探讨药品质量控制过程中OOS分析存在的问题

On Problems of OOS Investigations in Pharmaceutical Quality Control

目的:探讨目前药品检验领域在不合格检测结果(OOS)调查中存在的常见问题。方法:结合国内外主要法规或OOS指南,分析药品检验过程中出现的OOS现状,从实际出发进行深入分析。结果:就OOS的定义、产生的原因进行阐述,并就目前OOS分析中应强化或重点关注的问题进行了探讨:在调查的Ⅰa阶段,当检验员怀疑实验室错误时,应在丢弃供试样和标准样之前立即进行调查;在调查的Ⅰb阶段,实验室主管人员在对可能的原因进行客观评估时,应与检验员一起对检验方法性能进行评价,应特别关注所用定量方法是否得到充分的耐用性确认,方法本身产生OOS的概率有多大;对于已经进入法定方法范畴内的定性方法,是否有明确的判定终点等。进行第Ⅱ阶段的OOS调查时,实验室应根据实验方法的具体性能特点,对重新取样与复验、复验次数、逸出值是否该舍弃以及在报告结果时是否应该取平均值的问题进行预先设定,而不能随意变更;应避免重复试验到合格为止的方式;并应重视对产品情况的审核。进行第Ⅲ阶段的调查时,首先应开展方法适用性以及产品稳定性的评价实验;其次,应重视并充分运用统计学方法分析OOS发生的根源。结论:OOS调查是持续改进产品质量的一个重要控制工具,在国内药品质量控制领域已经引起重视,然而在实际操作中还存在许多不足。检验员在找出产生OOS的根源后,应以此为依据对检测方法或产品质量进行报告和改进。

Objective：To discuss the common problems existing in the investigation of out-of-specification （OOS） test results for pharmaceutical quality and test.Methods：Combined with the domestic and international regulations and OOS guidance, the insufifcient contents were deeply analyzed. Results： The deifnition andthe cause of OOS are explained, and problems which should be strengthened or focused on are discussed as follows： In phase Ia of OOS investigation, when suspecting there is a laboratory error in the test, the analyst should immediately investigate the problem before discarding test samples or standard sample; When in phase Ib of OOS investigation , the lab supervisor should objectively evaluate the performance of the test method with the analyst for assessing the possible reasons which resulted in OOS, and pay special attention to the problems if it is robust enough for a quantitative method or if there is a clear endpoint for the qualitative method; phraseⅡof OOS investigation is conducted, according to the speciifc characteristic of test method, the following problems should be predefined and cannot be changed arbitrarily： if resampling and retesting are needed and how many times of retesting should be done; if the outlier should be abandoned; and the result value should be reported by the mean value of the results. In addition, repeated trials should be avoided and more attention should be paid to the auditing of production.When phraseⅢof OOS investigation is conducted, ifrst, suitability test of the method and the stability of the product should be evaluated. Then, the analyst should make full use of the statistical methods to explore the cause of OOS. Conclusion：The investigation of OOS plays an important role in the products quality improvement, which is being taken seriously in the domestic drug quality control ifeld, while there are still many deifciencies or insufifciency in practice. The test method and product quality should be reported and improved based on the cause of OOS.