20150225 ECA新闻：数据完整性：FDA新的检查焦点 - 药群论坛

In recent years, the number of complaints in FDA Warning Letters with regard to data falsification and fraud - especially in analytical GMP laboratories regarding the use of chromatography data systems (CDS) - has been increasing. Triggered by the cases of fraud at Able Laboratories in 2007, the requirements for audits of data integrity during FDA Pre-Approval inspections have been set in the Compliance Programme Guide (CPG) 7346.832. Moreover, FDA's inspectors have been explicitly trained on computer systems and the data they contain.

近年，FDA警告信中关于数据做假和捏造----尤其是在GMP分析化验室关于色谱数据系统（CDS）--缺陷数目不断增加。2007年ABLE化验室数据做假的案例引起了FDA对批准前检查中对数据完整性进行审核的要求，该要求被放进了符合性计划指南（CPG）7346.832中。另外，FDA检查员还接受了计算机系统及其所包括数据的专门训练。

In 2014, three new contributions were added to FDA's Q&A webpage on Current Good Manufacturing Practices which reflect those current developments:

Question 6: Can electronic signatures be used instead of handwritten signatures for master production and control records?

Question 7: In warning letters to firms, why has FDA objected to the practice of using actual samples to perform system suitability testing (sometimes also referred to as "trial," "test," or "prep" runs)?

问7：在给公司的警告信中，为什么FDA反对使用实际的样品做系统适用性测试（有时也称为“试测”、“试检”或“预检”）？

Previously - already in 2010 - clarification had been provided through question 3 about the fact that the FDA always expects the electronic raw data for HPLC chromatograms. Keeping the printed chromatogram only is no longer sufficient to meet the CGMP expectations, since too many significant pieces of information would get lost.

之前---在2010年---已通过问3提供了关于FDA一直期望HPLC图谱的电子原始数据的说明。仅保留打印图谱不再满足CGMP的期望，因为有太多的重要信息片断会丢失。

This background explains the increased number of complaints about data integrity observed during FDA inspections. At present, this can be seen in many Warning Letters, especially in January 2015. Currently, typical findings are so-called "trial sample injection practices" through which companies try to disguise unfavourable OOS results. For example, please see the Apotex Warning Letter from 30 January 2015 and the Warning Letter for Micro Labs Limited from 9 January 2015.

该背景解释了FDA检查中，关于数据完整性缺陷数目的增加。目前，在许多警告信中都可以看到，尤其是在2015年1月。现在，典型的缺陷是所谓的“试检样品操作”，公司通过这种方式来伪装不好的OOS结果。例如，2015年1月30日签发的APOTEX的警告信和2015年1月9日的MICRO LABS的警告信。

1. Why is FDA concerned with the use of shared login accounts for computer systems? 为什么FDA关注使用计算机系统的共用登陆用户名？

Appropriate controls must be exercised to assure that changes to computerized master production or control records or other records, or input of laboratory data into computerized records, are only made by authorized personnel and there must be documentation controls that ensure that actions are attributable to a specific individual (§ 211.68(b), § 211.188(b)(11), § 211.194(a)(7) and (8)). When login credentials are shared and a specific individual cannot be identified through the login, this would not conform to the CGMP requirements in 21 CFR part 211. FDA requires systems controls, including documentation control, to be designed to meet CGMPs (§ 211.100).

必须实施适当的控制，以保证对计算机化主生产和检验文件及其它记录，或输入计算机化记录的化验室数据的改变仅可以由经过授权的人员进行操作。必须有文件记录控制来保证动作可以追踪到特定的个人(§ 211.68(b), § 211.188(b)(11), § 211.194(a)(7) and (8))。如果采用了共用的登录设置，则特定的个人不能在登录过程中被识别，则不符合21CFR第211部分的CGMP要求。FDA要求系统控制，包括文件记录控制，的设计符合CGMP要求 (§ 211.100)。

2. Can electronic signatures be used instead of handwritten signatures for master production and control records? 主生产和检测记录中的电子签名是否可用手写签名来替代？

Yes. An electronic signature may be used to fulfil the requirement in § 211.186(a) as explained in the Federal Register on September 8, 2008 (73 FR 51926). Firms using electronic signatures should document the controls used to ensure that they are able to identify the specific person who signed these records electronically.

可以。电子签名可以用于满足 2008年9月8日联邦注册 (73 FR 51926)中所解释的§ 211.186(a) 的要求。使用电子签名的公司应记录用来保证其可以识别对这些记录进行电子签名的特定签字人员的控制方式。

3. In warning letters to firms, why has FDA objected to the practice of using actual samples to perform system suitability testing (sometimes also referred to as “trial,” “test,” or “prep” runs)?在给公司的警告信中，为什么FDA反对使用实际的样品做系统适用性测试（有时也称为“试测”、“试检”或“预检”）？

FDA wants to discourage the practice of “testing into compliance.” In some situations, the use of actual samples to perform system suitability testing can be a means of testing into compliance. (See the guidance for industry Investigating Out-of-Specification Results.http://www.fda.gov/downloads/Drugs/Guidances/ucm070287.pdf)

FDA不鼓励“检测直到合格”的操作方式。在有些情形下，使用实际的样品进行系统适用性试验可能是“检测直到合格”的一种方式。（参见OOS结果行业指南）

According to USP, system suitability tests should include replicate injections of a standard preparation or other standard solutions to determine if requirements for precision are met (ref. USP General Chapter <621> Chromatography). System suitability tests, including the identity of the preparation to be injected and the rational for its selection, should be performed according to the firm’s established written procedures and the approved application or applicable compendial monograph (§ 211.160).

根据USP，系统适用性试验应包括标准制备液或其它标准溶液重复进针，以确定是否满足精密度的要求（参见USP通则<621>色谱）。系统适用性试验应根据公司建立的书面程序和批准的申报资料或适用的药典各论来实施 (§ 211.160)。

If an actual sample is to be used for system suitability, it should be a properly characterized secondary standard and written procedures should be established and followed (§ 211.160 and 211.165). All data should be included in the data set that is retained and subject to review unless there is documented scientific justification for its exclusion.

如果在系统适用性中使用一份实际的样品，则应是经过适当鉴定的工作标准品，且应建立书面程序并遵守该程序(§ 211.160 and 211.165)。除有书面和科学论证排除的数据外，所有数据均应包括在保存的数据系列中，并接受审核。