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Guidance for Industry
Process Validation: General Principles and Practices
Final Version January 2011 Draft 2008
I. INTRODUCTION
I. INTRODUCTION
简介
This guidance outlines the general principles
and approaches that FDA considers appropriate elements of process validation for the manufacture of human and animal drug and biological products, including active pharmaceutical ingredients (APIs or drug substances), collectively referred to in this
guidance as drugs or products. This guidance
incorporates principles and approaches that
all manufacturers can use to validate manufacturing processes.
本指南概括了一般的原则与方法，这些原则与方法是FDA 认为进行工艺验证的恰当要素，这些工艺被用于生产人用药、动物用药以及生物制品，包括活性药物成分(API 或药用物质)，在本指南中以上统称为药品或产品。本指南整合了一般的原则和方法，所有的生产企业都可以将这些原则和方法应用于生产工艺的验证。 This guidance outlines the general principles and approaches that FDA considers to be appropriate elements of process validation for the manufacture of human and animal drug and biological products, including active pharmaceutical ingredients (API or drug substance),
collectively referred to in this guidance as drugs or products. This guidance incorporates principles and approaches that all manufacturers can use in validating a
manufacturing process. 本指南概括了一般的原则与方法，这些原则与方法是FDA 认为进行工艺验证的恰当要素，这些工艺被用于生产人用药、动物用药以及生物制品，包括活性药物成分(API 或药用物质)，在本指南中以上统称为药品或产品。本指南整合了一般的原则和方法，所有的生产企业都可以将这些原则和方法应用于生产工艺的验证。
This guidance aligns process validation activities with a product lifecycle concept and with existing FDA guidance, including the FDA/International Conference on Harmonisation (ICH) guidances for industry, Q8(R2) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System.2 Although this guidance does not repeat the concepts and principles explained in those guidances, FDA encourages the use of modern pharmaceutical development concepts, quality risk man- agement, and quality systems at all stages of the manufacturing process lifecycle. 本指南将工艺验证活动与产品生命周期概念以及现有FDA 相关指南进行了协调；这些存在的FDA指南包括FDA/ICH指南，Q8(R2)药品研发指南、Q9质量风险管理指南和Q10制药质量体系指南。尽管本指南没有重复上述指南解释的概念和This guidance aligns process validation activities with the product lifecycle concept and with existing FDA guidance.2 2 See the FDA/International Conference on Harmonisation (ICH) guidances for industry: Q8 Pharmaceutical Development, Q9 Quality Risk Management, and when finalized, Q10 Pharmaceutical Quality System (a notice of availability for the May 2007 ICH draft guidance, Q10 Pharmaceutical Quality System, published in the Federal Register on July 13, 2007 (72 FR 38604)). We update guidance documents periodically. To make sure you have the most recent version of a guidance, check the CDER guidance page at https://www.doczj.com/doc/4910842313.html,/cder/guidance/index.htm, the CBER guidance page at
原则，FDA鼓励在药品制造工艺生命周期的各个阶段使用现代药品研发概念、质量风险管理和质量体系概念。 注释2To make sure you have the most recent version of a guidance, check the CDER guidance page at https://www.doczj.com/doc/4910842313.html,/Drugs/GuidanceComplianceR egulatoryInformation/Guidances/default.htm, the CBER guidance page at
https://www.doczj.com/doc/4910842313.html,/BiologicsBloodVaccines/Guida nceComplianceRegulatoryInformation/
Guidances/default.htm, or the CVM guidance page at
https://www.doczj.com/doc/4910842313.html,/AnimalVeterinary/GuidanceCo mplianceEnforcement/
GuidanceforIndustry/default.htm
https://www.doczj.com/doc/4910842313.html,/cber/guidelines.htm, or the CVM guidance page at https://www.doczj.com/doc/4910842313.html,/cvm/Guidance/published.htm . 本指南将工艺验证活动与产品生命周期概念以及现有FDA 相关指南（这里指得是Q8、Q9和Q10指南）进行了协调。 The lifecycle concept links product and process development, qualification of the commercial manufacturing process,3 and
maintenance of the process in a state of control
during routine commercial production.
