您當(dāng)前的位置：檢測(cè)資訊 > 法規(guī)標(biāo)準(zhǔn)
嘉峪檢測(cè)網(wǎng) 2025-08-05 21:59
制藥相關(guān)文件（如批生產(chǎn)記錄、涉及的SOP、驗(yàn)證報(bào)告、偏差記錄及其他文件），必須經(jīng)過(guò)妥善且精準(zhǔn)的審核。
在本文中，我們將學(xué)習(xí)如何以專(zhuān)業(yè)、系統(tǒng)且從容的姿態(tài)，開(kāi)展 GMP 文件審核工作。
審核 GMP 文件的分步流程
1. 了解文件類(lèi)型與用途
每份 GMP 文件都有特定作用：
批生產(chǎn)記錄（BMR） ：確保批次產(chǎn)品依照已批準(zhǔn)的生產(chǎn)工藝生產(chǎn)。
標(biāo)準(zhǔn)操作規(guī)程（SOP） ：明確保障流程一致性的可重復(fù)步驟。
驗(yàn)證方案與報(bào)告 ：證明工藝具備可重復(fù)性與穩(wěn)定性。
偏差報(bào)告 ：說(shuō)明并調(diào)查生產(chǎn)過(guò)程中發(fā)現(xiàn)的工藝異常情況。
對(duì)任何審核人員而言，理解文件的意圖及監(jiān)管層面的重要性至關(guān)關(guān)鍵。
2. 檢查版本控制與審批情況
文件審核時(shí)，需重點(diǎn)檢查文件是否存在過(guò)時(shí)或未經(jīng)授權(quán)使用的情況。
需確認(rèn)以下內(nèi)容：
所使用的文件是否為正確版本號(hào)？
文件是否經(jīng)授權(quán)人員批準(zhǔn)并簽字？
文件上是否標(biāo)注了生效日期及控制編號(hào)？
此類(lèi)檢查可避免使用過(guò)時(shí)的 SOP 和方案，防止引發(fā)嚴(yán)重的合規(guī)問(wèn)題。
3. 應(yīng)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(yīng)當(dāng)能夠識(shí)別執(zhí)行記錄任務(wù)的個(gè)人或計(jì)算機(jī)化系統(tǒng)以及執(zhí)行任務(wù)的時(shí)間，這也適用于對(duì)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(shuí)、何時(shí)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(yīng)清晰可辨—— 信息應(yīng)可讀且無(wú)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(dāng)電子數(shù)據(jù)的 “動(dòng)態(tài)” 特性（搜索、查詢、追溯等能力）對(duì)記錄的內(nèi)容和意義很重要時(shí)，使用合適的應(yīng)用程序與數(shù)據(jù)交互的能力對(duì)記錄的 “可用性” 至關(guān)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(dòng)、事件或決策的證據(jù)應(yīng)在其發(fā)生時(shí)進(jìn)行記錄。此類(lèi)文件應(yīng)作為對(duì)所做之事、所做決策以及決策原因（即當(dāng)時(shí)影響決策的因素）的準(zhǔn)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(wú)論是記錄在紙上（靜態(tài)）還是以電子方式記錄（通常為動(dòng)態(tài)，具體取決于系統(tǒng)的復(fù)雜性）。最初以動(dòng)態(tài)狀態(tài)捕獲的信息應(yīng)保持在該狀態(tài)下可用。
Accurate
準(zhǔn)確
Records need to be a truthful representation of facts to be accurate.
記錄必須真實(shí)反映事實(shí)，才能準(zhǔn)確。
Ensuring records are accurate is achieved through many elements of a robust pharmaceuti- cal quality system.
通過(guò)穩(wěn)健的制藥質(zhì)量體系的多個(gè)要素，可確保記錄準(zhǔn)確。
This can be comprised of:
這可以包括：
equipment related factors such as quali- fication, calibration, maintenance, and computer validation.
設(shè)備相關(guān)因素，如：確認(rèn)、校準(zhǔn)、維護(hù)和計(jì)算機(jī)驗(yàn)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(dòng)和行為的政策和程序，包括數(shù)據(jù)審查程序，以驗(yàn)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(píng)估和CAPA。
trained and qualified personnel who un- derstand the importance of following established procedures and document- ing their actions and decisions.
