Systems and methods for limiting sub-visible particles in syringes

Abstract

A method for limiting subvisible particles in a syringe partially filled with a drug product includes applying a quantity of silicone oil to a syringe barrel of the syringe, the quantity of silicone oil ranging from about 0.4 mg to about 0.6 mg. The syringe barrel includes a proximal end, a distal end, and a reservoir, and the drug product is disposed at the distal end of the reservoir at the distal end of the syringe barrel. The method also includes disposing a plunger portion within the syringe barrel to a depth within the syringe barrel and creating a gap between the plunger portion and the drug product. The plunger portion is spaced from the drug product, and the gap includes a gap length ranging from about 1.2 mm to about 3.5 mm.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 402,355, filed August 30, 2022, which is incorporated herein by reference in its entirety.

[0002] FIELD OF THE DISCLOSURE The present disclosure relates to syringes partially filled with drug products, and more particularly to systems and methods for restricting subvisible particles in large volume syringes partially filled with drug products. [Background technology]

[0003] A syringe is a medical delivery device used to administer a drug product to a patient. Syringes are often commercially available in pre-filled form, with a set dosage of the drug product already provided therein. Furthermore, some pre-filled syringes have been specially developed for integration with an auto-injector or other injector device. In order to be integrated with an auto-injector or other injector device, the pre-filled syringe must meet several requirements. One requirement is that the drug product in the pre-filled syringe must be in accordance with the United States Pharmacopeial Convention (USP), USP chapter 1 <787> (USP <787> ), and must comply with subvisible particle limits as defined by the USP ® Subvisible Particulate Matter in Therapeutic Protein Injections (including 6,000 particles / container ≥ 10 μm size and 600 particles / container ≥ 25 μm size). Due to the biopharmaceutical industry trend toward higher viscosities and potentially larger injection volumes, <787> There is a need for a syringe that can deliver larger doses subcutaneously while also meeting the subvisible particle limits of USP. <787> Because USP defines these limits per container rather than per volume, larger syringe systems inherently pose a greater challenge to adhering to the specified limits. <787> does not distinguish between inherently generated sub-visible particles, such as those generated by silicone oils, in determining the total sub-visible particle count.

[0004] Silicone oil, commonly used in the pharmaceutical industry, is typically applied to the inner surface of syringe barrels to facilitate plunger stopper movement during injection and / or device activation. However, silicone oil is known to be a major contributor to subvisible particle counts, including subvisible particles (SbVPs) in the 10 μm range. Furthermore, products transported through typical transport channels result in higher average subvisible particle counts compared to non-transported controls. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] United States Pharmacopeial Convention(USP),USP chapter <787> (USP <787> ),Subvisible Particulate Matter in Therapeutic Protein Injections Summary of the Invention [Means for solving the problem]

[0006] According to a first aspect of the present disclosure, a method for limiting subvisible particles in a syringe partially filled with a drug product includes applying a quantity of silicone oil to a syringe barrel of the syringe, the syringe barrel having a proximal end, a distal end, and a reservoir, the drug product being disposed within the distal end of the reservoir at the distal end of the syringe barrel, the quantity of silicone oil ranging from about 0.4 mg to about 0.6 mg. The method further includes disposing a plunger portion within the syringe barrel to a depth within the syringe barrel, the plunger portion being spaced apart from the drug product, and creating an air gap between the plunger portion and the drug product. The air gap has an air gap length ranging from about 1.2 mm to about 3.5 mm.

[0007] According to a second aspect of the present disclosure, a method for limiting sub-visible particles in a partially filled syringe includes applying a quantity of silicone oil to a syringe barrel of the syringe, the syringe barrel including a proximal end, a distal end, and a reservoir, the drug product being disposed within the distal end of the reservoir at the distal end of the syringe barrel, the quantity of silicone oil ranging from about 0.4 mg to about 0.6 mg. The method also includes placing the syringe in a carton and placing the carton in a suspension packout system configured to reduce the generation of sub-visible particles in the syringe during shipping. The suspension packout system includes packaging surrounding the carton containing the syringe, limiting contact of the carton with the packaging.

[0008] According to yet another aspect of the present disclosure, a syringe partially filled with a drug product includes a syringe barrel having a proximal end, a distal end, and a reservoir, the drug product being disposed at the distal end of the reservoir at the distal end of the syringe barrel. The syringe barrel contains silicone oil in an amount ranging from about 0.4 mg to about 0.6 mg, the amount of silicone oil being configured to limit the amount of sub-visible particles generated within the syringe barrel. The syringe further includes a plunger portion disposed at a depth within the syringe barrel and spaced apart from the drug product, and a gap disposed between the plunger portion and the drug product. The gap has a gap length ranging from about 1.2 mm to about 3.5 mm.

[0009] Further, in accordance with any one or more of the foregoing aspects, the syringe partially filled with a drug product and the method of limiting sub-visible particles within the syringe partially filled with a drug product may include any one or more of the following aspects:

[0010] In one form, applying a quantity of silicone oil to a syringe barrel may include applying the quantity of silicone oil to a syringe barrel comprising a reservoir having a fill volume in the range of about 1.0 mL to about 3.0 mL.

[0011] In another form, applying a quantity of silicone oil to the syringe barrel may include applying the quantity of silicone oil to an interior surface of the syringe barrel along a length of the syringe barrel, facilitating movement of a plunger during injection of a drug product of the syringe, and reducing the amount of sub-visible particles generated within the syringe.

[0012] In another form, disposing the plunger portion within the syringe barrel may include disposing a stopper within the syringe barrel to a depth within the syringe barrel, the stopper being spaced apart from the drug product.

[0013] In one form, creating a gap between the plunger portion and the drug product may include creating a gap between the distal-most point of the plunger portion and a meniscus of the drug product disposed within the distal end of the reservoir.

[0014] In another aspect, the method may further include placing the syringe in the carton and placing the carton in a suspension packout system configured to reduce generation of sub-visible particles in the syringe during transport of the carton. In one aspect, placing the carton in the suspension packout system may include placing the carton in a housing of the suspension packout system and positioning packaging material within the housing around at least a portion of the carton containing the syringe to limit contact of the carton with the packaging material during transport. The packaging material may include one or more of dunnage, foam, bubble wrap, or a cushioning plastic material.

[0015] In another form, the method may further include disposing the plunger portion within the syringe barrel to a depth within the syringe barrel, the plunger portion being spaced apart from the drug product. Additionally, disposing the plunger portion within the syringe barrel may include disposing a stopper within the syringe barrel to a depth within the syringe barrel, the stopper being spaced apart from the drug product.

[0016] In yet another aspect, the method may include creating an air gap between a plunger portion disposed within the syringe barrel and the drug product, the air gap having an air gap length in a range of about 1.2 mm to about 3.50 mm.

[0017] In yet another form, the syringe barrel may further include an interior surface and a length, and the quantity of silicone oil may be disposed on the interior surface along at least a portion of the length of the syringe barrel.

