关于数据完整性的警告信：FDA对第三方审计员和顾问的期望是什么？

20150212 ECA新闻：关于数据完整性的警告信：FDA对第三方审计员和顾问的期望是什么？  

2015-02-13 19:04:20|  分类： ECA新闻|

GMP News
12/02/2015

Warning Letters on Data Integrity: What does the FDA expect from Third Party Auditors and Consultants?

关于数据完整性的警告信：FDA对第三方审计员和顾问的期望是什么？

http://www.gmp-compliance.org/enews_04688_Warning-Letters-on-Data-Integrity-What-does-the-FDA-expect-from-Third-Party-Auditors-and-Consultants.html  

In some of the Warning Letters from fiscal year 2014 serious deviations with regard to the handling of electronic data (e.g. data manipulation) are listed. Typically, you can find in the Warning Letters the following statements:

在2014财年的一些警告信中，列出了关于电子数据处理有一些严重的偏差（例如，伪造数据）。在警告信中以下说法很典型：

• Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards (21 CFR 211.194(a)).
• 你公司未能保证化验室记录包括所有测试中生成的完整数据，无法保证其符合既定的质量标准和规格（21 CFR 211.194（a））
• Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).
• 你公司未能对计算机和相关系统进行适当控制，来保证只有经过授权的人员可以更改主生产和主检验记录，或其它记录 (21 CFR 211.68(b)).
• Your firm frequently performs “unofficial testing” of samples, disregards the results, and reports results from additional tests.
• 你公司频繁对样品进行“非正式测试”，将检测结果丢弃，而报告是另外的测试所获得的结果
• The inspection revealed your firm’s use of scratch paper containing critical manufacturing data. The data on these scratch paper records did not always match the data on the corresponding official batch records...
• 检查发现你公司在含有关键生产数据的纸张上有刮擦痕迹。在这些记录纸上的数据与对应的正式批记录上的数据有一些是不符合的
  

These quotations are taken from 4 Warning Letters which were all addressed to Indian pharmaceutical companies (please find here as an example a Warning Letter from February 2014). The GMP deviations detected during inspections with regard to electronic data are so elementary that the FDA urgently recommends to the companies concerned to occasionally get a Third Party Auditor who would first perform an in-depth GMP audit and then support the company remove the deficits with respect to data integrity. The consultants should be experts in this area.

这些引用是来自于4封警告信，都是签发给印度药品生产公司的（可以在2014年2月的警告信中看到其中一个例子）。在检查过程中发现的关于电子数据的GMP偏差非常低级，使得FDA紧急召开会议，推荐这些公司聘请第三方审计员来进行深入的GMP审计，然后支持公司消除关于数据完整性的缺陷。顾问应该是该领域的专家。

In the Warning Letters mentioned, the FDA defines which services the consultant has to bring ("Your data integrity expert should..." ). These requirements are largely identical in the 4 Warning Letters and consist of the following measures:

在这些警告信中提到，FDA指出了必须要接受哪种顾问服务（“你们的数据完整性专家应……”。在4封警告信里，这些要求大同小异，由以下措施组成：

• Gapless identification of all time periods where electronic data have been recorded and documented incorrectly.
• 识别出所有数据被不正确记录和书写的电子数据的时间段，不能有漏失
• Identification and interview of all employees who were employed at the site before, during, or shortly after these time periods. Activities in connection with systems, procedures and behaviour of the management which contributed to or caused the GMP deviations while handling electronic data should be detected.
• 找出在这段时间之前、之中和之后在工厂工作的所有员工，与他们面谈。找出与系统和程序相关的活动，和对于介入或导致电子数据处理中GMP偏差的管理行为
• Employees who left the company before, during, or shortly after these time periods should also be interviewed accordingly.
• 在这段时间之前、之中和之后离开公司的员工也要进行相应的面谈。
• Additional supporting indications of GMP non-compliant handling of electronic data should be identified. The involvement of other sites should be taken into consideration.
• 要识别处理电子数据GMP不符合性的其它支持性现象。要考虑是否有其它厂区卷入。
• The managers in charge during the time periods in question have to be identified by means of organigrams and SOPs. It must be revealed to what extent the top and middle management knew about or was involved in the data manipulation.
• 要通过组织机构图和SOP识别在该段时间内有牵连的负责管理的人员。必须揭示高层和中层管理人员对这些数据造假行为知道多少，涉入多深。
• The data integrity expert should find out whether managers who have been identified this way are still able to have an influence on the integrity of GMP relevant data (also with regard to applications for marketing authorisations). Internal reviews are to be extended to other sites which are known to be involved in violations of GMP-compliant handling of data.
• 数据完整性专家应找出采用这种方式所识别出的经理人还能对GMP相关（上市许可相关）数据的完整性具有影响力。内部审核要延伸到其它已知卷入数据处理GMP违规活动的厂区。
  

For the auditor processing these points, the task is similar to detective work - which is likely to be demanding and not pleasant - as it may be doubtful that he or she gets the fullest support from the company concerned. Yet, this detective work is essential in the interests of patient safety and is taken very seriously by the FDA, especially with Indian companies as the Agency doesn't rely on their capability to resolve the data integrity problems without external support.

对于该点的审计员，其任务也是相似的，要找出真相可能有压力，它让人不那么愉快---因为从公司角度来说可能他或她得不到完全的支持。但是，寻找真相的工作是必要的，是为了患者安全的利益，FDA对此相当的认真，特别是对印度公司，因为印度药监机构没有能力靠其自身力量来解决数据完整性问题，而必须依赖外部支持。

The requirements for GMP-compliant handling of electronic data will be covered at an ECA training course "Electronic GMP Systems" from 18 - 20 March 2015 in Prague, Czech Republic.

电子数据处理的GMP符合性要求将在ECA2015年3月18-20日在捷克布拉格举办的培训课“电子GMP系统”中包括。

来源：http://zhuyujiao1972.blog.163.com/blog/static/9869472720151137420516/

感谢分享，辛苦