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嘉峪檢測(cè)網(wǎng) 2020-12-14 10:14
11月11日，世界衛(wèi)生組織（WHO）發(fā)布了“研究和開(kāi)發(fā)設(shè)施的良好實(shí)踐” 指南（Good practices for research and development facilities）的征求意見(jiàn)稿。WHO指出，就開(kāi)發(fā)批、中試批生產(chǎn)以及相應(yīng)的穩(wěn)定性數(shù)據(jù)，目前沒(méi)有相關(guān)的法規(guī)指南對(duì)穩(wěn)定性、工藝驗(yàn)證和分析方法的開(kāi)發(fā)和驗(yàn)證提出具體要求，因此開(kāi)發(fā)本文件非常有必要。本文件為研發(fā)機(jī)構(gòu)提供了有關(guān)GMP方面的指南，目的是確保遵循正確的系統(tǒng)，保證產(chǎn)品、工藝、程序和數(shù)據(jù)的適當(dāng)性、可靠性和質(zhì)量。
本指南主體部分分為22個(gè)章節(jié)，內(nèi)容如下：
1.背景
2.簡(jiǎn)介
3.范圍
4.質(zhì)量管理
5.質(zhì)量風(fēng)險(xiǎn)管理
6.衛(wèi)生
7.確認(rèn)與驗(yàn)證
8.外包活動(dòng)
9.自檢和質(zhì)量審計(jì)
10.人員
11.培訓(xùn)
12.設(shè)施
13.設(shè)備和儀器
14.物料
15.文檔
16.加工和工藝驗(yàn)證
17.質(zhì)量控制
18.穩(wěn)定性研究
19.分析程序的制定
20.技術(shù)轉(zhuǎn)移
21.生命周期方法
22.清潔程序的開(kāi)發(fā)和清潔驗(yàn)證
以下是該指南的背景、簡(jiǎn)介和范圍方面的內(nèi)容：
1. Background 背景
In view of the recent need for the unprecedented fast development of health products for the treatment of COVID-19 therapies, the World Health Organization (WHO) Prequalification Inspection Services Team (PQT INS) raised the urgency for the development of good manufacturing practice (GMP) text to address the manufacturing of developmental batches, pilot batches and the sequential stability data that is submitted in product applications (dossiers) for marketing authorization and the prequalification of medical products.
鑒于最近迫切需要快速開(kāi)發(fā)用于新冠治療的健康產(chǎn)品，WHO資格預(yù)審檢查小組（PQT INS）提出了開(kāi)發(fā)GMP文件的緊迫性，以指導(dǎo)開(kāi)發(fā)批、中試批生產(chǎn)以及相應(yīng)的穩(wěn)定性數(shù)據(jù)，這些信息是在產(chǎn)品申請(qǐng)（申報(bào)資料）中提交，用于上市許可和醫(yī)療產(chǎn)品資格預(yù)審。
There are currently no regulatory guidelines which address this matter, although the data collected from these batches influence the following aspects of the product:
? stability;
? process validation; and
? analytical method development and validation.
盡管從這些批次中收集的數(shù)據(jù)會(huì)影響產(chǎn)品的以下幾個(gè)方面，但是目前沒(méi)有解決這些問(wèn)題的法規(guī)指南：
•穩(wěn)定性；
•工藝驗(yàn)證；
•分析方法的開(kāi)發(fā)和驗(yàn)證。
2. Introduction 簡(jiǎn)介
2.1. The modern era of the pharmaceutical industry, in particular focusing on chemical synthesis, began in the 19th century. The use of computerized systems in production and control is increasing rapidly. The ongoing evolution and advancement in the pharmaceutical industry is fundamental in the control and elimination of disease around the world.
制藥業(yè)的現(xiàn)代化始于19世紀(jì)，主要專(zhuān)注于化學(xué)合成藥物。在生產(chǎn)和控制中，計(jì)算機(jī)系統(tǒng)的使用正在迅速增加。制藥行業(yè)的不斷發(fā)展和進(jìn)步，對(duì)于控制和消除全球疾病至關(guān)重要。
2.2. With an ever increasing awareness of the risks in pharmaceutical production and control, and the life cycle approaches being followed, more and more emphasis is being placed on ensuring that the research and development of products are appropriately controlled and documented.
隨著人們對(duì)藥品生產(chǎn)和控制風(fēng)險(xiǎn)的認(rèn)識(shí)不斷提高，并且遵循了生命周期方法，越來(lái)越多的重點(diǎn)聚焦于：對(duì)產(chǎn)品的研究和開(kāi)發(fā)，確保進(jìn)行適當(dāng)?shù)目刂坪陀涗洝?/span>
2.3. Furthermore, as regulators request and review data and information such as the development data of products and processes, design of experiments, validation and stability results, it has become necessary to ensure that the facilities, quality systems, data and information meet the appropriate standards and good practices.
此外，隨著監(jiān)管機(jī)構(gòu)對(duì)數(shù)據(jù)和信息的索要和審查，例如產(chǎn)品和工藝的開(kāi)發(fā)數(shù)據(jù)、實(shí)驗(yàn)設(shè)計(jì)、驗(yàn)證和穩(wěn)定性結(jié)果，有必要確保設(shè)施、質(zhì)量體系、數(shù)據(jù)和信息符合適當(dāng)?shù)臉?biāo)準(zhǔn)和良好實(shí)踐。
2.4. This document intends to provide guidance on GMP to research and development facilities. It further aims to ensure that the correct systems are followed, ensuring appropriateness, reliability and the quality of products, processes, procedures and data. It further helps to help ensure that products meet the requirements for safety, efficacy and quality that they purport to possess.
本文檔旨在為研發(fā)機(jī)構(gòu)提供有關(guān)GMP的指南。它還旨在確保遵循正確的系統(tǒng)，確保產(chǎn)品、工藝、程序和數(shù)據(jù)的適當(dāng)性、可靠性和質(zhì)量。進(jìn)一步有助于確保產(chǎn)品滿(mǎn)足聲稱(chēng)具有的安全性、功效和質(zhì)量要求。
2.5. In addition to product development, other activities including the production of investigational products and pilot scale batches; process validation; cleaning procedure development; cleaning validation studies; as well as stability studies, are often undertaken in such facilities.
除產(chǎn)品開(kāi)發(fā)外，其他活動(dòng)包括試驗(yàn)用產(chǎn)品和中試批的生產(chǎn)；工藝驗(yàn)證；清潔程序的開(kāi)發(fā)；清潔驗(yàn)證研究；以及穩(wěn)定性研究，通常都是在此類(lèi)設(shè)施中進(jìn)行的。
2.6. The WHO document titled Good manufacturing practices for investigational pharmaceutical products for clinical trials in humans (1) specifically addresses the requirements and recommendations for products used in clinical trials. Other WHO guidelines address specific requirements and recommendations including but not limited to stability testing, analytical method validation, cleaning validation and the transfer of technology (TOT). (See the References and Further Reading sections).
WHO題為“試驗(yàn)用藥品的GMP”的文件專(zhuān)門(mén)針對(duì)臨床試驗(yàn)中使用的產(chǎn)品提出了要求和建議。世衛(wèi)組織的其他指南還針對(duì)具體要求和建議，包括但不限于穩(wěn)定性測(cè)試、分析方法驗(yàn)證、清潔驗(yàn)證和技術(shù)轉(zhuǎn)移（TOT）。
3. Scope 范圍
3.1. This guideline is applicable to research and development facilities of products manufactured by chemical synthesis, extraction, cell culture or fermentation, by recovery from natural sources, or by any combination of these processes. It further covers development of procedures and processes intended for transfer and use in marketing authorization applications, process validation, TOT (10)-related activities, validation (7), quality control laboratory activities (11), such as stability testing and development, and validation of cleaning procedures (see Figure 1 and section 4 below).
