ASTME250007中英文对照

1、ASTM E2500-07 Standard Guide for Specification, Design, and Verification of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment 1This standard is issued under the fixed designation E 2500; the number immediately following the designation indicates the year of original adoption o

2、r, in the case of revision. A number in parentheses indicates the year of last re-approval. A superscript epsilon () indicates an editorial change since the last revision or re-approval.制药、生物制药生产系统和设备的规范、设计、验证标准指南这个标准出版的固定名称是E2500;名称后紧接的数字表示最初版本的年份，或修订的情况。括号中的数字表示最近一次重新批准的年份。上标()表示自从最近一次修订或重新批准以来，编辑

3、修改情况。1. Scope范围1.1 This guide is applicable to all elements of pharmaceutical and biopharmaceutical manufacturing systems including: facility equipment, supporting utilities, associated process monitoring and control systems, and automation systems that have the potential to affect product quality a

4、nd patient safety.1.1本指南适用于制药和生物制药生产系统中，可能影响产品质量和病人安全的所有要素，其中包括：设施设备，公用支持系统，相关过程的监控和控制系统，自动化系统。1.2 For brevity, these are referred to throughout the rest of thin guide as manufacturing systems. 1.3 This guide may also be applied to laboratory, information, and medical device manufacturing systems. 1

5、.4 This guide is applicable to both new and existing manufacturing systems. The approach may be used for the implementation of changes to existing systems, and their continuous improvement during operation. 1.5 This guide is applicable throughout the life-cycle of the manufacturing system from conce

6、pt to retirement.1.2简要的说，这是一个全国通用的有关生产系统的小指南。1.3本指南也可以适用于实验室，信息和医疗设备制造系统。1.4本指南适用于新的和现有的生产系统。该方法可用于实行对现有系统的变更，并实现运行过程中，对现有系统的持续改进。1.5本指南适用于生产系统从概念到报废的整个生命周期。1.6 This standard does not address employee health and safety, environmental, or other non-GXP regulations. This standard does not purport to a

7、ddress all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.1.6该标准不涉及讨论雇员的健康和安全，环境，或其他非GXP的规定。这一标准不是讨论所有的安全问题，如果有的

8、话，与其使用相关。本标准的使用者的职责，是建立适当的安全和卫生标准，并在使用前确定限制性规范的适用性。2. Reference Documents参考文献2.1 ASTM Standards: 2E 2363 Terminology Relating to Process Analytical Technology in the Pharmaceutical Industry2.2 Other Publications:ICH Q8 Pharmaceutical Development Handbook3ICH Q9 quality Risk Handbook3Pharmaceutical c

9、GMPs for the 21st CenturyA Risk-Based Approach42.1美国试验与材料协会标准（简称：ASTM标准）E 2363制药工业过程分析技术的有关术语2.2其它出版物ICH Q8 药品研发手册ICH Q9 质量风险管理手册21世纪药品CGMP基于风险管理方法3. Terminology术语3.1 DefinitionsFor definitions of terms used in this guide, refer to Terminology E 2363.定义-这个指南中使用的术语的定义，请参阅E2363术语部分。3.1.1acceptance cri

10、teriathe criteria that a system or component must satisfy in order to be accepted by a user or other authorized entity.验收标准这个标准必须确保某一系统或组件能够被使用者或其他授权机构所接受。3.1.2design reviewsplanned and systematic reviews of specifications, design, and design development and continuous improvement changes performed

11、as appropriate throughout the life-cycle of the manufacturing system. Design reviews evaluate deliverables against standards and requirements, identify problems, and propose required corrective actions.设计回顾在整个生产系统的生命周期中，有计划、系统地对规范、设计、设计开发和持续改进情况进行适当的回顾审查。设计回顾可根据标准和要求，交付评价，找出问题，并提出必要的纠正措施。3.1.3manufa

12、cturing systemselements of pharmaceutical and biopharmaceutical manufacturing capability, including manufacturing systems, facility equipment, process equipment, supporting utilities, associated process monitoring and control systems, and automation systems, that have the potential to affect product

