《FDA行业指南委托生产质量协议中英文.pdf》由会员分享，可在线阅读，更多相关《FDA行业指南委托生产质量协议中英文.pdf（21页珍藏版）》请在三一文库上搜索。
1、FDA Guidance for Industry: Contract Manufacturing Arrangements for Drugs:Quality A greements Page 1 / 21 FDA 行业指南：药品委托生产安排：质量协议翻译： Julia Contract Manufacturing Arrangements for Drugs: Quality Agreements Guidance for Industry 行业指南：药品委托生产安排：质量协议 U.S. Department of Health and Human Services Food and Dr
2、ug Administration Center for Drug Evaluation and Research (CDER) Center for Biologics Evaluation and Research (CBER) Center for Veterinary Medicine (CVM) November 2016 Pharmaceutical Quality/Manufacturing Standards (CGMP) FDA Guidance for Industry: Contract Manufacturing Arrangements for Drugs:Quali
3、ty A greements Page 2 / 21 FDA 行业指南：药品委托生产安排：质量协议翻译： Julia Guidance for Industry Additional copies are available from: Office of Communications, Division of Drug InformationCenter for Drug Evaluation and Research Food and Drug Administration 10001 New Hampshire Ave., Hillandale Bldg., 4 th FloorSilv
4、er Spring, MD 20993-0002 Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 Email: druginfofda.hhs.gov http:/www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm and/or Office of Communication, Outreach and DevelopmentCenter for Biologics Evaluation and Research Food a
5、nd Drug Administration 10903 New Hampshire Ave., Bldg. 71, Room 3128Silver Spring, MD 20993-0002 Phone: 800-835-4709 or 240-402-8010 Email: ocodfda.hhs.gov http:/www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm and/or Policy and Regulations Staff, HFV-
6、6Center for Veterinary MedicineFood and Drug Administration 7519 Standish Place, Rockville, MD 20855 http:/www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/default.htm U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation a
7、nd Research (CDER) Center for Biologics Evaluation and Research (CBER) Center for Veterinary Medicine (CVM) November 2016 Pharmaceutical Quality/Manufacturing Standards (CGMP) FDA Guidance for Industry: Contract M anufacturing Arrangements for Drugs: Quality A greements Page 3 / 21 FDA 行业指南：药品委托生产安排
8、：质量协议翻译： Julia TABLE OF CONTENTS 目录 TABLE OF CONTENTS 目录 3 I. INTRODUCTION 前言 . 4 II. DEFININGTHEWHOAND WHAT OFCONTRACT MANUFACTURING 指定委托生产的人和事 6 III. RESPONSIBILITIESOFPARTIES INVOLVED IN CONTRACTMANUFACTURING委托生产所涉及各方的职责7 IV. DOCUMENTINGCGMPACTIVITIESIN QUALITYAGREEMENTS 在质量协议中记录CGMP 活动 10 A.What
9、 Is a Quality Agreement? 什么是质量协议？. 10 B.Elements of a Quality Agreement 质量协议的要素 11 V. ILLUSTRATIVESCENARIOS案例 17 A.Owners and Contract Facilities Are Both Responsible for CGMP 所有者和受托场所是否都对CGMP负 责？18 B. CGMPs Apply to all Contract Facilities, Including Analytical Testing Laboratories 适用于所有合同场所， 包括分析化
10、验室的CGMP . 19 C.Owners and Contract Facilities Perform Change Control Activities 所有者和受托方实施变更控制活动 20 VI. RECOMMENDATIONS 建议 21 FDA Guidance for Industry: Contract M anufacturing Arrangements for Drugs: Quality A greements Page 4 / 21 FDA 行业指南：药品委托生产安排：质量协议翻译： Julia Contract Manufacturing Arrangements
11、for Drugs:Quality Agreements Guidance for Industry 1 行业指南：药品委托生产安排：质量协议 This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative
12、 approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title page. 本指南代表FDA 当前对此问题的看法。它并未赋予任何人以任何权力，也不对FDA 和公众具有任 何强制约束。如果你有一个替代的方法满足适用的法律法规要求，你可以使用该方法。如需对替代 方法进行
13、讨论，请联系本指南标题页上的FDA 官方负责人。 I. INTRODUCTION 前言 This guidance describes FDA current thinking on defining, establishing, and documenting manufacturing activities of the parties involved in contract drug manufacturing subject to current good manufacturing practice (CGMP) requirements. In particular, we de