[0018] In another embodiment, the fill volume of the reservoir of the syringe barrel may range from about 1.0 mL to about 3.0 mL.

[0019] Alternatively, the plunger portion may be a stopper.

[0020] In yet another form, the gap length may include the distance between the distal-most point of the plunger portion and the meniscus of the drug product disposed at the distal end of the reservoir.

[0021] In yet another form, a suspension packout system may include a housing having an interior wall defining an interior region, packaging disposed within the housing adjacent to and / or at least partially around the interior wall, and a carton containing a syringe, wherein the carton may be positioned within the packaging and may be limited to contact with the packaging to reduce the amount of sub-visible particles generated within the syringe during shipping.

[0022] The present disclosure will be more fully understood from the following description taken in conjunction with the accompanying drawings. Some of the drawings may be simplified by the omission of selected elements for the purpose of more clearly showing other elements. The omission of such elements in some of the drawings does not necessarily indicate the presence or absence of the particular element in any of the illustrative embodiments, unless explicitly depicted in the corresponding written description. Also, none of the drawings are necessarily drawn to scale. [Brief explanation of the drawings]

[0023] [Figure 1] FIG. 1 is a partial cross-sectional view of a syringe partially filled with a drug product of the present disclosure. [Figure 2] 2 is a graph showing the effect of air gaps on subvisible particle generation in the syringe of FIG. 1. [Figure 3] 1 is a graph showing sub-visible particles as a function of gap length within a syringe of the present disclosure. [Figure 4] 1 is a graphical representation of the thickness of silicone oil along the length of a syringe barrel as a function of distance from the flange of the syringe. [Figure 5] 1 is a graph showing the effect of the amount of silicone oil on the generation of particles invisible to the naked eye. [Figure 6] 1 is a graph showing the effect of a silicone oil nozzle on sub-visible particle generation in a syringe. [Figure 7] 1 is a graph showing the effect of fill volume on subvisible particle generation in a syringe. [Figure 8] 1 is a suspension packout system having a syringe of the present disclosure disposed therein. DETAILED DESCRIPTION OF THE INVENTION

[0024] Generally, U.S.P. <787> A system and method are disclosed for optimizing high volume prefilled syringe production to meet the subvisible particle limits defined by 2014. The production attributes found to have the most impact and limit the average subvisible particle count include: (1) the amount of silicone placed within the syringe barrel of a large volume syringe, (2) a packout configuration system for limiting subvisible particles during syringe shipping, (3) the air gap length placed between the plunger portion and the drug product placed within the syringe barrel, and (4) the fill volume of the reservoir of the syringe barrel. More specifically, a method for limiting sub-visible particles in a syringe partially filled with a drug product may include one or more of the following steps: (1) applying silicone oil to an interior surface of a syringe barrel of the syringe in an amount ranging from about 0.4 mg to 0.6 mg; (2) utilizing a syringe barrel having a fill volume ranging from about 1.0 mL to about 3.0 mL; (3) placing a plunger portion within the syringe barrel to create an air gap between the plunger portion and the drug product, the air gap having an air gap length ranging from about 1.2 mm to about 3.5 mm; and (4) placing the syringe within a carton and placing the carton within packaging material within a housing of a suspension packout system, thereby reducing the generation of sub-visible particles in the syringe during movement and / or transportation of the carton.

[0025] More specifically, referring now to FIG. 1, a syringe 10 is shown partially filled with a drug product that meets the sub-visible particle limit. The syringe 10 includes a syringe barrel 12 having a proximal end 12a, a distal end 12b, an inner surface 12c, a flange 13 disposed near the proximal end 12a, and a reservoir 14. As described further below, the reservoir 14 may have a larger fill volume, such as a fill volume ranging from approximately 1.0 mL to 3.0 mL, while still meeting the required sub-visible particle limit. The drug product 16 is disposed within the distal end 14b of the reservoir 14 at the distal end 12b of the syringe barrel 12. Additionally, the inner surface 12c of the syringe barrel 12 has a quantity of silicone oil 18 applied thereto, the quantity of silicone oil 18 disposed on the inner surface 12c ranging from approximately 0.4 mg to approximately 0.6 mg. In one example, the optimal amount of silicone oil 18 disposed on the interior surface 12c is 0.5 mg, as further described below. The amount of silicone oil is configured to limit the amount of sub-visible particles generated within the syringe barrel 12.

[0026] Continuing with reference to FIG. 1 , the plunger portion 20 is positioned at a depth D within the syringe barrel 12, where the plunger portion 20 is spaced apart from the drug product 16. In one example, the plunger portion 20 is a stopper. Generally, as will be appreciated, two stopper techniques for positioning a plunger within a prefilled syringe can be used to position the plunger portion 20 within the syringe barrel 12: (1) a vent arrangement and (2) a vacuum assist. In a vent arrangement, the stopper 20 is placed over a thin tube (not shown), commonly referred to as a vent tube, and then inserted into the syringe 10. A plunger positioning pin (not shown) advances the stopper 20 down the tube to a depth determined by the length of the pin. The vent tube is then retracted, allowing the stopper 20 to expand and occlude the syringe diameter. In a vacuum assist, a vacuum chamber (not shown) is used to reduce the pressure within the prefilled syringe 10. Once the target vacuum pressure is reached, plunger portion 20 is placed into syringe barrel 12 to seal syringe 10, and the chamber is then depressurized. Plunger portion 20 is then advanced into syringe barrel 12 to a depth D where the "sealing pressure" equals the ambient, thus determining the plunger portion depth. Whether vacuum-assisted or vent-tube placement techniques are used to place plunger portion 20 into syringe barrel 12, there is no appreciable difference in the average subvisible particle count generated within syringe 10.

[0027] Syringe 10 further includes a gap 22 disposed between plunger portion 20 and drug product 16, with gap 22 having a length 23 ranging from about 1.2 mm to about 3.5 mm. More specifically, in one example, gap length is 1.4 mm, as shown in FIG. 1 . In another example, gap length 23 is 2.3 mm, and in another example, gap length is 3.5 mm. More generally, gap length 23 includes the distance between a distal-most point 24 of plunger portion 20 and a meniscus 25 of drug product 16 disposed within distal end 14b of reservoir 14. While FIG. 1 shows a specific length of gap 22, it will be understood that gap 22 length 23 may be any value in or between about 1.2 mm and about 3.5 mm and still be within the scope of the present disclosure. In traditional vacuum-assisted plunger placement systems, gap length 23 is determined by the amount of vacuum drawn prior to inserting plunger portion 20 into syringe barrel 12. As a stronger vacuum is drawn on syringe 10, gap 22 becomes smaller.

