CAJ | 학술논문

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 a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b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。
목적：탐토목전약품검험영역재불합격검측결과（OOS）조사중존재적상견문제。방법：결합국내외주요법규혹OOS지남，분석약품검험과정중출현적OOS현상，종실제출발진행심입분석。결과：취OOS적정의、산생적원인진행천술，병취목전OOS분석중응강화혹중점관주적문제진행료탐토：재조사적 a계단，당검험원부의실험실착오시，응재주기공시양화표준양지전립즉진행조사；재조사적b계단，실험실주관인원재대가능적원인진행객관평고시，응여검험원일기대검험방법성능진행평개，응특별관주소용정량방법시부득도충분적내용성학인，방법본신산생OOS적개솔유다대；대우이경진입법정방법범주내적정성방법，시부유명학적판정종점등。진행제Ⅱ계단적OOS조사시，실험실응근거실험방법적구체성능특점，대중신취양여복험、복험차수、일출치시부해사기이급재보고결과시시부응해취평균치적문제진행예선설정，이불능수의변경；응피면중복시험도합격위지적방식；병응중시대산품정황적심핵。진행제Ⅲ계단적조사시，수선응개전방법괄용성이급산품은정성적평개실험；기차，응중시병충분운용통계학방법분석OOS발생적근원。결론：OOS조사시지속개진산품질량적일개중요공제공구，재국내약품질량공제영역이경인기중시，연이재실제조작중환존재허다불족。검험원재조출산생OOS적근원후，응이차위의거대검측방법혹산품질량진행보고화개진。
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.