FDA警告信：药品生产过程中发生火灾（设备冒烟），偏差处理不当！

10月19日，FDA对Marcus Research Laboratory, Inc.的警告信中提及生产过程中发生火灾，偏差处理不当的缺陷。

该公司在批次生产过程中，生产人员发现药物反应器中正在冒烟。为了应对紧急的火灾风险，生产人员使用了灭火器。由于这一事件，生产没有正常进行。相关药物经历了不一致的温度暴露和额外的处理和保持时间。该公司只测试了受影响桶中物料的可用碘百分比，并放行进入下一工序。

同样，在另一批次生产过程中，生产人员再次发现反应器正在冒烟。生产停止，物料存放在未知条件下。该公司再次，只测试受影响的桶中的物料的可用碘百分比，并放行进入下一工序。

在这两种情况下，该公司都创建了偏差报告，但仅根据可用碘百分比的综合结果放行药物。但FDA对这种偏差处理并不接受！

缺陷翻译如下：

Failure to have the procedures andprocesses necessary to ensure the API manufactured at your facility meetestablished specifications for quality and purity.

未建立必要的程序和流程，以确保工厂所生产的 API 符合既定的质量和纯度标准。

Your firm manufactures povidone iodine (PVP-I), API which may beused by your customers to produce presurgical preparatory products. During theinspection, we observed that your Quality Unit (QU) released API lots100017872R and 100017911C without adequate procedures and processes to ensurethat critical deviations are investigated and resolved.

贵公司生产聚维酮碘（PVP-I）API。在检查过程中，我们注意到你们的质量部门 （QU） 放行了 API 批次 100017872R 和 100017911C，但没有适当的程序和流程以确保关键偏差得到调查和解决。

During the production of PVP-I lot 100017872R, on March 4, 2020,your production personnel observed PVP-I in reactor cabinet (b)(4) wassmoldering. In response to the risk of imminent fire, production personnel useda fire extinguisher. Due to this incident, production did not proceed asnormal. Associated drugs experienced inconsistent temperature exposure andadditional processing and hold times. Your firm only tested the affected drumsof material for percent of available iodine and released them for furtherprocessing.

在 2020 年 3 月 4 日生产 PVP-I 批 100017872R 时，你们的生产人员在反应器（b）（4）中观察到 PVP-I正在冒烟。为了应对紧急的火灾风险，生产人员使用了灭火器。由于这一事件，生产没有正常进行。相关药物经历了不一致的温度暴露和额外的处理和保持时间。你们公司只测试了受影响桶中物料的可用碘百分比，并放行进入下一工序。

Similarly, on August 18, 2020 during the production of PVP-I lot100017911C, your production personnel noted reactor cabinet (b)(4) wassmoking. Production was ceased, and the material was held in unknownconditions. Your firm again, solely tested the affected drums of material forpercent available iodine and released them for further processing.

同样，在 2020 年 8 月 18 日生产 PVP-I 批 100017911C 时，你们的生产人员发现反应器（b）（4）正在冒烟。生产停止，物料存放在未知条件下。你们公司再次，只测试受影响的桶中的物料的可用碘百分比，并放行进入下一工序。

In both instances, your firm created deviation reports butreleased drugs based solely on composite results of percent available iodine.Your drugs were exposed to excess heat, fire, smoke, and debris. Additionalcontaminants or other particulates from the use of the fire extinguisher mayhave also compromised the material. In addition, the associated drugsexperienced processing parameters beyond the normal validated state.

在这两种情况下，贵公司都创建了偏差报告，但仅根据可用碘百分比的综合结果放行药物。你们的药物暴露在额外的热、火灾、烟雾和碎屑中。使用灭火器产生的其他污染物或其他颗粒物也可能污染物料。此外，相关药物的工艺参数超出正常验证状态。

Your firm did not perform additional testing on lots 100017872Rand 100017911C to confirm that the API was not contaminated with harmfulparticulate matter or other contamination. Additionally, your firm lacked arisk or impact assessment to evaluate the exposure of the API to the extraneousdebris or contamination resulting from the incidents. The QU released lots100017872R and 100017911C without ensuring the critical deviation was fullyresolved, and any residual chemical contaminants and particulate risks werefully addressed.

贵公司没有对批次 100017872R 和 100017911C 进行额外的测试，以确认 API 未受到有害颗粒或其他污染物的污染。此外，贵公司缺乏风险或影响评估来评估 API 暴露于事故造成的无关碎片或污染。QU放行了批次100017872R和100017911C，但未确保关键偏差得到完全解决，且任何残留的化学污染物和颗粒物风险都得到了充分解决。

In your response, you stated that you are “currently seekingadvice from a consultant to determine the best path forward on addressing thismatter.” Your response is inadequate. You did not provide any supportingdocumentation that evaluated the impacted lots that you released. Specifically,you did not provide supporting documentation that would ensure the material wasfree of potentially harmful particulate matter and other extraneouscontamination given the intended use of the API, including the potential foruse in sterile drug products.

在答复中，你们表示，"目前正在向顾问征求意见，以确定解决此问题的最佳途径。你的回答不够充分。你们没有提供任何支持文档来评估你们所放行的受影响批次。具体来说，你们没有提供证明文件，以确保物料没有潜在的有害颗粒物和其他无关污染，因为预期使用 API，包括可用于无菌药物产品的潜力。

       文章来源：GMP办公室

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