This guidance supports process improvement
and innovation through sound science.
生命周期概念将产品与工艺开发、商业生产工艺
的确认以及维护工艺在日常商业生产中处于受
控状态连结在一起。本指南通过足够科学知识来
支持工艺优化和革新。
注释 3 In this guidance, the term commercial
manufacturing
process refers to the manufacturing
process resulting in commercial product (i.e., drug
that is marketed, distributed, and sold or intended to be sold). For the purposes of this guidance, the term commercial manufacturing process does not include clinical trial or treatment IND material. The lifecycle concept links product and
process development, qualification of the
commercial manufacturing process, and
maintenance of the process in a state of control
during routine commercial production.
This guidance promotes modern manufacturing
principles, process improvement, innovation,
and sound science.
生命周期概念将产品与工艺开发、商业生产工艺
的确认以及维护工艺在日常商业生产中处于受控
状态连结在一起。本指南可促进现代生产的原则、
工艺改进、创新并且形成完善的科学。
This guidance covers the following categories of drugs: H uman drugs V eterinary drugs
B iological and biotechnology products F inished products and active pharma ceutical ingredients (APIs or drug sub stances)4
The following categories of drugs are within the scope of this guidance: H uman dr ugs V eterinary drugs
B iological and biotechnology products
F inished products and active pharmaceutical ingredients (API or drug substance) 3
T he drug constituent of a combination (drug and medical device) product 以下类别的药品在本指南范围之内： ? 人用药物 ? 兽药 ? 生物制品和生物技术产品 ? 制剂产品与活性药物成分(API 或药用物质)3? 复合产品(药物和医疗设备)中的药物成分 注释4 Separate current good manufacturing practice (CGMP) regulations for drug components such as APIs (drug substances) and intermediates have not published as of the date of this guidance, but these components are subject to the statutory CGMP requirements of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 351(a)(2)(B)). Process validation for APIs is discussed in the FDA/ICH guidance for industry, Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (ICH Q7), available on the Internet at https://www.doczj.com/doc/4910842313.html,/Drugs/GuidanceComplianceR egulatoryInformation/Guidances/default.htm.
Section XII of ICH Q7 describes in detail the
principles for validating API processes.
T he drug constituent of a combination (drug and medical device) product 3 Separate current good manufacturing practice (CGMP) regulations for drug components such as APIs (drug substances) and intermediates have not published as of the date of this guidance, but these components are subject to the statutory CGMP requirements of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act) (21 U.S.C. 351(a)(2)(B)). Process validation for APIs is discussed in the FDA/ICH guidance for industry, Q7A Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (ICH Q7A), available on the Internet at https://www.doczj.com/doc/4910842313.html,/cder/guidance/index.htm. Section XII of ICH Q7A describes in detail the principles to be followed in validating API processes. 以下类别的药品在本指南范围之内： ? 人用药物 ? 兽药
? 生物制品和生物技术产品
? 制剂产品与活性药物成分(API 或药用物质)3? 复合产品(药物和医疗设备)中的药物成分 This guidance does not cover the following types of products: T ype A medicated articles and medicated feed M edical devices5 D ietary supplements H uman tissues intended for transplantation regulated under section 361 of the Public Health Service Act6 本指南不适用于以下类别的产品： ? A 型含药产品与含药饲料 ? 医疗器械 ? 膳食补充剂 ? 公共卫生服务法361 节下的移植用人体组织 注释5 Guidance on process validation for medical devices is provided in a separate document, Quality Management Systems –Process Validation,
edition 2, available at
The following categories of products are not covered by this guidance: T ype A medicated articles and medicated feed M edical devices D ietary supplements H uman tissues intended for transplantation regulated under section 361 of the Public Health Service Act4. 4 See the FDA guidance for industry, Validation of Procedures for Processing of Human Tissues Intended for Transplantation, available on the Internet at
https://www.doczj.com/doc/4910842313.html,/cber/guidelines.htm . 本指南不适用于以下类别的产品： ? A 型含药产品与含药饲料
? 医疗设备 ? 膳食补充剂
https://www.doczj.com/doc/4910842313.html,/sg3/sg3-final.html. See infra note 6.
