WHO GMP補(bǔ)充指南：驗(yàn)證(中英對(duì)照)講述

1、Annex 4 附件 4Supplementary guidelines on good manufacturing practices: validation 藥品生產(chǎn)質(zhì)量管理規(guī)范補(bǔ)充指南：驗(yàn)證1 Introduction 簡(jiǎn)介2 Scope 范圍 3 Glossary 術(shù)語(yǔ)4 Relationship between validation and qualication 驗(yàn)證和確認(rèn)之間的聯(lián)系5. Validation 5.1. Approaches to validation 驗(yàn)證方法5.2. Scope of validation 驗(yàn)證范圍5 Qualication 確認(rèn) 6 Calib

2、ration and verication 校準(zhǔn)和核實(shí)7 Validation master plan 驗(yàn)證主計(jì)劃8 Qualication and validation protocols 確認(rèn)和驗(yàn)證方案9 Qualication and validation reports 確認(rèn)和驗(yàn)證報(bào)告10 Qualication stages 確認(rèn)程序11 Change control 變更控制12 Personnel 人員References參考文獻(xiàn) Appendix 1 附錄1Validation of heating, ventilation and air-conditioning syste

3、ms 采暖、通風(fēng)和空氣凈化系統(tǒng)的驗(yàn)證Appendix 2 附錄2Validation of water systems for pharmaceutical use 制藥用水系統(tǒng)的驗(yàn)證Appendix 3 附錄3Cleaning validation 清潔驗(yàn)證Appendix 4 附錄4Analytical method validation 分析方法驗(yàn)證Appendix 5 附錄5Validation of computerized systems 計(jì)算機(jī)系統(tǒng)的驗(yàn)證Appendix 6 附錄6Qualication of systems and equipment 系統(tǒng)和設(shè)備的確認(rèn)Appen

4、dix 7 附錄7Non-sterile process validation 非滅菌工藝的驗(yàn)證1. Introduction 簡(jiǎn)介Validation is an essential part of good manufacturing practices (GMP). It is, therefore, an element of the quality assurance programme associated with a particular product or process. The basic principles of quality assurance have as

5、their goal the production of products that are t for their intended use. These principles are as follows: 驗(yàn)證是藥品生產(chǎn)管理規(guī)范（GMP）的一個(gè)重要組成部分；也正因如此，所以它同時(shí)也是產(chǎn)品或工藝的質(zhì)量保證計(jì)劃的一個(gè)不可或缺的要素。質(zhì)量保證的基本原則以生產(chǎn)出符合設(shè)計(jì)用途的產(chǎn)品為目的，它的主要內(nèi)容為：Quality, safety and efcacy must be designed and built into the product. 要事先設(shè)計(jì)質(zhì)量、安全和效力，并使之在產(chǎn)品中實(shí)現(xiàn)。Qu

6、ality cannot be inspected or tested into the product. 不能僅僅只考察和檢驗(yàn)成品的質(zhì)量。Each critical step of the manufacturing process must be validated. Other steps in the process must be under control to maximize the probability that the nished product consistently and predictably meets all quality and design spec

7、ications. 生產(chǎn)工藝的每一關(guān)鍵步驟都必須經(jīng)過(guò)驗(yàn)證，非關(guān)鍵步驟也必須得到控制，從而實(shí)現(xiàn)在最大程度上生產(chǎn)出符合全部質(zhì)量和既定標(biāo)準(zhǔn)的產(chǎn)品的目的。 Validation of processes and systems is fundamental to achieving these goals. It is by design and validation that a manufacturer can establish condence that the manufactured products will consistently meet their product speci c

8、ations. 工藝和系統(tǒng)的驗(yàn)證是實(shí)現(xiàn)上述目標(biāo)的基礎(chǔ)之一。通過(guò)對(duì)生產(chǎn)的設(shè)計(jì)和驗(yàn)證，可使生產(chǎn)出的產(chǎn)品持續(xù)符合標(biāo)準(zhǔn)，并建立一定的置信區(qū)間。Documentation associated with validation includes: 與驗(yàn)證有關(guān)的文件如下： standard operating procedures (SOPs) 標(biāo)準(zhǔn)操作規(guī)程（SOP） speci cations 合格標(biāo)準(zhǔn) validation master plan (VMP) 驗(yàn)證主計(jì)劃（VMP） qualication protocols and reports 確認(rèn)方案和確認(rèn)報(bào)告 validation protoco

