LEACHABLES FROM SINGLE-USE SYSTEMS AND IMPACT TO PRODUCT QUALITY

摘要

Application of single-use (SU) systems for the manufacturing of biologics have increased significantly over the years and pose challenges for pharmaceutical processing in terms of leachables and their potential impact on product quality. Our small-scale stressed/accelerated studies (conducted at > 25°C with elevated surface area to volume ratio) revealed increase in protein aggregation and sub-visible particles resulting from storage in disposable bags compare to other non-disposable storage containers (glass vials and stainless steel). Three classes of relevant leachable compounds are believed to potentially interact with protein and promote protein aggregation. We have repeatedly shown that some of the protein aggregates are dissociable by SDS and preventable by increasing polysorbate 20 levels (indicating hydrophobic leachable compounds). We have also observed covalent protein aggregates that are preventable by adding anti-oxidants (suggesting leachable compounds that promote strong protein crosslinking). Furthermore, we have observed protein aggregates that can be prevented by heat-treated bags prior to storage (indicating volatile compounds).