注释6 See the FDA guidance for industry, Validation of
Procedures for Processing of Human Tissues Intended for Transplantation, available on the Internet at
https://www.doczj.com/doc/4910842313.html,/BiologicsBloodVaccines/Guida nceComplianceRegulatoryInformation/ Guidances/default.htm.
? 公共卫生服务法361 节下的移植用人体组织 This guidance does not specify what information should be included as part of a regulatory submission. Interested persons can
refer to the appropriate guidance or contact the appropriate Center in determining the
type of information to include in a submission. 本指南没有具体说明哪些信息应包括在药政提交文件中，有兴趣的人士可以参照适当的指南或与适当的中心联系，以确定哪些类型的信息应包括在申报文件中。
This guidance does not specify what information should be included as part of a regulatory submission. Interested persons can refer to the appropriate guidance or contact the
appropriate Center in determining what information should be included in a submission.
本指南没有具体说明哪些信息应包括在药政提交文件中，有兴趣的人士可以参照适当的指南或与适当的中心联系，以确定哪些信息应包括在提交中。
This guidance also does not specifically discuss the validation of automated process
control systems (i.e., computer hardware and software interfaces), which are commonly integrated into modern drug manufacturing equipment. This guidance is relevant, however, to the validation of processes that include automated equipment in processing.
本指南也没有专门讨论自动化工艺控制系统的验证(即计算机硬件和软件界面)，这些常整合到现代药物生产设备中。当然，本指南也是与那些在生产中包括自动化设备在内的工艺验证相关的。
This guidance also does not specifically discuss the validation of automated process
control systems (i.e., computer hardware and software interfaces), which are commonly integrated into modern drug manufacturing equipment. This guidance is relevant, however, to the validation of processes that include automated equipment in processing.
本指南也没有专门讨论自动化工艺控制系统的验证(即计算机硬件和软件界面)，这些常整合到现代药物生产设备中。当然，本指南也是与那些在生产中包括自动化设备在内的工艺验证相关的。
FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required. FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.
FDA 的指南文件，包括本指南在内，并无法定的强制执行要求。相反地，指南描述的是官方目前对某一问题的考虑与观点，除非引入了具体的药政或法定要求，否则应仅视为建议。官方指南中所用的“应当”一词意味着建议或推荐某种情况，但并非必需。 FDA 的指南文件，包括本指南在内，并无法定的强制执行要求。相反地，指南描述的是官方目前对某一问题的考虑与观点，除非引入了具体的药政或法定要求，否则应仅视为建议。官方指南中所用的“应当”一词意味着建议或推荐某种情况，但并非必需。
II. BACKGROUND II. BACKGROUND
In the Federal Register of May 11, 1987 (52 FR 17638), FDA issued a notice announcing the availability of a guidance entitled Guideline on General Principles of Process Validation (the 1987 guidance).7 Since then, we have obtained additional experience through our regulatory oversight that allows us to update our recommendations to industry on this topic. This revised guidance conveys FDA’s current thinking on process validation and is consistent with basic principles first introduced in the 1987 guidance. The revised guidance also provides recommendations
that reflect some of the goals of FDA’s initiative entitled “Pharmaceutical CGMPs for the 21st Century ― A Risk-Based Approach,” particularly with regard to the use of technological advances in pharmaceutical manufacturing, as well as implementation of modern risk management and quality system tools and concepts.8 This revised guidance replaces the 1987 guidance. II.背景
