OPGL-specific antibodies, peptibodies, related proteins, and the like (also referred to as RANKL-specific antibodies, peptibodies, and the like), including fully humanized and human OPGL-specific antibodies, particularly fully humanized monoclonal antibodies; myostatin binding proteins, peptibodies, related proteins, and the like, including myostatin-specific peptibodies; IL-4 receptor-specific antibodies, peptides, related proteins, and the like, particularly those that inhibit activity mediated by binding of IL-4 and / or IL-13 to its receptor; Interleukin 1-receptor 1 ("IL1-R1")-specific antibodies, peptides, related proteins, and the like; Ang2-specific antibodies, peptides, related proteins, and the like; NGF-specific antibodies, peptides, related proteins, and the like; CD22-specific antibodies, peptibodies, related proteins, and the like, particularly human CD22-specific antibodies, such as epratuzumab, a fully humanized antibody specific for human CD22 having CAS Registry Number 501423-23-0, a human-mouse monoclonal antibody bound to the hLL2 kappa chain, humanized and fully human antibodies, including but not limited to, humanized and fully human monoclonal antibodies, including human CD22-specific IgG antibodies, such as clonal hLL2 gamma chain disulfide dimers; IGF-1 receptor-specific antibodies, peptibodies, related proteins, and the like, including but not limited to, anti-IGF-1R antibodies; B-7 related protein 1-specific antibodies, peptibodies, related proteins, and the like ("B7RP-1", which also refers to B7H2, ICOSL, B7h, CD275), including but not limited to, B7RP-specific fully human monoclonal IgG2 antibodies that bind to an epitope in the first immunoglobulin-like domain of B7RP-1, including but not limited to, those that inhibit the interaction of B7RP-1 with its natural receptor, ICOS, in activated T cells; IL-15-specific antibodies, peptibodies, related proteins, and the like, particularly humanized monoclonal antibodies, including HuMax IL-15 antibodies and related proteins, including but not limited to, 145c7;IFNγ-specific antibodies, peptibodies, related proteins, etc., including, but not limited to, human IFNγ-specific antibodies, fully human anti-IFNγ antibodies, TALL-1 specific antibodies, peptibodies, related proteins, etc., and other TALL-specific binding proteins; parathyroid hormone ("PTH") specific antibodies, peptibodies, related proteins, etc.; thrombopoietin receptor ("TPO-R") specific antibodies, peptibodies, related proteins, etc.; hepatocyte growth factor / scatter factor (HGF / SF):c, such as fully human monoclonal antibodies that neutralize HGF / SF. Hepatocyte growth factor ("HGF") specific antibodies, peptibodies, related proteins, etc., including those that target the Met axis (HGF / SF:c-Met); TRAIL-R2 specific antibodies, peptibodies, related proteins, etc.; Activin A specific antibodies, peptibodies, proteins, etc.; TGF-beta specific antibodies, peptibodies, related proteins, etc.; Amyloid-beta protein specific antibodies, peptibodies, related proteins, etc.; c-Kit specific antibodies, peptibodies, including but not limited to proteins that bind c-Kit and / or other stem cell factor receptors; Related Proteins, etc.; including, but not limited to, proteins that bind OX40L and / or other ligands of the OX40 receptor, including OX40L-specific antibodies, peptibodies, related proteins, etc.; Activase® (alteplase, tPA); Aranesp® (darbepoetin alfa), erythropoietin [30-asparagine, 32-threonine, 87-valine, 88-asparagine, 90-threonine], darbepoetin alfa, new erythropoiesis-stimulating protein (NESP); Epogen® (epoetin alpha or erythropoietin; GLP-1, Avonex® (interferon beta-1a); Bexxar® (tositumomab, an anti-CD22 monoclonal antibody); Betaseron® (interferon-beta); Campath® (alemtuzumab, an anti-CD52 monoclonal antibody); Dynepo® (epoetin delta); Velcade® (bortezomib); MLN0002 (anti-α4β7 mAb); MLN1202 (anti-CCR2 chemokine receptor mAb);Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker); Eprex® (epoetin alfa); Erbitux® (cetuximab, anti-EGFR / HER1 / c-ErbB-1); Genotropin® (somatropin, human