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

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of pharmaceutical sciences 2020-11, Vol.109 (11), p.3340-3351
Main Authors: Thakare, Vivek, Schmidt, Thomas, Rupprechter, Olga, Leibold, Julia, Stemmer, Susanne, Mischo, André, Bhattacharjee, Debarati, Prazeller, Peter
Format: Article
Language:English
Subjects:
Biotechnology
Cross-linked silicone
Injectables
Prefilled syringes
Protein aggregation
Protein formulation
Silicone oil
Subvisible particles
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0022-3549
1520-6017
DOI:10.1016/j.xphs.2020.08.018