[0028] Referring now to FIG. 2, a graph is shown illustrating the effect of the length 23 of the gap 22, specifically the proportional relationship between the length 23 of the gap 22 and the generation of sub-visible particles. Specifically, a shorter length 23 of the gap 22 correlates with lower sub-visible particle levels in the syringe 10. Additionally, data from testing syringes having gap lengths of 1.4 mm, 2.3 mm, and 3.5 mm is provided. For example, the sub-visible particle count per container for the syringe 10 having a gap length of 1.4 mm was below the USP limit of 6,000 sub-visible particles for the majority of each sample tested. Furthermore, the sub-visible particle count per container for the syringe 10 having a gap length of 2.3 mm was also, on average, below the USP limit of 6,000 sub-visible particles, as shown in FIG. 2. However, when the gap length is increased to 3.5 mm, the sub-visible particle count per container for syringe 10 exceeds the USP limit of 6,000 sub-visible particles for some samples tested, further indicating that larger gap lengths generally result in more sub-visible particles than smaller gap lengths.

[0029] [Table 1]

[0030] As demonstrated in Table 1 above, the effect of void length on average particle generation is proportionally related, with larger void lengths yielding significantly more particles than smaller void lengths. However, all data sets still captured samples above the USP limit of 6,000, although this occurred less frequently as void length decreased.

[0031] Referring now to Figure 3, a graph showing the number of sub-visible particles as a function of the gap length is shown. The average particle count for the associated gap is well approximated by a linear fit (R 2 = 0.9996). Therefore, in subsequent studies, a larger air gap length of 3.5 mm was assumed to be the worst case for subvisible particle generation. The 3.5 mm air gap syringe system produced an average of 7,231 particles with a standard deviation of 4,567, while the 1.40 mm produced an average of 2,372 particles with a standard deviation of 2,388. This represents an average reduction of 4,859 particles, representing a reduction in particle generation of approximately 67% and a reduction in standard deviation of approximately 48% from the 3.5 mm to 1.4 mm air gap.

[0032] Referring now to FIG. 4, a graphical representation of the amount, e.g., thickness, of silicone oil 18 disposed on the inner surface 12c of the syringe barrel 12 as a function of distance from the flange 13 of the syringe barrel 12 is shown. The thick dark line in the graph represents silicone profile data for syringes having a 0.7 mg amount of silicone oil, and the lighter line represents silicone profile data for syringes having a 0.5 mg amount of silicone oil 18. The silicone profile data, including the thickness of the amount of silicone oil 18, becomes significantly more uniform as the amount of silicone oil 18 applied to the inner surface 12c decreases over the length of the syringe barrel 12, e.g., at various distances from the flange 13. A reduction in the amount of silicone oil 18 applied is shown to result in fewer silicone oil particles in the drug product 16 while still providing the syringe 10 with acceptable glide force values.

[0033] Referring now to FIG. 5, the amount of silicone oil 18 applied to the inner surface 12c of the syringe barrel 12 significantly affects the generation of sub-visible particles, for example, during transportation of the syringe 10. Generally, increasing the amount of silicone oil 18 can help reduce the gliding force of the plunger within the syringe 10. Similarly, increasing the amount of silicone oil 18 can also lead to an increase in the amount of silicone oil particles present after transportation of the syringe 10, as shown in the PFS after 91.5 hours of simulated transportation, preventing the syringe 10 from meeting the sub-visible particle requirement. As shown in FIG. 5, when the syringe contained 0.7 mg of silicone oil 18, the syringe produced an average of 7,315 particles with a standard deviation of 4,096, which exceeded the required sub-visible particle limit of, for example, 6,000 particles per container. However, when syringe 10 contained a 0.5 mg amount of silicone oil 18, syringe 10 produced an average of 1,580 particles with a standard deviation of 696, which is well below the required subvisible particle limit. Reducing the amount of silicone oil 18 from 0.7 mg to 0.5 mg resulted in an average reduction of 5,735 particles, representing a 78% reduction in particle generation.

[0034] Referring now to FIG. 6 , a graph is shown illustrating the effect of a silicone oil nozzle on subvisible particle generation in a syringe 10 of the present disclosure. In the production of syringes 10, various silicone oil application techniques can be utilized to achieve target silicone oil profiles and amounts with varying tolerances. In one example, a production line used for a syringe 10 having a reservoir 14 with a 3.0 mL fill volume can utilize two nozzle systems to apply a quantity of silicone oil 18 to the inner surface 12c of the syringe barrel 12. One nozzle system, e.g., IVEK, with either an industrial or benchtop production scale, is a continuous airflow diving nozzle system, and the other nozzle system is an intermittent airflow diving nozzle, such as by Bausch+Strobel, with an industrial production scale. The tested sample contained a quantity of silicone oil 18 of 0.5 mg. As shown in FIG. 6 , the continuous airflow diving nozzle system, e.g., the IVEK nozzle, demonstrated improvement over the intermittent airflow diving nozzle, e.g., the Bausch+Strobel system, in terms of subvisible particle generation. However, both nozzle systems, which dispense 0.5 mg of silicone oil onto the inner surface 12c of the syringe barrel 12, are able to achieve the USP 1000 for a particle size of 10 μm, as shown, for example, in the results of FIG. <787> It has demonstrated the ability to stay below a limit, for example, below a limit of 6,000 particles per container.

[0035] As discussed above with respect to syringe 10 of FIG. 1, reservoir 14 of syringe barrel 12 may have a larger fill volume, such as a fill volume ranging from approximately 1.0 mL to 3.0 mL, while still meeting the required sub-visible particle limits. For example, referring to FIG. 7, it can be seen that smaller fill volumes generally result in fewer silicone particles. Therefore, a 3.0 mL fill volume for syringe 10 results in the greatest amount of sub-visible particle generation, e.g., after transport of syringe 10, compared to a lower fill volume of 1.0 mL, which results in the least amount of sub-visible particle generation. More specifically, as shown in FIG. 7, syringe 10 with a 3.0 mL fill volume produced an average of 1,580 particles with a standard deviation of 696, while syringe 10 with a 1.0 mL fill volume produced an average of 703 particles with a standard deviation of 339. This represents an average reduction of 876 particles, for example, a 55% reduction in particle occurrence from a 3.0 mL fill volume to a 1.0 mL fill volume, and a 51% standard deviation reduction.

[0036] Referring now to FIG. 8 , a suspension packout system 100 of the present disclosure is shown. The suspension packout system 100 includes a housing 110 having an interior wall 112 that defines an interior region 114. The suspension packout system 100 further includes packaging disposed within the housing 110 adjacent to and / or at least partially around the interior wall 112. In this example, the packaging 116 is disposed around substantially the entire interior wall 112 of the housing 110. Furthermore, in this example, there are four interior walls 112a, 112b, 112c, and 112d that form the rectangular-shaped housing 110. However, it will be understood that the housing 110, and therefore the interior walls 112, may take on various other shapes, such as circular and / or cylindrical, and still be within the scope of the present disclosure. For example, if the housing 110 is circular in shape, and the interior wall 112 is similarly cylindrical in shape, the packaging 116 is disposed around substantially the entire periphery of the interior wall 112. It will be appreciated that the packaging material 116 may include, for example, one or more of dunnage, foam, bubble wrap, peanuts, and / or cushioning plastic material and still be within the scope of the present disclosure.