本指南適用于研發(fā)設(shè)施，其通過(guò)化學(xué)合成、提取、細(xì)胞培養(yǎng)或發(fā)酵、天然來(lái)源回收或通過(guò)這些工藝的任何組合來(lái)生產(chǎn)產(chǎn)品。它進(jìn)一步涵蓋程序和流程的開(kāi)發(fā)，涉及轉(zhuǎn)移和用于上市許可申請(qǐng)、工藝驗(yàn)證、TOT相關(guān)的活動(dòng)、驗(yàn)證、QC實(shí)驗(yàn)室活動(dòng)（例如穩(wěn)定性檢驗(yàn)和開(kāi)發(fā)），以及清潔程序的驗(yàn)證（請(qǐng)參見(jiàn)下面的圖1和第4章）。
3.2. This guide excludes all vaccines, whole cells, whole blood and plasma, blood and plasma derivatives (plasma fractionation), medical gases, commercial products, radiopharmaceuticals and gene therapy products.
本指南不包括所有疫苗、全細(xì)胞、全血和血漿，血液和血漿衍生物（血漿分級(jí)分離）、醫(yī)用氣體、商業(yè)產(chǎn)品、放射性藥物和基因治療產(chǎn)品。
3.3. The good practices outlined below are to be considered general guides and they may be adapted to meet individual needs. The equivalence of alternative approaches, however, should be proven.
以下概述的良好實(shí)踐應(yīng)被視為通用指南，可以對(duì)其進(jìn)行調(diào)整以滿(mǎn)足特別需求。但是，應(yīng)證明替代方法的等效性。
3.4. In this guide, the term “should” indicates recommendations that are expected to apply unless shown to be inapplicable or replaced by an alternative demonstrated to provide an acceptable level of control.
本指南中，術(shù)語(yǔ)“應(yīng)該”表示預(yù)期將適用的建議，除非顯示為不適用，或被證明可以使用替代方案替代（需提供可接受的控制水平）。
3.5. This guide, as a whole, does not cover safety aspects for the personnel engaged in the research and development nor the aspects of protection of the environment. These controls are inherent responsibilities of the manufacturer and are governed by national laws.
總體而言，本指南未涵蓋從事研發(fā)的人員的安全方面，也未涵蓋環(huán)境保護(hù)的方面。這些控制是生產(chǎn)商的固有責(zé)任，并受?chē)?guó)家法律約束。
3.6. This guide is not intended to define registration requirements or modify pharmacopoeial requirements or other guideline recommendations. For details on process development, it is recommended that other guidelines, such as those published by The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), be read in conjunction with this document.
本指南無(wú)意定義注冊(cè)要求，或修改藥典要求，或其他指南建議。有關(guān)工藝開(kāi)發(fā)的詳細(xì)信息，建議與本文檔一起閱讀其他指南，例如ICH出版的相關(guān)指南。
3.7. This guide does not affect the ability of the responsible regulatory agency to establish specific registration or filing requirements. All commitments in registration and filing documents must be met. This document provides information to consider for a risk- and science-based approach in the research and development of medical products.
本指南不影響負(fù)責(zé)的監(jiān)管機(jī)構(gòu)建立特定注冊(cè)或備案要求的能力。必須遵守注冊(cè)和提交文件中的所有承諾。本文檔提供了：在醫(yī)療產(chǎn)品研發(fā)中，考慮基于風(fēng)險(xiǎn)和科學(xué)的方法的信息。
3.8. The main focus of the document is on pharmaceutical formulation and development. The principles described in this document may however be applied in facilities where other products such as vaccines, veterinary products and biopharmaceutical products are developed. The principles may also be considered, where appropriate, in facilities where medical devices are manufactured.
該文件的主要重點(diǎn)是藥物制劑和開(kāi)發(fā)。但是，本文檔中描述的原理可能適用于開(kāi)發(fā)其他產(chǎn)品（如疫苗、獸藥和生物制品）的設(shè)施。在適當(dāng)?shù)那闆r下，也可以在生產(chǎn)醫(yī)療器械的設(shè)施中考慮這些原則。
3.9. Due to the nature of research work, and an increasing expectation for compliance with standards in manufacture, the guidance in this document would normally be applied based on risk assessment, in an increasing manner, from research to commercial batch manufacturing. The stringency of GMP in research and development should increase as the process proceeds from early research work to the final steps of development and formulation, stability testing, process validation and cleaning validation.
由于研究工作的性質(zhì)、以及對(duì)生產(chǎn)標(biāo)準(zhǔn)合規(guī)性的期望越來(lái)越高，因此通?；陲L(fēng)險(xiǎn)評(píng)估，隨著從研究到商業(yè)批生產(chǎn)這一過(guò)程的推進(jìn)，本指南中的內(nèi)容越來(lái)越多地應(yīng)用。隨著從早期研究工作到最終步驟的過(guò)程，如開(kāi)發(fā)與配方、穩(wěn)定性測(cè)試、工藝驗(yàn)證和清潔驗(yàn)證，GMP在研究和開(kāi)發(fā)中的嚴(yán)格性應(yīng)逐漸增加。
Figure 1. Application of this guide
Early research – Research – Development/formulation – Registration batches
Increased compliance with Good Manufacturing Practices*
圖1.本指南的應(yīng)用
早期研究–研究–開(kāi)發(fā)/處方–注冊(cè)批次
更好地遵守GMP*
*The principles described in this guideline are applied, based on risk management principles, in an increased manner from early research to development to registration batches
*本指南中描述的原則基于風(fēng)險(xiǎn)管理原則，從早期研究，到開(kāi)發(fā)、再到注冊(cè)批次，其應(yīng)用越來(lái)越多。
4. 質(zhì)量管理
Quality management
4.1. There should be a quality management system encompassing adequate resources, a written organizational structure and procedures to follow.
應(yīng)該有一個(gè)質(zhì)量管理體系，包括充分的資源、書(shū)面話(huà)的組織結(jié)構(gòu)和可以遵循的程序。
4.2. The necessary resources should include, for example:
a) a sufficient number of appropriately qualified, trained personnel;
b) adequate premises and space;
c) suitable equipment and services;
d) appropriate materials, containers and labels；and
e) suitable storage and transport.
必要的資源應(yīng)包括，例如：
a）足夠數(shù)量的經(jīng)過(guò)適當(dāng)培訓(xùn)的有資質(zhì)人員；
b）充分的場(chǎng)所和空間；
c）合適的設(shè)備和服務(wù)；
d）適當(dāng)?shù)牟牧稀⑷萜骱蜆?biāo)簽；
e）適當(dāng)?shù)膬?chǔ)存和運(yùn)輸。
4.3. Roles, responsibilities and authorities should be defined, communicated and implemented.
角色、職責(zé)和權(quán)限應(yīng)定義、溝通和實(shí)施。
4.4. The quality system should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities.
質(zhì)量體系應(yīng)促進(jìn)創(chuàng)新和持續(xù)改進(jìn)，并加強(qiáng)藥物開(kāi)發(fā)與生產(chǎn)活動(dòng)之間的聯(lián)系。
4.5 All parts of the quality system should be adequately resourced and maintained, including with sufficient competent personnel, suitable premises, equipment and facilities.
質(zhì)量體系的所有部分應(yīng)有充分的資源和維護(hù)，包括有充分的有資質(zhì)人員，合適的場(chǎng)所、設(shè)備和設(shè)施。
4.6 Initial research, as well as development activities, should be defined and documented. The detail should be in accordance with risk assessment and the increasing scale of GMP requirements from early to final stages of development.