13、 quality and patient safety.生产系统-制药和生物制药生产能力的各要素，包括生产系统，设施设备，工艺设备，公共支持系统，相关的过程监测和控制系统，自动化系统，所有这些，都有可能影响产品质量和病人安全。3.1.4 subject matter experts (SMEs)individuals with specific expertise and responsibility in a particular area or field (for example, quality unit, engineering, automation, development, o

14、perations, and so forth).相关领域的专家（SMEs）-在某一特定领域或方面（例如，质量部门，工程学，自动化技术，研发，经营，等等），个人拥有的资格和特殊技能。3.1.5 verificationa systematic approach to verify that manufacturing systems, acting singly or in combination, are fit for intended use, have been properly installed, and are operating correctly. This is an um

15、brella term that encompasses all types of approaches to assuring systems are fit for use such as qualification, commissioning and qualification, validation, system validation or other.验证-是一个系统的方法，用来证实生产系统、单独或联合操作，是否符合其预定用途，是否已正确安装，并正确运行。这是一个总称，它包括所有确保系统适合其用途的方法，如确认，调试和确认，验证，系统验证或其他。1 This guide unde

16、r the jurisdiction of ASTM Committee E55 on Manufacture of Pharmaceutical Products and is the direct responsibility of Subcommittee E55.03 on General Pharmaceutical Standards.Current edition approved June 1,2007. Published August 2007.本指南由ASTM委员会E55（医药产品的生产）管辖, 具体由E55.03（一般的药品标准）小组委员会直接负责。当前版本2007年6

17、月1日批准。2007年8月出版。2 For referenced ASTM standards, visit the ASTM website, www. astm. org, or contact ASTM Customer Service at . for Annual Book of ASTM Standards volume information, refer to the standards Document Summary page on the ASTM website.有关ASTM标准，请访问ASTM的网站，. 或联系AS

18、TM客户服务网站 . ASTM标准的年刊信息，请参阅ASTM网站上本标准的文件摘要页。3 Available from International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use(ICH),ICH secretariat, c/o IFPMA,15ch. Louis-Dunant, P.O. Box 195,1211 Geneva 20,Switzerland, http:/www.ich.

19、org.可联系人用药品注册技术要求国际协调会(ICH), 转ICH秘书处，IEPMA,15号。邮政信箱Louis-Dunant 195,1211 Geneva 20，Switzerland、。4 Available from Food and Drug Administration(FDA),5600 Fishers Ln., Rockville, MD 20857, .可联系美国食品药品管理局(FDA), Fishers Ln., Rockville, MD 20857, .4. Summa

20、ry of Guide4.指南概述4.1 This guide describes a risk-based and science-based approach to the specification, design, and verification of manufacturing systems and equipment that have the potential to affect product quality and patient safety. 本指南以风险和科学为基础的方法，对潜在可能影响产品质量和病人安全的生产系统和设备的规范，设计和验证进行描述。4.2 This

21、 guide describes a systematic, efficient, and effective way of ensuring that manufacturing systems and equipment are fit for intended use, and that risk to product quality, and consequently to patient safety, are effectively managed to the extent that these are affected by such systems and equipment

22、.本指南描述了一个系统的、高效的和有效的方式，确保生产系统和设备符合预期的使用目的，而且对关乎产品质量和随后病人安全的风限进行有效管理，受系统和设备影响的风险都在范围内。4.3 The overall objective is to provide manufacturing capability to support defined and controlled processes that can consistently produce product meeting defined quality requirements. 总的目标是提供生产能力，以支持明确的、受控的工艺能够持续生产

23、出符合质量规范的产品。4.4 The approach described within this guide also supports continuous process capability improvements and enables innovation such as the implementation of Process Analytical Technology (PAT). 在本指南内描述的方法还支持生产工艺能力的持续改进，实现创新，如运用过程分析技术（PAT）4.5 The main elements of this guide are: 4.5.1 The un

