制药相关文件（如批生产记录、涉及的SOP、验证报告、偏差记录及其他文件），必须经过妥善且精准的审核。

在本文中，我们将学习如何以专业、系统且从容的姿态，开展 GMP 文件审核工作。

 

审核 GMP 文件的分步流程

1. 了解文件类型与用途

每份 GMP 文件都有特定作用：

批生产记录（BMR） ：确保批次产品依照已批准的生产工艺生产。

标准操作规程（SOP） ：明确保障流程一致性的可重复步骤。

验证方案与报告 ：证明工艺具备可重复性与稳定性。

偏差报告 ：说明并调查生产过程中发现的工艺异常情况。

对任何审核人员而言，理解文件的意图及监管层面的重要性至关关键。

2. 检查版本控制与审批情况

文件审核时，需重点检查文件是否存在过时或未经授权使用的情况。

需确认以下内容：

所使用的文件是否为正确版本号？

文件是否经授权人员批准并签字？

文件上是否标注了生效日期及控制编号？

此类检查可避免使用过时的 SOP 和方案，防止引发严重的合规问题。

3. 应用 ALCOA ++ 原则

ALCOA ++ 即：

Attributable

可归属

It should be possible to identify the individual or computerised system that performed a recorded task and when the task was performed. This also applies to any changes made to records, such as corrections, deletions, and changes where it is important to know who made a change, when, and why.

应当能够识别执行记录任务的个人或计算机化系统以及执行任务的时间，这也适用于对记录所做的任何变更，例如更正、删除和更改，其中必须知道谁、何时以及为什么。

Legible

清晰可读

All records should be legible – the information should be readable and unambiguous in order to be understandable and of use. This applies to all information that would be required to be consid- ered complete, including all original records or entries. Where the ‘dynamic’ nature of elec- tronic data (the ability to search, query, trend, etc.) is important to the content and meaning of the record, the ability to interact with the data using a suitable application is important to the ‘availability’ of the record.

所有记录应清晰可辨—— 信息应可读且无歧义，以便理解和使用。这适用于所有需要被视为完整的信息，包括所有原始记录或条目。当电子数据的 “动态” 特性（搜索、查询、追溯等能力）对记录的内容和意义很重要时，使用合适的应用程序与数据交互的能力对记录的 “可用性” 至关重要。

Contemporaneous

同步

The evidence of actions, events or decisions should be recorded as they take place. This doc- umentation should serve as an accurate attesta- tion of what was done, or what was decided and why, i.e. what influenced the decision at that time.

活动、事件或决策的证据应在其发生时进行记录。此类文件应作为对所做之事、所做决策以及决策原因（即当时影响决策的因素）的准确证明。

Original

原始

The original record can be described as the first capture of information, whether recorded on pa- per (static) or electronically (usually dynamic, depending on the complexity of the system). In- formation that is originally captured in a dy- namic state should remain available in that state.

原始记录可被描述为信息的首次捕获，无论是记录在纸上（静态）还是以电子方式记录（通常为动态，具体取决于系统的复杂性）。最初以动态状态捕获的信息应保持在该状态下可用。

Accurate

准确

Records need to be a truthful representation of facts to be accurate.

记录必须真实反映事实，才能准确。

Ensuring records are accurate is achieved through many elements of a robust pharmaceuti- cal quality system.

通过稳健的制药质量体系的多个要素，可确保记录准确。

This can be comprised of:

这可以包括：

equipment related factors such as quali- fication, calibration, maintenance, and computer validation.

设备相关因素，如：确认、校准、维护和计算机验证。

policies and procedures to control ac- tions and behaviours, including data re- view procedures to verify adherence to procedural requirements.

控制活动和行为的政策和程序，包括数据审查程序，以验证是否符合程序要求。

deviation management including root cause analysis, impact assessments and CAPA.

偏差管理，包括根本原因分析、影响评估和CAPA。

trained and qualified personnel who un- derstand the importance of following established procedures and document- ing their actions and decisions.

经培训和确认的人员，他们理解遵循既定程序并记录其活动和决定的重要性。

Together, these elements aim to ensure the accu- racy of information, including scientific data that is used to make critical decisions about the quality of products.

这些要素共同确保信息的准确性，包括用于对产品质量作出关键决策的科学数据。

Complete

完整

All information that would be critical to recreat- ing an event is important when trying to under- stand the event. It is important that information is not lost or deleted. The level of detail required for an information set to be considered complete would depend on the criticality of the infor- mation. A complete record of data generated electronically includes relevant metadata.

在尝试理解事件时，所有对重现事件至关重要的信息都非常重要。必须确保信息不丢失或被删除。一个信息集被视为“完整”所需的详细程度取决于信息的重要性。电子生成数据的完整记录应包括相关元数据。

Consistent

一致

Information should be created, processed, and stored in a logical manner that has a defined consistency. This includes policies or proce- dures that help control or standardize data (e.g. chronological sequencing, date formats, units of measurement, approaches to rounding, signifi- cant digits, etc.).