14、scribe how parties involved in contract drug manufacturing can use quality agreements to delineate their manufacturing activities to ensure compliance with CGMP. 本指南讲述了FDA 当前对于受到CGMP 约束的药品委托生产所涉及各方如何定义、设立 和记录生产活动的看法，尤其是药品委托各方如何使用质量协议来描绘其生产活动，以 确保符合CGMP 。 For purposes of this guidance, we use certain
15、 terms with the following specific meanings: 在本指南中，我们使用了特定的术语，其在指南中的含义如下： Current Good Manufacturing Practice (CGMP) refers to requirements in the Federal Food, Drug, and Cosmetic Act (FD 21 CFR parts 210 and 211; and 21 CFR part 600. 7 Section 501 of the FD describe how changes to processes, equipm
16、ent, methods, and specifications will be managed; and permit the owner to audit its contractorfacilities for compliance with CGMP. ICH 行业指南Q7原料药GMP 指南建议所有者对合同场所进行评估，以确保受托方场 所在指定的操作方面符合CGMP 。它还建议所有者与受托方之间有一份书面批准的协议， 在其中详细定义生产职责，包括各方的质量措施。书面协议还应说明对分包的考虑、描述 如何管理工艺、设备、方法和质量标准变更、允许所有者就是否符合CGMP 方面审计其受 托方的
17、场所。 ICH guidance for industry Q9 Quality Risk Management offers a systematic approach to quality risk management as part of an effective quality system. It discusses quality risk management principles such as risk assessment, risk communication, and risk review and provides examples of tools that ca
18、n be used to make effective and efficient risk-based decisions in, for example, auditing and arranging quality agreements with contract manufacturers. ICH 行业指南Q9风险管理提供了质量风险管理的系统方法，它是有效质量体系的一部 分。它讨论了质量风险管理原则，如风险评估、风险沟通和风险审核，并给出了一些工具 的使用实例，这些工具可以用于做出基于风险的有效且高效的决策，如在审计和安排委托 生产质量协议方面。 ICH guidance for i
19、ndustry Q10 Pharmaceutical Quality System states that, as part of a pharmaceutical quality system, the owner is ultimately responsible for ensuring that “processes are in place to assure the control of outsourced activities and quality of purchased materials.” 17 It indicates that these processes sh
20、ould incorporate quality risk management and include the following critical activities: ICH 行业指南Q10药品质量体系声明，作为药物质量体系的一部分，所有者对于确保 “ 有程序确保外包活动的控制和所购物料的质量” 有最终责任。它指出这些程序应整合在质 量风险管理中，并包括以下关键活动： Assessing the suitability and competence of potential contractors before outsourcing operations or selecting m
21、aterial suppliers. This could be accomplished through audits, material evaluations, or other qualification criteria. 在将操作外包或选择物料供应商之前，评估潜在合同方的可持续性和资质。可以通 过审计、物料评估或其它确认标准来实现。 Defining the manufacturing responsibilities and communication processes for quality- related activities of the involved partie
22、s. For outsourced activities, these should be in a written agreement. 界定相关各方质量相关活动的生产职责和沟通流程。对于外包活动，应该在书面协 议上界定。 16 In ICH Q7, the term company is used rather than owner and is used to refer to an API manufacturer. 在 ICH Q7 中，使用的是“公司”而不是“所有者”来指原料药生产商。 17 In ICH Q10, the term company is used rather t
23、han owner. 在 ICH Q10 中，使用的是“公司”而不是“所有者”。 FDA Guidance for Industry: Contract M anufacturing Arrangements for Drugs: Quality A greements Page 10 / 21 FDA 行业指南：药品委托生产安排：质量协议翻译： Julia Monitoring and reviewing the performance of the contract facility and identifying and implementing any needed improveme
24、nts. 监测和审核受托场所的表现，识别并实施所需的改进措施。 Monitoring incoming ingredients and materials to ensure they are from approved sources using the agreed-upon supply chain. 监测进厂成分和物料，以确保他们是来自批准过的来源，并且使用的是经过认可的 供应链。 FDA encourages parties engaged in contract manufacturing to implement quality management practices. Thi
25、s guidance is intended to build upon the quality risk management principles and recommendations outlined above and to illustrate key points in developing and executing quality agreements that describe and support contract manufacturing arrangements. FDA鼓励委托生产各方实施质量管理规范。本指南意在建立上述质量风险管理原则和建议， 解释制订和执行质