在1987 年5 月11 日的联邦公报(52 FR 17638)上，FDA 发布了一个通告，宣布了题为工艺验证的一般原则指南(1987 年指南)的问世5。自那以来，通过我们的药政监管获得的额外经验，使得我们能够为业界更新我们关于这一议题的推荐建议。本修订指南传达了FDA 关于工艺验证的目前思考，并与1987 年指南最早引入的基本原则相一致。本修订后的指南同样提供了能反映FDA 倡议的“21 世纪制药cGMP－基于风险的办法”中某些目标的建议，特别是关于在药品生产中使用先进技术，以及实施现代风险管理和质量管理体系的工具和概念。当最终完成后，本修订后的指南将取代1987 年的指南。 In the Federal Register of May 11, 1987 (52 FR 17638), FDA issued a notice announcing the availability of a guidance entitled Guideline on General Principles of Process Validation (the 1987 guidance). 5 Since then, we have obtained additional experience through our regulatory oversight that allows us to update our recommendations to industry on this topic. This revised guidance conveys FDA’s current thinking on process validation
and is consistent with basic principles first introduced in the 1987 guidance. This guidance also provides recommendations that reflect some of the goals of FDA’s initiative entitled “Pharmaceutical CGMPs for the 21st Century – A Risk-Based Approach,” particularly with regard to the use of technological advances in pharmaceutical manufacturing, as well as implementation of modern risk management and quality system tools and
concepts. When finalized, this guidance will replace the 1987 guidance.
5 The 1987 guidance was prepared by a working group that included representation from the Center for Devices and Radiological Health (CDRH). Since that time, CDRH elected to publish its own process validation guidance through the Global Harmonization Task Force. The principles and
recommendations in that document, Quality Management Systems – Process Validation, edition 2 (available on the Internet at
https://www.doczj.com/doc/4910842313.html,/sg3/sg3final.html), are also useful to consider for drug manufacturing
注释7 The 1987 guidance was prepared by a working group that included representation from the Center for Devices and Radiological Health (CDRH). Since that time, CDRH elected to reference a process validation guidance prepared in coopera- tion with the Global Harmonization Task Force
(GHTF). The principles and recommendations in that document, Quality Management Systems –
Process Validation, edition 2 (available on the
Internet at https://www.doczj.com/doc/4910842313.html,/sg3/sg3-final.html)are also useful to consider for drug manufacturing processes.
注释8 See “Pharmaceutical cGMPS for the 21st Century
— A Risk-Based Approach: Second Progress Report and Implementation Plan,” available at https://www.doczj.com/doc/4910842313.html,/Drugs/DevelopmentApprovalP rocess/
Manufacturing/QuestionsandAnswersonCurr entGoodManufacturingPracticescGMPfor- Drugs/ucm071836.htm.
processes. II.背景
在1987 年5 月11 日的联邦公报(52 FR 17638)上，FDA 发布了一个通告，宣布了题为工艺验证的一般原则指南(1987 年指南)的问世5。自那以来，通过我们的药政监管获得的额外经验，使得
我们能够为业界更新我们关于这一议题的推荐建议。本修订指南传达了FDA 关于工艺验证的目前
思考，并与1987 年指南最早引入的基本原则相一致。本指南同样提供了能反映FDA 倡议的“21 世纪制药cGMP－基于风险的办法”中某些目标的建议，特别是关于在药品生产中使用先进技术，以
及实施现代风险管理和质量管理体系的工具和概念。当最终完成后，本指南将取代1987 年的指南。FDA has the authority and responsibility to
inspect and evaluate process validation performed by manufacturers. The CGMP regulations for validating pharmaceutical (drug)
manufacturing require that drug products be produced with a high degree of assurance of meeting all the attributes they are intended to possess (21 CFR 211.100(a) and 211.110(a)).
