20160120 ECA新闻：CADILA印度厂收到FDA警告信

20160120 ECA新闻：CADILA印度厂收到FDA警告信

GMP News
20/01/2016

Current FDA Warning Letter for Manufacturer Cadila in India

CADILA印度厂收到FDA警告信

The FDA addressed a Warning Letter to the Indian Manufacturer Cadila Healthcare Limited in India (two production sites for APIs and medicinal products) on 23 December 2015. The letter focuses on the inappropriate review of OOS results and the lack of data integrity. It specifically addresses the following issues:

FDA刚于2015年12月23日，给CADILA印度厂签发了警告信（原料药和制剂两个工厂）。该警告信主要关注了对OOS结果的不适当的审核，缺乏数据完整性。其中特别强调了以下问题：

OOS:

OOS results in the laboratory haven't been properly examined. There have been deviations in the manufactured warfarin sodium tablets in association with potency and content uniformity specifications. Those deviations had already been observed in past inspections of the FDA. The CAPA measures taken so far were thus ineffective.

化验室的OOS结果没有被适当检查。生产的华法令钠片剂的效价和含量均一度偏出质量标准。所采取CAPA措施因此至今无效。

The manufacturing process for those tablets is not sufficiently controlled.

这些片剂的生产工艺控制不充分。

The company is asked to list all batches of the warfarin sodium tablets together with their OOS and Out-of-Trend (OOT!) results - not only those manufactured for the US-American market but all batches for all markets!

公司被要求列出所有批次的华法令钠片剂及其OOS和OOT结果----不仅仅是那是为美国市场生产的批次，而是所有市场的所有批次。

In its response to the FDA, the company should also make propositions on how to optimise process design in the manufacturing organisation in order to improve in the future content uniformity, assay, thickness or other relevant critical quality attributes. Concerning this, estimations with regard to the process capability should also flow in.

在对FDA的回复中，该公司还应说明如何在其生产组织内优化工艺设计，以提高其将来的含量均一度、含量、厚度或其它相关的关键质量属性。关于此点，还要包括其工艺能力的预计。

Furthermore - at Cadila - external complaints from diverse pharmacies or wholesalers haven't been completely followed up and no root cause analysis has ever been completed.

另外，在CADILA----来自不同药房和批发商的投诉没有进行完整的跟踪，没有进行完整的根本原因分析。

Integrity of data/ computerised system: 数据/计算机系统的完整性

With regard to computerised systems, there are no sufficient controls in place before modifying or deleting data. In the QC laboratory, the inspection team found out that the laboratory manager had the ability to delete data from the Karl Fischer Tiamo software as the audit trail function wasn't activated. Moreover, 8 analysts had to share one single username and password combination. Consequently, it couldn't be demonstrated who had operated this instrument system.

关于计算机化系统，在修改或删除数据之前没有进行充分的控制。在QC化验室，检查组发现化验室经理可以从卡尔费休滴定软件中删除数据，因为其审计追踪功能没有激活。另外，有8个化验员共用同一个用户名和密码组合。这样，无法证明是谁操作了此仪器。

The FDA also noticed that a data containing the moisture content results had been deleted. The deletion of the data hasn't been considered at all during the batch release decision - i.e. the deletion of this data has neither been identified nor reviewed.

FDA还注意到含有水分结果的一个数据被删除了。在批放行决策时完全没有考虑数据删除的问题----也就是说，该数据的删除既没有被发现也没有被审核。

Finally, the FDA criticised the records of "unofficial" lab notebooks for quality-related documents several times.
最后，FDA数次批评了其记录质量相关文件的“非正式”记录本。

All in all, there are major concerns with regard to the authenticity and reliability of data generated in that company. The FDA has required a comprehensive CAPA plan within 15 workings days on receipt of the Warning Letter.
总而方之，此公司产生的数据的可信度和可靠性是主要的问题。FDA已要求其在收到该警告信的15个工作日内制订一份综合的CAPA计划。

To find out more details please see the complete Cadila Healthcare Limited Warning Letter.
更多细节，参见完整的警告信。

Source: FDA, USA

来源美国

FDA

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