Can Cross-Linked Siliconized PFS Come to the Rescue of the Biologics Drug Product?

Abstract

Silicone can present a challenge during the development of a biologics drug product particularly in pre-filled syringe (PFS). Due to silicone related challenges, substantial changes in components and manufacturing of the PFS are being sought. Cross-linking of the silicone being one of them, can help reduce mobilization of the silicone into drug product whilst retaining its functionality of lubrication during injection. In this work, we systematically compare the stability of a fusion protein and monoclonal antibody formulation in conventionally siliconized and cross-linked siliconized PFS available from commercial manufacturers. The two types of syringes did not influence the aggregation profile of proteins as determined by HP-SEC. Compared to conventionally siliconized PFS, a cross-linked siliconized PFS can have a favorable or indifferent impact (depending on vendor) on the sub-visible particles profile as assessed by light obscuration and microflow imaging. The different PFS after 24 months of long-term storage showed comparable functionality attributes like break-loose/gliding force and silicone oil distribution. Cross-linked siliconized PFS can offer an incremental advantage over conventionally siliconized PFS for the moderately concentrated protein solutions, however the differences in the quality of these PFS amongst manufacturers is an important aspect that needs to be considered as shown in this study.