[0037] As further shown in FIG. 8 , the suspension packout system 100 also includes and / or is configured to receive a carton 118 containing syringes 10; typically, multiple syringes 10 are disposed within the carton 118. So configured, the carton 118 is limited to contact with the packaging material 116, such as during shipping and / or movement of the carton 118, reducing the amount of sub-visible particles generated within the syringes 10 during movement. During testing, a standard, conventional packout system produced an average of 1,580 particles / container with a standard deviation of 696, while the suspension packout system 100 of FIG. 8 produced an average of 566 particles / container with a standard deviation of 405. This represents an average reduction of 1,015 particles / container, for example, a 64% reduction in particle generation and a 42% reduction in standard deviation from the standard, conventional packout system.

[0038] In light of at least the above, various methods of limiting sub-visible particles within syringe 10 and system 100 will be appreciated. For example, in one example, an exemplary method of limiting sub-visible particles within syringe 10 partially filled with drug product 16 includes applying an amount of silicone oil 18 to syringe barrel 12 of syringe 10, such as along the length of syringe barrel 12, which, as described above, includes proximal end 12a, distal end 12b, and reservoir 14. Drug product 16 is disposed within distal end 14b of reservoir 14 at distal end 12b of syringe barrel 12, with the amount of silicone oil ranging from about 0.4 mg to about 0.6 mg, to reduce the amount of sub-visible particles generated based on the amount of silicone oil 18 applied. In one example, applying a quantity of silicone oil 18 includes applying a quantity of silicone oil 18 to syringe barrel 12, where reservoir 14 has a fill volume ranging from about 1.0 mL to about 3.0 mL. In another example, applying a quantity of silicone oil 18 to syringe barrel 12 includes applying the quantity of silicone oil 18 to inner surface 12c of syringe barrel 12 along the length of the syringe barrel, where the quantity of silicone oil 18 facilitates movement of plunger portion 20 during injection of drug product 16 within syringe 10 while simultaneously reducing the amount of sub-visible particles generated within syringe 10.

[0039] The method further includes placing the carton 118 containing the syringe 10 within a suspension packout system 100 configured to reduce generation of sub-visible particles within the syringe 10 during transport. The suspension packout system 100 includes packaging material 116 spaced at least partially around the carton 118 containing the syringe 10 to limit contact of the carton 118 containing the syringe 10 to the packaging material 116. In one example, limiting contact of the carton 118 containing the syringe 10 to the packaging material 116 includes limiting contact of the carton 118 containing the syringe 10 to one or more of dunnage, foam, bubble wrap, or cushioning plastic material to maintain the position of the carton 118 within the suspension packout system 100 during movement of the suspension packout system 100 and / or the carton 118.

[0040] The method may also include disposing plunger portion 20 within syringe barrel 12 to a depth D within syringe barrel 12 such that plunger portion 20 is spaced from drug product 16. In some examples, disposing plunger portion 20 within syringe barrel 12 includes disposing stopper 20 within syringe barrel 12 to a depth D within syringe barrel 12, such that stopper 20 is spaced from drug product 16. The method may also include creating a gap 22 between plunger portion 20 still disposed within syringe barrel 12 and drug product 16, the gap comprising a gap length 23 ranging from about 1.2 mm to about 3.5 mm, and in one example, gap length 23 is 1.4 mm. In another example, gap length 23 is 2.3 mm, and in another example, gap length 23 is 3.5 mm.

[0041] Another exemplary method of limiting subvisible particles in a syringe 10 partially filled with a drug product 16 includes applying a quantity of silicone oil 18 to a syringe barrel 12 of the syringe 10, the syringe barrel 12 including a proximal end 12a, a distal end 12b, and a reservoir 14. The drug product 16 is disposed within the distal end 14b of the reservoir 14 at the distal end 12b of the syringe barrel 12, the quantity of silicone oil 18 being in the range of about 0.4 mg to about 0.6 mg. The method also includes disposing a plunger portion 20 within the syringe barrel 12 to a depth D within the syringe barrel 12 and creating a gap 22 between the plunger portion 20 and the drug product 16, the gap 22 having a gap length 23 in the range of about 1.2 mm to about 3.5 mm.

[0042] In some examples of this method, applying a quantity of silicone oil 18 to syringe barrel 12 similarly includes applying a quantity of silicone oil 18 to syringe barrel 12 having reservoir 14 with a fill volume ranging from about 1.0 mL to about 3.0 mL. In one example, the fill volume is 3.0 mL, as described above. Additionally, applying the quantity of silicone oil 18 to syringe barrel 12 may further include applying the quantity of silicone oil 18 to inner surface 12c of syringe barrel 12 to facilitate movement of plunger portion 20 during injection of the syringe's drug product and to reduce the amount of sub-visible particles generated within syringe 10.

[0043] Further, disposing the plunger portion 20 within the syringe barrel 12 may include disposing the stopper 20 within the syringe barrel 12 to a depth D within the syringe barrel 12, wherein the stopper 20 is spaced from the drug product 16. Further, creating a gap 22 between the plunger portion 20 and the drug product 16 may include creating a gap 22 between a distal-most point of the plunger portion 20 and a meniscus 25 of the drug product 16 disposed within the distal end 14b of the reservoir 14. Still further, after creating the gap 22 between the plunger portion 20 and the drug product 16, the method may further include disposing the syringe 10 within a carton 118, and thereafter disposing the carton 118 within a suspension packout system 100 configured to reduce generation of subvisible particles within the syringe 10 during movement of the carton 118. Additionally, placing the carton 118 within the suspension packout system 100 may include placing the carton 118 within the housing 110 of the suspension packout system 100 and positioning packaging material 116 within the housing 110 at least partially around the carton 118 containing the syringe 10 to limit contact of the carton 118 with the packaging material 116 during movement. The packaging material 116 may include one or more of dunnage, foam, or a cushioning plastic material.