24、derlying key concepts that should be applied,4.5.2 A description of the specification, design, and verification process, and 4.5.3 A description of the required supporting processes.4.5本指南的主要要素是：4.5.1以下根本的关键概念必须应用，4.5.2一个对规范，设计和验证过程的描述4.5.3一个对必需的辅助性工艺的描述5. Significance and Use意义和用途5.1 Application of

25、 the approach described within this guide is intended to satisfy international regulatory expectations insuring that manufacturing systems and equipment are fit for intended use, and to satisfy requirements for design, installation, operation, and performance. 5.2 The approach described in this guid

26、e applies concepts and principles introduced in the FDA initiative, Pharmaceutical cGMPs for the 21st CenturyA Risk-Based Approach.5.3 This guide may be used independently or in conjunction with other proposed E55 standards to be published by ASTM International. 5.1这个指南中所描述的方法的应用，目的是为了满足国际规范所期望的那样：使

27、生产系统和设备符合预期的用途，满足设计，安装，运行及性能的要求。5.2本指南中描述的方法所运用的概念和原理，在FDA发起的，21世纪药品生产cGMPs-一个基于风险分析的方法中有介绍。5.3本指南可单独使用或与ASTM国际部出版的E55号标准联合使用。6. Key Concepts重要概念6.1 This guide applies the following key concepts: Risk-based Approach Science-based Approach Critical Aspects of Manufacturing Systems Quality by Design G

28、ood Engineering Practice Subject Matter Expert Use of Vendor Documentation Continuous Process Improvement6.1本指南使用以下重要概念： 基于风险的方法 基于科学的方法 生产系统的关键方面 质量源于设计 良好的工程实践 专门领域的专家 供应商文件的使用 工艺持续改进6.2 Risk-based Approach: 6.2.1 Risk management should underpin the specification, design, and verification process,

29、 and be applied appropriately at each stage. 6.2.2 Two primary principles of quality risk management are identified in ICH Q9: The evaluation of the risk to quality should be based on scientific knowledge and ultimately link to the protection of the patient. The level of effort, formal

30、ity and documentation of the quality risk management process should be commensurate with the level of risk. 6.2.3 These principles should be applied to specification，design, and verification of manufacturing systems.6.2.4 The scope and extent of quality risk management for specification, design, and

31、 verification activities and documentation should be based on the risk to product quality and patient safety. 6.2基于风险的方法6.2.1风险管理应该支持规范，设计和验证过程，并在每一阶段适当应用。6.2.2在ICH Q9中明确了质量风险管理的两个基本原则：质量风险评价必须以科学知识为基础，并最终与保护病人安全相联系。质量风险管理实施的力度、形式和文件必须与风险级别（程度）相匹配。6.2.3这些原理必须应用于生产系统的规范，设计和验证。6.2.4与规范、设

32、计、验证有关的质量风险管理和文件系统的广度和深度，都必须以产品质量风险和病人安全为基础。6.3 Science-based Approach: 6.3.1 Product and process information, as it relates to product quality and patient safety, should be used as the basis for making science-and risk-based decisions that ensure that the manufacturing systems are designed and veri

33、fied to be fit for their intended use. 6.3.2 Examples of product and process information to consider include: critical quality attributes (CQAs), critical process parameters (CPPs), process control strategy information, and prior production experience.6.3基于科学的方法6.3.1产品和工艺的信息，如果与产品质量和病人安全有关，都必须作为科学风险

34、决策的基础，确保生产系统设计和验证至符合其预定用途。6.3.2例如，应考虑的产品和工艺信息的包括：关键质量属性（ CQAs ），关键工艺参数（CPPs），过程控制策略信息，和以往的生产经验。6.4 Critical Aspects of Manufacturing Systems: 6.4.1 Critical aspects of manufacturing systems are typically functions, features, abilities, and performance or characteristics necessary for the manufacturi