9、ls and reports. The implementation of validation work requires considerable resources such as: 驗(yàn)證方案和驗(yàn)證報(bào)告。執(zhí)行驗(yàn)證工作時(shí)，需要的資源有：Time: generally validation work is subject to rigorous time schedules. 時(shí)間：通常，驗(yàn)證工作必須嚴(yán)格按照時(shí)間表的安排開(kāi)展。Financial: validation often requires the time of specialized personnel and expensive

10、 technology. 資金：驗(yàn)證工作的執(zhí)行常常需要專業(yè)人員和昂貴的技術(shù)支持。Human: validation requires the collaboration of experts from various dis-ciplines (e.g. a multidisciplinary team, comprising quality assurance, en-gineering, manufacturing and other disciplines, depending on the product and process to be validated). 人員：驗(yàn)證工作的開(kāi)展

11、要求有不同領(lǐng)域的專家的合作（如一支由來(lái)自多個(gè)領(lǐng)域的專家組成的驗(yàn)證團(tuán)隊(duì)，根據(jù)待驗(yàn)證的產(chǎn)品和工藝的要求，包括質(zhì)量保證、工程、生產(chǎn)和其它領(lǐng)域）。These guidelines aim to give guidance to inspectors of pharmaceutical manu-facturing facilities and manufacturers of pharmaceutical products on the requirements for validation. The main part covers the general principles of validat

12、ion and qualication. In addition to the main part, appendices on vali-dation and qualication (e.g. cleaning, computer and computerized systems, equipment, utilities and systems, and analytical methods) are included. 這些指導(dǎo)方針能給藥品生產(chǎn)設(shè)施的檢查員及藥品生產(chǎn)商提供關(guān)于驗(yàn)證要求的指導(dǎo)。正文部分的內(nèi)容主要是關(guān)于驗(yàn)證和確認(rèn)，附錄中另有其它方面的內(nèi)容（如清潔、計(jì)算機(jī)和計(jì)算機(jī)化系統(tǒng)、設(shè)備

13、、公用工程和公用系統(tǒng)、分析方法等）。2. Scope 范圍2.1 These guidelines focus mainly on the overall concept of validation and are intended as a basic guide for use by GMP inspectors and manufacturers. It is not the intention to be prescriptive in specic validation require-ments. This document serves as general guidance o

14、nly, and the principles may be considered useful in its application in the manufacture and control of active pharmaceutical ingredients (APIs) and nished pharmaceutical products. Validation of specic processes and products, for example in ster-ile product manufacture, requires much more consideratio

15、n and a detailed approach that is beyond the scope of this document. 這里給出的指導(dǎo)方針主要涵蓋了關(guān)于驗(yàn)證的所有方面，可供GMP檢查員和生產(chǎn)商作為基本指南使用，但不可將本文視作驗(yàn)證要求的專門(mén)說(shuō)明文章；而應(yīng)當(dāng)僅將本文視為一般的指南。在遞交關(guān)于活性藥物成分（API）和藥物成品的生產(chǎn)和控制資料時(shí)，本文列出的基本原則也可作為參考。特定工藝和產(chǎn)品的驗(yàn)證，如滅菌生產(chǎn)，通常需要考慮更多的方面以及詳細(xì)的方法，本文的內(nèi)容不足以滿足它們的需要。2.2 There are many factors affecting the different t

16、ypes of validation and it is, therefore, not intended to dene and address all aspects related to one particular type of validation here. 驗(yàn)證的類型雖然繁多，但卻有許多共同的因素能對(duì)之形成影響；因此，本文不會(huì)列舉和闡述某種特定類型的驗(yàn)證的所有方面。2.3 Manufacturers should plan validation in a manner that will ensure regulatory compliance and ensuring tha

17、t product quality, safety and consis-tency are not compromised. 設(shè)計(jì)驗(yàn)證時(shí)，生產(chǎn)商應(yīng)當(dāng)要保證驗(yàn)證程序符合法規(guī)的要求，并能保證該程序能驗(yàn)證產(chǎn)品的質(zhì)量、安全和工藝的持續(xù)性。2.4 The general text in the main part of these guidelines may be appli-cable to validation and qualication of premises, equipment, utilities and systems, and processes and procedures.