[0044] Various experiments related to the syringe 10, system 100, and method of the present disclosure described above were conducted to confirm various results and advantages of the present disclosure. More specifically, exemplary sample syringes used in the experiments included an OMPI 3.0 mL syringe and a Daikyo-Seiko 3.0 mL Flurotec-coated Plungee. The sample syringes were filled with 3.1 mL of drug product, for example, using the automated stopper placement technology described above. The sample syringes were then packaged as prefilled syringes in a package consisting of three 14-count rounded trays packaged in a standard carton for syringe systems. The sample syringes were then subjected to a transportation simulation, after which they were manually extruded, and the subvisible particle counts per MET-404639 (HIAC) and MET-403619 (MFI) were measured. Additionally, other methods of SbVP quantification were utilized, such as the Microscopic Particle Count Test for Quantifying Liquid Borne Subvisible Particle Matter (MET-401787) and the HORIZON Aura System from Halo Labs. This series of studies utilized a transport test sequence typically performed as part of a transport operational qualification (TOQ) study. This included a 91.5-hour simulated transport test in which a syringe was subjected to numerous repeated drops, significant vibrations, and pressure changes, mimicking transport factors that would occur during actual transport of the syringe. For example, a significant increase in subvisible particles in the syringe beyond acceptable limits occurs after such agitation. For this test, the cycling chamber was programmed to maintain a constant 18°C ​​for the duration of the simulation, as this was intended to simulate sample transport prior to subvisible particle testing and not to test the ability of insulated shippers to maintain a temperature between 2 and 8°C. A summary of the data from the performed experiments is provided in Table 2 below.

[0045] [Table 2]

[0046] [Table 3]

[0047] As shown in Table 2, for example, a sample syringe having a fill volume of 3 mL, a gap length of 3.5 mm, and an amount of silicone oil of 0.5 mg, for example, had no samples that failed the subvisible particle limit requirements.

[0048] Additionally, various attributes potentially related to particle count reduction were investigated to mitigate and / or limit the generation of sub-visible particles within the syringe, with the following attributes demonstrating the greatest reduction in particle count: (1) amount of silicone, (2) packout configuration, (3) void length, and (4) fill volume. Table 3 below lists the attributes that have the greatest impact and are therefore used, for example, in the systems and methods of the present disclosure. Attributes that were found to have no impact whatsoever on particle generation are also included in the table.

[0049] [Table 4]

[0050] In light of at least the above, various advantages of the systems and methods of the present disclosure will be appreciated: The syringe 10 and associated methods apply and maintain an optimal amount of silicone oil 18 along the desired length of the syringe barrel 12 to reduce sub-visible particles within the syringe 10 to meet required sub-visible particle limits while maintaining lubrication to facilitate movement of the plunger portion 20 (e.g., during injection). Additionally, the packaging material 116 of the suspension packout system 100 disposed around the carton 118 containing the syringe 10 mitigates and / or reduces the impact on the syringe 10 and limits sub-visible particles within the syringe 10 during shipping, particularly during any drops that have been found to often generate the most sub-visible particles. Furthermore, by reducing and / or having a gap length 22 in the range of about 1.2 mm to about 3.5 mm, for example, the surface area of ​​the syringe barrel 12 available for fluid movement within the syringe 10 is reduced, resulting in a reduced amount of siliconized surface area of ​​the syringe barrel 12 exposed to the drug product 16. Furthermore, the amount of fluid movement available to potentially remove some of the silicone oil 18 from the interior surface of the syringe barrel 12 is reduced due to the reduced gap length 22 and surface area of ​​the syringe barrel 12, resulting in a more uniform amount of silicone oil 18 being maintained on the interior surface 12c of the syringe barrel 12, for example. Still further, by having a reservoir 14 with a smaller fill volume, for example, in the range of about 1.0 mL to about 3.0 mL, the plunger portion 20 is moved to a lower depth D within the syringe barrel 12, again reducing the exposed surface area within the syringe barrel 12. The amount of silicone oil 18 also reduces the amount of sub-visible particles so produced.

[0051] Furthermore, by implementing the above-described amount of silicone oil 18 within the syringe barrel 12 of the syringe 10, placing the syringe 10 having such silicone oil 18 characteristics within a carton 118, and placing the carton 118 within the packaging 116 of the suspension packout system 100, a 94% reduction in average sub-visible particle generation within the syringe 10 was achieved with a standard deviation of 84%. Furthermore, the sub-visible particle counts were consistently below the limits defined (e.g., as described above) for the novel features of the present disclosure.

[0052] The above description describes various devices, assemblies, components, subsystems, and methods of use related to drug delivery devices. The devices, assemblies, components, subsystems, methods, or drug delivery devices may further include or be used in conjunction with drugs, including, but not limited to, the drugs identified below and their generic and biosimilar counterparts. The term drug, as used herein, can be used interchangeably with other similar terms and can refer to any type of pharmaceutical or therapeutic material, including traditional and non-traditional pharmaceutical drugs, nutraceuticals, supplements, biologics, biologically active agents and compositions, large molecules, biosimilars, bioequivalents, therapeutic antibodies, polypeptides, proteins, small molecules, and generic drugs. Non-therapeutic injectable materials are also included. Drugs may be in liquid form, lyophilized form, or reconstituted from a lyophilized form. The following exemplary list of drugs should not be considered exhaustive or limiting.

[0053] The drug is contained in a reservoir. In some cases, the reservoir is a primary container that is either filled or pre-filled with the drug for treatment. The primary container can be a vial, cartridge, or pre-filled syringe.

[0054] In some embodiments, the reservoir of the drug delivery device can be loaded with, or the device can be 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 filgrastim, PEGylated G-CSF, PEGylated hu-Met-G-CSF) and Neupogen® (filgrastim, G-CSF, hu-Met-G-CSF), UDENYCA® (pegfilgrastim-cbqv), Ziextenzo® (LA-EP2006; pegfilgrastim-bmez), or FULPHILA (pegfilgrastim-bmez).

[0055] In other embodiments, the drug delivery device may contain or be used with an erythropoiesis-stimulating agent (ESA), which may be in liquid or lyophilized form. An ESA is any molecule that stimulates erythropoiesis. In some embodiments, the ESA is an erythropoiesis-stimulating protein. As used herein, "erythropoiesis-stimulating protein" refers to any protein that directly or indirectly causes activation of the erythropoietin receptor, for example, by binding to the receptor and causing receptor dimerization. Erythropoiesis-stimulating proteins include erythropoietin and variants, analogs, or derivatives thereof 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. Erythropoiesis-stimulating proteins include Epogen® (epoetin alfa), Aranesp® (darbepoetin alfa), Dynepo® (epoetin delta), Mircera® (methoxypolyethylene glycol-epoetin beta), Hematide®, MRK-2578, INS-22, Retacrit® (epoetin zeta), Neorecormon® (epoetin beta), Silapo® (epoetin zeta), and Binocrit® (epoetin beta). Epoetin alfa), epoetin alfa Hexal, Abseamed® (epoetin alfa), Ratioepo® (epoetin theta), Eporatio® (epoetin theta), Biopoin® (epoetin theta), epoetin alfa, 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.

