重组生物技术产品连续制造中病毒安全控制的一般考量

General considerations for viral safety control in continuous manufacturing of recombinant biotechnology products

连续制造是重组生物技术产品生产工艺未来的发展方向之一,ICH Q13等重要技术文件的出台也为其应用实践提供了指导意见。但在病毒安全控制领域,连续制造与既往常见的批制造模式在控制理念和措施上都存在较大差异。本文将从连续制造的工艺特性入手,对生产用原材料控制、生产过程中的检定和病毒去除/灭活工艺验证三方面内容进行初步探讨。同时,由于重组生物技术产品连续制造的案例仍然有限,更为全面、细致的控制策略和措施仍有待于研发和生产经验的进一步积累和完善。建议该类产品在申报前与监管机构进行充分沟通交流,以科学、严谨的试验设计确保受试者或患者的用药安全。

Continuous manufacturing is one of the development directions of the production process of recombinant biotechnology products in the future.The promulgation of important technical documents such as ICH Q13 also provides guidance for its application practice.However,in the field of viral safety control,there are great differences in control concepts and measures between continuous manufacturing and previous batch manufacturing mode.Starting with the process characteristics of continuous manufacturing,this paper makes a preliminary discussion on three aspects,which are the control of raw materials,in-process test,and virus removal/inactivation process validation.At the same time,as the cases of continuous manufacturing of recombinant biotechnology products are still limited,more comprehensive and meticulous control strategies and measures still need further accumulated and improved based on R&D and production experience.It is suggested that the applicants of this kind of products should fully communicate with the regulatory authorities before the application,so as to ensure the safety of the subjects or patients through scientific and rigorous trial design.