經(jīng)培訓(xùn)和確認(rèn)的人員，他們理解遵循既定程序并記錄其活動(dòng)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(zhǔn)確性，包括用于對(duì)產(chǎn)品質(zhì)量作出關(guān)鍵決策的科學(xué)數(shù)據(jù)。
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?yán)斫馐录r(shí)，所有對(duì)重現(xiàn)事件至關(guān)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(gè)信息集被視為“完整”所需的詳細(xì)程度取決于信息的重要性。電子生成數(shù)據(jù)的完整記錄應(yīng)包括相關(guān)元數(shù)據(jù)。
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(chuàng)建、處理和存儲(chǔ)應(yīng)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(guī)范數(shù)據(jù)的政策或程序（例如，按時(shí)間順序排列、日期格式、計(jì)量單位、四舍五入規(guī)則、有效數(shù)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(yīng)確保在可能需要用到它們的整個(gè)期間內(nèi)都能留存。也就是說(shuō)，在記錄保存期限內(nèi)，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(guī)定的保存期限內(nèi)，記錄應(yīng)隨時(shí)可供審查。所有負(fù)責(zé)審查的人員均可以可讀格式訪問(wèn)記錄，無(wú)論是日常放行決定、調(diào)查、趨勢(shì)分析、年度報(bào)告、審計(jì)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(guò)記錄標(biāo)識(shí)來(lái)追蹤數(shù)據(jù)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(jù) 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(zé)任人？
Is the handwriting in the document legible?
文件中的手寫(xiě)內(nèi)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(guī)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(shù)據(jù)和時(shí)間是否為實(shí)時(shí)記錄且可追溯？
4. Cross-Check Against SOPs and Protocols
4. SOP、方案之間交叉核對(duì)
Documents like BMRs and log books should have procedures as defined in standard operating procedures.
批生產(chǎn)記錄、操作日志等文件，需嚴(yán)格遵循SOP中規(guī)定的流程。
During review:
審核時(shí)需執(zhí)行以下動(dòng)作：
Confirm that all steps during manufacturing were followed as per SOPs
確認(rèn)生產(chǎn)全流程的每一步均嚴(yán)格遵循 SOP 執(zhí)行
Any deviation happened must be documented with corrective and preventive action
若發(fā)生偏差，需完整記錄偏差內(nèi)容及對(duì)應(yīng)的CAPA
Check if raw materials, instruments and parameters match with defined protocol
核對(duì)原輔料、儀器設(shè)備及工藝參數(shù)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(gè)實(shí)例：若某 SOP 要求 “壓片、包衣后需執(zhí)行目視檢查”，則需確認(rèn)該步驟在 BMR 中已標(biāo)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(guī)范（GDP）
During the review of documents, check if the document follows the general GDP rules.
審核文件時(shí)，需驗(yàn)證其是否符合良好文件規(guī)范（GDP） 的通用要求。
No overwriting - use single line strikeouts on the wrong entries
禁止 “覆蓋書(shū)寫(xiě)”—— 對(duì)錯(cuò)誤內(nèi)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(guī)范簽名并標(biāo)注日期
Correction fluid should not be used for hiding mistakes
嚴(yán)禁用 “涂改液” 掩蓋錯(cuò)誤
Entry must be made in indelible ink.
記錄需使用不褪色墨水（如藍(lán) / 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(xiàng) —— 不適用時(shí)需填寫(xiě) “NA”（避免后期隨意補(bǔ)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(tǒng)一數(shù)據(jù)格式：日期建議用 YYYY-MM-DD 格式，時(shí)間（如適用）需采用24 小時(shí)制（避免歧義，保證規(guī)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(xiàng)必填內(nèi)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(guān)責(zé)任人員的簽名
Equipment ID and calibration status
設(shè)備編號(hào)及校準(zhǔn)狀態(tài)
Raw material Batch/Lot number
原輔料批號(hào)
Data logs like temperature, pressure, weight and times
溫度、壓力、重量、時(shí)間等數(shù)據(jù)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(guī)問(wèn)題，需立即開(kāi)展調(diào)查。
7. Review for Consistency of Data
7. 審核數(shù)據(jù)的一致性
Consistency shows effective process control. Look for:
數(shù)據(jù)一致性體現(xiàn)生產(chǎn)流程的管控有效性，需重點(diǎn)核查以下內(nèi)容：
Uniformity and time recorded and ideal process durations
數(shù)據(jù)的統(tǒng)一性、記錄時(shí)間與理論工藝時(shí)長(zhǎng)是否匹配
No conflict data in BMRs, logbooks and QC reports
批次生產(chǎn)記錄、操作日志與QC報(bào)告之間無(wú)數(shù)據(jù)沖突
Reproducibility was maintained in multiple batches
多批生產(chǎn)中工藝可重復(fù)性是否穩(wěn)定
Inconsistent documents can raise issues during audits and inspections.
數(shù)據(jù)矛盾的文件，極可能在審計(jì)、檢查環(huán)節(jié)引發(fā)重大問(wèn)題。
8.Evaluate Deviation Handling and Their Investigations
8. 評(píng)估偏差處理及調(diào)查質(zhì)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(jīng)歷 識(shí)別→調(diào)查→合理性說(shuō)明 全流程，且必須關(guān)聯(lián)CAPA。審核時(shí)，若僅以 “人為失誤” 等淺層理由搪塞、未做根本原因分析，需嚴(yán)肅質(zhì)疑。
9. Check Sign-offs and Authorization
9. 檢查簽字和批準(zhǔn)
Document approval in pharmaceuticals is not just a formality but they confirm accountability. Check that:
制藥行業(yè)的文件批準(zhǔn)絕非形式流程，而是明確責(zé)任歸屬的關(guān)鍵。需檢查：
Each section of process is signed by the responsible operator or supervisor.
