Q1. Audit Trail Review required before Each Batch Release?
是否需要在每批放行前審核審計(jì)追蹤？
A1. The requirements for the Audit Trail and its review are formulated in Annex 11 of the EU GMP Guidelines: 9 Audit Trails: "Consideration should be given, based on a risk assessment, to building into the system the creation of a record of all GMP-relevant changes and deletions (a system generated "audit trail"). For change or deletion of GMP-relevant data the reason should be documented. Audit trails need to be available and convertible to a generally intelligible form and regularly reviewed". The reason for the change or deletion of GMP-relevant data should be documented. Audit Trails must be available, convertible into a generally readable form and regularly reviewed.
EU GMP 指南附錄 11 中規(guī)定了審計(jì)追蹤及其審核的要求（第 9 條 “審計(jì)追蹤”）：“應(yīng)基于風(fēng)險(xiǎn)評(píng)估，考慮在系統(tǒng)中建立所有與 GMP 相關(guān)的變更和刪除的記錄（系統(tǒng)生成的‘審計(jì)追蹤’）。對(duì)于與 GMP 相關(guān)數(shù)據(jù)的變更或刪除，應(yīng)記錄原因。審計(jì)追蹤需可供查閱、可轉(zhuǎn)換為通用可理解的形式，并且定期審核。” 與 GMP 相關(guān)數(shù)據(jù)變更或刪除的原因應(yīng)予以記錄。審計(jì)追蹤必須可供查閱、可轉(zhuǎn)換為通用可讀形式，并且定期審核。
If one first looks at the information provided by the legal basis of EU-GMP Annex 11 Section 9 Audit Trails, there are no concrete instructions as to when an Audit Trail is to be reviewed. Here, you can only find the specification concerning the regular examination: "Audit Trails must be available, convertible into a generally readable form and checked regularly".
如果首先查看EU GMP 附錄 11 第 9 條 “審計(jì)追蹤” 的法律依據(jù)所提供的信息，其中并未就審計(jì)追蹤應(yīng)于何時(shí)審核給出具體指示。在此處，你只能找到有關(guān)定期檢查的規(guī)范：“審計(jì)追蹤必須可供查閱、可轉(zhuǎn)換為通用可讀形式，并且定期檢查。”
The EU GMP Annex 11 Section 8 "Printouts" is much more concrete: "8.2 - For records supporting batch release it should be possible to generate printouts indicating if any of the data has been changed since the original entry."
EU GMP 附錄 11 第 8 條 “打印輸出” 則具體得多：“8.2 - 對(duì)于支持批次放行的記錄，應(yīng)能夠生成打印輸出，以表明自原始錄入以來(lái)是否有任何數(shù)據(jù)發(fā)生過(guò)變更。”
Conclusion:This clearly addresses the documentation related to lot release and involves modified data. This can only mean that an Audit Trail check of the data to be seen in connection with the batch release must also be checked before the release.
結(jié)論：這明確涉及與批次放行相關(guān)的文件記錄，并且涉及經(jīng)修改的數(shù)據(jù)。這只能意味著，與批次放行相關(guān)聯(lián)的數(shù)據(jù)的審計(jì)追蹤審查也必須在放行前進(jìn)行。
Although the PIC/S document PI 041 GOOD PRACTICES FOR DATA MANAGEMENT AND INTEGRITY IN REGULATED GMP/GDP ENVIRONMENTS doesn't constitute a legal basis, it can be assumed that inspectors worldwide will follow the provisions and requirements of this guidance. Here, it is again confirmed that all Audit Trails to be seen in connection with batch release must also be reviewed before release: "9.4 Audit trails for computerised systems: 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."