應(yīng)該定義和記錄初步研究以及開(kāi)發(fā)活動(dòng)。其詳細(xì)程度，應(yīng)與風(fēng)險(xiǎn)評(píng)估、以及從開(kāi)發(fā)的早期到最終階段不斷增加的GMP要求相一致。
4.7 The quality system should ensure, as applicable and according to the stage of research and development, that:
質(zhì)量體系應(yīng)根據(jù)研究和開(kāi)發(fā)階段的要求，確保：
•managerial responsibilities are clearly specified in job descriptions;
在崗位說(shuō)明書(shū)中明確規(guī)定管理職責(zé)；
•instructions and procedures are written in clear and unambiguous language;
指導(dǎo)和程序以清晰明確的語(yǔ)言編寫(xiě)；
•procedures are correctly carried out;
正確執(zhí)行程序；
•records are made (manually and/or by recording instruments) during production and quality control;
在生產(chǎn)和質(zhì)量控制期間（手動(dòng)和/或通過(guò)記錄儀器）進(jìn)行記錄；
•any significant deviations are recorded, investigated and the appropriate action taken;
記錄、調(diào)查任何重大偏差，并采取適當(dāng)措施；
•records are maintained;
保持記錄；
•there is a system for quality risk management (QRM);
有質(zhì)量風(fēng)險(xiǎn)管理（QRM）系統(tǒng)；
•arrangements are made for the manufacture, supply and use of the correct starting and packaging materials;
對(duì)于生產(chǎn)、供應(yīng)和使用正確的起始和包裝材料，進(jìn)行相應(yīng)的安排；
•all necessary controls on starting materials, intermediate products, bulk products and other in-process controls are carried out;
對(duì)原材料、中間體、半成品和其它中制措施，進(jìn)行所有必要的控制；
•calibrations and validations are carried out where appropriate;
適當(dāng)時(shí)，進(jìn)行校準(zhǔn)和驗(yàn)證；
•the product and process knowledge is managed;
產(chǎn)品和工藝知識(shí)得到管理；
•products are designed and developed in accordance with applicable good practices (GxP);
根據(jù)適用的良好實(shí)踐（GxP）設(shè)計(jì)和開(kāi)發(fā)產(chǎn)品；
•production and control operations are clearly specified in written form;
以書(shū)面形式，明確規(guī)定生產(chǎn)和控制操作；
•continual improvement is facilitated through the implementation of quality improvements appropriate to the current level of process and product knowledge;
通過(guò)實(shí)施適合于當(dāng)前工藝和產(chǎn)品知識(shí)水平的質(zhì)量改進(jìn)，來(lái)促進(jìn)持續(xù)改進(jìn)；
•product realization is achieved;
完成產(chǎn)品的可實(shí)現(xiàn)化；
•cleaning procedures are developed and validated;
制定并驗(yàn)證清潔程序；
•stability testing is done following written procedures and protocols；and
按照書(shū)面程序和草案進(jìn)行穩(wěn)定性測(cè)試；
•data meet ALCOA+ requirements.
•數(shù)據(jù)符合ALCOA +要求。
4.8 There should be periodic management review with the involvement of senior management.
應(yīng)在高級(jí)管理層的參與下，進(jìn)行定期的管理層審查。
5.質(zhì)量風(fēng)險(xiǎn)管理
Quality risk management
5.1. A system of quality risk management (QRM) should be implemented. The system should ensure that risks are identified based on scientific knowledge and experience. The appropriate controls should be identified and implemented to mitigate risks.
應(yīng)實(shí)施質(zhì)量風(fēng)險(xiǎn)管理（QRM）系統(tǒng)。該系統(tǒng)應(yīng)確保根據(jù)科學(xué)知識(shí)和經(jīng)驗(yàn)確定風(fēng)險(xiǎn)。應(yīng)確定并實(shí)施適當(dāng)?shù)目刂拼胧?，以減輕風(fēng)險(xiǎn)。
5.2. The level of effort, formality and documentation of the QRM process is commensurate with the level of risk and the stage from research to development, to commercial batch manufacturing and control (see Figure 1).
QRM流程的工作量、形式和文件記錄的水平，應(yīng)與風(fēng)險(xiǎn)水平以及從研究、到開(kāi)發(fā)再到商業(yè)批生產(chǎn)和控制的階段相對(duì)應(yīng)（見(jiàn)圖1）。
5.3. Systems should be in place to manage and minimize the risks inherent in research and development in order to ensure the ultimate quality, safety and efficacy of products；and the reliability of data.
應(yīng)建立系統(tǒng)來(lái)管理和減少研發(fā)中固有的風(fēng)險(xiǎn)，以確保產(chǎn)品的最終質(zhì)量，安全性和有效性；以及數(shù)據(jù)的可靠性。
5.4. Risk assessments should be periodically reviewed in light of improvements, current technology, scientific knowledge and experience.
應(yīng)根據(jù)改進(jìn)情況、當(dāng)前技術(shù)、科學(xué)知識(shí)和經(jīng)驗(yàn)，定期審查風(fēng)險(xiǎn)評(píng)估。
6. 清潔與衛(wèi)生
Sanitation and hygiene
6.1. Procedures should be implemented to maintain sanitation and hygiene. The scope of sanitation and hygiene covers personnel, premises, equipment and apparatus, production materials and containers, and products for cleaning and disinfection.
應(yīng)執(zhí)行程序，以保持清潔與衛(wèi)生。清潔和衛(wèi)生范圍包括人員、場(chǎng)所、設(shè)備和器具、生產(chǎn)材料、容器，以及清潔和消毒產(chǎn)品。
6.2. Potential sources of contamination should be eliminated.
應(yīng)消除潛在的污染源。
7. 確認(rèn)與驗(yàn)證
Qualification and validation
7.1. Qualification and validation required should be identified based on risk assessment and, in addition, should be appropriate to the stage of research and development.
應(yīng)基于風(fēng)險(xiǎn)評(píng)估來(lái)確定所需的確認(rèn)與驗(yàn)證，此外，還應(yīng)適合于研發(fā)階段。
7.2. The qualification and validation policy and approach should be defined and documented, for example, in a validation master plan.
例如，應(yīng)在驗(yàn)證主計(jì)劃中，定義和記錄確認(rèn)與驗(yàn)證的策略及方法。
7.3. Where qualification and validation is carried out, the responsibility of performing validation should be clearly defined.
在進(jìn)行確認(rèn)與驗(yàn)證時(shí)，應(yīng)明確規(guī)定執(zhí)行驗(yàn)證的責(zé)任。
7.4. Qualification and validation should provide documentary evidence that specifications and other requirements are met. Protocols and reports should be made available, when required.
確認(rèn)與驗(yàn)證應(yīng)提供證明，即滿(mǎn)足質(zhì)量標(biāo)準(zhǔn)和其它要求的書(shū)面證據(jù)。必要時(shí)，應(yīng)提供草案和報(bào)告。
7.5. Where process validation, cleaning validation and analytical procedure validation is done as a part of development, procedures and protocols should be followed. Reports should be available and retained.
在開(kāi)發(fā)過(guò)程中，進(jìn)行工藝驗(yàn)證、清潔驗(yàn)證和分析方法驗(yàn)證時(shí)，應(yīng)遵循程序和草案。報(bào)告應(yīng)可查，并進(jìn)行保留。
8.外包活動(dòng)
Outsourced activities
8.1. Outsourced activities should be correctly defined, agreed and controlled through a written agreement.
應(yīng)通過(guò)書(shū)面協(xié)議，正確定義、約定和控制外包活動(dòng)。
8.2. All responsibilities and arrangements for activities, such as quality control testing and technology transfer, should be clearly described.
所有活動(dòng)的職責(zé)和安排，例如QC檢驗(yàn)和技術(shù)轉(zhuǎn)讓?zhuān)紤?yīng)予以明確說(shuō)明。
委托方
The contract giver
8.3. The contract giver is responsible for assessing the suitability and competence of the contract acceptor to successfully carry out the work or tests required and for approval of the contract activities.
委托方負(fù)責(zé)評(píng)估受托方成功完成所需工作或檢驗(yàn)的適用性和能力，并負(fù)責(zé)批準(zhǔn)合同活動(dòng)。
8.4. The contract giver should provide the contract acceptor with all the information necessary to carry out the contracted operations correctly.