18、More specic principles of quali-cation and validation are addressed in the appendices. Semi-automatic or fully automatic clean-in-place (CIP) systems and other special cases should be treated separately. 這里列出的指導(dǎo)方適用于平面布局、設(shè)備、公用工程和工用系統(tǒng)、工藝和規(guī)程的驗(yàn)證和確認(rèn)，更多的關(guān)于驗(yàn)證和確認(rèn)的專屬方法可參見(jiàn)附錄；半自動(dòng)或全自動(dòng)在線清潔（CIP）系統(tǒng)和其它特殊系統(tǒng)應(yīng)當(dāng)單獨(dú)對(duì)待。3.

19、 Glossary 術(shù)語(yǔ)The denitions given below apply to the terms used in these guidelines. They may have different meanings in other contexts. 以下是指導(dǎo)方針中使用的術(shù)語(yǔ)的定義；需注意，它們?cè)谄渌墨I(xiàn)中出現(xiàn)時(shí)，可能有不同的含義。calibration 校準(zhǔn)The set of operations that establish, under specied conditions, the relation-ship between values indicated by

20、 an instrument or system for measuring (for example, weight, temperature and pH), recording, and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard. Limits for acceptance of the results of measuring should be established. 在規(guī)定的條件下，

21、用來(lái)建立測(cè)量用（例如測(cè)量重量、溫度和pH值）、記錄用、控制用儀器或系統(tǒng)、及物料測(cè)量?jī)x器測(cè)得的值與已知參照標(biāo)準(zhǔn)的相應(yīng)值之間的關(guān)系的粗操作；在該項(xiàng)操作中，還應(yīng)建立測(cè)量結(jié)果的合格限。 computer validation計(jì)算機(jī)驗(yàn)證 Documented evidence which provides a high degree of assurance that a computerized system analyses, controls and records data correctly and that data processing complies with predetermine

22、d speci cations. 用以保證計(jì)算機(jī)化系統(tǒng)可提供正確的分析、控制和記錄數(shù)據(jù)及保證數(shù)據(jù)處理符合既定標(biāo)準(zhǔn)的文件證明。Commissioning試運(yùn)行 The setting up, adjustment and testing of equipment or a system to ensure that it meets all the requirements, as specied in the user requirement speci-cation, and capacities as specied by the designer or developer. Commis

23、-sioning is carried out before qualication and validation. 根據(jù)用戶需求說(shuō)明書(shū)所述及設(shè)計(jì)人員或研發(fā)人員的能力，用來(lái)保證設(shè)備或儀器的裝配、調(diào)整和測(cè)試符合要求，及保證設(shè)備或儀器滿足其設(shè)計(jì)和研發(fā)人員的要求的活動(dòng)。試運(yùn)行應(yīng)先于確認(rèn)和驗(yàn)證執(zhí)行。concurrent validation 同步驗(yàn)證Validation carried out during routine production of products intended for sale. 針對(duì)銷售產(chǎn)品的常規(guī)生產(chǎn)過(guò)程進(jìn)行的驗(yàn)證。cleaning validation清潔驗(yàn)證 Docum

24、ented evidence to establish that cleaning procedures are remov-ing residues to predetermined levels of acceptability, taking into con-sideration factors such as batch size, dosing, toxicology and equipment size. 在考慮了批量、劑量、毒理學(xué)和設(shè)備大小因素的前提下，用以表明清潔方法去除殘余物的能力可滿足既定合格標(biāo)準(zhǔn)的文件證明。design qualication (DQ)設(shè)計(jì)確認(rèn)（DQ）

25、Documented evidence that the premises, supporting systems, utilities, equipment and processes have been designed in accordance with the re-quirements of GMP. 用以表明廠房建筑、支持系統(tǒng)、公用工程、設(shè)備和工藝的設(shè)計(jì)符合GMP要求的證明文件。good engineering practices (GEP) 工程設(shè)計(jì)規(guī)范（GEP）Established engineering methods and standards that are app