[0056] Among certain exemplary proteins are the specific proteins described below, including fusions, fragments, analogs, variants, or derivatives thereof: 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, peptibodies, related proteins, and the like, which particularly inhibit activities mediated by binding of IL-4 and / or IL-13 to its receptor; and IL-4 receptor-specific antibodies, peptibodies, related proteins, and the like, which inhibit activities mediated by binding of IL-4 and / or IL-13 to its receptor. Interleukin 1-receptor 1 ("IL1-R1")-specific antibodies, peptibodies, related proteins, etc.; Ang2-specific antibodies, peptibodies, related proteins, etc.; NGF-specific antibodies, peptibodies, related proteins, etc.; CD22-specific antibodies, peptibodies, related proteins, etc., particularly dimers of human-mouse monoclonal hLL2 gamma chain disulfide bound to human-mouse monoclonal hLL2 kappa chain, e.g., the human CD22 of epratuzumab (CAS Registry Number 501423-23-0). Human CD22-specific antibodies, including, but not limited to, humanized and fully human monoclonal antibodies, particularly including, but not limited to, human CD22-specific IgG antibodies, such as bispecific fully humanized antibodies; IGF-1 receptor-specific antibodies, peptibodies, and related proteins, including, but not limited to, anti-IGF-1R antibodies; B-7-related protein 1-specific antibodies, peptibodies, and related proteins (also referred to as "B7RP-1", as well as B7H2, ICOSL, B7h, and CD275), including, but not limited to, B7RP-specific fully human monoclonal IgG2 antibodies, including, but not limited to, fully human IgG2 monoclonal antibodies that bind to an epitope in the first immunoglobulin-like domain of B7RP-1; HuMax, e.g., 145c7 IL-15 specific antibodies, peptibodies, related proteins, etc., including, but not limited to, IL-15 antibodies and related proteins, particularly humanized monoclonal antibodies; human IFNIFN-γ specific antibodies, peptibodies, related proteins, etc., including but not limited to, IFN-γ specific antibodies, and including but not limited to, fully human anti-IFN-γ 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 ("HGF") specific antibodies, peptibodies, related proteins, etc., including those targeting HGF / SF; and antibodies targeting the c-Met axis (HGF / SF:c-Met). hepatocyte growth factor ("HGF")-specific antibodies, peptibodies, related proteins, etc., including those that bind to hepatocyte growth factor ("HGF") receptors; TRAIL-R2-specific antibodies, peptibodies, related proteins, etc.; activin A-specific antibodies, peptibodies, proteins, etc.; TGF-β-specific antibodies, peptibodies, related proteins, etc.; amyloid β protein-specific antibodies, peptibodies, related proteins, etc.; c-Kit-specific antibodies, peptibodies, related proteins, including, but not limited to, proteins that bind to c-Kit and / or other stem cell factor receptors. etc.; OX40L-specific antibodies, peptibodies, related proteins, etc., including but not limited to proteins that bind to OX40L and / or other ligands of the OX40 receptor; Activase® (alteplase, tPA), Aranesp® (darbepoetin alfa), erythropoietin [30-asparagine, 32-threonine, 87-valine, 88-asparagine, 90-threonine], darbepoetin alfa, novel erythropoiesis-stimulating protein (NESP), Epog en® (epoetin alfa, 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-β4β7mAb), 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, biosimilars of Herceptin® or other products containing trastuzumab for the treatment of breast and gastric cancer, Humatrope® (somatropin, human growth hormone), Humira® (adalimumab), Mab), 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, ganitumab, 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-BlySmAb), Metalyse® (tenecteplase, t-PA analog), Mircera® (methoxypolyethylene glycol-epoetin beta), Mylotarg® (gemtuzumab ozogamicin), Raptiva® (efalizumab), Cimzia® (certolizumab pegol, CDP870), Soliris™ (eculizumab), pexelizumab (anti-C5 complement), 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 monoclonal antibody), Reopro® (abciximab, anti-GPIIb / IIia 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® (ba ciliximab), Prexige® (lumiracoxib), Synagis® (palivizumab), 145c7-CHO (anti-IL15 antibody, see U.S. Pat. No. 7,153,507), Tysabri® (natalizumab, anti-β-integrin 4 mAb), Valortim® (MDX-1303, anti-anthrax protective antigen mAb), ABthrax™, Xolair® (omalizumab), ETI211 (anti-MRSA mAb), IL-1 trap (the Fc portion of human IgG1 and the extracellular domains of both IL-1 receptor components (type I receptor and receptor accessory protein)), VEGF trap (the Ig domain of VEGFR1 fused to the Fc of IgG1), Zenapax® (daclizumab), Zenapax® (daclizumab, anti-IL-2R 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), CNTO148 (golimumab, anti-TNF- mAb), HGS-ETR1 (mapatumumab, a human anti-TRAIL receptor-1 mAb), HuMax-CD20 (ocrelizumab, an anti-CD20 human mAb), HuMax-EGFR (zalutumumab), M200 (volociximab, an anti-C5-1 integrin mAb), MDX-010 (ipilimumab, an anti-CTLA-4 mAb, and VEGFR-1 (IMC-18F1), anti-BR3 mAb, anti-C. difficile toxin A and toxin BC mAbs MDX-066 (CDA-1) and MDX-1388), anti-CD22dsFv-PE38 antibody (CAT-3888 and CAT-8015), anti-CD25 mAb (HuMax-TAC), anti-CD3 mAb (NI-0401), anti-CD30 mAb (MDX-060), MDX-1333 (anti-IFNAR), anti-CD38 mAb (HuMax CD38), anti-CD40L mAb, anti-Cripto mAb, anti-CTGF-Idiopathic Pulmonary Disease (FG-3019), anti-CTLA4 mAb, anti-eosinophil 1 mAb (CAT-213), anti-FGF8 mAb, anti-Gamma-Glucoside GD2 mAb, anti-GM2 mAb, anti-GDF-8 mAb (MYO-029), anti-GM-CSF receptor mAb (CAM-3001), anti-HepC mAb (HuMax HepC), anti-IFN? mAb (MEDI-545, MDX-198), anti-IGF1R mAb, anti-IGF-1R mAb (HuMax-Inflam), anti-IL12 mAb (ABT-874), anti-IL12 / IL23 mAb (CNTO1275), anti-IL13 mAb (CAT-354), anti-IL2Ra mAb (HuMax-TAC), anti-IL5 receptor mAb, anti-Ig receptor mAb (MDX-018, CNTO95), anti-IP10 ulcerative colitis mAb (MDX-1100), BMS-66513, anti-mannos receptor / hCG mAb (MDX-1307), anti-metastatic dsFv-PE38 conjugate (CAT-5001), anti-PD1 mAb (MDX-1106 (ONO-4538)), anti-PDGFR antibody (IMC-3G3), anti-TGFβ mAb (GC-1008), anti-TRAIL receptor-2 antibody (HGS-ETR2), anti-TWEAK mAb, anti-VEGFR / Flt-1 mAb, and anti-ZP3 mAb (HuMax-ZP3).