35、ng process and systems to ensure consistent product quality and patient safety. They should be identified and documented based on scientific product and process understanding. 6.4.2 For brevity these are referred to throughout the rest of this guide as critical aspects. 6.4.3 Verification activities

36、 should focus on these aspects of manufacturing systems and should be documented. The verification process is defined in 生产系统的关键方面：6.4.1生产系统的关键方面通常是功能，特征，性能，和持续保持产品质量和病人安全所必须的生产工艺和系统的性能或特征。他们应该在科学的产品和工艺的理解基础上进行确定并记录。6.4.2简而言之，作为关键方面，可参阅本指南的其余部分。6.4.3验证事务应侧重于生产系统的这些方面，并应记录在案。工艺验证参见7.4。6.5 Qual

37、ity by Design: 质量源于设计6.5.1 Quality by design concepts should applied to ensure that critical aspects are designed into systems during the specification and design process. The critical aspects of the design and associated acceptance criteria should be documented. 在规范和工艺设计过程中，必须应用质量源于设计的概念，确保关键方面都设计入

38、系统中。设计的关键方面和相关验收标准应记录在案。6.5.2 Assurance that manufacturing systems are fit for intended use should not rely solely upon verification after installation, but be achieved by a planned and structured verification approach applied throughout the system life cycle. 确保生产系统符合其预期的用途，不能仅仅依赖于安装后的验证，而是应做到将有计划，

39、有组织的验证方法应用于系统的整个生命周期。6.6 Good Engineering Practice: 良好的工程实践：6.6.1 Good Engineering Practice (GEP) should underpin and support the specification, design, and verification activities. 良好的工程实践（GEP）应当巩固和支持规范，设计和验证活动6.6.2 Good Engineering Practice is defined as those established engineering methods and s

40、tandards that are applied throughout the life cycle to deliver appropriate and effective solutions.良好的工程实践定义为，那些为得到适当和有效的解决办法，而建立工程方法和应用于整个生命周期的标准。6.6.3 Examples of Good Engineering Practices include:6.6.3良好的工程实践例子包括： Specification, design, and installation activities should take full account

41、 of all applicable requirements, including GXP, safety, health, environmental, ergonomic, operational, maintenance, recognized industry standards, and other statutory requirements. 规范，设计和安装活动应充分考虑到所有适用的要求，包括GXP，安全，卫生，环境，人类工程学，操作，维护，公认的行业标准，和其他法定要求. Adequate provisions related to quali

42、ty should be included in specification, design, procurement, and other contractual documents. 在规范，设计，采购，和其他合同文件中应包括有足够的与质量有关的条款。 Life-cycle documentation covering planning, specification, design, verification, installation, acceptance, and maintenance should be produced. 必须制定涵盖计

43、划，规范，设计，验证，安装，验收，维保等整个生命周期的文件。 An appropriate degree of oversight and control should be achieved by suitable verification of execution, construction and installation activities. 对实施验证，施工和安装等活动进行合适的确认，达到适当程度的监督和控制。6.7 Subject Matter Experts: 6.7相关领域的专家：6.7.1 Subject matter experts are d

44、efined as those individuals with specific expertise and responsibility in a particular area or field (for example, quality unit, engineering, automation, development, operations and so forth). 6.7.1相关领域专家的定义是，那些在特定领域里有专业技能和资质的人（例如质量部门，工程，自动化技术，研发，生产等）。6.7.2 Subject matter experts should take the lea

45、d role in the verification of manufacturing systems as appropriate within their area of expertise and responsibility. 6.7.2相关领域专家，在他们相应的专业技能和资格领域内，在生产体系验证中起带头作用。6.7.3 Subject matter expert responsibilities include planning and defining verification strategies, defining acceptance criteria, selection

46、 of appropriate test methods, execution of verification tests, and reviewing results. 6.7.3相关领域专家的职责，包括计划和制定验证策略，制定验收标准，选择适当的测试方法，实施验证测试并评价结果。6.8 Use of Vendor Documentation: 6.8供应商文件的使用：6.8.1 Vendor documentation, including test documents may be used as part of the verification documentation, provi