26、量协议中的关键点，在协议中描述和支持合同生产安排。 IV.DOCUMENTING CGMP ACTIVITIES IN QUALITY AGREEMENTS 在质量协议中记录CGMP活 动 If an owner employs a contract facility for all or part of the manufacturing (including processing, packing, holding, or testing) of a drug or drug product, the owner quality unit is responsible for approv
27、ing or rejecting the contract facility product or service 18 . The contract facility is also required to comply with statutory CGMP and applicable CGMP regulations, including requirements for its quality unit 19 . CGMP regulations require that quality unit activities and procedures be in writing, an
28、d that these procedures be followed 20 . 如果一个所有者使用了一个合同工厂来实施药品生产中所有的生产操作（包括加工、包装、 保存和检测），则所有者的质量部门要负责批准和拒收合同工厂的产品或服务。受托场所 也需要符合法定的CGMP 和适用的CGMP 法规，包括对其质量部门的要求。CGMP 法规要 求制订并遵守书面的质量部门活动和程序。 Implementing a written quality agreement can facilitate compliance with CGMP and, in particular, with 21 CFR 211
29、.22(d), which states that quality unit activities and procedures should be in writing. FDA recommends that owners and contract facilities establish a written quality agreement to describe their respective CGMP-related roles, responsibilities, and activities in drug manufacturing. It is important to
30、note that quality agreements cannot be used to delegate statutory or regulatory responsibilities to comply with CGMP. The following sections describe the Agency current thinking regarding the documentation of agreed-upon manufacturing activities in a quality agreement, as well as the basic elements
31、of a quality agreement. 实施书面的质量协议可以有助于符合CGMP ，尤其是21CFR211.22（ d）的要求，在其中说 明了应有书面的质量部门活动和程序。FDA 建议所有者和合同场所建立一份书面的质量协 议，以描述双方在药品生产中各自的CGMP 相关义务、职责和活动。很重要的一点是要注 意质量协议不能用于委托符合CGMP 的法定或法规职责。以下部分描述了当局当前对质量 协议中双方同意的生产活动的文件记录方面以及质量协议基本要素看法。 A.What Is a Quality Agreement? 什么是质量协议？ A quality agreement is a com
32、prehensive written agreement between parties involved in the contract manufacturing of drugs that defines and establishes each party s manufacturing activities 18 Section 501(a)(2)(B) of the FD 21 CFR 211.22(a). 19 21 CFR 210.2(b); 21 CFR 211.22(a). 20 21 CFR 211.22(d). FDA Guidance for Industry: Co
33、ntract M anufacturing Arrangements for Drugs: Quality A greements Page 11 / 21 FDA 行业指南：药品委托生产安排：质量协议翻译： Julia in terms of how each will comply with CGMP. In general, the quality agreement should clearly state which party the owner or the contract facility or both carries out specific CGMP activitie
34、s. It should cover activities mentioned in section 501(a)(2)(B) of the FD 21 CFR 211.22(a). 24 See section 301(a) of the FD&C Act. FDA Guidance for Industry: Contract M anufacturing Arrangements for Drugs: Quality A greements Page 14 / 21 FDA 行业指南：药品委托生产安排：质量协议翻译： Julia drugs for multiple owners. 质量
35、协议的本部分应识别出受托方要实施生产操作的指定地点，包括地址和每个地点所提 供的具体服务。其中应指出何方将验证工艺，确认和维护与委托操作相关的设备和适用系 统。其中包括信息技术和自动化控制系统、环境监测和空间分级、公用系统和其它所有必 须维护以在CGMP 条件下实施合同生产操作的设备和设施。安排还要识别何方应批准设备 验证、确认和维护活动。另外，如果受托方为多个所有者生产药品时，协议应指出各方要 如何沟通关于防止交叉污染和维护可追溯性的信息。 c.Materials management 物料管理 This section of a quality agreement should indic
36、ate which party will establish specifications for components as well as which party will establish processes for auditing, qualifying, and monitoring component suppliers. It should also identify which party will conduct required sampling and testing in compliance with CGMP. This section of the quali
37、ty agreement should address how the parties will ensure appropriate inventory management, including labeling, label printing, inventory reconciliation, and product status identification (e.g., quarantine). The agreement should address how the contract facility will prevent mix-ups and cross- contami