26、lied throughout the project life-cycle to deliver appropriate, cost-effective solutions. 對(duì)于項(xiàng)目的整個(gè)運(yùn)作周期，建立了工程方法和技術(shù)標(biāo)準(zhǔn)來(lái)設(shè)計(jì)適當(dāng)且又低本高效的解決方法。installation qualication (IQ) 安裝確認(rèn)（IQ）The performance of tests to ensure that the installations (such as machines, measuring devices, utilities and manufacturing areas) u

27、sed in a manufactur-ing process are appropriately selected and correctly installed and operate in accordance with established speci cations. 為證明某一生產(chǎn)工藝中使用到的設(shè)備（如設(shè)備、測(cè)量?jī)x器、公用工程和生產(chǎn)區(qū)域）的安裝地點(diǎn)的選擇、設(shè)備的安裝和運(yùn)行達(dá)到設(shè)定的要求而進(jìn)行的各種運(yùn)行試驗(yàn)。operational qualication (OQ)運(yùn)行確認(rèn)（OQ） Documented verication that the system or subsystem

28、performs as intended over all anticipated operating ranges. 為證明系統(tǒng)或系統(tǒng)的組成設(shè)備達(dá)到設(shè)定的運(yùn)行要求而進(jìn)行的文件化確認(rèn)工作。 performance qualication (PQ) 性能確認(rèn)（PQ）Documented verication that the equipment or system operates consistently and gives reproducibility within de ned specications and parameters for prolonged periods. (In

29、the context of systems, the term “process validation” may also be used.) 為證明設(shè)備或系統(tǒng)可長(zhǎng)期實(shí)現(xiàn)設(shè)計(jì)性能的文件化確認(rèn)工作，如正確運(yùn)轉(zhuǎn)并表現(xiàn)出良好的再現(xiàn)性。（就系統(tǒng)而言，性能確認(rèn)即“工藝驗(yàn)證”。）process validation 工藝驗(yàn)證Documented evidence which provides a high degree of assurance that a specic process will consistently result in a product that meets its prede

30、ter-mined specications and quality characteristics. 為證明某工藝可持續(xù)生產(chǎn)出符合既定標(biāo)準(zhǔn)且擁有規(guī)定的質(zhì)量特性的產(chǎn)品的文件化工作。prospective validation 前驗(yàn)證Validation carried out during the development stage on the basis of a risk analysis of the production process, which is broken down into individual steps; these are then evaluated on t

31、he basis of past experience to determine whether they may lead to critical situations. 在生產(chǎn)工藝投入使用前的研發(fā)階段開(kāi)展的驗(yàn)證工作；它通常以風(fēng)險(xiǎn)分析為基礎(chǔ)，并被分解為單個(gè)步驟來(lái)驗(yàn)證。根據(jù)過(guò)去的經(jīng)驗(yàn)對(duì)前驗(yàn)證進(jìn)行評(píng)估，判斷該工藝是否會(huì)導(dǎo)致關(guān)鍵情況的出現(xiàn)。qualication 確認(rèn)Action of proving and documenting that any premises, systems and equip-ment are properly installed, and/or work corre

32、ctly and lead to the expected results. Qualication is often a part (the initial stage) of validation, but the individual qualication steps alone do not constitute process validation. 為證明所有廠房建筑、系統(tǒng)和設(shè)備均正確安裝且/或正確運(yùn)行，并能實(shí)現(xiàn)預(yù)期結(jié)果的文件化證明活動(dòng)。確認(rèn)常常是驗(yàn)證的（起始階段的）一個(gè)部分，但單獨(dú)的確認(rèn)步驟不是驗(yàn)證。retrospective validation 回顧性驗(yàn)證Involves

33、the evaluation of past experience of production on the condition that composition, procedures, and equipment remain unchanged. 在產(chǎn)品組成、操作規(guī)程和設(shè)備不發(fā)生改變的情況下，評(píng)估分析生產(chǎn)的歷史數(shù)據(jù)。revalidation 再驗(yàn)證Repeated validation of an approved process (or a part thereof) to ensure continued compliance with established requirement