47、ding the regulated company has assessed the vendor, and has evidence of: 6.8.1供应商文件（包括一些测试文件），都可用作验证文件的一部分，只要供应商经负法律责任的公司评价，并且证明： An acceptable vendor quality system, 有一个可接受的供应商质量体系 Vendor technical capability, and 供应商具技术能力，并且 Vendor application of GEP such that in

48、formation obtained from the vendor will be accurate and suitable to meet the purpose of verification. 供应商应用GEP，因而从供应商获得的有关信息是准确的和合适的并符合验证目标。6.8.2 If inadequacies are found in the vendor quality system, technical capability, or application of GEP, then the regulated company may choose to mitig

49、ate potential risks by applying specific, targeted, additional verification checks or other controls rather than repeating vendor activities and replicating vendor documentation. 6.8.2如果在供应商质量体系，技术能力或GEP应用中发现有不足之处，负法律责任的公司可通过应用特定的、有针对性的、额外的验证检查，或其它控制方式来转移风险，而不是重复供应商的行为和复制供应商文件。6.8.3 The decision and

50、 justification to use vendor documentation, to support the verification of critical aspects of the manufacturing element, should be based on the intended use of the manufacturing system, and should be documented and approved by subject matter experts including the quality unit.6.8.3使用供应商文件来支持生产要素关键方

51、面的验证的决定和判断，必须以生产系统的预期用途为基础，必须记录在案并经过相关专业领域专家（包括质量部门）认可。6.9 Continuous Improvement: 6.9持续改进6.9.1 As experience is gained in commercial production, opportunities for improvements should be sought bases on periodic review and evaluation, operational and performance data, and root-cause analysis of fail

52、ures. 6.9.1当在商业化生产中积累一定的经验后，应在周期性的回顾评价、性能数据以及分析失败的根本原因的基础上，寻找机会改进工艺。6.9.2 Change management should provide a dependable mechanism for prompt implementation of technically sound improvements following the approach to specification, design, and verification described in this guide. 6.9.2变更管理应遵循本指南中所描述

53、的规范，设计和验证方法，为迅速实施合理的技术改进，提供一个可靠的机制。7. Process工艺7.1 OverviewThe process of specification, design, and verification of manufacturing systems should include the following activities: 概述-生产系统的规范，设计和验证过程应当包括下列活动： Requirements definition 明确需求 Specification and design 规范和设计 Verification 验证 Acceptance and r

54、elease 验收和放行7.1.1 Good Engineering Practice should be applied throughout the process. 7.1.1整个生产工艺都必须应用GEP。7.1.2 Risk management should be performed as appropriate to evaluate the risks to product quality and patient safety related to the manufacturing system and corresponding design solution. Risk m

55、anagement is a supporting process and is defined in 8.2. 风险管理应对生产系统中与产品质量和患者安全相关的风险进行适当的评估，并提出相应的设计方案。风险管理是一个辅助性工艺，在8.2中有对它的描述。7.1.3 Design reviews should be performed as appropriate throughout the life-cycle of the manufacturing system. The design review process is a supporting process and is defin

56、ed 8.3. 7.1.3适当的设计审核应贯穿整个生产系统的生命周期。设计审核是一个辅助性工艺，在8.3中有对它的描述。7.1.4 Change management should be applied throughout the process. The change management process is supporting process and is defined 8.4. 7.1.4整个过程还必须应用变更管理，变更管理是也是一个辅助性工艺，在8.4中有对它的描述。7.2 Requirements Definition:7.2.1 Specific requirements

57、should be identified and should provide the basis of further specification, design, and verification of the manufacturing system.7.2.2 These specific requirements relative to product quality and patient safety should be based upon: Product knowledge and understanding, Process knowledge and understanding, Regulatory requirements, and Company quality requirements.7.2.3 Product and process knowledge and understanding, including knowledge of sources of variability in the product and process, the identification of critical quality attributes, and scientific data g