第一章 质量管理
一、原则Principle
生产许可证持有厂家只能生产医药产品，以确保药品符合其预期的使用目的，符合销售许可证的要求，并不因药品安全性、质量或药效方面的问题而给患者带来风险。达到这一质量目标是高层管理者的责任，同时也需要公司各部门、各层次的职员以及公司的供应商和销售商的参与并承担义务。为了确保达到该质量目标，必须全面设计并正确贯彻实施包括GMP 与质量控制(QC)在内的质量保证(QA)体系。该体系应用文件明文规定并对其有效性加以监控。质量保证体系的所有部门都必须充分配备胜任的人员，适宜足够的厂房、设备及设施。与此同时，生产许可证持有者及受权人员具有另外的法律责任。
The holder of a Manufacturing Authorisation must manufacture medicinal products so as to ensure that they are fit for their intended use, comply with the requirements of the Marketing Authorisation and do not place patients at risk due to inadequate safety, quality or efficacy. The attainment of this quality objective is the responsibility of senior management and requires the participation and commitment by staff in many different departments and at all levels within the company, by the company’s suppliers and by the distributors. To achieve the quality objective in a reliable manner there must be a comprehensively designed and correctly implemented system of Quality Assurance incorporating Goo
d Manufacturing Practice and thus Quality Control. It should be fully documented and its effectiveness monitored. All parts of the Quality Assurance system should be adequately resourced with competent personnel, and suitable and sufficient premises, equipment and facilities. There are additional legal responsibilities for the holder of the Manufacturing Authorisation and for the Qualified Person(s).
1.1 质量保证、GMP 和质量控制的基本概念是内在相互联系的。这里叙述的主要目的是强调它们之间的关系以及药品生产和控制中的重要性。The basic concepts of Quality Assurance, Good Manufacturing Practice and Quality Control are inter-related. They are described here in order to emphasise their relationships and their fundamental importance to the production and control of medicinal products.
accessible是什么意思中文
二、质量保证Quality Assurance
1.2 质量保证是一个宽泛的概念，它包括影响产品质量的所有问题，是确保药品质量符合预期使用目的而进行组织管理的总和。因此质量保证是由GMP 本规范之外的其他因素所组成。Quality Assurance is a wide ranging concept which covers all matters which individually or collectively influence the quality of a product. It is the total sum of the organised arrangements made with the object of ensuring that medicinal products are of the quality required for their intended use. Quality Assurance therefore incorporates Good Manufacturing Practice plus other factors outside the scope of this Guide.
质量保证体系对于药品的生产而言，应保证：The system of Quality Assurance appropriate for the manufacture of medicinal products should ensure that:
(1) 药品的设计与开发应按照GMP 和GLP 的要求进行；medicinal products are designed and developed in a way that takes account of the requirements of Good Manufacturing Practice and Good Laboratory Practice;
(2) 生产和控制操作应有明确规定，并采用GMP；production and control operations are clearly specified and Good Manufacturing Practice adopted;
(3) 明确规定管理职责；managerial responsibilities are clearly specified;
(4) 安排生产、供应和使用正确的原、辅、包材料；arrangements are made for the manufacture, supply and use of the correct starting and packaging materials;
(5) 对中间产品进行必要的控制、进行其他任何过程控制和验证；all necessary controls on intermediate products, and any other in-process controls and validations are carried out;
(6) 按照规定的程序，正确地加工与核查成品；the finished product is correctly processed and checked, according to the defined procedures;
(7) 在受权人确认批产品按照销售许可证和其他与药品生产、检验和释放有关的法规要求进行生产和质量控制，并签发合格证之前，药品不得销售或供应；medicinal products are not sold or supplied before a Qualified Person has certified that each production batch has been produced and controlled in accordance with the requirements of the Marketing Authorisation and any other regulations relevant to the production, control and release of medicinal products;
(8) 尽可能对药品贮存、销售及随后的处理做出满意的安排，以保证药品在货架寿命期内的质量；satisfactory arrangements exist to ensure, as far as possible, that the medicinal products are stored, distributed and subsequently handled so that quality is maintained throughout their shelf life;
(9) 建立自检和/或质量审计程序，定期对质量保证体系的有效性和适用性进行评价。there is a procedure for Self-Inspection and/or quality audit which regularly appraises the effectiveness and applicability of the Quality Assurance system.
三、药品生产质量管理规范(GMP)Good Manufacturing Practice for Medicinal Products
1.3 GMP 是质量保证的一部分，它确保药品始终按照适合于其使用目的的质量标准进行生产和控制，并符合销售许可证的要求。
1.3 Good Manufacturing Practice is that part of Quality Assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the Marketing Authorisation or product specification.