流程各環(huán)節(jié)均由責(zé)任操作人員 / 主管簽字確認(rèn)
Review and verification signatures are done with the date.
審核、確認(rèn)類(lèi)簽字需同步標(biāo)注日期
Quality assurance has signed and approved the final version of document.
QA部門(mén)已簽字批準(zhǔn)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(cuò)誤的簽字會(huì)直接導(dǎo)致文件失效，甚至阻礙批放行。
10. Confirm Traceability
10. 確認(rèn)可追溯性
Every document should be traceable:
每份文件都應(yīng)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(chǎn)步驟
From deviations to CAPA closures
從偏差到CAPA的閉環(huán)
From test results to source data including instruments and logs
從檢驗(yàn)結(jié)果到原始數(shù)據(jù)(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(huán)節(jié)的可追溯性，保障了生產(chǎn)流程或分析過(guò)程的真實(shí)性。
文件審核中需警惕的常見(jiàn)錯(cuò)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(diǎn)留意的典型錯(cuò)誤：
Check if entries are made before the activity is performed
核查記錄是否在操作執(zhí)行前就已填寫(xiě)（防范 “預(yù)填記錄” 問(wèn)題 ）
Any backdated entries in process steps
生產(chǎn)步驟中存在回溯性填寫(xiě)（如倒簽日期、事后補(bǔ)填 ）
Any data mismatch (like weight recorded in balance log does not match with BMR)
數(shù)據(jù)不匹配（例如天平日志記錄的重量與批生產(chǎn)記錄不一致 ）
Use of any abbreviations without their explanation
使用縮寫(xiě)但未做釋義（需保證術(shù)語(yǔ)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(fù)制粘貼錯(cuò)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(shí)別，規(guī)范的文件審核可有效規(guī)避代價(jià)高昂的錯(cuò)誤
文件審核人員的最佳實(shí)踐
You should stay updated with the latest GMP guidelines like NMPA, FDA, EU-GMP and WHO-GMP.
需及時(shí)掌握 NMPA、FDA、歐盟 GMP、世衛(wèi)組織 GMP 等最新法規(guī)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(cāng)促審核 —— 快速過(guò)審易遺漏關(guān)鍵細(xì)節(jié)（質(zhì)量源于嚴(yán)謹(jǐn) ）
Collaborate with quality assurance, production and quality control teams when there is any doubt.
遇存疑內(nèi)容時(shí)，協(xié)同QA、生產(chǎn)、QC團(tuán)隊(duì)確認(rèn)
Get trained regularly in good documentation practices, data integrity and quality management system documentation.
定期接受良好文件規(guī)范、數(shù)據(jù)完整性、質(zhì)量管理體系文件培訓(xùn)
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(huán)境下的文件審核絕非形式化 “打勾”，而是守護(hù)產(chǎn)品質(zhì)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(guī)性與產(chǎn)品質(zhì)量的基石。審核批生產(chǎn)記錄、SOP、驗(yàn)證報(bào)告或偏差表時(shí)，應(yīng)用本指南原則，確保每份文件從內(nèi)部審計(jì)到 FDA 檢查都經(jīng)得起嚴(yán)格檢驗(yàn)。
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(zhì)量控制部門(mén)未能在藥品批放行前審查生產(chǎn)及控制記錄（包括設(shè)備清潔記錄和組件測(cè)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(jù)，或者在產(chǎn)品放行數(shù)月后才進(jìn)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(chǎn)品放行前，質(zhì)量部門(mén)并未對(duì)批生產(chǎn)記錄的完整性和準(zhǔn)確性進(jìn)行審核。具體而言，諸如滅菌參數(shù)和環(huán)境監(jiān)測(cè)數(shù)據(jù)等關(guān)鍵步驟并未與既定標(biāo)準(zhǔn)進(jìn)行核對(duì)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(chǎn)區(qū)域發(fā)現(xiàn)了未經(jīng)批準(zhǔn)的SOP文件版本。質(zhì)量部門(mén)未執(zhí)行相關(guān)程序以確保僅使用已批準(zhǔn)的現(xiàn)行文件，從而導(dǎo)致了文件的無(wú)序分發(fā)。
來(lái)源：Internet
關(guān)于我們 聯(lián)系我們 營(yíng)業(yè)執(zhí)照 全國(guó)服務(wù)電話：400-818-0021 嘉峪檢測(cè)版權(quán)所有 備案號(hào)：京ICP備14047019號(hào)-2 
京公網(wǎng)安備11010802046783號(hào)