growth hormone); Herceptin® (trastuzumab, anti-HER2 / neu(erbB2) receptor mAb); Kanjinti™ (trastuzumab-anns) anti-HER2 monoclonal antibody, a biosimilar of Herceptin® or another product containing trastuzumab for the treatment of breast or gastric cancer; Humatrope® (somatropin, human growth hormone); Humira® (adalimumab); Vectibix® ) (panitumumab), Xgeva® (denosumab), Prolia® (denosumab), immunoglobulin G2 human monoclonal antibody against RANK ligand, Enbrel® (etanercept, TNF receptor / Fc fusion protein, TNF blocker), Nplate® (romiplostim), rilotumumab, ganitumumab, conatumumab, brodalumab, insulin in solution; Infergen® (interferon alfacon-1); Natrecor® (nesiritide; recombinant human B-type natriuretic peptide (hBNP); Kineret® (anakinra); Leukine® (sargamostim, rhuGM-CSF); LymphoCide® (epratuzumab, anti-CD22 mAb); Benlysta™ (lymphostat B, belimumab, anti-BlyS mAb); Metalyse® (tenecteplase, t-PA analog); Mircera® (methoxypolyethylene glycol-epoetin beta); Mylotarg® (gemtuzumab ozogamicin); Raptiva® (efalizumab); Cimzia® (certolizumab pegol, CDP 870); Soliris™ (eculizumab); pexelizumab (anti-complement C5); Numax® (MEDI-524); Lucentis® (ranibizumab);Panorex® (17-1A, edrecolomab); Trabio® (lerdelimumab); TheraCim hR3 (nimotuzumab); Omnitarg (pertuzumab, 2C4); Osidem® (IDM-1); OvaRex® (B43.13); Nuvion® (vigilizumab); cantuzumab mertansine (huC242-DM1); NeoRecormon® (epoetin beta); Neumega® (oprelvekin, human interleukin-11); Orthoclone OKT3® (muromonab-CD3, anti-CD3 monoclonal antibody); Procrit® (epoetin alfa); Remicade® (infliximab, anti-TNF alpha monoclonal antibody); Reopro® (abciximab, anti-GP lIb / Ilia receptor monoclonal antibody; Actemra® (anti-IL6 receptor mAb); Avastin® (bevacizumab), HuMax-CD4 (zanolimumab); Mvasi™ (bevacizumab-awwb); Rituxan® (rituximab, anti-CD20 mAb);Tarceva® (erlotinib);Roferon-A®-(interferon alpha-2a);Simulect® (basiliximab);Prexige® (lumiracoxib);Synagis® (palivizumab);145c7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507);Tysabri® (natalizumab, anti-α4 integrin mAb);Valortim® (MDX-1303, anti-B. anthracis protective antigen mAb);ABthrax®;Xolair® (omalizumab);ETI211 (anti-MRSA mAb);IL-1 trap (Fc portion of human IgG1 and extracellular domain of both IL-1 receptor components (type I receptor and receptor accessory protein));VEGF trap (IgG1 Ig domain of VEGFR1 fused to Fc; Zenapax® (daclizumab); Zenapax® (daclizumab, an anti-IL-2Rα mAb);Zevalin® (ibritumomab tiuxetan); Zetia® (ezetimibe); Orencia® (atacicept, TACI-Ig); anti-CD80 monoclonal antibody (galiximab); anti-CD23 mAb (lumiliximab); BR2-Fc (huBR3 / huFc fusion protein, soluble BAFF antagonist); CNTO 148 (golimumab, anti-TNFα mAb); HGS-ETR1 (mapatuzumab; human anti-TRAIL receptor-1 mAb); HuMax-CD20 (ocrelizumab, anti-CD20 human mAb); HuMax-EGFR (zalutumumab); M200 (volociximab, anti-α5β1 integrin mAb); MDX-010 (ipilimumab, anti-CTLA-4 mAb and VEGFR-1 (IMC-18F1); anti-BR3 mAbs; anti-C. difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388; anti-CD22 dsFv-PE38 conjugates (CAT-3888 and CAT-8015); anti-CD25 mAb (HuMax-TAC); anti-CD3 mAb (NI-0401); adecatumumab; anti-CD30 mAb (MDX-060); MDX-1333 (anti-IFNAR); anti-CD38 mAb (HuMax CD38); anti-CD40L mAb; anti-Cripto mAb; anti-CTGF idiopathic pulmonary fibrosis stage 1 fibrogen (FG-3019); anti-CTLA4 mAb; anti-eotaxin 1 mAb (CAT-213); anti-FGF8 mAb; anti-ganglioside GD2 mAb;Anti-ganglioside GM2 mAb;Anti-GDF-8 human mAb (MYO-029);Anti-GM-CSF receptor mAb (CAM-3001);Anti-HepC mAb (HuMax HepC);Anti-IFNα mAb (MEDI-545, MDX-198);Anti-IGF1R mAb;Anti-IGF-1R mAb (HuMax-Inflam);Anti-IL12 mAb (ABT-874); anti-IL12 / IL23 mAb (CNTO 1275); anti-IL13 mAb (CAT-354); anti-IL2Ra mAb (HuMax-TAC); anti-IL5 receptor mAb; anti-integrin receptor mAb (MDX-018, CNTO 95);Anti-IP10 ulcerative colitis mAb (MDX-1100);BMS-66513;anti-mannose receptor / hCGβ mAb (MDX-1307); anti-mesothelin dsFv-PE38 conjugate (CAT-5001); anti-PD1 mAb (MDX-1106 (ONO-4538)); anti-PDGFRα antibody (IMC-3G3); anti-TGFβ mAb (GC-1008); anti-TRAIL receptor-2 human mAb (HGS-ETR2); anti-TWEAK mAb; anti-VEGFR / Flt-1 mAb; and anti-ZP3 mAb (; HuMax-ZP3).

