FDA无菌原料药检查指南.doc

GUIDE TO INSP?ECTIONS OF ST?ERILE DRUG SU?BSTANCE MANUF?ACTURERS FDA无?菌原料药检查指南 Note?: This docume?nt is referen?ce material f?or investigat?ors and other? FDA personne?l. The docume?nt does not b?ind FDA, and ?does no confe?r any rights,? privileges, ?benefits, or ?immunities fo?r or on any p?erson(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、?利益或豁免权。 One o?f the more di?fficult proce?sses to inspe?ct and one wh?ich has prese?nted consider?able problems? over the yea?rs is that of? the manufact?ure of steril?e bulk drug s?ubstances. Wi?thin the past? several year?s, there have? been a numbe?r of batches ?of sterile bu?lk drug subst?ances from di?fferent manuf?acturers whic?h exhibited m?icrobiologica?l contaminati?on. One manuf?acturer had a?pproximately ?100 batches c?ontaminated i?n a 6 month t?ime period. A?nother had ap?proximately 2?5 batches con?taminated in ?a similar per?iod. Other ma?nufacturers h?ave had recal?ls due to the? lack of assu?rance of ster?ility. Althou?gh the Inspec?tion Guide fo?r Bulk Drug S?ubstances pro?vides some di?rection for t?he inspection? of the steri?le bulk drug ?substance, it? does not pro?vide the deta?iled directio?n 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?的生产。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?一些生产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。 INTRODUCT?ION简介 In the ?manufacture o?f the sterile? bulk powders?, it is impor?tant to recog?nize that the?re is no furt?her processin?g of the fini?shed sterile ?bulk powder t?o remove cont?aminants or i?mpurities suc?h as particul?ates, endotox?ins and degra?dants. 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，再也没有别的处理来去?除微粒、内毒素和降解物。 ?As with other? inspections,? any rejected? batches, alo?ng with the v?arious reason?s for rejecti?on, should be? identified e?arly in the i?nspection to ?provide direc?tion for the ?investigator.? For example,? lists of bat?ches rejected? and/or retes?ted over a pe?riod of tim