[0057] In some embodiments, the drug delivery device may contain or be used in conjunction with a sclerostin antibody, such as, but not limited to, romosozumab, brosozumab, BPS 804 (Novartis), Evenity™ (romosozumab-aqqg), or another product containing romosozumab for the treatment of postmenopausal osteoporosis and / or fracture healing, and in other embodiments, a monoclonal antibody (IgG) that binds to human proprotein 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 contain or be used in conjunction with rilotumumab, bixalomer, trebananib, ganitumab, conatumumab, motesanib diphosphate, brodalumab, vidupiprant, or panitumumab. In some embodiments, the reservoir of the drug delivery device may be loaded with, or the device may be used in conjunction with, IMLYGIC® (talimogene laherparepvec) or another oncolytic HSV for the treatment of melanoma or other cancers, including, but not limited to, OncoVEX GALV / CD; OrienX010; G207,1716; NV1020; NV12023; NV1034; and NV1042. In some embodiments, the drug delivery device may contain, or be used in conjunction with, an endogenous tissue inhibitor of metalloproteinases (TIMP), such as, but not limited to, TIMP-3. In some embodiments, the drug delivery device may contain, or be used in conjunction with, Aimovig® (erenumab-aooe), an anti-human CGRP-R (calcitonin gene-related peptide type 1 receptor), or another product containing erenumab for the treatment of migraines. Antagonist antibodies of 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, may also be delivered using the drug delivery devices of the present disclosure.Additionally, bispecific T cell engager (BiTE®) molecules, such as, but not limited to, BLINCYTO® (blinatumomab), can be used in or with the drug delivery devices of the present disclosure. In some embodiments, the drug delivery device can contain or be used in conjunction with an APJ large molecule 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 can contain or be used in conjunction with Avsola™ (infliximab-axxq), an anti-TNF-α monoclonal antibody and biosimilar to Remicade® (infliximab) (Janssen Biotech, Inc.), or another product containing infliximab for the treatment of autoimmune diseases. 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 contain 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 contain or be used in conjunction with Parsabiv™ (etelcalcetide HCl, KAI-4169) or another product containing etelcalcetide HCl 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 contain or be used in conjunction with ABP 798 (rituximab), a biosimilar candidate for Rituxan® / MabThera™, or another product containing an anti-CD20 monoclonal antibody. In some embodiments, the drug delivery device may contain or be used in conjunction with a VEGF antagonist, such as a non-antibody VEGF antagonist, and / or a VEGF-Trap (Ig domain 2 from VEGFR1 and Ig domain 3 from VEGFR2 fused to the Fc domain of IgG1), such as aflibercept. In some embodiments, the drug delivery device may contain or be used in conjunction with ABP 959 (eculizumab), a biosimilar candidate for Soliris®, or another product containing a monoclonal antibody that specifically binds to complement protein C5. In some embodiments, the drug delivery device may contain or be used in conjunction with Rozibafusp alfa (formerly AMG 570), a novel bispecific antibody-peptide conjugate that simultaneously blocks 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 a myotrope that directly targets the cardiac contractile machinery, or another product containing a small molecule selective cardiac myosin activator. In some embodiments, the drug delivery device may contain sotorasib (formerly known as AMG 510), a KRASG12C small molecule inhibitor, or another product containing a KRASG12C small molecule inhibitor.In some embodiments, the drug delivery device may contain or be used in conjunction with tezepelumab, a human monoclonal antibody that inhibits the action of thymic stromal lymphopoietin (TSLP), or another product containing a human monoclonal antibody that inhibits the action of TSLP. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 714, a human monoclonal antibody that binds to interleukin-15 (IL-15), or another product containing a human monoclonal antibody that binds to interleukin-15 (IL-15). In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 890, a small interfering RNA (siRNA) that reduces lipoprotein(a), also known as Lp(a), or another product containing a small interfering RNA (siRNA) that reduces lipoprotein(a). In some embodiments, the drug delivery device may contain or be used with ABP 654 (a human IgG1 kappa antibody), a biosimilar candidate for Stelara®, or another product containing a human IgG1 kappa antibody and / or binding to the p40 subunit of the human cytokines interleukin (IL)-12 and IL-23. In some embodiments, the drug delivery device may contain or be used with Amjevita™ or Amgevita™ (formerly ABP501) (a mab anti-TNF human IgG1), a biosimilar candidate for Humira®, or another product encompassing a human mab anti-TNF human IgG1. In some embodiments, the drug delivery device may contain or be used with AMG 160, or another product containing 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 contain or be used in conjunction with another product containing AMG 119 or delta-like ligand 3 (DLL3) CAR T (chimeric antigen receptor T cell) cell therapy.In some embodiments, the drug delivery device may contain or be used with another product containing AMG 119, or a delta-like ligand 3 (DLL3) CAR T (chimeric antigen receptor T cell) cell therapy. In some embodiments, the drug delivery device may contain or be used with another product containing AMG 133, or a gastric inhibitory polypeptide receptor (GIPR) antagonist and GLP-1R agonist. In some embodiments, the drug delivery device may contain or be used with another product containing AMG 171, or a growth differentiation factor 15 (GDF15) analog. In some embodiments, the drug delivery device may contain or be used with another product containing AMG 176, or a small molecule inhibitor of myeloid cell leukemia 1 (MCL-1). In some embodiments, the drug delivery device may contain or be used with AMG 199, or a half-life extended (HLE) bispecific T-cell engager construct (BiTE®). In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 256, or another product containing an anti-PD-1 x IL21 mutein and / or IL-21 receptor agonist designed to selectively activate the interleukin-21 (IL-21) pathway in programmed cell death-1 (PD-1)-positive cells. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 330, or another product containing an anti-CD33 x anti-CD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 404, or another product containing a human anti-programmed cell death-1 (PD-1) monoclonal antibody being investigated as a treatment for patients with solid tumors. In some embodiments, the drug delivery device may house or be used in conjunction with AMG 427 or another product containing a half-life extended (HLE) anti-fms-like tyrosine kinase 3 (FLT3) x anti-CD3 BiTE® (bispecific T-cell engager) construct.In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 430 or another product containing an anti-Jagged-1 monoclonal antibody. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 506 or another product containing a multispecific FAPx4-1BB-targeted DARPin® biologic under investigation as a treatment for solid tumors. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 509 or another product containing a bivalent T cell engager and designed using XmAb® 2+1 technology. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 562 or another product containing a half-life extended (HLE) CD19xCD3 BiTE® (bispecific T cell engager) construct. In some embodiments, the drug delivery device may contain or be used in conjunction with efavalukin alfa (formerly AMG 592) or another product containing an IL-2 mutein Fc fusion protein. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 596, or another product containing a CD3 x epidermal growth factor receptor vIII (EGFRvIII) BiTE® (bispecific T-cell engager) molecule. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 673, or another product containing a half-life extended (HLE) anti-CD33 x anti-CD3 BiTE® (bispecific T-cell engager) construct. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 701, or another product containing a half-life extended (HLE) anti-B-cell maturation antigen (BCMA) x anti-CD3 BiTE® (bispecific T-cell engager) construct. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 757 or another product containing a half-life extended (HLE) anti-delta-like ligand 3 (DLL3) x anti-CD3 BiTE® (bispecific T-cell engager) construct. In some embodiments, the drug delivery device may contain or be used in conjunction with AMG 910 or another product containing a half-life extended (HLE) epithelial cell tight junction protein claudin 18.2 x CD3 BiTE® (bispecific T-cell engager) construct.