信息的创建、处理和存储应采用逻辑方式，并具有明确的一致性。这包括有助于管控或规范数据的政策或程序（例如，按时间顺序排列、日期格式、计量单位、四舍五入规则、有效数字等）。

Enduring

持久

Records should be kept in a manner such that they exist for the entire period during which they might be needed. This means they need to remain intact and accessible as an indelible/du- rable record throughout the record retention pe- riod.

记录的保存方式，应确保在可能需要用到它们的整个期间内都能留存。也就是说，在记录保存期限内，它们需作为不可磨灭/ 持久的记录，保持完整且可查阅 。

Available

可用

Records should be available for review at any time during the required retention period, acces- sible in a readable format to all applicable per- sonnel who are responsible for their review whether for routine release decisions, investiga- tions, trending, annual reports, audits or inspec- tions.

在规定的保存期限内，记录应随时可供审查。所有负责审查的人员均可以可读格式访问记录，无论是日常放行决定、调查、趋势分析、年度报告、审计或检查。

Traceable

可追溯

Traceability is the ability to trace the his- tory, modification or location of data by means of recorded identifications.

可追溯性是通过记录标识来追踪数据的历史、修改或位置的能力。

Review the document for entries and signature according to the ALCOA++ principles. Check the document for:

依据 ALCOA ++ 原则，审核文件的记录条目与签名。需检查文件是否符合以下要求：

Is each entry attributable to an individual?

每条记录是否可归属到具体责任人？

Is the handwriting in the document legible?

文件中的手写内容是否清晰可辨？

Are corrections made in the document as per good documentation practices?

文件修改是否遵循良好文件规范（如划改流程、签名追溯等）？

Are data and timings in the document real time and traceable?

文件中的数据和时间是否为实时记录且可追溯？

4. Cross-Check Against SOPs and Protocols

4. SOP、方案之间交叉核对

Documents like BMRs and log books should have procedures as defined in standard operating procedures.

批生产记录、操作日志等文件，需严格遵循SOP中规定的流程。

During review:

审核时需执行以下动作：

Confirm that all steps during manufacturing were followed as per SOPs

确认生产全流程的每一步均严格遵循 SOP 执行

Any deviation happened must be documented with corrective and preventive action

若发生偏差，需完整记录偏差内容及对应的CAPA

Check if raw materials, instruments and parameters match with defined protocol

核对原辅料、仪器设备及工艺参数是否与既定方案一致

For example, if a SOP says to perform a visual inspection after compression and coating, then ensure this step is marked completed in BMR.

举个实例：若某 SOP 要求 “压片、包衣后需执行目视检查”，则需确认该步骤在 BMR 中已标记为 “完成”。

5. Ensure Legibility and GDP Compliance of Documents

5. 确保文件清晰可读且符合良好文件规范（GDP）

During the review of documents, check if the document follows the general GDP rules.

审核文件时，需验证其是否符合良好文件规范（GDP） 的通用要求。

No overwriting - use single line strikeouts on the wrong entries

禁止 “覆盖书写”—— 对错误内容需用单横线划改

Corrections made in the document must be signed and dated properly

文件修改处需规范签名并标注日期

Correction fluid should not be used for hiding mistakes

严禁用 “涂改液” 掩盖错误

Entry must be made in indelible ink.

记录需使用不褪色墨水（如蓝 / 黑色钢笔，防止篡改）

No blanket should remain empty (write NA if not applicable)

不得留存空白项 —— 不适用时需填写 “NA”（避免后期随意补填）

Also, confirm that data in a standard format like DD-MM-YYYY and time entries should be in 24-hour format, where applicable.

此外，需统一数据格式：日期建议用 YYYY-MM-DD 格式，时间（如适用）需采用24 小时制（避免歧义，保证规范性）。

6. Check for Completeness of Documents

6. 检查文件的完整性

The document is considered incomplete if even one required field is missing. Check documents for:

若缺失任意一项必填内容，文件即判定为不完整。需检查文件是否包含以下信息：

Signatures of responsible personnel for activity

操作相关责任人员的签名

Equipment ID and calibration status

设备编号及校准状态

Raw material Batch/Lot number

原辅料批号

Data logs like temperature, pressure, weight and times

温度、压力、重量、时间等数据记录

Attachment and support in data like graphs, tables and annexures

附件和图表、表格中的引用信息

Incomplete documentation is common GMP violation and it should be immediately investigated.

文件不完整是典型的 GMP 违规问题，需立即开展调查。

7. Review for Consistency of Data

7. 审核数据的一致性

Consistency shows effective process control. Look for:

数据一致性体现生产流程的管控有效性，需重点核查以下内容：

Uniformity and time recorded and ideal process durations

数据的统一性、记录时间与理论工艺时长是否匹配

No conflict data in BMRs, logbooks and QC reports

批次生产记录、操作日志与QC报告之间无数据冲突

Reproducibility was maintained in multiple batches

多批生产中工艺可重复性是否稳定

Inconsistent documents can raise issues during audits and inspections.

