CAPA不充分导致FDA警告信

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Deviations and CAPA are still hotlydebated topics in GMP inspections. This is shown once again by a recent WarningLetter issued by the U.S. Food and Drug Administration (FDA).

偏差和CAPA仍然是GMP检查中争论的热点问题。FDA最近发布的一封警告信再次表明了这一点。

In this Warning Letter, the FDA tellsthe Indian company Jubilant Life Sciences that it failed to investigate"unexplained discrepancy or failure". In particular, the authoritymentions the management of deviations and CAPA:

在这封警告信中，FDA告诉印度公司JubilantLife Sciences，未能调查“无法解释的差异或不合格”。管理局特别提到偏差管理和CAPA：

The FDA found that investigations (rootcause analysis) for the deviations and complaints were insufficient. Inparticular, the causes described were not adequately substantiated andinvestigations were not extended to other potentially affected batches. Inaddition, corrective and preventive actions (CAPA) were not implemented asplanned and their effectiveness was not sufficiently assessed.

FDA发现对偏差和投诉的调查(根本原因分析)是不足的。特别是，所述的原因没有得到充分的证实，调查也没有扩展到其他可能受影响的批次。此外，CAPA没有按照计划执行，其有效性也没有得到充分评估。

This is described with two examples:

可以通过两个例子来描述：

After a problem with the particle sizeof an excipient used, a wrong inner label on a drum was determined as thereason. A total of four drums were delivered in one consignment. However, thecompany had already discarded the three other drums from this consignment bythe time of the investigation. It was therefore assumed that only this one drumwas incorrectly labelled. The FDA could not comprehend this. In addition, onlytwo batches of the 12 batches of tablets made from excipients in question wererecalled.

在使用的辅料粒度出现问题后，确定是桶上的内标签错误造成的。总共有四桶货在一次发货中发出。然而，在调查期间，该公司已经丢弃了这批货物中的另外三桶。因此，假定只有这一个桶的标签是错误的。FDA无法理解这一点。此外，在12批使用该问题辅料的片剂中，只有两批被召回。

There were also complaints about"peeling, rippled, wet, discolored, and sticking tablets" for severalbatches of Pantoprazole tablets. Irregularities were also found in retentionsamples examined. However, the company then only tested samples with minordefects (discolorations). Further tests on tablets with damage to thefunctional coating were missed. This meant that the full scope of the problemcould not be recorded at all. A recall was initiated when further batches withdefective coatings were discovered after the investigations had been completed.

还有几批泮托拉唑片出现“剥落、起皱、潮湿、变色、粘片”的投诉。在留样中也发现了异常现象。然而，该公司只测试了有轻微缺陷(变色)的样品。没有对功能包衣受损的药片进行进一步的测试。这意味着根本无法记录问题的全部范围。在调查完成后，当发现更多批次的包衣存在缺陷时，就会启动召回。

The FDA now expects a"comprehensive, independent assessment of your overall system forinvestigations of deviations, atypical events, complaints, out-of-specificationresults, and failures", including an assessment of CAPA effectiveness.

FDA现在期望“对您的整个体系进行全面、独立的评估，以调查偏差、非典型事件、投诉、OOS结果和失败”，包括对CAPA有效性的评估。

For the Pantoprazole tablets, a"summary of all atypical or failing dissolution test results […] including,but not limited to, those related to complaints, stability, and release in thelast four years" is required.

对于泮托拉唑片，需要“所有非典型或未通过溶出度测试结果的摘要，包括但不限于过去四年中与投诉、稳定性和放行有关的结果”。

In general, an independent,retrospective review of all complaints and related investigations for batcheswithin the expiration period is expected.

一般情况下，希望对所有投诉查进行独立、回顾性的审核，并对在保质期内的有关批次进行调查。

Shadow_Way

感谢分享啊

冷雪清风

这些所采取的CAPA真是无语啊

syhorchid

谢谢分享

时光里的繁星

这调查是什么操作

昀亦然

感谢楼主，你一定要多多分享哈。

Javen.

掩耳盗铃