委托方應(yīng)向受托方提供正確執(zhí)行合同規(guī)定的操作所需的所有信息。
8.5. The contract giver should ensure that the contract acceptor is fully aware of any hazards associated with the product, work or tests.
委托方應(yīng)確保受托方充分意識(shí)到與產(chǎn)品、工作或檢驗(yàn)有關(guān)的任何危險(xiǎn)。
8.6. The contract giver should review and assess the records and results related to the outsourced activities.
委托方應(yīng)審查和評(píng)估與外包活動(dòng)有關(guān)的記錄和結(jié)果。
8.7. The contract giver is responsible for ensuring that the contract accepter understands that his or her activities may be subject to inspection by the competent authorities.
委托方有責(zé)任確保受托方了解：其活動(dòng)可能受到主管當(dāng)局的檢查。
受托方
The contract accepter
8.8. The contract accepter must have adequate premises, equipment, knowledge, experience and competent personnel to satisfactorily carry out the work ordered by the contract giver.
受托方必須具有充分的場(chǎng)所、設(shè)備、知識(shí)、經(jīng)驗(yàn)和勝任的人員，方能成功地執(zhí)行委托方所下令的工作。
8.9. The contract accepter should not pass to a third party any of the work entrusted under the contract without the contract giver’s prior evaluation and approval of the arrangements.
未經(jīng)委托方的事先評(píng)估和批準(zhǔn)，受托方不得將合同所委托的任何工作交給第三方。
協(xié)議
The agreement
8.10. The technical aspects of the agreement should be drawn up by competent persons suitably knowledgeable in the field of research, development and GMP.
該協(xié)議的技術(shù)方面應(yīng)由在研究、開(kāi)發(fā)和GMP領(lǐng)域具有適當(dāng)知識(shí)的主管人員起草。
8.11. The agreement should describe the handling of materials, such as samples and products, if they are out of specification or rejected.
該協(xié)議應(yīng)描述材料（例如樣品和產(chǎn)品）的處理方法（如不合格或被拒絕時(shí)）。
8.12. The agreement should permit the contract giver to audit the facilities and activities of the contract acceptor.
該協(xié)議應(yīng)允許：委托方對(duì)受托方的設(shè)施和活動(dòng)進(jìn)行審計(jì)。
9. 自檢和質(zhì)量審計(jì)
Self-inspection and quality audits
9.1. There should be a written self-inspection programme.
應(yīng)該有一個(gè)書(shū)面的自檢計(jì)劃。
9.2. Self-inspections should be performed routinely and may be, in addition, performed on special occasions.
自檢應(yīng)常規(guī)進(jìn)行，此外，還可以在特殊情況下進(jìn)行。
9.3 The team responsible for self-inspection should consist of personnel with the appropriate knowledge and experience, free from bias.
負(fù)責(zé)自檢的團(tuán)隊(duì)?wèi)?yīng)由具有適當(dāng)知識(shí)和經(jīng)驗(yàn)、且沒(méi)有偏見(jiàn)的人員組成。
9.4 Self-inspections should cover at least the following items:
自檢應(yīng)至少包括以下幾項(xiàng)內(nèi)容：
a) personnel;
b) premises including personnel facilities;
c) maintenance of buildings and equipment;
d) storage of starting materials and finished products;
e) equipment;
f) production and in-process controls;
g) quality control;
h) documentation;
i) sanitation and hygiene;
j) qualification and validation;
k) calibration of instruments or measurement systems;
l) control of labels；and
m) results of previous self-inspections and any corrective steps taken.
a）人員；
b）包括人員設(shè)施在內(nèi)的場(chǎng)所；
c）廠房和設(shè)備的維修；
d）原材料和成品的儲(chǔ)存；
e）設(shè)備；
f）生產(chǎn)和過(guò)程控制；
g）質(zhì)量控制；
h）文件；
i）清潔與衛(wèi)生；
j）確認(rèn)和驗(yàn)證；
k）儀器或測(cè)量系統(tǒng)的校驗(yàn)；
l）標(biāo)簽控制；
m）先前自檢的結(jié)果以及采取的任何糾正措施。
9.5 The outcome of the self-inspection should be documented. Corrective actions and preventive actions should be identified and implemented. There should be an effective follow-up programme.
自檢的結(jié)果應(yīng)形成文件。應(yīng)確定和實(shí)施糾正和預(yù)防措施。應(yīng)該有一個(gè)有效的后續(xù)計(jì)劃。
9.6 Self-inspections may be supplemented by quality audits.
質(zhì)量審計(jì)可以補(bǔ)充自檢。
10.人員
Personnel
10.1 Individual responsibilities should be clearly defined and understood by the persons concerned and recorded as written descriptions.
有關(guān)人員應(yīng)明確定義和理解個(gè)人責(zé)任，并記錄為書(shū)面說(shuō)明。
10.2 All personnel should be aware of the principles of this guideline and other applicable GxPs.
所有人員均應(yīng)了解本指南和其它適用的GxP原則。
10.3 Steps should be taken to prevent unauthorized people from entering storage, production and quality control areas.
應(yīng)采取措施防止未經(jīng)授權(quán)的人員進(jìn)入存儲(chǔ)、生產(chǎn)和質(zhì)量控制區(qū)域。
10.4. The heads of production and quality unit should be independent of each other.
生產(chǎn)主管和質(zhì)量主管應(yīng)相互獨(dú)立。
10.5. Smoking, eating, drinking, chewing and keeping plants, food, drink, smoking material and personal medicines should not be permitted in any area where they might adversely influence product quality.
禁止在任何可能對(duì)產(chǎn)品質(zhì)量產(chǎn)生不利影響的區(qū)域吸煙、進(jìn)食、飲用、咀嚼和儲(chǔ)存植物、食物、飲料、吸煙材料和個(gè)人藥品。
11. 培訓(xùn)
Training
11.1. Training should be provided in accordance with a written programme that covers topics such as the theory and practice of GMP and the duties assigned to them.
應(yīng)按照書(shū)面計(jì)劃提供培訓(xùn)，其中應(yīng)涵蓋GMP的理論和實(shí)踐以及分配給他們的職責(zé)等主題。
11.2. The effectiveness of training should be assessed.
應(yīng)評(píng)估培訓(xùn)的有效性。
11.3. Training and assessment records should be kept.
應(yīng)保留培訓(xùn)和評(píng)估記錄。
11.4. Where appropriate, specific training should be given on the handling of highly active, toxic, infectious or sensitizing materials.
在適當(dāng)時(shí)，應(yīng)進(jìn)行有關(guān)高活性、有毒、傳染性或致敏性物質(zhì)處理的專(zhuān)門(mén)培訓(xùn)。
12. 設(shè)施
Premises
12.1. Premises should be located, designed, constructed, adapted and maintained to suit the operations to be carried out.
設(shè)施的位置、設(shè)計(jì)、構(gòu)造、調(diào)整和維護(hù)應(yīng)適合要執(zhí)行的操作。
12.2. The layout and design should aim to minimize the risk of errors and permit effective cleaning and maintenance in order to avoid cross-contamination, build-up of dust or dirt and, in general, any adverse effect on the products and activities.
布局和設(shè)計(jì)應(yīng)旨在最大程度地減少錯(cuò)誤風(fēng)險(xiǎn)，并進(jìn)行有效的清潔和維護(hù)，以避免交叉污染，灰塵或污垢的堆積，并且通常避免對(duì)產(chǎn)品和活動(dòng)產(chǎn)生不利影響。
12.3. Where product dust is generated, measures should be taken to avoid cross-contamination and to facilitate cleaning.
在產(chǎn)生產(chǎn)品粉塵的地方，應(yīng)采取措施避免交叉污染并促進(jìn)清潔。
12.4. Premises should be cleaned according to detailed written procedures. Records should be maintained.
設(shè)施應(yīng)按照詳細(xì)的書(shū)面程序進(jìn)行清潔。記錄應(yīng)予以保留。
12.5. Electrical supply, lighting, temperature, humidity and ventilation should be appropriate.
應(yīng)有適當(dāng)?shù)碾娫?、照明、溫度、濕度和通風(fēng)。
12.6. Toilets, rest and refreshment rooms should be separate from production and control areas.
廁所、息室和休閑室應(yīng)與生產(chǎn)和控制區(qū)域分開(kāi)。
12.7. Animal houses should be well isolated from other areas, with a separate entrance (animal access) and air-handling facilities.
