Evaluation of piston movement and container integrity under severe storage conditions in plastic and glass prefilled syringes
Lloyd Waxman, Harold Murray and Vinod Vilivalam
Purpose: The shipment and storage of biopharmaceuticals in prefilled syringes (PFS) places new demands on PFS performance. Studies compared package integrity of glass and plastic PFS: piston movement was evaluated under reduced pressures to simulate transport by air in non-pressurized holds, and container closure integrity was tested on PFS that had been frozen or frozen and thawed, since some biopharmaceuticals are stored and transported in the frozen state. Piston release and travel forces were also measured in plastic PFS since in order to be competitive with siliconized glass PFS, the functional characteristics of plastic PFS must meet or exceed the criteria established for glass PFS.
Methods: To examine piston movement under reduced pressures, glass and Daikyo Crystal Zenith® (CZ) plastic 1 mL PFS were filled with water with consistent bubble size. Syringes were mounted vertically in an acrylic vacuum leak detector box that could be evacuated to a desired vacuum level. Metrics and photography were performed to gauge piston movement. Separately, container closure integrity was tested on frozen, and frozen and thawed glass and plastic syringes using a dye ingress assay. Siliconized glass and plastic 1 mL Luer Lock (LL) PFS were filled with sucrose solution and frozen at -20°C. One-half of each type was thawed before testing; the rest were tested without thawing. Piston release and travel forces in both glass and plastic LL syringes were measured on an Instron Material Testing System after filling and piston placement.
Results: Under reduced pressure equivalent to 16,000 feet altitude, pistons in neither glass nor plastic PFS moved. However, when pressure was reduced to the equivalent of 18,000 feet altitude, only pistons in glass PFS moved (9-9.5mm). When the pressure was further reduced, equivalent to 21,500 feet altitude, pistons in plastic syringes also moved. When container closure integrity was tested on filled frozen syringes, syringes made of plastic or glass did not leak. In addition, no leakage was detected in glass or plastic syringes frozen and then thawed at room temperature. Piston release and travel forces in plastic syringes remained relatively consistent during long-term storage while those in glass syringes showed more variability between syringes and greater fluctuation in both forces as a function of distance.
Conclusions: Prefilled syringe systems made of CZ plastic, which utilize Flurotec®-laminated pistons, are silicone-free and offer several advantages for packaging of biopharmaceuticals. The reduced pressure at high altitudes may cause piston movement and provide a pathway for microbial ingress as the piston returns to its original position when the reduced pressure is removed. Pistons in siliconized glass PFS moved readily under these conditions compared to the plastic syringe system, perhaps due to CZ’s silicone oil-free feature. While both CZ and glass syringes maintained container closure integrity after freeze/thaw, plastic is break resistant, providing advantages for low-temperature storage and transport of biopharmaceuticals, and the absence of silicone eliminates the possibility of silicone-induced aggregation of sensitive biologics. In addition, the piston release and travel forces in plastic syringes remained relatively consistent during long-term storage at room temperature or at 4-8°C while those in glass syringes showed more variability, possibly due to the redistribution of silicone over time.
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