制藥相關文件（如批生產記錄、涉及的SOP、驗證報告、偏差記錄及其他文件），必須經過妥善且精準的審核。

在本文中，我們將學習如何以專業、系統且從容的姿態，開展 GMP 文件審核工作。

 

審核 GMP 文件的分步流程

1. 了解文件類型與用途

每份 GMP 文件都有特定作用：

批生產記錄（BMR） ：確保批次產品依照已批準的生產工藝生產。

標準操作規程（SOP） ：明確保障流程一致性的可重復步驟。

驗證方案與報告 ：證明工藝具備可重復性與穩定性。

偏差報告 ：說明并調查生產過程中發現的工藝異常情況。

對任何審核人員而言，理解文件的意圖及監管層面的重要性至關關鍵。

2. 檢查版本控制與審批情況

文件審核時，需重點檢查文件是否存在過時或未經授權使用的情況。

需確認以下內容：

所使用的文件是否為正確版本號？

文件是否經授權人員批準并簽字？

文件上是否標注了生效日期及控制編號？

此類檢查可避免使用過時的 SOP 和方案，防止引發嚴重的合規問題。

3. 應用 ALCOA ++ 原則

ALCOA ++ 即：

Attributable

可歸屬

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.

應當能夠識別執行記錄任務的個人或計算機化系統以及執行任務的時間，這也適用于對記錄所做的任何變更，例如更正、刪除和更改，其中必須知道誰、何時以及為什么。

Legible

清晰可讀

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.

所有記錄應清晰可辨—— 信息應可讀且無歧義，以便理解和使用。這適用于所有需要被視為完整的信息，包括所有原始記錄或條目。當電子數據的 “動態” 特性（搜索、查詢、追溯等能力）對記錄的內容和意義很重要時，使用合適的應用程序與數據交互的能力對記錄的 “可用性” 至關重要。

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.

活動、事件或決策的證據應在其發生時進行記錄。此類文件應作為對所做之事、所做決策以及決策原因（即當時影響決策的因素）的準確證明。

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.

原始記錄可被描述為信息的首次捕獲，無論是記錄在紙上（靜態）還是以電子方式記錄（通常為動態，具體取決于系統的復雜性）。最初以動態狀態捕獲的信息應保持在該狀態下可用。

Accurate

準確

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

記錄必須真實反映事實，才能準確。

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

通過穩健的制藥質量體系的多個要素，可確保記錄準確。

This can be comprised of:

這可以包括：

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

設備相關因素，如：確認、校準、維護和計算機驗證。

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

控制活動和行為的政策和程序，包括數據審查程序，以驗證是否符合程序要求。

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

偏差管理，包括根本原因分析、影響評估和CAPA。

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

經培訓和確認的人員，他們理解遵循既定程序并記錄其活動和決定的重要性。

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.

這些要素共同確保信息的準確性，包括用于對產品質量作出關鍵決策的科學數據。

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.

在嘗試理解事件時，所有對重現事件至關重要的信息都非常重要。必須確保信息不丟失或被刪除。一個信息集被視為“完整”所需的詳細程度取決于信息的重要性。電子生成數據的完整記錄應包括相關元數據。

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.).

信息的創建、處理和存儲應采用邏輯方式，并具有明確的一致性。這包括有助于管控或規范數據的政策或程序（例如，按時間順序排列、日期格式、計量單位、四舍五入規則、有效數字等）。

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.

記錄的保存方式，應確保在可能需要用到它們的整個期間內都能留存。也就是說，在記錄保存期限內，它們需作為不可磨滅/ 持久的記錄，保持完整且可查閱 。

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.

在規定的保存期限內，記錄應隨時可供審查。所有負責審查的人員均可以可讀格式訪問記錄，無論是日常放行決定、調查、趨勢分析、年度報告、審計或檢查。

Traceable

可追溯

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

可追溯性是通過記錄標識來追蹤數據的歷史、修改或位置的能力。

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

依據 ALCOA ++ 原則，審核文件的記錄條目與簽名。需檢查文件是否符合以下要求：

Is each entry attributable to an individual?

每條記錄是否可歸屬到具體責任人？

Is the handwriting in the document legible?

文件中的手寫內容是否清晰可辨？

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

文件修改是否遵循良好文件規范（如劃改流程、簽名追溯等）？

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

文件中的數據和時間是否為實時記錄且可追溯？

4. Cross-Check Against SOPs and Protocols

4. SOP、方案之間交叉核對

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

批生產記錄、操作日志等文件，需嚴格遵循SOP中規定的流程。

During review:

審核時需執行以下動作：

Confirm that all steps during manufacturing were followed as per SOPs

確認生產全流程的每一步均嚴格遵循 SOP 執行

Any deviation happened must be documented with corrective and preventive action

若發生偏差，需完整記錄偏差內容及對應的CAPA

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

核對原輔料、儀器設備及工藝參數是否與既定方案一致

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

舉個實例：若某 SOP 要求 “壓片、包衣后需執行目視檢查”，則需確認該步驟在 BMR 中已標記為 “完成”。

5. Ensure Legibility and GDP Compliance of Documents

5. 確保文件清晰可讀且符合良好文件規范（GDP）

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

審核文件時，需驗證其是否符合良好文件規范（GDP） 的通用要求。

No overwriting - use single line strikeouts on the wrong entries

禁止 “覆蓋書寫”—— 對錯誤內容需用單橫線劃改

Corrections made in the document must be signed and dated properly

文件修改處需規范簽名并標注日期

Correction fluid should not be used for hiding mistakes

嚴禁用 “涂改液” 掩蓋錯誤

Entry must be made in indelible ink.

