Global CMC Development, Sanofi, Framingham, Massachusetts, USA.
Gene Therapy Development, Pfizer, Chesterfield, Missouri, USA.
Biotechnol Bioeng. 2021 Sep;118(9):3287-3301. doi: 10.1002/bit.27670. Epub 2021 Jan 25.
There has been increasing momentum recently in the biopharmaceutical industry to transition from traditional batch processes to next-generation integrated and continuous biomanufacturing. This transition from batch to continuous is expected to offer several advantages which, taken together, could significantly improve access to biologics drugs for patients. Despite this recent momentum, there has not been a commercial implementation of a continuous bioprocess reported in the literature. In this study, we describe a successful pilot-scale proof-of-concept demonstration of an end-to-end integrated and continuous bioprocess for the production of a monoclonal antibody (mAb). This process incorporated all of the key unit operations found in a typical mAb production process, including the final steps of virus removal filtration, ultrafiltration, diafiltration, and formulation. The end-to-end integrated process was operated for a total of 25 days and produced a total of 4.9 kg (200 g/day or 2 g/L BRX/day) of the drug substance from a 100-L perfusion bioreactor (BRX) with acceptable product quality and minimal operator intervention. This successful proof-of-concept demonstrates that end-to-end integrated continuous bioprocessing is achievable with current technologies and represents an important step toward the realization of a commercial integrated and continuous bioprocessing process.
最近，在生物制药行业中，从传统的批处理工艺向新一代集成化和连续生物制造的转变势头日益强劲。这种从批处理到连续处理的转变预计将带来几个优势，这些优势加在一起，可以显著改善患者获得生物药物的机会。尽管最近有这种势头，但文献中尚未报道商业实施连续生物过程的情况。在这项研究中，我们描述了一个成功的、基于试点规模的概念验证，展示了一种用于生产单克隆抗体 (mAb) 的端到端集成和连续生物工艺。该工艺整合了典型的 mAb 生产工艺中的所有关键单元操作，包括病毒去除过滤、超滤、渗滤和制剂的最终步骤。该端到端集成工艺总共运行了 25 天，从 100 升灌注生物反应器 (BRX) 中生产了总共 4.9 公斤（200 克/天或 2 克/升 BRX/天）的药物物质，产品质量可接受，操作人员干预最小。这个成功的概念验证表明，端到端集成的连续生物加工是可以实现的，这代表了朝着实现商业化的集成和连续生物加工过程迈出的重要一步。
