某制药车间无菌工艺模拟试验研究

Aseptic Process Simulation Test in a Pharmaceutical Workshop

目的 分析在工艺、物料、设施、设备和人员确定的条件下,某制药车间生产无菌产品的能力,并识别生产过程中的薄弱环节。方法 根据国家药品监督管理局发布指南中提出的无菌工艺模拟(APS)试验“最差条件”,在正常工作条件边缘下对工艺条件进行APS试验设计,并完成培养基模拟灌装试验。结果 APS试验包括无菌培养基配制、无菌培养基灌装、冻干压塞、轧盖、培养与检查、促生长试验、环境监测、模拟灌装后清洗等步骤。在此条件下,灌装完成的产品均无微生物生长;对培养14 d后的样品进行微生物促生长试验,科氏葡萄球菌、滕黄微球菌、坚强芽孢杆菌、胶红酵母菌、奥斯陆莫拉氏菌和耐盐枝孢菌均生长良好。结论 制药车间的日常无菌灌装工艺、环境、洁净室操作人员的无菌操作技术等的规范,有助于保障生产药品的质量和无菌性。

Objective To analyze the ability of a pharmaceutical workshop to produce the aseptic products under the specific conditions of process,materials,facilities,equipment and personnel,and to identify the weak links in the production process.Methods According to the "worst conditions" of aseptic process simulation(APS) test in the guidelines issued by the National Medical Products Administration,the APS test was designed for the process conditions under the above "worst conditions",and the media-fill simulation test was conducted.Results The APS test included aseptic medium preparation,aseptic medium fill,lyophilization and tamping,capping,culture and inspection,growth promotion test,environmental monitoring and washing after the media-fill simulation test. Under this condition,no microorganism grew in the filled products. The samples cultured for 14 d were selected for the microbial growth promotion test,which showed that Staphylococcus cohnii,Micrococcus luteus,Bacillus firmus,Rhodotorula mucilaginosa,Moraxella osloensis and Cladosporium halotolerans all grew well.Conclusion The standardization of the daily aseptic fill process,environment and aseptic operation technology of the operators in the clean room of the pharmaceutical workshop is helpful to ensure the quality and sterility of the produced drugs.