[0069] In some embodiments, the drug delivery device may include or be used with sclerostin antibodies, such as, but not limited to, romosozumab, brosozumab, BPS804 (Novartis), Evenity™ (romosozumab-aqqg), other products containing romosozumab for the treatment of postmenopausal osteoporosis and / or fracture healing, and in other embodiments, monoclonal antibodies (IgG) that bind to human protein convertase subtilisin / kexin type 9 (PCSK9). Such PCSK9-specific antibodies include, but are not limited to, Repatha® (evolocumab) and Praluent® (alirocumab). In other embodiments, the drug delivery device may include or be used with rilotumumab, bixalomer, trebananib, ganitumumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, or panitumumab. In some embodiments, the reservoir of the drug delivery device may be loaded with or used with IMLYGIC® (talimogene laherparepvec) or another oncolyte HSV, including but not limited to OncoVEXGALV / CD, OrienX010, G207, 1716, NV1020, NV12023, NV1034, and NV1042 for the treatment of melanoma or other cancers. In some embodiments, the drug delivery device may contain or be used with an endogenous tissue metalloproteinase inhibitor (TIMP), such as, but not limited to, TIMP-3. In some embodiments, the drug delivery device may contain or be used with Aimovig® (erenumab-aooe), another product containing anti-human CGRP-R (calcitonin gene-related peptide type 1 receptor) or erenumab, for the treatment of migraine headaches. Antagonist antibodies against the human calcitonin gene-related peptide (CGRP) receptor, such as, but not limited to, erenumab and bispecific antibody molecules that target the CGRP receptor and other headache targets, can also be delivered by the drug delivery devices of the present disclosure.Bispecific T cell engager (BiTE®) antibodies, such as, but not limited to, BLINCYTO® (blinatumomab), may also be used in or with the drug delivery device of the present disclosure. In some embodiments, the drug delivery device may include or be used in conjunction with an APJ macromolecular agonist, such as, but not limited to, apelin or an analog thereof. In some embodiments, a therapeutically effective amount of anti-thymic stromal lymphopoietin (TSLP) or a TSLP receptor antibody is used in or with the drug delivery device of the present disclosure. In some embodiments, the drug delivery device may include or be used in conjunction with Avsola™ (infliximab-axxq), an anti-TNF-alpha monoclonal antibody, a biosimilar of Remicade® (infliximab) (Janssen Biotech, Inc.), or another product containing infliximab, for the treatment of autoimmune disease. In some embodiments, the drug delivery device may contain or be used in conjunction with Kyprolis® (carfilzomib), (2S)-N-((S)-1-((S)-4-methyl-1-((R)-2-methyloxiran-2-yl)-1-oxopentan-2-ylcarbamoyl)-2-phenylethyl)-2-((S)-2-(2-morpholinoacetamido)-4-phenylbutanamido)-4-methylpentanamide, or another product containing carfilzomib for the treatment of multiple myeloma. In some embodiments, the drug delivery device may include or be used in conjunction with Otezla® (apremilast), N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide, or another product containing apremilast, for the treatment of various inflammatory diseases. In some embodiments, the drug delivery device may include or be used in conjunction with Parsabiv™ (etelcalcetide hydrochloride, KAI-4169) or another product containing etelcalcetide hydrochloride, for the treatment of secondary hyperparathyroidism (sHPT), such as in patients with chronic kidney disease (KD) undergoing hemodialysis.In some embodiments, the drug delivery device may include or be used with ABP798 (rituximab), a biosimilar candidate of Rituxan® / MabThera brand, or another product that includes an anti-CD20 monoclonal antibody. In some embodiments, the drug delivery device may include or be used with a VEGF antagonist, such as a non-antibody VEGF antagonist, and / or a VEGF-Trap, such as aflibercept (Ig domain 2 from VEGFR1 and Ig domain 3 from VEGFR2 fused to the Fc domain of IgG1). In some embodiments, the drug delivery device may include or be used with ABP959 (eculizumab), a biosimilar candidate of Soliris®, or another product that includes a monoclonal antibody that specifically binds to complement protein C5. In some embodiments, the drug delivery device may include or be used with Rozibafusp alfa (formerly AMG570), a novel bispecific antibody-peptide complex that simultaneously inhibits ICOSL and BAFF activity. In some embodiments, the drug delivery device may contain or be used in conjunction with Omecamtiv mecarbil, a small molecule selective cardiac myosin activator, or myotrope, which directly targets the contractile machinery of the heart, or another product containing a small molecule selective cardiac myosin activator. In some embodiments, the drug delivery device may contain KRAS. G12CThe drug delivery device may include or be used with Sotorasib (formerly AMG 510), a small molecule inhibitor, or another product that includes a small molecule inhibitor of KRASG12C. In some embodiments, the drug delivery device may include or be used with Tezepelumab, a human monoclonal antibody that inhibits the action of Thymic Stromal Lymphopoietin (TSLP), or another product that includes a human monoclonal antibody that inhibits the action of TSLP. In some embodiments, the drug delivery device may include or be used with AMG714, a human monoclonal