FDA 有权力和责任来检查和评估生产厂家所实施的工艺验证。用于药品生产验证的cGMP 法规要求药品应具有高度保证来生产以符合其预期拥有的所有属性(见21CFR211.100(a)与211.110(a))。
FDA has the authority and responsibility to
inspect and evaluate process validation performed by manufacturers. The CGMP regulations for validating pharmaceutical (drug)
manufacturing require that drug products be produced with a high degree of assurance of meeting all the attributes they are intended to possess (21 CFR 211.100(a) and 211.110(a)).
FDA 有权力和责任来检查和评估生产厂家所实施的工艺验证。用于药品生产验证的cGMP 法规要求药品应具有高度保证来生产以符合其预期拥有的所有属性(见21CFR211.100(a)与211.110(a))。A. Process Validation and Drug Quality A 工艺验证和药品质量
Effective process validation contributes significantly to assuring drug quality. The basic principle of quality assurance is that a drug Effective process validation contributes significantly to assuring drug quality. The basic principle of quality assurance is that a drug
should be produced that is fit for its intended
use. This principle incorporates the understanding that the following conditions exist: Q uality, safety, and efficacy are designed
or built into the product.
Q uality cann ot be adequately assured merely by in-process and finishedproduct
inspection or testing.
E ach step of a manufacturing process
is controlled to assure that the finished product meets all quality attributes including specifications.有效的工艺验证为保证产品质量发挥了重大作用。质量保证的基本原则是药物生产应符合其预期使用目的；这一原则整合了对下列情况的理解： ? 产品质量、安全性和有效性系由设计而得，或融入产品。 ? 仅仅对中控和成品进行监控或检测，质量不能得到充分的保证。 ? 对每一步的生产工艺进行控制，以确保成品符合所有设计特性与质量属性，包括规格标准。有效的工艺验证为保证产品质量发挥了重大作用。质量保证的基本原则是药物生产应符合其预期使用目的；这一原则整合了对下列情况的理解：? 产品质量、安全性和有效性系由设计而得，或融入产品。 ? 仅仅对中控和成品进行监控或检测，质量不能得到充分的保证。 ? 对每一步的生产工艺进行控制，以确保成品符合所有质量属性，包括质量标准。 should be produced that is fit for its intended use; this principle incorporates the understanding that the following conditions exist:
Q uality, safety, and efficacy are designed or built into the product. Q uality cannot be adequately assured
merely by in-process and finishedproduct inspection or testing. E ach step of a manufacturing process is controlled to assure that the finished product meets all design characteristics
and quality attributes including specifications. 有效的工艺验证为保证产品质量发挥了重大作用。质量保证的基本原则是药物生产应符合其预期使用目的；这一原则整合了对下列情况的理解：? 产品质量、安全性和有效性系由设计而得，或融入产品。 ? 仅仅对中控和成品进行监控或检测，质量不能得到充分的保证。 ? 对每一步的生产工艺进行控制，以确保成品符合所有设计特性与质量属性，包括规格标准。有效的工艺验证为保证产品质量发挥了重大作用。质量保证的基本原则是药物生产应符合其预期使用目的；这一原则整合了对下列情况的理解： ? 产品质量、安全性和有效性系由设计而得，或融入产品。 ? 仅仅对中控和成品进行监控或检测，质量不能得到充分的保证。 ? 对每一步的生产工艺进行控制，以确保成品符合所有设计特性与质量属性，包括规格标准。 B. Approach to Process Validation 工艺验证方法
For purposes of this guidance, process validation is defined as the collection and evaluation of data, from the process design stage
through commercial production, which establishes scientific evidence that a process is
capable of consistently delivering quality product. Process validation involves a series of activities taking place over the lifecycle of the product and process. This guidance describes process validation activities in three stages.
For purposes of this guidance, process validation is defined as the collection and evaluation of data, from the process design stage throughout production, which establishes scientific evidence that a process is capable of consistently delivering quality products. Process validation involves a series of activities taking place over the lifecycle of the
product and process. This guidance describes the process validation activities in three stages.