38、nation. FDA does not expect the agreement to contain a complete description of the supply chain for each component. However, the agreement should define responsibility for physical control of materials at different points in the manufacturing process. For example, the quality agreement should cover
39、responsibilities for proper conditions for storing and transporting or shipping materials. It should define each party s roles in storage and transport whether from the contract facility back to the owner or to another contract facility for further operations. This includes defining activities for m
40、onitoring or validating shipping conditions as appropriate. 质量协议的本部分应指明哪方要建立成分的质量标准，以及哪方要建立审计、确认和监测 成分供应商的流程。其中还要识别出哪方要按CGMP 要求实施所需的取样的检测。质量协 议的本部分应说明各方要如何确保适当的在库管理，包括贴标、标签打印、库存数据平衡 以及产品状态识别（例如待验）。协议应说明受托方要如何防止混药和交叉污染。FDA 并 不要求在协议中包括每个成分的供应链完整描述。但是，协议中应界定生产过程不同阶段 物料的实物控制职责。例如，质量协议应覆盖物料存贮、运输和发运的适当条件的
41、职责。 其中应界定各方在存贮和运输中的职责- 是从合同生产场所送回至所有者，还是发给另一 个合同生产场所用于进一步操作。其中包括适当时监测和验证运输条件的活动。 d.Product-specific considerations 与产品相关的考虑 A comprehensive quality agreement may address specific considerations related to individual products. The owner and contract facility might opt to include this information in a
42、n appendix, or directly in the body of the quality agreement. In either case, if included, this section of the quality agreement should include the parties expectations of each other regarding: 一份全面的质量协议可以说明与单个产品相关的特定考虑。所有者和受托方可以选择将此 信息放在附录中，或直接放在质量协议的正文中。不管放在哪里，如果质量协议中包括了 这些内容，则该部分应包括各方对另一方在以下方面的要求
43、： Product/component specifications 产品 /组分质量标准 Defined manufacturing operations, including batch numbering processes 定义的生产操作，包括批编号流程 Responsibilities for expiration/retest dating, storage and shipment, and lot disposition 有效期 /复验期、存贮和运输以及批处理责任 FDA Guidance for Industry: Contract M anufacturing Arrang
44、ements for Drugs: Quality A greements Page 15 / 21 FDA 行业指南：药品委托生产安排：质量协议翻译： Julia Responsibilities for process validation, including design, qualification, and ongoing verification and monitoring 工艺验证，包括设计、确认、和持续确认和监测方面职责 Provisions to allow owner personnel access to the contract facility when appr
45、opriate 允许所有者人员在适当时进入受托方场所的条款 The quality agreement also should indicate how owners will transfer knowledge, such as product and process development information, to contract facilities to ensure a drug can be manufactured in compliance with CGMP, and conversely how contract facilities should share w
46、ith owners product quality information gained throughout the product life cycle. This applies to knowledge about all drugs, including drugs subject to an approved application (e.g., new drug application) and nonprescription drug products marketed under an over-the-counter drug monograph. 质量协议也应说明所有者
47、要如何转移知识，如产品和工艺研发信息，给受托方，以确保药 品生产符合CGMP ，并反向获取受托方如何与所有者分享在产品生命周期中获得的产品质 量信息。这适用于所有药品的知识，包括需要批准的申报的药品（例如，新药申报）和根 据 OTC 药品各论上市销售的非处方药品。 Owners that hold an approved drug application should be aware of application and approval requirements that could affect manufacturing activities. Both parties to a qu
48、ality agreement should share relevant information to ensure compliance with CGMP and other applicable requirements of the FD&C Act. 持有已批准药品申报的所有者应了解可能会影响生产活动的申报和批准要求。质量协议的 双方均应分享相关信息，以确保符合CGMP 和其它适用的FD&C 法案要求。 e.Laboratory controls 实验室控制 The owner and contract facility should both have access to adequate laboratory facilities for testing of their drugs. A quality agreement will help each party meet this need by defining roles and responsibilities for laboratory controls. We recommend the following elements: 所有者和受托方双方均应具备足够的化验室设施用于检测其药品。质量协议将有助于双方 通过界定