動(dòng)物房應(yīng)與其它區(qū)域隔離開(kāi)，并有單獨(dú)的入口（動(dòng)物通道）和空氣處理設(shè)施。
12.8. Storage areas should be of sufficient capacity with proper separation and segregation between materials, based on risk assessment.
根據(jù)風(fēng)險(xiǎn)評(píng)估，存儲(chǔ)區(qū)域應(yīng)具有充分的容量，并在物料之間進(jìn)行適當(dāng)?shù)母綦x和分離。
12.9. Storage areas should be clean and dry, designed or adapted to ensure the required storage conditions are maintained. Conditions should be controlled, monitored and recorded where appropriate.
儲(chǔ)存區(qū)域應(yīng)清潔干燥，通過(guò)設(shè)計(jì)或調(diào)整，確保維持所需的儲(chǔ)存條件。在適當(dāng)情況下，應(yīng)控制、監(jiān)測(cè)和記錄條件。
12.10. Segregation should be provided for the storage of quarantined, released and rejected materials and products.
應(yīng)有不同的分區(qū)，以存儲(chǔ)隔離、釋放和拒收的材料和產(chǎn)品。
12.11. Certain materials, such as highly active, radioactive materials and narcotics, should be stored in safe and secure areas.
某些材料，例如高活性、放射性材料和麻醉品，應(yīng)存儲(chǔ)在安全的地方。
12.12. Materials identified for testing should be sampled in accordance with written procedures and analysed for compliance with their specifications.
對(duì)于確定要進(jìn)行檢驗(yàn)的材料，應(yīng)按照書(shū)面程序進(jìn)行取樣，并分析其是否符合質(zhì)量標(biāo)準(zhǔn)。
12.13. The stages in production, including weighing, compounding, and packaging, should be done in a manner to prevent contamination, cross-contamination and mix-ups.
對(duì)于生產(chǎn)的各個(gè)階段（包括稱(chēng)重、配料和包裝），應(yīng)以防止污染、交叉污染和混淆的方式進(jìn)行。
12.14. Quality control (QC) laboratories should be separated from production areas. They should be designed to suit the operations to be carried out in them. There should be sufficient space, instruments, equipment and the appropriate reference materials, solvents and reagents.
質(zhì)量控制（QC）實(shí)驗(yàn)室應(yīng)與生產(chǎn)區(qū)域分開(kāi)。它們的設(shè)計(jì)應(yīng)適合要在其中執(zhí)行的操作。應(yīng)該有充分的空間、儀器、設(shè)備以及適當(dāng)?shù)臉?biāo)準(zhǔn)品、溶劑和試劑。
13.設(shè)備與儀器
Equipment and instruments
13.1. Equipment and instruments should be located, designed, constructed, adapted and maintained to suit the operations to be carried out. They should allow for effective cleaning and maintenance in order to avoid cross-contamination and a build-up of dust or dirt.
設(shè)備和儀器的放置、設(shè)計(jì)、構(gòu)造、改裝和維護(hù)應(yīng)適合要執(zhí)行的操作。它們應(yīng)進(jìn)行有效的清潔和維護(hù)，以避免交叉污染和灰塵或污垢的堆積。
13.2. Pipework, instruments and devices should be adequately marked.
管道、儀器和設(shè)備應(yīng)適當(dāng)標(biāo)記。
13.3. Balances and other measuring equipment of an appropriate range and precision should be available for production and control operations and should be calibrated on a scheduled basis.
應(yīng)有適當(dāng)范圍和精度的天平和其它測(cè)量設(shè)備，可用于生產(chǎn)和控制操作，并應(yīng)按計(jì)劃進(jìn)行校驗(yàn)。
13.4. Equipment and instruments should be thoroughly cleaned on a scheduled basis.
設(shè)備和儀器應(yīng)定期進(jìn)行徹底清潔。
13.5. Defective equipment and instruments should be removed from operational areas or be clearly labelled as defective in order to prevent use.
有缺陷的設(shè)備和儀器應(yīng)從操作區(qū)域移開(kāi)，或清楚地標(biāo)記為有缺陷的，以防止誤用。
14.物料
Materials
14.1. Materials should be purchased from approved suppliers.
材料應(yīng)從批準(zhǔn)的供應(yīng)商處購(gòu)買(mǎi)。
14.2. Materials, identified through risk assessment, should be quarantined immediately after receipt, sampled and tested in accordance with specifications.
通過(guò)風(fēng)險(xiǎn)評(píng)估識(shí)別的材料，應(yīng)在收到后立即進(jìn)行隔離，并按照質(zhì)量標(biāo)準(zhǔn)進(jìn)行取樣和檢驗(yàn)。
14.3. Materials released by the quality department and within their shelf life should be used.
應(yīng)使用質(zhì)量部門(mén)放行的且在有效期內(nèi)的材料。
14.4. Materials identified through risk assessment should be stored under the appropriate conditions as specified on their labels and in an orderly fashion to permit segregation, stock rotation and a first-expire, first-use rule.
對(duì)于通過(guò)風(fēng)險(xiǎn)評(píng)估識(shí)別的材料，應(yīng)在標(biāo)簽上規(guī)定的適當(dāng)條件下，以有條理的方式存儲(chǔ)，以實(shí)現(xiàn)區(qū)別管理、庫(kù)存更新和先到期先使用的規(guī)則。
14.5. The dispensing of materials for the production of a batch should be done according to a written procedure. Materials should be accurately weighed or measured into clean and properly labelled containers.
用于批生產(chǎn)的材料分配應(yīng)按照書(shū)面程序進(jìn)行。材料應(yīng)準(zhǔn)確稱(chēng)量或測(cè)量，放入干凈且貼有標(biāo)簽的容器中。
14.6. No materials used for operations, such as cleaning, the lubrication of equipment and pest control, should come into direct contact with the product. Where possible, such materials should be of a suitable grade (e.g. food grade) to minimize health risks.
勿將用于操作的材料（例如清潔、設(shè)備潤(rùn)滑和病蟲(chóng)害防治）直接與產(chǎn)品接觸。在可能的情況下，此類(lèi)材料應(yīng)采用合適的等級(jí)（例如食品等級(jí)），以最大程度地降低健康風(fēng)險(xiǎn)。
14.7. Water used should be suitable for its intended use.
使用的水應(yīng)適合其預(yù)期用途。
14.8. Packaging materials should be stored in secure conditions so as to exclude the possibility of unauthorized access.
包裝材料應(yīng)存放在安全的條件下，以防止未經(jīng)授權(quán)的使用。
14.9. Intermediate and bulk products should be kept under appropriate conditions.
中間產(chǎn)品半成品應(yīng)保持在適當(dāng)?shù)臈l件下。
14.10. Finished products should be stored under suitable conditions.
成品應(yīng)在適當(dāng)?shù)臈l件下存儲(chǔ)。
14.11. Rejected materials and products should be clearly marked as such and stored separately in restricted areas. They should be handled in an appropriate and timely manner. Whatever action is taken should be approved by authorized personnel and recorded.
拒收的材料和產(chǎn)品應(yīng)清晰標(biāo)明，并分別存放在限制區(qū)域中。應(yīng)該以適當(dāng)和及時(shí)的方式處理它們。采取的任何措施均應(yīng)由授權(quán)人員批準(zhǔn)并記錄。
14.12. Toxic substances and flammable materials should be stored in suitably designed, separate, enclosed containers and, as required, by national legislation. All waste materials should be stored in a safe manner and disposed of at regular intervals to avoid accumulation.