antibody that binds to interleukin-15 (IL-15), or another product that includes a human monoclonal antibody that binds to interleukin-15 (IL-15). In some embodiments, the drug delivery device may include or be used with MG890, a small interfering RNA (siRNA) that lowers lipoprotein(a), also known as Lp(a), or another product that includes a small interfering RNA (siRNA) that lowers lipoprotein(a). In some embodiments, the drug delivery device may include or be used with ABP654 (human IgG1 kappa antibody), a biosimilar candidate of Stelara®, or another product that includes a human IgG1 kappa antibody and / or binds to the p40 subunit of the human cytokines interleukin (IL)-12 and IL-23. In some embodiments, the drug delivery device may include or be used with Amjevita™ or Amgevita™ (formerly ABP501) (mab anti-TNF human IgG1), a biosimilar candidate of Humira®, or another product that includes a human mab anti-TNF human IgG1. In some embodiments, the drug delivery device may include or be used with AMG160, or another product that includes a half-life extended (HLE) anti-prostate specific membrane antigen (PSMA) x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may include or be used in conjunction with another product that includes AMG119, or a delta-like ligand 3 (DLL3) CAR T (chimeric antigen receptor T cell) cell therapy.In some embodiments, the drug delivery device may include or be used with another product that includes AMG119, or a delta-like ligand 3 (DLL3) CAR T (chimeric antigen receptor T cell) cell therapy. In some embodiments, the drug delivery device may include or be used with another product that includes AMG133, or a gastric inhibitory polypeptide receptor (GIPR) antagonist and a GLP-1R agonist. In some embodiments, the drug delivery device may include or be used with another product that includes AMG171, or a growth differentiation factor 15 (GDF15) analog. In some embodiments, the drug delivery device may include or be used with another product that includes AMG176, or a small molecule inhibitor of myeloid cell leukemia 1 (MCL-1). In some embodiments, the drug delivery device may include or be used with AMG199, or a half-life extended (HLE) bispecific T cell engager construct (BiTE®). In some embodiments, the drug delivery device may include or be used with AMG256, or another product that includes an anti-PD-1 x IL21 mutein and / or IL-21 receptor agonist designed to selectively turn on the interleukin 21 (IL-21) pathway in programmed cell death-1 (PD-1) positive cells. In some embodiments, the drug delivery device may include or be used with AMG330, or another product that includes an anti-CD33 x anti-CD3 BiTE® (bispecific T cell engager) structure. In some embodiments, the drug delivery device may include or be used with AMG404, or another product that includes a human anti-programmed cell death-1 (PD-1) monoclonal antibody that is being investigated as a treatment for patients with solid tumors. In some embodiments, the drug delivery device may include or be used with AMG427, or another product that includes a half-life extended (HLE) anti-fms-like tyrosine kinase 3 (FLT3) x anti-CD3 BiTE® (bispecific T cell engager) structure. In some embodiments, the drug delivery device may contain or be used in conjunction with another product that contains AMG430 or an anti-Jagged-1 monoclonal antibody.In some embodiments, the drug delivery device may include or be used with another product that includes AMG506, or a multispecific FAPx4-1BB targeted DARPin® biologic under investigation as a treatment for solid tumors. In some embodiments, the drug delivery device may include or be used with AMG509, or another product that includes a bivalent T cell engager, designed using XmAb® 2+1 technology. In some embodiments, the drug delivery device may include or be used with AMG562, or another product that includes a half-life extended (HLE) CD19xCD3BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may include or be used with efabarukin alpha (formerly AMG592), or another product that includes an IL-2 mutein Fc fusion protein. In some embodiments, the drug delivery device may include or be used in conjunction with AMG596 or another product that includes a CD3 x epidermal growth factor receptor vIII (EGFRvIII) BiTE® (bispecific T cell engager) molecule. In some embodiments, the drug delivery device may include or be used in conjunction with AMG673 or another product that includes a half-life extended (HLE) anti-CD33 x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may include or be used in conjunction with AMG 701, or another product that includes a half-life extended (HLE) anti-B cell maturation antigen (BCMA) x anti-CD3 BiTE® (bispecific. In some embodiments, the drug delivery device may include or be used in conjunction with another product that includes a half-life extending (HLE) anti-delta-like ligand 3 (DLL3) x anti-CD3 BiTE® (bispecific T cell engager) structure. In some embodiments, the drug delivery device may include or be used in conjunction with another product that includes a half-life extending (HLE) anti-delta-like ligand 3 (DLL3) x anti-CD3 BiTE® (bispecific T cell engager) structure. In some embodiments, the drug delivery device may include or be used in conjunction with AMG 910 or another product that includes a half-life extending (HLE) epithelial cell tight junction protein claudin 18.2 x CD3 BiTE® (bispecific T cell engager) structure.