34、s. 重復(fù)對(duì)獲準(zhǔn)工藝（或工藝的某個(gè)部分）的驗(yàn)證，以證實(shí)已驗(yàn)證狀態(tài)沒(méi)有發(fā)生漂移、工藝依然符合既定要求。standard operating procedure (SOP) 標(biāo)準(zhǔn)操作規(guī)程（SOP）An authorized written procedure giving instructions for performing opera-tions not necessarily specic to a given product or material but of a more general nature (e.g. equipment operation, maintenance and

35、 cleaning; vali-dation; cleaning of premises and environmental control; sampling and in-spection). Certain SOPs may be used to supplement product-speci c master batch production documentation. 具有約束力的書(shū)面規(guī)程，它描述了如何進(jìn)行操作。標(biāo)準(zhǔn)操作規(guī)程所針對(duì)的內(nèi)容廣泛，其中包括但不限于給定的產(chǎn)品或物料（還可用來(lái)說(shuō)明如設(shè)備的操作、維護(hù)和清潔；驗(yàn)證；廠房建筑的清潔和環(huán)境控制；取樣和檢查等）。某些特定的SOP可視

36、為某些產(chǎn)品專屬的批生產(chǎn)主文件的補(bǔ)充部分。validation 驗(yàn)證Action of proving and documenting that any process, procedure or method actually and consistently leads to the expected results. 為證明工藝、程序或方法在實(shí)際使用中能持續(xù)實(shí)現(xiàn)預(yù)期結(jié)果的文件化證明活動(dòng)。validation protocol (or plan) (VP) 驗(yàn)證方案（或計(jì)劃）（VP）A document describing the activities to be performed in

37、 a validation, in-cluding the acceptance criteria for the approval of a manufacturing process or a part thereof for routine use. 一個(gè)闡述如何進(jìn)行對(duì)常規(guī)生產(chǎn)工藝或生產(chǎn)工藝的一部分進(jìn)行驗(yàn)證并確定其驗(yàn)證合格標(biāo)準(zhǔn)的文件。validation report (VR)驗(yàn)證報(bào)告（VR） A document in which the records, results and evaluation of a completed validation programme are as

38、sembled and summarized. It may also contain proposals for the improvement of processes and/or equipment. 已完成的驗(yàn)證方案的記錄、結(jié)果和評(píng)估文件。它常常包括工藝和/或設(shè)備的改進(jìn)措施的內(nèi)容。validation master plan (VMP) 驗(yàn)證主計(jì)劃（VMP）The VMP is a high-level document that establishes an umbrella validation plan for the entire project and summarizes

39、 the manufacturers overall phi-losophy and approach, to be used for establishing performance adequacy. It provides information on the manufacturers validation work programme and denes details of and timescales for the validation work to be performed, including a statement of the responsibilities of

40、those implementing the plan. VMP是整個(gè)項(xiàng)目工程的驗(yàn)證計(jì)劃的概述文件，它總結(jié)了生產(chǎn)商采用的所有方法，可用來(lái)證明性能的完備能力。驗(yàn)證主計(jì)劃里有關(guān)于生產(chǎn)商的驗(yàn)證計(jì)劃的資料，待執(zhí)行的驗(yàn)證工作的時(shí)間表，還包括執(zhí)行驗(yàn)證計(jì)劃的人員的職責(zé)。verication核查T(mén)he application of methods, procedures, tests and other evaluations, in ad-dition to monitoring, to determine compliance with the GMP principles. 為檢查GMP條例的落實(shí)力度，

41、而使用的除監(jiān)控之外的方法、程序、試驗(yàn)和其它評(píng)估分析措施。worst case 最差狀況A condition or set of conditions encompassing the upper and lower processing limits for operating parameters and circumstances, within SOPs, which pose the greatest chance of product or process failure when compared to ideal con-ditions. Such conditions do

42、not necessarily include product or process failure. 系指導(dǎo)致產(chǎn)品或工藝失敗的概率高于正常運(yùn)行工藝的某個(gè)條件或一組條件（包括SOP中規(guī)定的運(yùn)行參數(shù)和狀態(tài)的上限和下限），這些狀況不一定包括產(chǎn)品或工藝的失敗。4. Relationship between validation and quali cation 驗(yàn)證和確認(rèn)之間的聯(lián)系Validation and qualication are essentially components of the same concept. The term qualication is normally use