有毒物質(zhì)和易燃材料應(yīng)存儲(chǔ)在適當(dāng)設(shè)計(jì)的單獨(dú)的密閉容器中，并應(yīng)根據(jù)國(guó)家法規(guī)進(jìn)行存儲(chǔ)。所有廢物均應(yīng)以安全的方式進(jìn)行存儲(chǔ)，并應(yīng)定期進(jìn)行處置，以免積累。
15. 文檔
Documentation
15.1. Documentation includes specifications and procedures for materials and methods of production and control. The design and use of documents depend upon the research and development facility. The scope and extent should be established based on risk assessment and the stage of research and development (see Figure 1).
文件包括材料的質(zhì)量標(biāo)準(zhǔn)、程序和生產(chǎn)及控制方法。文件的設(shè)計(jì)和使用取決于研發(fā)機(jī)構(gòu)。應(yīng)根據(jù)風(fēng)險(xiǎn)評(píng)估和研發(fā)階段來(lái)確定范圍和程度（見(jiàn)圖1）。
15.2. Documents should be designed, prepared, reviewed and authorized for use.
文件應(yīng)經(jīng)過(guò)設(shè)計(jì)、準(zhǔn)備、審核和授權(quán)使用。
15.3. Documents should be reviewed periodically and kept up-to-date. Superseded documents should be retained for a defined period of time.
文件應(yīng)定期審查，并保持最新?tīng)顟B(tài)。被取代的文件應(yīng)在規(guī)定的時(shí)間內(nèi)進(jìn)行保留。
15.4. Entries of data and information should be clear and legible.
數(shù)據(jù)和信息輸入應(yīng)清晰易讀。
15.5. Data (and records for storage) may be recorded by electronic data-processing systems or by photographic or other reliable means. Batch production and control records should be protected throughout the defined period of retention.
數(shù)據(jù)（以及用于存儲(chǔ)的記錄）可以通過(guò)電子數(shù)據(jù)處理系統(tǒng)、或圖片或其它可靠方式進(jìn)行記錄。在規(guī)定的保留期內(nèi)，批生產(chǎn)和控制記錄應(yīng)受到保護(hù)。
15.6. Labels should be clear, unambiguous and in the company’s agreed format.
標(biāo)簽應(yīng)清晰、明確，并采用公司批準(zhǔn)的格式。
15.7. There should be appropriately authorized and dated specifications, including tests on identity, purity and quality, for starting materials and for finished products.
應(yīng)有適當(dāng)?shù)氖跈?quán)和標(biāo)注日期的質(zhì)量標(biāo)準(zhǔn)，包括對(duì)原材料和成品的鑒別、純度和質(zhì)量的檢驗(yàn)項(xiàng)目。
15.8. Pharmacopoeias, reference standards, reference spectra and other reference materials should be available in the QC laboratory.
在質(zhì)量控制實(shí)驗(yàn)室內(nèi)，應(yīng)有藥典、標(biāo)準(zhǔn)品、參考光譜和其它參考材料。
15.9. Specifications should contain appropriate information such as the designated name; internal code reference; and qualitative and quantitative requirements with acceptance limits. Other data may be added to the specification.
質(zhì)量標(biāo)準(zhǔn)應(yīng)包含適當(dāng)?shù)男畔?，例如指定的名稱(chēng)；內(nèi)部代碼參考；定性和定量要求，以及可接受限度?？梢蕴砑悠渌鼣?shù)據(jù)到質(zhì)量標(biāo)準(zhǔn)中。
15.10. The packaging material should be examined for compliance with the specification.
應(yīng)檢查包裝材料是否符合質(zhì)量標(biāo)準(zhǔn)。
15.11. Specifications for intermediate and bulk products should be available where the need has been identified.
確定需求后，應(yīng)提供中間體和半成品的質(zhì)量標(biāo)準(zhǔn)。
15.12. Specifications for finished products should be available and include the required information.
應(yīng)有成品質(zhì)量標(biāo)準(zhǔn)，并包括必需的信息。
15.13. A master formula, containing the relevant information, should be available for the product and batch size to be manufactured.
應(yīng)有包含相關(guān)信息的主配方，并可用于要生產(chǎn)的產(chǎn)品和批量。
15.14. Packaging instructions should exist for the products to be packed.
包裝產(chǎn)品應(yīng)有包裝指導(dǎo)。
15.15. A batch processing record should be kept for each batch processed. It should be based on the relevant parts of the current specifications on record.
對(duì)于每個(gè)已加工的批次，應(yīng)保留一個(gè)批記錄。它應(yīng)基于當(dāng)前質(zhì)量標(biāo)準(zhǔn)（出現(xiàn)在記錄上）的相關(guān)部分。
15.16. During processing, detailed information should be recorded at the time each action is taken and, after completion, the record should be dated and signed by the person responsible for the processing operations.
在加工過(guò)程中，應(yīng)在執(zhí)行每個(gè)操作時(shí)記錄詳細(xì)信息；操作完成后，記錄應(yīng)標(biāo)注日期并由加工操作的負(fù)責(zé)人簽名。
15.17. A batch packaging record should be kept for each batch or part batch processed.
對(duì)于每個(gè)加工批次或部分加工批次，應(yīng)保留批包裝記錄。
15.18. Standard operating procedures (SOP) and corresponding records, where required, should be available. These include, but are not limited to, for example:
a) equipment assembly and cleaning;
b) personnel training, clothing and hygiene;
c) maintenance;
d) sampling;
e) analytical apparatus and instrument calibration;
f) testing;
g) release and rejection；and
h) pest control.
如果需要，應(yīng)提供標(biāo)準(zhǔn)操作程序（SOP）和相應(yīng)的記錄。這些包括但不限于例如：
a）設(shè)備組裝和清潔；
b）人員培訓(xùn)、更衣和衛(wèi)生；
c）維護(hù)；
d）取樣；
e）分析儀器和儀器校驗(yàn)；
f）檢驗(yàn)；
g）放行和拒放；
h）蟲(chóng)害防治。
15.19. Cross-contamination should be avoided by taking the appropriate technical or organizational measures.
應(yīng)通過(guò)采取適當(dāng)?shù)募夹g(shù)或組織措施，來(lái)避免交叉污染。
15.20. Before any processing operation is started, steps should be taken to ensure that the work area and equipment are clean and free from any starting materials, products, product residues, labels or documents not required for the current operation.
在開(kāi)始任何加工操作之前，應(yīng)采取步驟，以確保工作區(qū)域和設(shè)備清潔，且沒(méi)有當(dāng)前操作不需要的任何起始原料、產(chǎn)品、產(chǎn)品殘留物、標(biāo)簽或文件。
15.21. To prevent cross-contamination and mix-ups, different products should not be packaged in close proximity.
為避免交叉污染和混淆，不同產(chǎn)品包裝時(shí)不應(yīng)過(guò)于靠近。
16.加工和工藝驗(yàn)證
Processing and process validation
Note: For details on process validation, see WHO Technical Report Series, No. 1019, Annex 3, Appendix 7, 2019.
注：有關(guān)工藝驗(yàn)證的詳細(xì)信息，請(qǐng)參閱WHO技術(shù)報(bào)告系列第1019號(hào)，附錄3，附件7（2019年）。
加工
Processing
Note: For more details on specific aspects relating to process development, see ICH Q 11.
注意：有關(guān)與工藝開(kāi)發(fā)相關(guān)的特定方面的更多詳細(xì)信息，請(qǐng)參閱ICH Q 11。
16.1. The selection of the starting materials and manufacturing process should be carefully considered in order to ensure that the intended product will meet the intended standards of safety, efficacy and quality in a consistent manner.
應(yīng)仔細(xì)考慮原材料和生產(chǎn)工藝的選擇，以確保目標(biāo)產(chǎn)品以一致的方式滿(mǎn)足安全、功效和質(zhì)量的目標(biāo)標(biāo)準(zhǔn)。
16.2. Knowledge management and risk assessment principles should be applied. Quality attributes, critical quality attributes, process parameters and critical process parameters should be defined and documented.
