生物制品微生物质量控制与快速微生物检测的研究进展

Research Progress of Microbial Quality Control and Rapid Microbiological Detection of Biological Products

关键词:  生物制品  快速微生物检测  质量控制  微生物限度  无菌  合规性

Key words:  biological products  rapid microbial detection  quality control  microbial limit  sterility  compliance

摘要:

微生物作为生物制品质量控制关键的安全性指标,是工艺控制和产品放行的关键参数。经典的微生物检查耗时长,无法实时反馈产品现状和工艺控制情况,会对短货架期或需要快速放行生物制品的放行周期产生不利影响。探索快速微生物检测方法(rapid microbiological method,RMM)替代经典方法可解决上述问题,且符合过程分析技术理念。基于微生物培养的RMM通过分析培养液的理化特性变化来判断是否存在微生物,如BacT/ALERT^®系统等。基于活细胞识别的RMM多采用固相细胞计数和流式细胞仪等进行。基于分子水平的RMM通过分析微生物的特征分子来判定是否存在微生物。美国食品药品监督管理局、美国药典和欧洲药典等均提出了RMM理念,第一款RMM Pallchek在2004年已用于制药行业。从2010年版起,中国药典也纳入了微生物检验替代方法指导原则。本文对生物制品微生物质量控制与快速微生物检测方法进行综述。

Abstract:

As the key safety index of the quality control of biological products, microorganism is the critical parameter of process control and product release. The classic microbiological inspection is time-consuming and can’t feed-back the product status and process control in real time, which has a negative impact on short shelf life or the need for rapid release of biological products release cycle. Exploring alternative methods of rapid microbiological method(RMM) can solve the above problems and conform to the concept of process analysis technology. RMM based on microbial culture can determine whether there are microorganisms by analyzing the changes of physicochemical properties of culture medium, such as BacT/ALERT^® system. RMM based on living cell recognition mostly uses solid phase cell counting and flow cytometry. RMM based on the molecular level is determined by analyzing the characteristic molecules of microorganisms. Food and Drug Administration, United States Pharmacopeia and European Pharmacopeia all put forward the concept of RMM, and the first RMM Pallchek was used in the pharmaceutical industry in 2004. Since the 2010 edition, the Chinese Pharmacopoeia has also included guidelines for alternative methods of microbiological testing. In this paper, microbial quality control and rapid microbial detection methods of biological products are reviewed.