43、d for equipment, utilities and systems, and validation for processes. In this sense, qualication is part of validation. 驗(yàn)證和確認(rèn)系同一概念的基本組成部分，即是說(shuō)它們是同義詞。“確認(rèn)”這個(gè)詞往往用在設(shè)備、公用工程和系統(tǒng)以及工藝驗(yàn)證中；在這層意義上，確認(rèn)是驗(yàn)證的一部分。5. Validation 驗(yàn)證5.1 Approaches to validation 驗(yàn)證方法5.1.1 There are two basic approaches to validation one ba

44、sed on evi-dence obtained through testing (prospective and concurrent validation), and one based on the analysis of accumulated (historical) data (retrospective validation). Whenever possible, prospective validation is preferred. Retro-spective validation is no longer encouraged and is, in any case,

45、 not appli-cable to the manufacturing of sterile products. 驗(yàn)證有兩種基本方法其一是以試驗(yàn)（前驗(yàn)證和同步驗(yàn)證）獲取的證據(jù)為基礎(chǔ)，另一種則以積累的（歷史）數(shù)據(jù)（回顧性驗(yàn)證）為基礎(chǔ)。驗(yàn)證時(shí)，應(yīng)當(dāng)盡可能的使用前驗(yàn)證，而不鼓勵(lì)執(zhí)行回顧性驗(yàn)證；要特別指出的是，無(wú)論何時(shí)，回顧性驗(yàn)證都不適用于無(wú)菌產(chǎn)品的生產(chǎn)。5.1.2 Both prospective and concurrent validation, may include: 前驗(yàn)證和同步驗(yàn)證可能包括的內(nèi)容如下：l extensive product testing, which may inv

46、olve extensive sample testing (with the estimation of condence limits for individual results) and the demonstration of intra- and inter-batch homogeneity; 大量產(chǎn)品測(cè)試，包括大量的樣品測(cè)試（以及單個(gè)結(jié)果的置信限的評(píng)估）和批間及批內(nèi)均一性的證明；l simulation process trials; 模擬生產(chǎn)試驗(yàn)；l challenge/worst case tests, which determine the robustness of t

47、he process; and 挑戰(zhàn)性/最差狀況試驗(yàn)，以證明工藝的耐用性；以及l(fā) control of process parameters being monitored during normal production runs to obtain additional information on the reliability of the process. 監(jiān)控正常運(yùn)行的生產(chǎn)過(guò)程的工藝參數(shù)的控制措施，以獲取可證明該工藝的可靠性的資料。5.2 Scope of validation 驗(yàn)證范圍5.2.1 There should be an appropriate and sufcien

48、t system including organizational structure and documentation infrastructure, sufcient personnel and nancial resources to perform validation tasks in a timely manner. Management and persons responsible for quality assurance should be involved. 為了及時(shí)執(zhí)行驗(yàn)證工作，應(yīng)當(dāng)建立一個(gè)適當(dāng)且能滿足需要的系統(tǒng)，包括組織機(jī)構(gòu)和文件管理的下層組織結(jié)構(gòu)、充足的人力和財(cái)政

49、資源，同時(shí)還應(yīng)指定質(zhì)量保證的管理和責(zé)任人。5.2.2 Personnel with appropriate qualications and experience should be responsible for performing validation. They should represent different departments depending on the validation work to be performed. 執(zhí)行驗(yàn)證工作的人員應(yīng)當(dāng)具備相應(yīng)的資格和經(jīng)驗(yàn)，并對(duì)驗(yàn)證負(fù)責(zé)。根據(jù)待執(zhí)行的驗(yàn)證工作的需要，決定由哪些部門(mén)的人員參與驗(yàn)證工作的執(zhí)行。5.2.3 There