應(yīng)該使用知識(shí)管理和風(fēng)險(xiǎn)評(píng)估原則。應(yīng)定義和記錄質(zhì)量屬性、關(guān)鍵質(zhì)量屬性，工藝參數(shù)和關(guān)鍵工藝參數(shù)。
16.3. The design of experiments should cover identified variables.
實(shí)驗(yàn)設(shè)計(jì)應(yīng)涵蓋已識(shí)別的變量。
工藝驗(yàn)證
Process validation
16.4. Process validation is usually initiated by research and development organizations. During this stage, the validation is also referred to as “process design”. (In a traditional or historical approach, this was often referred to as “prospective validation”).
工藝驗(yàn)證通常由研發(fā)組織發(fā)起。在此階段，驗(yàn)證也稱(chēng)為“工藝設(shè)計(jì)”。（在傳統(tǒng)或歷史方法中，這通常被稱(chēng)為“預(yù)驗(yàn)證”）。
16.5. Product development activities provide key inputs to the process design stage. Laboratory or pilot-scale models designed to be representative of the commercial process can be used to estimate variability.
產(chǎn)品開(kāi)發(fā)活動(dòng)為工藝設(shè)計(jì)階段提供了重要的輸入信息。設(shè)計(jì)實(shí)驗(yàn)室或中試規(guī)模模型，以代表商業(yè)工藝，可用于估計(jì)變異性。
16.6. Process design should normally cover the design of experiments, process development, the manufacture of products for use in clinical trials, pilot-scale batches and technology transfer.
設(shè)計(jì)通常應(yīng)涵蓋：實(shí)驗(yàn)設(shè)計(jì)、工藝開(kāi)發(fā)、用于臨床試驗(yàn)的產(chǎn)品生產(chǎn)、中試規(guī)模的批次和技術(shù)轉(zhuǎn)移。
16.7. Process design should be verified during product development. Process design should cover aspects for the selection of materials; expected production variation; selection of production technology/process and qualification of the unitary processes that form the manufacturing process as a whole; selection of in-process controls; tests；inspection; and its suitability for the control strategy.
在產(chǎn)品開(kāi)發(fā)過(guò)程中，應(yīng)確認(rèn)工藝設(shè)計(jì)。工藝設(shè)計(jì)應(yīng)涵蓋材料選擇的各個(gè)方面；預(yù)期產(chǎn)量變化；選擇生產(chǎn)技術(shù)/工藝，并對(duì)構(gòu)成整個(gè)生產(chǎn)工藝的單一工藝進(jìn)行確認(rèn)；選擇過(guò)程控制；檢驗(yàn)；檢查;及其對(duì)控制策略的適用性。
16.8. As the validation data are intended to be used in applications for marketing authorizations, all batch data, results and related information should be clear, detailed and in compliance with ALCOA+.
由于驗(yàn)證數(shù)據(jù)將用于上市許可的申請(qǐng)，因此所有批次數(shù)據(jù)、結(jié)果和相關(guān)信息應(yīng)清晰、詳細(xì)，且符合ALCOA +的要求。
17.質(zhì)量控制
Quality control
17.1 The QC unit should be independent from production.
質(zhì)量控制單元應(yīng)獨(dú)立于生產(chǎn)。
17.2 There should be adequate resources available to ensure that all the QC arrangements are effectively and reliably carried out.
應(yīng)有充分的資源，來(lái)確保有效且可靠地執(zhí)行所有質(zhì)量控制安排。
17.3 Activities and responsibilities of the QC unit include:
質(zhì)量控制部門(mén)的活動(dòng)和職責(zé)包括：
a) sampling and testing (e.g. starting materials, packaging materials, intermediate products, bulk products and finished products);
b) performing the necessary qualification and validation;
c) evaluating, maintaining and storing reference standards for substances;
d) ensuring that stability programme and testing is done;
e) participating in environmental monitoring; and
f) participating in QRM programmes.
a）取樣和檢驗(yàn)（例如原材料、包裝材料、中間體、半成品和成品）;
b）進(jìn)行必要的確認(rèn)和驗(yàn)證；
c）評(píng)估、維護(hù)和存儲(chǔ)標(biāo)準(zhǔn)品；
d）確保完成穩(wěn)定性計(jì)劃和檢驗(yàn)；
e）參與環(huán)境監(jiān)測(cè)；
f）參加QRM計(jì)劃。
17.4 Appropriate records should be kept, demonstrating that all the required activities were performed.
應(yīng)保留適當(dāng)?shù)挠涗洠员砻饕淹瓿伤斜匦璧幕顒?dòng)。
17.5 Sufficient samples of materials and products should be retained for a defined period of time.
應(yīng)在規(guī)定的時(shí)間內(nèi)，保留足夠的材料和產(chǎn)品樣品。
17.6 Appropriate reference standards should be used. Standards should be stored in an appropriate way.
應(yīng)使用適當(dāng)?shù)臉?biāo)準(zhǔn)品。標(biāo)準(zhǔn)品應(yīng)以適當(dāng)?shù)姆绞酱鎯?chǔ)。
17.7. Whenever official reference standards exist, these should preferably be used.
只要存在官方標(biāo)準(zhǔn)品，就應(yīng)優(yōu)先使用。
17.8. Where secondary and working standards are established and used, these should be tested at regular intervals to ensure that they are fit for their intended use.
在建立和使用二級(jí)和工作標(biāo)準(zhǔn)品時(shí)，應(yīng)定期檢驗(yàn)這些標(biāo)準(zhǔn)品，以確保它們適合其預(yù)期用途。
17.9. Reference standards should be appropriately labelled with at least the following information:
a) name of the material;
b) batch or lot number and control number;
c) date of preparation;
d) shelf life;
e) potency; and
f) storage conditions.
標(biāo)準(zhǔn)品至少應(yīng)適當(dāng)標(biāo)記以下信息：
a）材料名稱(chēng)；
b）批號(hào)以及控制號(hào)；
c）準(zhǔn)備日期；
d）有效期；
e）活性；和
f）儲(chǔ)存條件。
18. 穩(wěn)定性研究
Stability studies
Note: See guideline on stability testing of active pharmaceutical ingredients and finished pharmaceutical products , WHO Technical Report Series, No. 1010, Annex 10, 2018.
注：見(jiàn)《關(guān)于活性藥物成分和成品的穩(wěn)定性測(cè)試指南》，世衛(wèi)組織技術(shù)報(bào)告系列，第1010號(hào)，附錄10，2018年。
18.1. Where stability determination is initiated by research and development organizations, a written programme should be developed and implemented to include elements such as:
由研究和開(kāi)發(fā)組織發(fā)起穩(wěn)定性研究時(shí)，應(yīng)制定并實(shí)施書(shū)面計(jì)劃，包括以下內(nèi)容：
a) a complete description of the medicine involved in the study；
b) the complete set of testing procedure, parameters and limits;
c) attributes such as potency or assay and physical characteristics；
d) evidence that these tests indicate stability;
e) the testing schedule for each medicine;
f) provision for special storage conditions; and
g) provision for adequate sample retention.
a）研究中所涉及藥物的完整描述；
b）整套檢驗(yàn)程序、參數(shù)和限度；
c）活性或含量和物理特性等屬性；
d）這些檢驗(yàn)可以表明穩(wěn)定性的證據(jù)；
e）每種藥物的檢驗(yàn)時(shí)間表；
f）特殊存儲(chǔ)條件的規(guī)定；
g）提供充分的留樣能力。
18.2. Sampling should be done in accordance with written procedures.
取樣應(yīng)按照書(shū)面程序進(jìn)行。
18.3. Sample preparation and testing procedures should be detailed and followed. Any deviations from the procedures should be clearly documented.