[0070] Although the drug delivery devices, assemblies, components, subsystems and methods have been described in terms of several exemplary embodiments, the present invention is not limited thereto. The detailed description is exemplary only and does not describe all possible embodiments of the present disclosure. Many alternative embodiments can be realized that fall within the scope of the claims that define the invention disclosed herein, using either current technology or technology developed after the filing date of this patent.

[0071] The detailed description is illustrative only and does not describe all possible embodiments of the present disclosure. Many alternative embodiments can be realized that fall within the scope of the claims defining the invention disclosed herein, using either current technology or technology developed after the filing date of this patent. Those skilled in the art will recognize that a wide range of modifications, variations, and combinations may be made with respect to the above-described embodiments without departing from the spirit and scope of the invention disclosed herein, and that such modifications, variations, and combinations are deemed to be within the scope of the inventive concept.

Claims

1. 1. A system for inspecting a tubular container after capping, wherein at least a portion of the tubular container is at least partially transparent, the system comprising: a digital image data acquisition device having an image sensor and a backlight, the digital image data acquisition device configured to cause the backlight to emit light of a predetermined intensity, the digital image data acquisition device configured to acquire image data from the image sensor while at least a portion of the tubular container and at least a portion of the plunger are positioned between the image sensor and the backlight while the backlight is emitting light, the image data representing a silhouette of at least the portion of the tubular container and at least the portion of the plunger within the tubular container; a digital image processing engine configured to determine a depth of the plunger within the tubular container based on the image data.

2. 2. The system of claim 1, wherein the image data represents at least a portion of a flange of the tubular container, and the digital image data acquisition device is further configured to control the intensity of the backlight based on the transparency of at least the portion of the flange.