50、should be proper preparation and planning before validation is performed. There should be a specic programme for validation activities. 執(zhí)行驗(yàn)證之前，應(yīng)有充分的準(zhǔn)備和計(jì)劃。應(yīng)針對(duì)具體的驗(yàn)證活動(dòng)，制訂專門(mén)的計(jì)劃。5.2.4 Validation should be performed in a structured way according to the documented procedures and protocols. 應(yīng)根據(jù)成文的程序和方案，以設(shè)計(jì)好

51、的方式執(zhí)行驗(yàn)證工作。5.2.5 Validation should be performed: 驗(yàn)證應(yīng)： for new premises, equipment, utilities and systems, and processes and procedures; 在新的廠房建筑、設(shè)備、公用工程和系統(tǒng)、工藝和方法上執(zhí)行； at periodic intervals; and 定期執(zhí)行； when major changes have been made. 在發(fā)生了重大變更后執(zhí)行。(Periodic revalidation or periodic requalication may be

52、substituted, where appropriate, with periodic evaluation of data and information to establish whether requalication or revalidation is required.) （在適當(dāng)?shù)那闆r下，可用數(shù)據(jù)和資料的定期評(píng)估代替定期再驗(yàn)證或定期再確認(rèn)，以確定是否需要進(jìn)行再驗(yàn)證或再確認(rèn)。）5.2.6 Validation should be performed in accordance with written protocols. A written report on the ou

53、tcome of the validation should be produced. 應(yīng)根據(jù)書(shū)面方案執(zhí)行驗(yàn)證。驗(yàn)證的結(jié)果應(yīng)當(dāng)以書(shū)面報(bào)告的形式給出。5.2.7 Validation should be done over a period of time, e.g. at least three consecutive batches (full production scale) should be validated, to demon-strate consistency. Worst case situations should be considered. 驗(yàn)證項(xiàng)目的執(zhí)行時(shí)間的設(shè)定應(yīng)

54、能證明驗(yàn)證對(duì)象的持續(xù)性。如驗(yàn)證應(yīng)當(dāng)至少在三個(gè)連續(xù)批上開(kāi)展（生產(chǎn)規(guī)模）。驗(yàn)證時(shí)，要考慮最差狀況。5.2.8 There should be a clear distinction between in-process controls and validation. In-process tests are performed during the manufacture of each batch according to specications and methods devised during the develop-ment phase. Their objective is to

55、monitor the process continuously. 過(guò)程控制和驗(yàn)證之間應(yīng)有明顯的區(qū)別。為監(jiān)測(cè)工藝的連續(xù)性，應(yīng)根據(jù)針對(duì)研發(fā)階段設(shè)計(jì)的技術(shù)標(biāo)準(zhǔn)和方法，開(kāi)展每批產(chǎn)品生產(chǎn)的過(guò)程測(cè)試。5.2.9 When a new manufacturing formula or method is adopted, steps should be taken to demonstrate its suitability for routine processing. The dened process, using the materials and equipment speci ed, shou

56、ld be shown to result in the consistent yield of a product of the required quality. 采用新的生產(chǎn)配方或方法時(shí)，應(yīng)證明它們對(duì)常規(guī)工藝的適應(yīng)性。驗(yàn)證時(shí)，應(yīng)使用規(guī)定的物料和設(shè)備，運(yùn)行既定的工藝，持續(xù)得到的產(chǎn)品質(zhì)量應(yīng)符合要求。5.2.10 Manufacturers should identify what validation work is needed to prove that critical aspects of their operations are appropriately controlled.

57、Signicant changes to the facilities or the equipment, and processes that may affect the quality of the product should be validated. A risk assessment approach should be used to determine the scope and extent of validation required. 生產(chǎn)商需明白為了證明他們的操作的關(guān)鍵問(wèn)題得到了合理的控制，應(yīng)采取哪些驗(yàn)證工作。比如，對(duì)產(chǎn)品質(zhì)量可能產(chǎn)生影響的廠房設(shè)施、設(shè)備和工藝的重大變更是需要驗(yàn)證的。為確定需要開(kāi)展的驗(yàn)證的范圍和驗(yàn)證的程度，可使用風(fēng)險(xiǎn)評(píng)估的方法。1 6. Qualication 確認(rèn)6.1 Qualication should be completed before process validation is per-formed. The process of qualication should be a logical, systematic