GMP 涉及生产和质量控制，其基本要求如下：
Good Manufacturing Practice is concerned with both production and quality control. The basic requirements of GMP are that:
(1) 所有生产工艺应有明确规定，根据经验进行系统的审核，并证明能够始终如一地生产出符合质量标准的药品。all manufacturing processes are clearly defined, systematically reviewed in the light of experience and shown to be capable of consistently manufacturing medicinal products of the required quality and complying with their specifications;
(2) 应对生产工艺的关键步骤和工艺的重要变更进行验证。critical steps of manufacturing processes and significant changes to the process are validated;
(3) 提供所有GMP 必需的设施，包括：all necessary facilities for GMP are provided including:
a. 资历合格并经过培训的人员；appropriately qualified and trained personnel;
b. 适宜的厂房和空间；adequate premises and space;
c. 合适的设备及配套设施；suitable equipment and services;
d. 正确的物料、容器和标签；correct materials, containers and labels;
e. 经批准的程序和指令；approved procedures and instructions;
f. 合适的贮存设施和运输设备。suitable storage and transport;
(4) 指令和程序应使用清楚明了的语言，并适用于所提供的设施。 instructions and procedures are written in an instructional form in clear and unambiguous language, specifically applicable to the facilities provided;
(5) 操作者应经过培训，以便按正确地按照程序进行操作。operators are trained to carry out procedures correctly;
(6) 生产过程中采用手工和/或记录仪填写记录，以证明已完成的所有生产步骤是按照确定的程序和指令要求进行的，产品达到预期的质量和数量。任何重要偏差都应详细记录和调查。records are made, manually and/or by recording instruments, during manufacture which demonstrate that all the steps re
quired by the defined procedures and instructions were in fact taken and that the quantity and quality of the product was as expected. Any significant deviations are fully recorded and investigated;
(7) 采用合适的方式保存生产记录（包括销售记录），以便追溯各批产品的完整历史。records of
manufacture including distribution which enable the complete history of a batch to be traced, are retained in a comprehensible and accessible form;
(8) 应将产品销售（批发）中影响质量的风险减至最低限度。the distribution (wholesaling) of the products minimises any risk to their quality;
(9) 建立从销售或供应渠道收回任何一批产品的系统。a system is available to recall any batch of product, from sale or supply;
(10) 了解上市产品的用户投拆，调查质量缺陷的原因，并采取的相应的整改措施，以避免再次发生。complaints about marketed products are examined, the causes of quality defects investigated and appropriate measures taken in respect of the defective products and to prevent reoccurrence.
四、质量控制(QC) Quality Control
1.4. 质量控制是GMP 的一部分，它涉及取样、质量标准和质量检验、机构、文件和放行程序，以确保进行必要的相关检验，在判定质量符合要求之前，物料不得使用，产品不得销售或供应。Quality Control is that part of Good Manufacturing Practice which is concerned with sampling, specifications and testing, and with the organisation, documentation and release procedures which ensure that the necessary and relevant tests are actually carried out and that materials are not released for use, nor products released for sale or supply, until their quality has been judged to be satisfactory.
质量控制的基本要求如下：The basic requirements of Quality Control are that:
(1) 有适宜的设施、经过培训的人员和批准的程序，以便对原辅料、包装材料、中间产品、待包装品和成品进行取样、检查、测试以及必要时按照GMP 要求对环境进行监测。adequate facilities, trained personnel and approved procedures are available for sampling, inspecting and testing starting materials, packaging materials, intermediate, bulk, and finished products, and where appropriate for monitoring environmental conditions for GMP purposes;
(2) 由质量部门批准的人员并使用已批准的方法对原辅料、包装材料、中间产品、待包装品和成品进行取样。samples of starting materials, packaging materials, intermediate products, bulk products and finished products are taken by personnel and by methods approved by Quality Control;
(3) 对检验方法进行验证。test methods are validated;
(4) 采用手工和/或记录仪进行记录，以证明规定的取样、检查和测试程序均已完成。详细记录出现的任何偏差，并进行调查。records are made, manually and/or by recording instruments, which demonstrate that all the required sampling, inspecting and testing procedures were actually carried out. Any deviations are fully recorded and investigated;
(5) 成品应含有符合销售许可证规定的定性、定量要求的活性成分，应具有规定的纯度，包装在合适容器中，并正确加贴标签。the finished products contain active ingredients complying with the qualitative and quantitative composition of the Marketing Authorisation, are of the purity required, and are enclosed within their proper containers and correctly labelled;
(6) 记录应包括检查结果以及物料、中间产品、待包装品和成品依照质量标准进行检验的评价结果。产品评价包括对有关生产文件的审核与评价以及对偏离规定程序的偏差的评价。records are made of the results of inspection and that testing of materials, intermediate, bulk, and finished products is formally assessed against specification. Product assessment includes a review and evaluation of relevant roduction documentation and an assessment of deviations from specified rocedures;
(7) 任何一批产品在未经受权人按照销售许可证的要求审核并签发合格证之前，不得放行销售或供应。n
o batch of product is released for sale or supply prior to certification by a qualified Person that it is in accordance with the requirements of the Marketing Authorisation;
(8) 原料有充足的对照品，产品应保留以便用于将来必须的产品检验，除产品的大包装外，产品保留最终包装形式。sufficient reference samples of starting materials and products are retained to permit future examination of the product if necessary and that the product is retained in its
final pack unless exceptionally large packs are produced.