3. The system of claim 2 , wherein the digital image data acquisition device is further configured to control an integration period of the image sensor based on the intensity of the backlight.

4. 4. The system of claim 1, wherein the image data represents at least a portion of a flange of the tubular container, and the digital image data acquisition device is further configured to control an integration period of the image sensor based on a transparency of at least the portion of the flange.

5. The system of any one of claims 1 to 3, further comprising a tray, at least a portion of the tray being disposed between the backlight, the at least a portion of the tubular container, and the at least a portion of the plunger.

6. The system of any one of claims 1 to 3, further comprising an intermediate holder, wherein an optically unobstructed portion of the intermediate holder is positioned between the backlight, the at least a portion of the tubular container, and the at least a portion of the plunger.

7. The system of any one of claims 1 to 3, further comprising a stage, wherein the stage passes the at least a portion of the tubular container and the at least a portion of the plunger under imaging optics of the digital image data acquisition device.

8. 1. A method for inspecting a tubular container, comprising: providing a plurality of tubular vessels in a tray; providing an intermediate holder; aligning the intermediate holder with the tray; transferring the plurality of tubular containers from the tray to the intermediate holder; disposing the plurality of tubular containers and the intermediate holder between an image sensor and a backlight; acquiring image data from the image sensor while at least a portion of the tubular container and at least a portion of a plunger are positioned between the image sensor and the backlight while the backlight is illuminated, the image data representing a silhouette of at least the portion of the tubular container and at least a portion of a plunger within the tubular container; A method comprising:

9. The method of claim 8 , further comprising determining a depth of the plunger within the tubular container based on the image data.

10. The method of claim 8 or 9, further comprising a removal tool, and transferring the plurality of tubular containers from the tray to the intermediate holder comprises using the removal tool to remove the plurality of tubular containers from the tray.

11. 10. The method of claim 8 or 9, wherein the image data represents a plurality of pre-filled syringes in the intermediate holder, the intermediate holder including a plurality of optically unobstructed areas, and each pre-filled syringe is aligned with at least one respective optically unobstructed area.

12. 10. The method of claim 8 or 9, wherein the intermediate holder includes a plurality of V-block receptacles, the tubular container being self-centering within each V-block.

13. 1. A non-transitory computer-readable medium having stored thereon computer-readable instructions that, when executed by a processor, cause the processor to perform a post-capture tubular container inspection, wherein at least a portion of the tubular container is at least partially transparent, the computer-readable medium comprising: a backlight control module that, when executed by the processor, causes the processor to cause a backlight to emit light at a predetermined intensity; a digital image data acquisition module that, when executed by the processor, causes the processor to acquire image data from the image sensor while at least a portion of the tubular container and at least a portion of a plunger within the tubular container are positioned between the image sensor and the backlight while the backlight is illuminated, the image data representing a silhouette of at least the portion of the tubular container and at least the portion of the plunger; 1. A computer-readable medium comprising:

14. 14. The computer-readable medium of claim 13, further comprising an inspection data generation module that, when executed by the processor, causes the processor to generate inspection data based on the image data, the inspection data representing a distal edge of the tubular vessel.

15. 14. The computer-readable medium of claim 13, further comprising an inspection data generation module that, when executed by the processor, causes the processor to generate inspection data based on the image data, the inspection data representing a distal edge of the plunger.

16. 14. The computer-readable medium of claim 13, further comprising an inspection data generation module that, when executed by the processor, causes the processor to generate inspection data based on the image data, the inspection data representing a depth of the plunger within the tubular container.

17. 17. The computer-readable medium of claim 13, wherein the image data represents at least a portion of a flange of the tubular container, and the processor controls the intensity of the backlight based on the transparency of at least the portion of the flange.

18. The computer-readable medium of any one of claims 13 to 16, wherein an integration period of the image sensor is based on the predetermined intensity of the backlight.

19. 17. The computer-readable medium of claim 13, wherein the image data represents at least a portion of a flange of the tubular container, and wherein an integration period of the image sensor is based on a transparency of at least the portion of the flange.

20. 17. The computer-readable medium of any one of claims 13 to 16, wherein the image data represents first image data acquired at a first time point threaded with second image data acquired at the second time point, the image data representing a mosaic.

Images