本指南将工艺验证定义为收集并评估从工艺设计阶段一直到商业化生产的数据，用这些数据来确立科学证据，证明该工艺能够始终如一地生产出优质产品。工艺验证涉及到了在产品生命周期及生产中所发生的一系列活动。本指南将工艺验证活动描述为三个阶段。
S tage 1
– Process Design: The commercial manufacturing process is defined
during this stage based on knowledge
gained through development and
scale-up activities.
S tage 2
– Process Qualification: During
this stage, the process design is evaluated
to determine if the process is
capable of reproducible commercial manufacturing.
S tage 3
– Continued Process Verification: Ongoing assurance is gained during
routine production that the process
remains in a state of control.
第1 阶段―工艺设计：在该阶段，基于从开发和放大试验活动中得到的知识确定商业化生产工艺。
第2 阶段―工艺确认：在这一阶段，对已经设计的工艺进行评估，以确定这个工艺是否能够进行重复性的商业化生产。
第3 阶段―持续工艺核实：工艺的受控状态在日常生产中得到持续地保证。本指南将工艺验证定义为收集并评估从工艺设计阶段一直到生产的数据，用这些数据来确立科学证据，证明该工艺能够始终如一地生产出优质产品。工艺验证涉及到了在产品生命周期及生产中所发生的一系列活动。本指南将工艺验证活动描述为三个阶段。
S tage 1
– Process Design: The commercial process is defined during this
stage based on knowledge gained
through development and scale-up activities.
S tage 2
– Process Qualification: During
this stage, the process design is confirmed
as being capable of reproducible
commercial manufacturing.
S tage 3
– Continued Process Verification: Ongoing assurance is gained during
routine production that the process
remains in a state of control.
第1 阶段―工艺设计：在该阶段，基于从开发和放大试验活动中得到的知识确定工业化生产工艺。
第2 阶段―工艺确认：在这一阶段，对已经设计的工艺进行确认，证明其能够进行重复性的商业化生产。
第3 阶段―持续工艺核实：工艺的受控状态在日常生产中得到持续地保证。
This guidance describes activities typical of
each stage, but in practice, some activities
might occur in multiple stages.
本指南描述了每一阶段的典型活动，但在实践中，有些活动可能在多个阶段出现。This guidance describes activities typical in
each stage, but in practice, some activities in different stages might overlap.
本指南描述了每一阶段的典型活动，但在实践中，有些活动在不同的阶段可能会重叠。
Before any batch from the process is commercially distributed for use by consumers, a manufacturer should have gained a high degree
of assurance in the performance of the manufacturing process such that it will consistently produce APIs and drug products
meeting those attributes relating to identity, strength, quality, purity, and potency. The assurance should be obtained from objective information and data from laboratory-, pilot-, Before any batch from the process is commercially distributed for use by consumers, a manufacturer should have gained a high degree
of assurance in the performance of the manufacturing process such that it will consistently produce APIs and drug products
meeting those attributes relating to identity, strength, quality, purity, and potency. The assurance should be obtained from objective information and data from laboratory-, pilot-,
and/or commercial-scale studies. Information
and data should demonstrate that the commercial manufacturing process is capable of consistently producing acceptable quality products within commercial manufacturing conditions.
从某工艺商业化销售给消费者使用前的任何一批，生产企业应该已经获得对该生产工艺性能的高度保证，即它将始终如一地生产出能满足关于鉴别、含量、质量、纯度和效价属性要求的原料药与制剂产品。这些保证应该从产品小试、中试和/或大生产研究的客观信息和数据中得到。这些信息和数据应该能够证明该商业化生产工艺有能力在其商业生产条件下，持续地生产出可接受的优质产品。and/or commercial scale studies. Information
and data should demonstrate that the commercial manufacturing process is capable of consistently producing acceptable quality products within commercial manufacturing conditions, including those conditions that
pose a high risk of process failure.
