Issue link: https://www.e-digitaleditions.com/i/1511466
12 BioPharm International ® Manufacturing and Facilities eBook 2023 www.biopharminternational.com Manufacturing: Tech Transfer the executed batch record documentation once batch production has terminated, which should include critical process parameters from all man- ufacturing processes, real-time documentation from each step, information on equipment/in- strument and drug formulation, and the elec- tronic audit trail of all software systems used. DP compliance, DP MSAT, and DP quality authors all co-review and approve any batch-related de- viations to support a comprehensive root cause analysis and make a solid corrective and preven- tiv actions (CAPA) plan to support on-time batch release and make any improvements/mitigation actions to the manufacturing process through a rigorous quality system. • Quality testing: quality control (QC) testing is car- ried out to demonstrate that the product meets good manufacturing practice (GMP) guidelines A Look at Supply Chain for Scale Up In speaking with Suzanne Aldington, senior principal scientist, Downstream Processing, Biologics, and Lucas Lin, se- nior principal scientist, Global Process Development Implementation, Biologics, both at Lonza, BioPharm International® took a pulse on the supply chain lifeline for biologics in the post-pandemic setting. Discussion revolved around any impact the current state of the supply chain may be imparting on scale-up activities in downstream bioprocessing. BioPharm: Post-pandemic, where do scale-up operations stand? Is it business as usual, or are issues (such as supply chain constraints) making it difficult to implement scale-up in downstream processing, especially for new monoclonal antibodies (mAbs) or recombinant proteins? Aldington (Lonza): There are still issues that are impacting process development, such as successfully developing a process using a specific chromatography resin to ensure the removal of product-related impurities, only to discover that the resin lead time is extremely long and that the resin will not be available in time for the GMP [good manufacturing practice] batch. The issue is exacerbated for new molecular format products, which require less frequently used resins. Further development work is then required with a resin that is available in time for the GMP batch for the customer to achieve their IND/IMPD [investigational new drug/investigational medicinal product dossier] filing. A plausible mitigation strategy would be considering a central storage location for certain resins known to have longer lead times. Lin (Lonza): Looking specifically at depth filters, they are used in primary recovery all the time regardless of clinical or commercial scale. The supply chain dip during the pandemic had long-lasting effects even through to the post-pandemic era, where many customers had to work with their CDMOs [contract development and manufacturing organizations] to change their filters to at-the-time less commonly used ones. Processes that reached clinical stages during the pandemic, and are now moving into commercial post-pandemic, pose an additional challenge of navigating the depth filter selection, with important considerations to be made regarding the supply strategy of platform vs. non-platform filters. BioPharm: Specifically for downstream bioprocessing of mAbs, recombination proteins, and emerging therapies (e.g., gene therapies), what supplies may still be in shortage, or may still be constrained/restricted? Aldington (Lonza): Speed to GMP is key, and delays due to consumable lead times must be avoided. Certain chromatography resins are still in short supply, giving rise to new challenges when considering storing resins for repeated use rather than single use. Lin (Lonza): Depth filter supply has picked back up post-pandemic, but long supply lead time is still a challenge, impacting the flexibility in addressing customers' needs, especially drop-in processes (external processes tech- transferring into a new organization) that use non-platform filters. BioPharm: With new biosimilars entering the market now and/or in the next few years, will downstream scale-up be an issue for them based on the current state of the supply chain? Aldington (Lonza): With the requirements to scale-up, obtaining the required volumes of chromatography resins to manufacture biosimilars will prove challenging. While resins can be re-used to some extent, they have a limited life, so supply issues will likely impact the future production of biosimilars and supply to patients. Lin (Lonza): The rise of biosimilars will likely be less of an issue for depth filters (and any other filters for bioburden reduction/control or viral reduction). — Feliza Mirasol