EU | 欧洲药监局检查中发现的验证/确认方面缺陷

European Authority's Inspection Findings in the Area Validation/Qualification

欧洲药监局检查中发现的验证/确认方面缺陷

The US American Food and Drug Administration (FDA) has long been publishing inspection results in so-called Warning Letters. Those letters are freely available on the Internet. Since a few years now, major violations of GMP have been published in a European inspection database. The British Regulatory Authority (MHRA) does this in a much more detailed way. Read the following examples published by the MHRA on the topic area validation/qualification from 2015.

美国FDA长期以来以所谓警告信的方式发布检查结果。这些函件可以在网络上自由获取。几年前，GMP的主要违规情况也在欧洲检查数据库中开始发布。英国药监（MHRA）则采用了更为详细的方法。请看以下自2015年以来MHRA发布的在验证/确认主题上的例子：

In the top 10 of MHRA's inspection deficiencies 2015, the topic validation occupies rank 8. However, no critical deficiency was found. Most "major" deficiencies concerned the validation report and changes to the validation plans.

2015年MHRA检查缺陷的前10中，验证占位第8。但是并没有关键缺陷。大部分“主要”缺陷是验证报告，以及对验证计划的变更。

Regarding the topic qualification, the MHRA presents the following exemplary deficiencies:

关于确认的问题，MHRA给出了以下缺陷典型：

Lack of design phase (DQ, URS) for new equipment 

一些设备缺乏设计阶段（DQ，URS）确认

Qualification documents provided by equipment suppliers were not integrated into the company's pharmaceutical quality system to ensure appropriate review.

设备供应商提供的确认文件没有结合到公司的药品质量体系中以确保其受到适当的审核

The use of suppliers' documentation for the qualification was criticised a second time: the OQ protocol for an HVAC system obtained from a supplier hadn't been compared and checked with the company's requirements prior to its approval.

使用供应商确认文件记录里受到批评：一个HVAC系统的OQ方案是来自供应商的，但在批准之前没有与公司的需求进行比较和检查

One heat tunnel equipment hadn't been fully qualified in the OQ. 

灭菌隧道在OQ里没有进行全面确认

With regard to the topic cleaning validation, the MHRA criticised that:

关于清洁验证问题，MHRA批评说：

The effective removal of organic compounds couldn't be assured.

不能确保有机化合物能被有效清除

The effectiveness of sprayballs used for vessel cleaning hadn't been demonstrated nor controlled.

用于容器清洁的喷淋球的有效性没有证明也没有控制

The permitted limits for carryover of organic molecules had neither been set nor risk assessed.

没有为有机分子残留设立允许限度，也没有进行风险评估

No swab samples had been taken - in particular from difficult to clean areas where other methods or determining residues may not be effective.

没有取擦拭样品---尤其是难以清洁的区域，这些区域使用其他取样方法和残留检测可能没有效果

There was no scientific rationale to support the selection of products used for the cleaning validation.

没有科学合理性来支持清洁验证所选的产品

Concerning process validation, the MHRA gave the following examples deficiencies:

关于工艺验证，MHRA给出了以下缺陷例子：

The performance and process validation activities didn't include any assessment of all critical parameters (e.g. tablet dimensions and embossing).

性能验证和工艺验证活动没有包括对关键参数的评估（例如，片剂尺寸和刻印）

Not every aspect of manufacturing was covered by process validation (e.g. the use of small coating pans as opposed to the validated automated system).

工艺验证中没有包括生产的所有方面（例如，使用小包衣锅，而不是经过验证的自动化系统）

Validation batches were released before process qualification had been completed.

验证批次在工艺确认还没有完成之前就已放行

It is interesting to note that the MHRA criticised twice that the companies inspected had no formal processes for implementing changes in the GMP regulations. Annex 15 - which became applicable as revised version in October 2015 - had been explicitly mentioned once.

有意思的是看到MHRA两次批评了受检公司没有正式的流程来实施GMP法规方面的变更。附录15---现在适用2015年10月修订版本---被明确提到一次。

You can find the complete MHRA's report on GMDP findings on their website.

完整的MHRA报告可以在其官网上找到。