近日，FDA发布了对美国Pharmasol Corporation工厂的警告信，其中提及关于质量部门的缺陷，在检查中，检查员发现实验室OOS、投诉、偏差等调查和CAPA未能在规定时间内关闭，尤其是有40个偏差未能及时关闭，更有甚者，延迟了一年多仍未关闭。

而工厂的解释是：由于质量系统紧张，贵公司繁琐的程序以及资源管理效率低下造成。并提出将重组质量部门, 并增加化学家、一个新的稳定性主管和一个质量保证总监。

但是FDA并不接受，“在 2015年 FDA 的检查中, 也发现了类似的 QU 缺陷。在对 2015年检查的回复中, 你也承诺将加强对调查的监督, 配置新的资源, 并聘请新的稳定性协调员。然而, 同样的严重问题依然存在。”

此外，尽管SOP中规定了稳定性样品从稳定性试验箱中取出后XX时间内检验样品，但是实际上并未遵循。甚至稳定性样品在取出254天后才进行检验。公司管理层在检查时无法解释这种偏差。

FDA还一如既往的翻了这家公司的垃圾桶，发现了丢弃的记录。这些记录显示入库容器和瓶盖的检验存在OOS结果。而最终记录中仅报告了合格结果。该公司则表示写这些记录的员工已不在公司, 这些组件在重新检测时是合格的。

FDA落下缺陷并发了警告信！

缺陷摘译如下：

Your firm failed to establish an adequate quality control unit, and procedures applicable to the quality control unit, with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a) and (d)).

贵公司未能建立适当的质量控制单元和适用于质量控制单元的程序, 使其足以批准或拒绝所有部件、药品容器、密封部件、中间物料、包装材料、标签和药品 (21 CFR 211.22(a) 和 (d))。

You lack adequate quality oversight. Your quality unit (QU)failed to review, approve, and close investigations (e.g., laboratory,complaint, and deviations) and CAPA within reasonable time limits. For example,at the time of our inspection, more than 40 deviations were open after yourspecified due dates. One was open for more than a year.

贵公司缺乏足够的质量监督。你们的质量部门 (QU) 未能在合理的时间内审查、批准和关闭调查(例如实验室、投诉和偏差) 和 CAPA。例如, 在检查期间, 我们发现有40个偏差在指定的截止日期之后仍未关闭，其中一个延迟了一年多。

Theseopen investigations included significant drug product quality issues, such asleaking containers, deviations from key production parameters (e.g., mixingspeeds), and OOS solvent assay results in finished drug product releasetesting. During our inspection, you explained that you believed that lapses inquality system performance were due to the strained quality system, your firm’scumbersome procedures, and inefficient management ofresources.

这些未关闭的调查包括严重的药品质量问题, 如容器泄漏、偏离关键生产参数 (如混合速度) 以及在成品产品放行检验中的溶剂检测OOS结果。在检查过程中, 你们解释说，你们认为质量体系表现的失误是由质量体系紧张，贵公司繁琐的程序以及资源管理效率低下造成的。

Additionally, your QU did not follow your own procedure forout-of-limit results in your environmental monitoring for viable organisms,which requires investigation and room disinfection. You also did not test foryeasts and molds for two months: you claimed the culture media, (b)(4), were unavailable.

此外, 你们的 QU 在处理环境监测微生物超标结果时未遵循你们的程序要求进行调查和房间消毒。你们也有两个月没有监测酵母和霉菌: 你们声称没有培养基(b)(4)。

Inyour response you committed to restructuring your QU and adding chemists, a newstability supervisor, and a director of quality assurance. You wrote that allmicrobiologically “sensitive” drug products manufactured met all releasecriteria. You also wrote that you would use a contract microbiology laboratoryif you were unable to procure (b)(4) inthe future.

在你们的回复中, 你们说将重组质量部门, 并增加化学家、一个新的稳定性主管和一个质量保证总监。你们写道, 所有制造的微生物 "敏感" 药物产品都符合所有放行标准。你们还写道, 如果将来无法实现 (b)(4), 你们将使用合同微生物实验室。

Yourresponse was inadequate. Regarding your firm’s response on environmentalmonitoring, you did not explain why your QU failed to investigate the cause ofout-of-limit results or why your QU did not disinfect the room as required byyour procedures. Additionally, you failed to provide a CAPA to ensure thatalternate qualified suppliers of microbial test media are available forenvironmental testing to ensure that sampling is performed as required toverify that your facility is maintained in a clean and sanitarycondition.

你们的回复是不充分的，关于贵公司对环境监测的回复, 你们没有解释为什么QU 未能调查超标的原因, 也没有解释为什么QU 没有按照程序的要求对房间进行消毒。此外, 你们未能提供 CAPA 来确保微生物检验培养基的其他合格供应商可用于环境监测, 以确保根据需要进行取样, 以确认你们的设施是否保持在清洁卫生的条件。

You were cited for similar QU failures in the 2015 FDAinspection. In your response to the 2015 inspection, you promised to enhanceoversight of investigations, allocate new resources, and hire a new stabilitycoordinator. However, significant related problems persisted.

在 2015年 FDA 的检查中, 也发现了类似的 QU 缺陷。在对 2 0 1 5年检查的回复中, 你也承诺将加强对调查的监督, 配置新的资源, 并聘请新的稳定性协调员。然而, 同样的严重问题依然存在。

Your firm failed to establish and followan adequate written testing program designed to assess the stabilitycharacteristics of drug products (21 CFR 211.166(a)).

贵公司未能建立并遵循用以评估药品稳定性的书面测试程序 (21 CFR211.166(a))。

Youdid not test stability samples pulled from stability chambers within the (b)(4) time frame required byyour procedure. In one instance, an 18-month stability sample (b)(4) was not tested until 254days after the sample was received in the laboratory. Your firm’s managementcould not explain this discrepancy at the time of the inspection.

你们未能按照规程要求在稳定性样品从稳定性试验箱中取出后XX时间内检验样品。其中, 18个月的稳定性样品 (b)(4) 直到实验室收到样品254天后才进行检验。贵公司的管理层在检查时无法解释这种偏差。

Your firm failed to thoroughly investigate any unexplaineddiscrepancy or failure of a batch or any of its components to meet any of itsspecifications, whether or not the batch has already been distributed (21 CFR211.192).

贵公司未能彻底调查批次或其任何组件任何不明原因的偏离或不符合其质量标准, 无论是否已分发 (21 CFR 211.192)。

Our FDA investigator found improperly discarded worksheets in arecycling bin. These worksheets indicated OOS results for measurements ofincoming containers and caps for your (b)(4) drugproduct. The final worksheet in your files only reported passing results andthere was no reference to OOS measurements.

我们的检查人员在垃圾桶里发现了丢弃的记录。这些记录显示了用于生产XX产品的入库容器和瓶盖的检验存在OOS结果。而你们的最终记录中仅报告了合格结果, 也没有引用 OOS 检测结果。

Inyour response, you stated that the employee who created these records is nolonger with the firm, and these components passed upon reexamination. You alsoreported that you updated your “good documentation practices” procedure andyour procedure for sampling and releasing components.

在你们的答复中, 你们表示写这些记录的员工已不在公司, 这些组件在重新检测时是合格的。你们还报告说, 你们更新了《良好文件记录规范》规程以及《组件取样和放行规程》。

Yourresponse was inadequate, because it did not provide the re-examination results(including raw data and worksheets) for the bottles and caps to show they metyour acceptance criteria.

你们的回复是不充分的, 因为它没有提供瓶子和瓶盖的重新检测结果 (包括原始数据和记录), 以显示它们符合你们的接受标准。