記錄需使用不褪色墨水（如藍 / 黑色鋼筆，防止篡改）

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

不得留存空白項 —— 不適用時需填寫 “NA”（避免后期隨意補填）

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，需統一數據格式：日期建議用 YYYY-MM-DD 格式，時間（如適用）需采用24 小時制（避免歧義，保證規范性）。

6. Check for Completeness of Documents

6. 檢查文件的完整性

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

若缺失任意一項必填內容，文件即判定為不完整。需檢查文件是否包含以下信息：

Signatures of responsible personnel for activity

操作相關責任人員的簽名

Equipment ID and calibration status

設備編號及校準狀態

Raw material Batch/Lot number

原輔料批號

Data logs like temperature, pressure, weight and times

溫度、壓力、重量、時間等數據記錄

Attachment and support in data like graphs, tables and annexures

附件和圖表、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 違規問題，需立即開展調查。

7. Review for Consistency of Data

7. 審核數據的一致性

Consistency shows effective process control. Look for:

數據一致性體現生產流程的管控有效性，需重點核查以下內容：

Uniformity and time recorded and ideal process durations

數據的統一性、記錄時間與理論工藝時長是否匹配

No conflict data in BMRs, logbooks and QC reports

批次生產記錄、操作日志與QC報告之間無數據沖突

Reproducibility was maintained in multiple batches

多批生產中工藝可重復性是否穩定

Inconsistent documents can raise issues during audits and inspections.

數據矛盾的文件，極可能在審計、檢查環節引發重大問題。

8.Evaluate Deviation Handling and Their Investigations

8.  評估偏差處理及調查質量

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.

所有偏差需經歷 識別→調查→合理性說明 全流程，且必須關聯CAPA。審核時，若僅以 “人為失誤” 等淺層理由搪塞、未做根本原因分析，需嚴肅質疑。

9. Check Sign-offs and Authorization

9. 檢查簽字和批準

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

制藥行業的文件批準絕非形式流程，而是明確責任歸屬的關鍵。需檢查：

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

流程各環節均由責任操作人員 / 主管簽字確認

Review and verification signatures are done with the date.

審核、確認類簽字需同步標注日期

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

QA部門已簽字批準文件最終版本

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

缺失或錯誤的簽字會直接導致文件失效，甚至阻礙批放行。

10. Confirm Traceability

10. 確認可追溯性

Every document should be traceable:

每份文件都應具備可追溯性：

From raw material to finished product

從原輔料到成品

From SOPs to manufacturing steps

從SOP到生產步驟

From deviations to CAPA closures

從偏差到CAPA的閉環

From test results to source data including instruments and logs

從檢驗結果到原始數據(包括儀器記錄和操作日志 )

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

各環節的可追溯性，保障了生產流程或分析過程的真實性。

 

文件審核中需警惕的常見錯誤

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

以下為 GMP 文件審核人員需重點留意的典型錯誤：

Check if entries are made before the activity is performed

核查記錄是否在操作執行前就已填寫（防范 “預填記錄” 問題 ）

Any backdated entries in process steps

生產步驟中存在回溯性填寫（如倒簽日期、事后補填 ）

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

數據不匹配（例如天平日志記錄的重量與批生產記錄不一致 ）

Use of any abbreviations without their explanation

使用縮寫但未做釋義（需保證術語清晰可追溯 ）

Any missing attachments or signatures

缺失附件或簽名

Any copy paste errors in electronic documents

電子文件中存在復制粘貼錯誤

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

若能在審核階段盡早識別，規范的文件審核可有效規避代價高昂的錯誤

 

文件審核人員的最佳實踐

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

需及時掌握 NMPA、FDA、歐盟 GMP、世衛組織 GMP 等最新法規指南

Use a checklist for effective review and reduce human errors.

借助檢查表提升效率，降低人為失誤

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

切勿倉促審核 —— 快速過審易遺漏關鍵細節（質量源于嚴謹 ）

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

遇存疑內容時，協同QA、生產、QC團隊確認

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

定期接受良好文件規范、數據完整性、質量管理體系文件培訓

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 環境下的文件審核絕非形式化 “打勾”，而是守護產品質量與患者健康的核心防線。詳盡且可追溯的文件審核，是保障合規性與產品質量的基石。審核批生產記錄、SOP、驗證報告或偏差表時，應用本指南原則，確保每份文件從內部審計到 FDA 檢查都經得起嚴格檢驗。

檢查缺陷

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."

質量控制部門未能在藥品批放行前審查生產及控制記錄（包括設備清潔記錄和組件測試記錄），以確保符合既定程序。大量記錄缺乏已被審核的證據，或者在產品放行數月后才進行審核。

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."

在產品放行前，質量部門并未對批生產記錄的完整性和準確性進行審核。具體而言，諸如滅菌參數和環境監測數據等關鍵步驟并未與既定標準進行核對審核。

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."

在生產區域發現了未經批準的SOP文件版本。質量部門未執行相關程序以確保僅使用已批準的現行文件，從而導致了文件的無序分發。