本文以實(shí)驗(yàn)室數(shù)據(jù)審核為例，結(jié)合相關(guān)法規(guī)和指南的要求，探討審計(jì)追蹤審核的行業(yè)最佳實(shí)踐，不當(dāng)之處請(qǐng)大家批準(zhǔn)指正。

       在展開(kāi)這個(gè)問(wèn)題前，首先分享一張色譜分析流程圖，圖片來(lái)自PDA TR80實(shí)驗(yàn)室數(shù)據(jù)完整性管理系統(tǒng)：

       從流程圖中可以看出數(shù)據(jù)審核是是數(shù)據(jù)分析完成后、對(duì)外發(fā)布（放行）前的關(guān)鍵環(huán)節(jié)，而審計(jì)追蹤的審核又是數(shù)據(jù)審核中至關(guān)重要的一部分。

       以色譜分析為例，讓我們看一下色譜分析檢測(cè)中有哪些審計(jì)追蹤：

       對(duì)于色譜分析來(lái)說(shuō)，審計(jì)追蹤主要分為以下幾類：

       1、系統(tǒng)審計(jì)追蹤（PDA 80 中建議QA應(yīng)定期審核系統(tǒng)的審計(jì)追蹤）

       2、文件夾審計(jì)追蹤

       3、方法、序列、結(jié)果審計(jì)追蹤

       這些審計(jì)追蹤在數(shù)據(jù)發(fā)布前應(yīng)都應(yīng)進(jìn)行審核，審計(jì)追蹤的審核由誰(shuí)來(lái)進(jìn)行？是否必須由QA進(jìn)行審核？是接下來(lái)要與大家探討的點(diǎn)。

       我們先看一下法規(guī)和指南中的規(guī)定：

       1、FDA DI問(wèn)答 Who should review audit trails?

       Audit trail review is similar to assessing cross-outs on paper when reviewing data. Personnel responsible for record review under CGMP should review the audit trails that capture changes to data associated with the record as they review the rest of the record (e.g., §§ 211.22(a), 211.101(c) and (d), 211.103, 211.182, 211.186(a), 211.192, 211.194(a)(8), and 212.20(d)).

       FDA數(shù)據(jù)完整性問(wèn)答中對(duì)于該問(wèn)題有明確的回復(fù)"按照CGMP相關(guān)條款，負(fù)責(zé)審核記錄的人員應(yīng)該審核審計(jì)追蹤"，其中194實(shí)驗(yàn)室記錄部分，具體的規(guī)定如下

       21CFR PART 211.194 Lab Records

       (a) Laboratory records shall include complete data derived from all tests necessary to assure compliance with established specifications and standards, including examinations and assays, as follows：

       The initials or signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards.

       實(shí)驗(yàn)室記錄應(yīng)該包括完整數(shù)據(jù)的信息：原始記錄的準(zhǔn)確性、完整性、標(biāo)準(zhǔn)符合性第二人審核的簽名。

       2、EU GMP

       The date and signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with established standards.

       實(shí)驗(yàn)室記錄應(yīng)該包括完整數(shù)據(jù)的信息：原始記錄的準(zhǔn)確性、完整性、標(biāo)準(zhǔn)符合性第二人審核的簽名。

       3、WHO 良好文件數(shù)據(jù)規(guī)范：

       Supervisors responsible for reviewing electronic data should learn which audit trails in the system track significant data changes and how these might be most efficiently accessed as part of their review.

       負(fù)責(zé)審核電子數(shù)據(jù)的實(shí)驗(yàn)室主管應(yīng)掌握審計(jì)追蹤與關(guān)鍵數(shù)據(jù)修改的對(duì)應(yīng)關(guān)系。

       4、MHRA數(shù)據(jù)完整性指南

       Reviewers should have sufficient knowledge and system access to review relevant audit trails, raw data and metadata (see also 'data governance').

       審核員應(yīng)具備足夠的知識(shí)和系統(tǒng)權(quán)限來(lái)審核相關(guān)的審計(jì)追蹤、原始數(shù)據(jù)和元數(shù)據(jù)（也參見(jiàn)"數(shù)據(jù)管理"）

       5、PIC/S 數(shù)據(jù)完整性指南

       Laboratory records for testing steps should also be reviewed by designated personnel (e.g.: second analysts) following completion of testing. Reviewers are expected to check all entries, critical calculations, and undertake appropriate assessment of the reliability of test results in accordance with data-integrity principles.

       在完成檢測(cè)后，還應(yīng)由指定人員（例如：第二分析員）審核檢測(cè)步驟的實(shí)驗(yàn)室記錄。審核員應(yīng)根據(jù)數(shù)據(jù)可靠性原則檢查所有條目、關(guān)鍵計(jì)算，并對(duì)檢驗(yàn)結(jié)果的可靠性進(jìn)行適當(dāng)?shù)脑u(píng)估。

       Companies should implement procedures that outline their policy and processes to determine the data that is required in audit trails, and the review of audit trails in accordance with risk management principles. Critical audit trails related to each operation should be independently reviewed with all other records related to the operation and prior to the review of the completion of the operation (e.g. prior to batch release) so as to ensure that critical data and changes to it are acceptable. This review should be performed by the originating department, and where necessary verified by the quality unit, e.g. during self-inspection or investigative activities.

       公司應(yīng)實(shí)施概述其政策和流程的規(guī)程，以確定審計(jì)追蹤所需的數(shù)據(jù)，并根據(jù)風(fēng)險(xiǎn)管理原則審核審計(jì)追蹤。每項(xiàng)操作相關(guān)的關(guān)鍵審計(jì)追蹤應(yīng)與該操作的所有其它記錄一起獨(dú)立核查，并在該操作的完成情況審核之前（例如，在批放行之前）進(jìn)行，以確保關(guān)鍵數(shù)據(jù)及其更改是可接受的。審計(jì)追蹤的審核應(yīng)由數(shù)據(jù)產(chǎn)生部門進(jìn)行，必要時(shí)由質(zhì)量部門核實(shí)，例如：在自查或調(diào)查活動(dòng)中。

       綜合以上法規(guī)和指南的要求，總結(jié)分析如下：

       1、審計(jì)追蹤的審核應(yīng)該與相關(guān)的記錄一并進(jìn)行審核，可由數(shù)據(jù)產(chǎn)生部門進(jìn)行審核。

       2、企業(yè)應(yīng)基于風(fēng)險(xiǎn)的控制，對(duì)于關(guān)鍵性的數(shù)據(jù)的審計(jì)追蹤由質(zhì)量部門（QA）定期核查。

       3、以色譜分析為例：審計(jì)追蹤由實(shí)驗(yàn)室第二人進(jìn)行審核，同時(shí)對(duì)于系統(tǒng)層面的審計(jì)追蹤，QA定定期進(jìn)行檢查。

       作者簡(jiǎn)介：

       Windshower，就職于國(guó)內(nèi)大型制藥企業(yè)，十五年以上實(shí)驗(yàn)室工作經(jīng)驗(yàn)，數(shù)據(jù)完整性主題專家，多年質(zhì)量管理經(jīng)驗(yàn)，精通QC相關(guān)藥典法規(guī)知識(shí)，多年國(guó)內(nèi)外審計(jì)認(rèn)證經(jīng)驗(yàn)。