FDA无菌原料药检查指南.docVIP

GUIDE TO INSPECTIONS OF STERILE DRUG SUBSTANCE MANUFACTURERS FDA无菌原料药检查指南 Note: This document is reference material for investigators and other FDA personnel. The document does not bind FDA, and does no confer any rights, privileges, benefits, or immunities for or on any person(s). 注：本文件是FDA现场检查官和其他FDA人员的参考资料。本文件并不束缚FDA，也不赋予任何人任何权利、特权、。 One of the more difficult processes to inspect and one which has presented considerable problems over the years is that of the manufacture of sterile bulk drug substances. Within the past several years, there have been a number of batches of sterile bulk drug substances from different manufacturers which exhibited microbiological contamination. One manufacturer had approximately 100 batches contaminated in a 6 month time period. Another had approximately 25 batches contaminated in a similar period. Other manufacturers have had recalls due to the lack of assurance of sterility. Although the Inspection Guide for Bulk Drug Substances provides some direction for the inspection of the sterile bulk drug substance, it does not provide the detailed direction needed. 多年来现场检查最难的也是出现问题最多的领域就是无菌原料药的。在过去几年中，有数批来自不同制造商的无菌原料药出现了微生物污染。一个制造商在6个月中有100批产品有污染。另一个在相同的时间内出现了25批污染。其它一些商由于缺少无菌保证而召回了产品。虽然大宗原料药的现场检查指南在对无菌原料药的检查上提供了一些指导，但它未能提供所需要的详细指导。INTRODUCTION简介In the manufacture of the sterile bulk powders, it is important to recognize that there is no further processing of the finished sterile bulk powder to remove contaminants or impurities such as particulates, endotoxins and degradants. 在大宗无菌粉的制造中，认识到下面一点很重要，即最终无菌粉生产出来之后，再也没有别的来去除微粒、内毒素和降解物。As with other inspections, any rejected batches, along with the various reasons for rejection, should be identified early in the inspection to provide direction for the investigator. For example, lists of batches rejected and/or retested over a period of time should be obtained from the manufacturer to provide direction for coverage to be given to specific processes or systems. Because some of the actual sterile b