五、产品质量回顾Product Quality Review
1.5. 应对所有获得许可证的药品，包括那些仅供出口的药品，进行定期或滚动式的质量回顾以证明所用工艺的始终一致性，起始原料和成品现行质量标准的适当性，并重点反映出变化趋势以及产品和工艺的改进。产品质量回顾一般情况下每年进行一次，并形成文件，应考虑到以前所作的产品质量回顾并至少应包括以下内容：
1.5. Regular periodic or rolling quality reviews of all licensed medicinal products, including export only products, should be conducted with the objective of verifying the consistency of the existing process, the appropriateness of current specifications for both starting materials and finished product to highligh
t any trends and to identify product and process improvements. Such reviews should normally be conducted and documented annually, taking into account previous reviews, and should include at least:
(1) 对产品中所使用的原辅料进行质量回顾，特别是那些由新供应商提供的原辅料。A review of starting materials and packaging materials used for the product, especially those from new sources.
(2) 对关键的过程控制和成品的检验结果进行质量回顾。A review of critical in-process controls and finished product results.
(3) 对所有不符合质量标准的批次进行回顾。A review of all batches that failed to meet established specification(s) and their investigation.
(4) 对所有关键性的偏差或不符合项以及与之相关的调查、整改结果和预防措施的有效性进行回顾。A review of all significant deviations or non-conformances, their related investigations, and the effectiveness of resultant corrective and preventative actions taken.
(5) 对所有工艺或检验方法的变更进行回顾。A review of all changes carried out to the processes or analytical methods.
(6) 对销售许可证变更内容的申报/批准/拒绝批准的情况进行回顾，包括第三国（出口国）申报的资料。A review of Marketing Authorisation variations submitted/granted/refused, including those for third country (export only) dossiers.
(7) 对稳定性监测结果进行回顾。A review of the results of the stability monitoring programme and any adverse trends.
(8) 对所有与质量相关的退货、投诉、召回、调查进行回顾。A review of all quality-related returns, complaints and recalls and the investigations performed at the time.
(9) 对以前整改措施的适合性进行回顾。A review of adequacy of any other previous product process or equipment corrective actions.
(10)对于新销售许可证和销售许可证变更，则对其执行情况进行回顾。For new marketing authorisations and variations to marketing authorisations, a review of post-marketing commitments.
(11)相关设备和公用系统的验证状态，如暖通空调系统、水系统、压缩空气等。The qualification status of relevant equipment and utilities, e.g. HVAC, water, compressed gases, etc.
(12)已进行验证的设备清单和再验证的日期。A review of Technical Agreements to ensure that they are
up to date.
生产厂家和销售许可证的持有者，若不是同一主体时，应对产品质量回顾的结果进行评价，应评价是否应采取整改措施和预防措施或是否应进行再验证。进行整改的原因应形成文件。对于已同意的整改措施和预防措施应通过有效的方法适时完成。应有适用的管理程序，应在自检中对这些程序的有效性进行确认。
The manufacturer and marketing authorisation holder, where different, should evaluate the results of this review and an assessment should be made whether corrective and preventative action or any revalidation should be undertaken. Reasons for such corrective actions should be documented. Agreed corrective and preventative actions should be completed in a timely and effective manner. There should be management procedures for the
ongoing management and review of these actions and the effectiveness of these procedures verified during selfinspection.
产品质量回顾可根据产品类型进行相应的科学分类，例如：固体制剂、液体制剂、无菌产品等。Quality reviews may be grouped by product type, e.g. solid dosage forms, liquid dosage forms, sterile products, etc. where scientifically justified.
当生产厂家与销售许可证的持有者不是同一主体时，双方之间应签订技术协议详细说明在产品质量回顾中各自相应的职责。负责成品质量的受权人与销售许可证持有者应确保产品质量回顾适时进行，并且确保其结果的准确性。
Where the marketing authorisation holder is not the manufacturer, there should be a technical agreement in place between the various parties that defines their respective responsibilities in producing the quality review. The Qualified Person responsible for final batch certification together with the marketing authorisation holder should ensure that the quality review is performed in a timely manner and is accurate.

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