数据矛盾的文件，极可能在审计、检查环节引发重大问题。

8.Evaluate Deviation Handling and Their Investigations

8.  评估偏差处理及调查质量

Every deviation must be identified, investigated and justified and it should be linked to corrective and preventive action (CAPA). During review, any simple reason of deviation like human error without any deeper analysis should be questioned.

所有偏差需经历 识别→调查→合理性说明 全流程，且必须关联CAPA。审核时，若仅以 “人为失误” 等浅层理由搪塞、未做根本原因分析，需严肃质疑。

9. Check Sign-offs and Authorization

9. 检查签字和批准

Document approval in pharmaceuticals is not just a formality but they confirm accountability. Check that:

制药行业的文件批准绝非形式流程，而是明确责任归属的关键。需检查：

Each section of process is signed by the responsible operator or supervisor.

流程各环节均由责任操作人员 / 主管签字确认

Review and verification signatures are done with the date.

审核、确认类签字需同步标注日期

Quality assurance has signed and approved the final version of document.

QA部门已签字批准文件最终版本

Missing or incorrect sign-offs make the document invalid that can cause issues in batch release.

缺失或错误的签字会直接导致文件失效，甚至阻碍批放行。

10. Confirm Traceability

10. 确认可追溯性

Every document should be traceable:

每份文件都应具备可追溯性：

From raw material to finished product

从原辅料到成品

From SOPs to manufacturing steps

从SOP到生产步骤

From deviations to CAPA closures

从偏差到CAPA的闭环

From test results to source data including instruments and logs

从检验结果到原始数据(包括仪器记录和操作日志 )

Traceability of the steps ensures the authenticity of the process or analysis.

各环节的可追溯性，保障了生产流程或分析过程的真实性。

 

文件审核中需警惕的常见错误

The following are some typical errors that any GMP document reviewer should watch.

以下为 GMP 文件审核人员需重点留意的典型错误：

Check if entries are made before the activity is performed

核查记录是否在操作执行前就已填写（防范 “预填记录” 问题 ）

Any backdated entries in process steps

生产步骤中存在回溯性填写（如倒签日期、事后补填 ）

Any data mismatch (like weight recorded in balance log does not match with BMR)

数据不匹配（例如天平日志记录的重量与批生产记录不一致 ）

Use of any abbreviations without their explanation

使用缩写但未做释义（需保证术语清晰可追溯 ）

Any missing attachments or signatures

缺失附件或签名

Any copy paste errors in electronic documents

电子文件中存在复制粘贴错误

A proper document review can help prevent costly mistakes if they are caught early during review.

若能在审核阶段尽早识别，规范的文件审核可有效规避代价高昂的错误

 

文件审核人员的最佳实践

You should stay updated with the latest GMP guidelines like NMPA, FDA, EU-GMP and WHO-GMP.

需及时掌握 NMPA、FDA、欧盟 GMP、世卫组织 GMP 等最新法规指南

Use a checklist for effective review and reduce human errors.

借助检查表提升效率，降低人为失误

Don’t review documents in a hurry because a quick review can miss critical details.

切勿仓促审核 —— 快速过审易遗漏关键细节（质量源于严谨 ）

Collaborate with quality assurance, production and quality control teams when there is any doubt.

遇存疑内容时，协同QA、生产、QC团队确认

Get trained regularly in good documentation practices, data integrity and quality management system documentation.

定期接受良好文件规范、数据完整性、质量管理体系文件培训

Document review in a GMP environment is not just ticking the checkboxes; it is safeguarding the product quality and patient health. A detailed and traceable document review ensures regulatory compliance and product quality. Apply the principles of this guide when you are reviewing BMRs, SOPs, validation reports or deviation forms to ensure that every document is perfect for internal audits to FDA inspections.

GMP 环境下的文件审核绝非形式化 “打勾”，而是守护产品质量与患者健康的核心防线。详尽且可追溯的文件审核，是保障合规性与产品质量的基石。审核批生产记录、SOP、验证报告或偏差表时，应用本指南原则，确保每份文件从内部审计到 FDA 检查都经得起严格检验。

检查缺陷

缺陷原文：

"Quality Control Unit failed to review production and control records (including equipment cleaning logs and component testing records) to ensure compliance with established procedures prior to release of drug product batches. Numerous records lacked evidence of review or were reviewed months after distribution."

质量控制部门未能在药品批放行前审查生产及控制记录（包括设备清洁记录和组件测试记录），以确保符合既定程序。大量记录缺乏已被审核的证据，或者在产品放行数月后才进行审核。

缺陷原文：

"Batch production records were not reviewed for completeness and accuracy by the quality unit prior to release. Specifically, critical steps such as sterilization parameters and environmental monitoring data were not verified against established specifications."

在产品放行前，质量部门并未对批生产记录的完整性和准确性进行审核。具体而言，诸如灭菌参数和环境监测数据等关键步骤并未与既定标准进行核对审核。

缺陷原文：

"Unapproved versions of SOPs were found in production areas. Quality unit did not implement a procedure to ensure only current approved documents were in use, leading to uncontrolled document distribution."

在生产区域发现了未经批准的SOP文件版本。质量部门未执行相关程序以确保仅使用已批准的现行文件，从而导致了文件的无序分发。