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.

中文翻译：

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端到端集成和连续生物制造过程的中试示范

最近，生物制药行业从传统的批量工艺过渡到下一代集成和连续生物制造的势头越来越大。这种从分批到连续的转变预计将提供几个优势，这些优势结合起来可以显着改善患者获得生物制剂的机会。尽管最近有这种势头，但文献中报道的连续生物过程还没有商业化实施。在这项研究中，我们描述了用于生产单克隆抗体 (mAb) 的端到端集成和连续生物过程的成功中试规模验证演示。这个过程包含了典型 mAb 生产过程中的所有关键单元操作，包括病毒去除过滤、超滤、渗滤和配制。端到端集成工艺共运行 25 天，从 100 L 灌注生物反应器（BRX ) 具有可接受的产品质量和最少的操作员干预。这一成功的概念验证表明，通过当前技术可以实现端到端集成连续生物加工，并且代表了朝着实现商业集成和连续生物加工过程迈出的重要一步。