盡管 PIC/S 文件 PI 041《受管制的 GMP/GDP 環(huán)境中數(shù)據(jù)管理和完整性的良好實(shí)踐》并不構(gòu)成法律依據(jù)，但可以推測(cè)，全球的檢查員都會(huì)遵循該指南的規(guī)定和要求。在此處，再次確認(rèn)了所有與批次放行相關(guān)聯(lián)的審計(jì)追蹤都必須在放行前進(jìn)行審核：“9.4 計(jì)算機(jī)化系統(tǒng)的審計(jì)追蹤：與每項(xiàng)操作相關(guān)的關(guān)鍵審計(jì)追蹤應(yīng)與該操作的所有其他記錄一起，在對(duì)操作完成情況進(jìn)行審核之前（例如，在批次放行之前）進(jìn)行獨(dú)立審核，以確保關(guān)鍵數(shù)據(jù)及其變更均可接受。”
遺留系統(tǒng)整改
Q1. Most of the equipment in QC is 'off the shelf' and preconfigured. The audit trail cannot be adjusted or is preconfigured. How should this be handled?
QC大多數(shù)設(shè)備為 “現(xiàn)成產(chǎn)品” 且已預(yù)先配置。審計(jì)追蹤無(wú)法調(diào)整或已預(yù)先配置。應(yīng)當(dāng)如何處理這種情況？
A1. If the audit trail cannot be configured, a risk assessment must first be carried out to check whether it covers all the essential requirements for this device. If this is not the case, another supplier should be chosen whose audit trail meets the requirements. If this is not possible, the only solution is to manually log the uncovered actions in a logbook and a corresponding SOP.
若審計(jì)追蹤無(wú)法配置，則必須首先開展風(fēng)險(xiǎn)評(píng)估，核查該設(shè)備是否符合所有必要的要求。如不符合，應(yīng)選擇另一個(gè)符合審計(jì)追蹤要求的供應(yīng)商。若無(wú)法實(shí)現(xiàn)，唯一的解決方案是在手動(dòng)在日志中記錄未涵蓋的操作，并制定相應(yīng)的SOP。
Q2. How to handle Legacy Systems if no audit trail is available or a "user login" is not possible?
若遺留系統(tǒng)既無(wú)審計(jì)追蹤可用，也無(wú)法實(shí)現(xiàn) “用戶登錄”，應(yīng)如何處理？
A2. First of all, it can be deduced from the contents of the EU GMP Guidelines Annex 11 that an audit trail in connection with GMP-relevant data and their modification should be available in a computerised system. If this functionality was not yet available at the time the system was purchased, it should first be checked whether an update with the audit trail functionality is now available for this system. If this is not the case, an appropriate alternative should be introduced. EU GMP Annex 11 does not describe what this alternative should look like.
首先，從EU GMP 指南附錄 11 的內(nèi)容可推知，與 GMP 相關(guān)數(shù)據(jù)及其修改相關(guān)的審計(jì)追蹤，應(yīng)在計(jì)算機(jī)化系統(tǒng)中可用。若該系統(tǒng)采購(gòu)時(shí)此功能尚未具備，則應(yīng)首先檢查當(dāng)前是否有針對(duì)該系統(tǒng)的、含審計(jì)追蹤功能的更新。若不存在此類更新，則應(yīng)引入適當(dāng)?shù)奶娲桨浮U GMP 附錄 11 未闡述該替代方案應(yīng)具備何種形式。
Possible solution:One possibility would be to use handwritten audit trail logbooks. This alternative is also proposed by the PIC/S document PI 041 GOOD PRACTICES FOR DATA MANAGEMENT AND INTEGRITY IN REGULATED GMP/GDP ENVIRONMENTS:
可能的解決方案：一種可能性是使用手寫的審計(jì)追蹤日志。PIC/S 文件 PI 041《受監(jiān)管的 GMP/GDP 環(huán)境中數(shù)據(jù)管理和完整性的良好實(shí)踐》也提出了這種替代方案：
9.4 Audit trails for computerised systems:If no electronic audit trail system exists a paper based record to demonstrate changes to data may be acceptable until a fully audit trailed (integrated system or independent audit software using a validated interface) system becomes available. These hybrid systems are permitted, where they achieve equivalence to integrated audit trail, such as described in Annex 11 of the PIC/S GMP Guide.