[0058] Although the drug delivery devices, assemblies, components, subsystems, and methods have been described in terms of exemplary embodiments, they are not limited to the exemplary embodiments. The detailed description should be construed as merely exemplary and does not describe every possible embodiment of the present disclosure. Many alternative embodiments can be implemented using either current technology or technology developed after the filing date of this patent, and still fall within the scope of the claims that define the invention disclosed herein.

[0059] Those skilled in the art will recognize that various modifications, variations and combinations may be made to the above-described embodiments without departing from the spirit and scope of the present invention disclosed herein, and that such modifications, variations and combinations are to be construed as being within the scope of the present invention.

Claims

1. 1. A method for limiting sub-visible particles in a syringe partially filled with a drug product, comprising: applying a quantity of silicone oil to a syringe barrel of a syringe, the syringe barrel including a proximal end, a distal end, and a reservoir, a drug product disposed at the distal end of the reservoir at the distal end of the syringe barrel, the quantity of silicone oil ranging from about 0.4 mg to about 0.6 mg; disposing a plunger portion within the syringe barrel to a depth within the syringe barrel, the plunger portion being spaced apart from the drug product; creating an air gap between the plunger portion and the drug product, the air gap having an air gap length in the range of about 1.2 mm to about 3.5 mm; A method comprising:

2. 10. The method of claim 1, wherein applying a quantity of silicone oil to a syringe barrel comprises applying the quantity of silicone oil to the syringe barrel, the syringe barrel comprising the reservoir having a fill volume ranging from about 1.0 mL to about 3.0 mL.

3. 3. The method of claim 1 or 2, wherein applying a quantity of silicone oil to a syringe barrel comprises applying the quantity of silicone oil to an interior surface of the syringe barrel along a length of the syringe barrel, facilitating movement of the plunger during injection of the drug product of the syringe, and reducing the amount of sub-visible particles generated within the syringe.

4. 4. The method of claim 1, wherein disposing a plunger portion within the syringe barrel comprises disposing a stopper within the syringe barrel to a depth within the syringe barrel, the stopper being spaced apart from the drug product.

5. 5. The method of claim 1, wherein creating a gap between the plunger portion and the drug product comprises creating the gap between a distal-most point of the plunger portion and a meniscus of the drug product disposed at the distal end of the reservoir.

6. 6. The method of any one of claims 1 to 5, wherein after creating an air gap between the plunger portion and the drug product, the method further comprises placing the syringe in a carton and placing the carton in a suspension packout system configured to reduce generation of sub-visible particles in the syringe during transportation of the carton.

7. 7. The method of claim 6, wherein placing the carton in a suspension packout system includes placing the carton in a housing of the suspension packout system and positioning packaging material within the housing at least partially around the carton containing the syringe to limit contact of the carton with the packaging material during movement, the packaging material comprising one or more of dunnage, foam, bubble wrap, or cushioning plastic material.

8. 1. A method for limiting sub-visible particles in a syringe partially filled with a drug product, comprising: applying a quantity of silicone oil to a syringe barrel of a syringe, the syringe barrel including a proximal end, a distal end, and a reservoir, a drug product disposed at the distal end of the reservoir at the distal end of the syringe barrel, the quantity of silicone oil ranging from about 0.4 mg to about 0.6 mg; placing the syringe in a carton; placing the carton in a suspension packout system configured to reduce generation of sub-visible particles within the syringe during transport, the suspension packout system including packaging surrounding the carton containing the syringe to limit contact of the carton with the packaging; A method comprising:

9. 10. The method of claim 8, wherein limiting contact of the carton to packaging material comprises limiting the contact of the carton to one or more of dunnage, foam, bubble wrap, or cushioning plastic material to maintain the position of the carton within the suspension packout system during transport.

10. 10. The method of claim 8 or 9, further comprising disposing a plunger portion within the syringe barrel to a depth within the syringe barrel, the plunger portion being spaced apart from the drug product.

11. 11. The method of claim 10, wherein disposing a plunger portion within the syringe barrel includes disposing a stopper within the syringe barrel to a depth within the syringe barrel, the stopper being spaced apart from the drug product.

12. 12. The method of claim 10 or 11, further comprising creating an air gap between the plunger portion disposed within the syringe barrel and the drug product, the air gap having an air gap length in the range of about 1.2 mm to about 3.5 mm.

13. 13. The method of any one of claims 8 to 12, wherein applying a quantity of silicone oil comprises applying the quantity of silicone oil to the syringe barrel, the syringe barrel comprising the reservoir having a fill volume in the range of about 1.0 mL to about 3.0 mL.

14. 14. The method of claim 8, wherein applying a quantity of silicone oil to a syringe barrel comprises applying the quantity of silicone oil to an interior surface of the syringe barrel, the quantity of silicone oil facilitating movement of the plunger during injection of the drug product within the syringe while reducing the amount of sub-visible particles generated within the syringe.

15. A syringe partially filled with a drug product, a syringe barrel including a proximal end, a distal end, and a reservoir, wherein a drug product is disposed at the distal end of the reservoir at the distal end of the syringe barrel, and wherein the syringe barrel has an amount of silicone oil ranging from about 0.4 mg to about 0.6 mg, the amount of silicone oil being configured to limit the amount of sub-visible particles generated within the syringe barrel; a plunger portion disposed at a depth within the syringe barrel, the plunger portion being spaced apart from the drug product; a gap disposed between the plunger portion and the drug product, the gap having a gap length in the range of about 1.2 mm to about 3.5 mm; , a syringe.

16. 16. The syringe of claim 15, wherein the syringe barrel further includes an interior surface and a length, and the quantity of silicone oil is disposed on the interior surface along the length of the syringe barrel.

17. 17. The syringe of claim 15 or 16, wherein the fill volume of the reservoir of the syringe barrel ranges from about 1.0 mL to about 3.0 mL.

18. A syringe according to any one of claims 15 to 17, wherein the plunger portion is a stopper.

19. 19. A syringe according to any one of claims 15 to 18, wherein the gap length comprises the distance between the distal-most point of the plunger portion and a meniscus of the drug product disposed within the distal end of the reservoir.

20. 1. A suspension packout system comprising: a housing having an interior wall defining an interior region; packaging disposed within the housing adjacent to and / or at least partially around the inner wall; 16. A carton containing the syringe of claim 15, wherein the carton is disposed within the packaging material and is limited to contact with the packaging material to reduce the amount of sub-visible particles generated within the syringe during shipping. Includes a suspension packout system.

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