樣品制備和檢驗(yàn)程序應(yīng)詳細(xì)說(shuō)明，并得到遵循。與程序的任何偏差均應(yīng)清楚進(jìn)行記錄。
18.4. The results and data generated should be documented and include the evaluation and the conclusions of the study.
產(chǎn)生的結(jié)果和數(shù)據(jù)應(yīng)形成文件，包括評(píng)估和研究的結(jié)論。
18.5. Where stability data are intended to be used in applications for marketing authorizations, all batch data, results and related information should be clear, detailed and in compliance with ALCOA+.
如果計(jì)劃在上市許可申請(qǐng)中使用穩(wěn)定性數(shù)據(jù)，則對(duì)于所有批次數(shù)據(jù)、結(jié)果和相關(guān)信息，應(yīng)清晰、詳細(xì)，且符合ALCOA +。
18.6. Records should be maintained for a defined period of time.
在規(guī)定的時(shí)間內(nèi)，應(yīng)對(duì)記錄進(jìn)行維護(hù)。
19.分析程序開(kāi)發(fā)
Analytical procedure development
19.1. Analytical procedures developed by research and development organizations should be appropriately recorded.
研發(fā)組織制定的分析程序應(yīng)適當(dāng)記錄。
19.2. As the procedures are usually intended to be transferred to quality control units in manufacturing facilities of commercial batches, procedures and records should be sufficiently detailed to ensure that TOT will be successful.
通常要將程序轉(zhuǎn)移到商業(yè)批生產(chǎn)設(shè)施中的QC單元，因此程序和記錄應(yīng)足夠詳細(xì)，以確保TOT成功。
19.3. Analytical procedures should be appropriately validated.
分析程序應(yīng)適當(dāng)驗(yàn)證。
Note: For details on analytical procedure validation, see WHO Technical Report Series, No. 1019, Annex 3, Appendix 4, 2019.
注：有關(guān)分析程序驗(yàn)證的詳細(xì)信息，請(qǐng)參閱WHO技術(shù)報(bào)告系列第1019號(hào)附錄3，附件4，2019年。
20.技術(shù)轉(zhuǎn)移
Transfer of technology
Note: For details on transfer of technology, see WHO Technical Report Series, No. 961, Annex 7, 2011 (update in progress).
注意：有關(guān)技術(shù)轉(zhuǎn)移的詳細(xì)信息，請(qǐng)參閱WHO技術(shù)報(bào)告系列，第961號(hào)，附錄7，2011年（正在更新）。
20.1. Development work, including programmes, procedures, protocols, specifications and validation from research and development organizations, may be transferred to production and quality control sites.
開(kāi)發(fā)工作，包括計(jì)劃、程序、草案、質(zhì)量標(biāo)準(zhǔn)和研發(fā)組織的驗(yàn)證，可以轉(zhuǎn)移到生產(chǎn)和質(zhì)量控制場(chǎng)所。
20.2. Data and information relating to equipment, instruments, manufacturing, and testing should be detailed, traceable and available.
與設(shè)備、儀器、生產(chǎn)和檢驗(yàn)有關(guān)的數(shù)據(jù)和信息，應(yīng)詳細(xì)、可追溯，具備可及性。
20.3. Authorized procedures should be followed when transferring technology from research and development organizations to production and quality control facilities.
將技術(shù)從研發(fā)組織轉(zhuǎn)移到生產(chǎn)和質(zhì)量控制設(shè)施時(shí)，應(yīng)遵循已批準(zhǔn)的程序。
21.生命周期方法
Life cycle approach
21.1. Industry should implement policies and procedures that will encourage science-based and risk-based approaches in product research and development.
行業(yè)應(yīng)實(shí)施政策和程序，以鼓勵(lì)在產(chǎn)品研發(fā)中采用基于科學(xué)和基于風(fēng)險(xiǎn)的方法。
21.2. Continual improvement should be encouraged across the entire product life cycle.
在整個(gè)產(chǎn)品生命周期中應(yīng)鼓勵(lì)持續(xù)改進(jìn)。
21.3. Knowledge gained from the commercial manufacturing of a product, as well as knowledge gained from other products, can be used to further improve process understanding and process performance.
從產(chǎn)品的商業(yè)生產(chǎn)中獲得的知識(shí)，以及從其它產(chǎn)品中獲得的知識(shí)，可用于進(jìn)一步改善工藝?yán)斫夂凸に囆阅堋?/span>
21.4. New technologies and the review and interpretation of statistical evaluation of results from validation and other processes, as well as other applicable data and information, should be considered in order to encourage continual improvement during the process development stage of the life cycle of the product.
為了鼓勵(lì)在產(chǎn)品生命周期的工藝開(kāi)發(fā)階段不斷改進(jìn)，應(yīng)考慮使用新技術(shù)；并對(duì)驗(yàn)證和其它工藝結(jié)果的統(tǒng)計(jì)評(píng)估、以及其它適用的數(shù)據(jù)和信息，進(jìn)行審查和解釋。
21.5. Where appropriate, these should be shared and transferred to commercial manufacturing facilities.
在適當(dāng)情況下，應(yīng)將這些共享并轉(zhuǎn)移到商業(yè)生產(chǎn)設(shè)施中。
22.清潔程序的開(kāi)發(fā)和清潔驗(yàn)證
Cleaning procedure development and cleaning validation
Note: For details on cleaning validation, see WHO Technical Report Series, No. 1019, Annex 3, Appendix 3, 2019 and the WHO Points to consider when including HBELs in cleaning validation, TRS XXX, Annex 2, 2021.
注意：有關(guān)清潔驗(yàn)證的詳細(xì)信息，請(qǐng)參閱WHO技術(shù)報(bào)告系列第1019號(hào)，附錄3，附件3，2019年；以及將HBEL納入清潔驗(yàn)證時(shí)要考慮的重點(diǎn)，TRS XXX，附錄2，2021年。
22.1. Research and development facilities are often involved in the development and validation of cleaning procedures. QRM principles should be applied in cleaning procedure development and cleaning validation.
研究和開(kāi)發(fā)設(shè)施經(jīng)常參與清潔程序的開(kāi)發(fā)和驗(yàn)證。QRM原則應(yīng)應(yīng)用于清潔程序開(kāi)發(fā)和清潔驗(yàn)證。
22.2. The development of cleaning procedures should include cleanability.
清潔程序的制定應(yīng)包括可清潔性。
22.3. Health Based Exposure Limits (HBELs) should be considered in the approach to cleaning validation.
在進(jìn)行清潔驗(yàn)證的方法中，應(yīng)考慮基于健康的暴露限度（HBEL）。
22.4. The sampling of procedures should include swab and rinse samples. Maximum Safe Residue, Maximum Safe Surface Residue and Visible Residue Limits should be considered in the new cleaning validation approach.
程序的取樣應(yīng)包括棉簽和沖洗樣品。在新的清潔驗(yàn)證方法中，應(yīng)考慮最大安全殘留物、最大安全表面殘留物和可見(jiàn)殘留物限度。
22.5. The development of the analytical procedures to be used in the testing for residues should be appropriately documented. The procedures should be validated.
應(yīng)適當(dāng)記錄用于殘留檢驗(yàn)的分析程序的開(kāi)發(fā)。該程序應(yīng)經(jīng)過(guò)驗(yàn)證。
22.6. Procedures for sampling and testing, and the results obtained, should meet ALCOA+ principles. The data and information should be retained over the life cycle of the product.
取樣和檢驗(yàn)程序，以及獲得的結(jié)果應(yīng)符合ALCOA +原則。數(shù)據(jù)和信息應(yīng)在產(chǎn)品的生命周期內(nèi)保留。
22.7. Procedures and protocols should be followed for the TOT to commercial manufacturing sites. Records should be maintained.
在向商業(yè)生產(chǎn)場(chǎng)所技術(shù)轉(zhuǎn)移過(guò)程中，應(yīng)遵守程序和草案。記錄應(yīng)予以保留。
來(lái)源：蒲公英
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