9.4 計(jì)算機(jī)化系統(tǒng)的審計(jì)追蹤：若不存在電子審計(jì)追蹤系統(tǒng)，則在具備完整審計(jì)追蹤功能（集成系統(tǒng)或使用經(jīng)驗(yàn)證接口的獨(dú)立審計(jì)軟件）的系統(tǒng)可用之前，用以證明數(shù)據(jù)變更的紙質(zhì)記錄可能是可接受的。若這些混合系統(tǒng)能達(dá)到與集成審計(jì)追蹤等效的效果（如 PIC/S GMP 指南附錄 11 中所述），則允許使用。
Q3. Does the audit trail have to be printable?
審計(jì)追蹤必須可打印嗎？
A3. Everything must always be printable.
所有內(nèi)容必須始終可打印。
EU GMP附錄11計(jì)算機(jī)化系統(tǒng) 第8章：
8.1 It should be possible to obtain clear printed copies of electronically stored data.
應(yīng)該能夠獲取電子存儲(chǔ)數(shù)據(jù)的清晰打印副本。
8.2 For records supporting batch release it should be possible to generate printouts indicating if any of the data has been changed since the original entry.
對(duì)于用以支持批放行的記錄，應(yīng)可以生成打印輸出，表明自原始條目以來(lái)是否有任何數(shù)據(jù)被更改。
國(guó)家藥監(jiān)局-《藥品記錄與數(shù)據(jù)管理要求》：
第二十一條 采用電子記錄的計(jì)算機(jī)（化）系統(tǒng)至少應(yīng)當(dāng)滿足以下功能要求：
（一）保證記錄時(shí)間與系統(tǒng)時(shí)間的真實(shí)性、準(zhǔn)確性和一致性；
（二）能夠顯示電子記錄的所有數(shù)據(jù)，生成的數(shù)據(jù)可以閱讀并能夠打?。?/span>
（三）系統(tǒng)生成的數(shù)據(jù)應(yīng)當(dāng)定期備份，備份與恢復(fù)流程必須經(jīng)過(guò)驗(yàn)證，數(shù)據(jù)的備份與刪除應(yīng)有相應(yīng)記錄；
（四）系統(tǒng)變更、升級(jí)或退役，應(yīng)當(dāng)采取措施保證原系統(tǒng)數(shù)據(jù)在規(guī)定的保存期限內(nèi)能夠進(jìn)行查閱與追溯。
檢查缺陷
Deficiencies related to the audit trail found during inspections:
檢查中發(fā)現(xiàn)的與審計(jì)追蹤相關(guān)的缺陷：
A staff member in a quality control laboratory has the rights of a system administrator. For example, he/she was able to make undetectable changes to the audit trail during self-performed analyses or to turn the audit trail on or off.
質(zhì)量控制實(shí)驗(yàn)室的一名員工擁有系統(tǒng)管理員權(quán)限。例如，其在自行開展分析期間，能夠?qū)徲?jì)追蹤進(jìn)行無(wú)法察覺(jué)的修改，或開啟 / 關(guān)閉審計(jì)追蹤功能。
There was no described action to be taken if problems were found during the audit trail review.
對(duì)于審計(jì)追蹤審核過(guò)程中發(fā)現(xiàn)問(wèn)題時(shí)應(yīng)采取的行動(dòng)，未作明確規(guī)定。
There was no clear policy on who is allowed to disable the audit trail functionality of system XYZ and how this should be documented.
對(duì)于何人有權(quán)禁用系統(tǒng) XYZ 的審計(jì)追蹤功能，以及該操作應(yīng)如何記錄，未制定清晰政策。
A HPLC station was used in the laboratory to determine the API content of a tablet. The batch release is done without review of relevant audit trail data. Entries in the audit trail could indicate a deviation; the QP should be aware of this deviation prior to release.
實(shí)驗(yàn)室使用某高效液相色譜（HPLC）工作站測(cè)定片劑的活性藥物成分（API）含量，但批次放行時(shí)未審核相關(guān)審計(jì)追蹤數(shù)據(jù)。審計(jì)追蹤中的記錄可能揭示偏差，質(zhì)量受權(quán)人（QP）應(yīng)在放行前知曉該偏差。
There is no documented guidance and instructions on how to handle the audit trail.
對(duì)于如何處置審計(jì)追蹤，未制定書面指導(dǎo)文件及操作規(guī)范。
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