从某工艺商业化销售给消费者使用前的任何一批，生产企业应该已经获得对该生产工艺性能的高度保证，即它将始终如一地生产出能满足关于鉴别、含量、质量、纯度和效价属性要求的原料药与制剂产品。这些保证应该从产品小试、中试和/或大生产研究的客观信息和数据中得到。这些信息和数据应该能够证明该商业化生产工艺有能力在其商业生产条件，也包括那些造成工艺失败的高风险条件下，一贯地生产出可接受的优质产品。
A successful validation program depends
upon information and knowledge from product and process development. This knowledge
and understanding is the basis for establishing
an approach to control of the manufacturing process that results in products
with the desired quality attributes. Manufacturers should:
U nderstand the sources of variation
D etect the presence and degree of variation
U nderstand the impact of variation on
the process and ultimately on product
attributes
C ontrol the variation in a manner commensurate
with the risk it represents to
the process and product
一个成功的验证程序取决于来自产品与工艺开发的信息与知识，这种知识与理解是建立适合于生产工艺的某一控制方法的基础，而这个工艺可以生产出具有期望质量属性的产品。
生产企业应当：
? 了解变异来源
? 检测变异是否存在以及发生的程度
? 理解变异对工艺，以及最终对产品属性的影响? 使用与工艺和产品风险相适应的方法来控制变异A successful validation program depends
upon information and knowledge from product and process development. This knowledge
and understanding is the basis for establishing
an approach to control that is appropriate
for the manufacturing process.
Manufacturers should:
u nderstand the sources of variation
d etect th
e presence an
d degre
e o
f variation
u nderstand the impact of variation on
the process and ultimately on product
attributes
c ontrol the variation in a manner commensurate
with the risk it represents to
the process and product
一个成功的验证程序取决于来自产品与工艺开发的信息与知识，这种知识与理解是建立适合于生产工艺的某一控制方法的基础。生产企业应当：? 了解变异来源
? 检测变异是否存在以及发生的程度
? 理解变异对工艺，以及最终对产品属性的影响? 使用与工艺和产品风险相适应的方法来控制变异
Each manufacturer should judge whether it
has gained sufficient understanding to provide
a high degree of assurance in its manufacturing
process to justify commercial distribution
of the product. Focusing exclusively
on qualification efforts without also understanding
the manufacturing process and associated
variations may not lead to adequate
assurance of quality. After establishing and
confirming the process, manufacturers must
maintain the process in a state of control
over the life of the process, even as materials,
equipment, production environment,
personnel, and manufacturing procedures
change.9
每个生产企业应当判断是否已经对此获得了足
够的理解，即对其生产工艺提供一个高度保证，
从而证明其产品商业化销售的正当性。没有对生
产工艺和相关变异的理解而仅仅注重于资质性
的成果，不可能带来对质量的足够保证。在工艺
建立并确认后，生产企业必须保证该工艺在其工
艺生命周期内处于受控状态，既使是在材料、设
备、生产环境、人员和生产工艺变更的条件下。
注释9 The statute and regulations described in
section
III of this guidance explain the requirement that
the methods and facilities used for the
manufacturing
of drugs be operated and administered
under control sufficient to assure that the identity,
strength, purity, and quality of a drug are as they
purport or are represented to possess.
Each manufacturer should judge whether it
has gained sufficient understanding to provide
a high degree of assurance in its manufacturing
process to justify commercial distribution
of the product. Focusing on qualification
efforts without understanding the manufacturing
process may not lead to adequate
assurance of quality. After establishing and
confirming the process, manufacturers must
maintain the process in a state of control
over the life of the process, even as materials,
equipment, production environment,
personnel, and manufacturing procedures
change.6
6
The statute and regulations described in section
III of this guidance explain the requirement that
the methods and facilities used for the
manufacturing
of drugs be operated and maintained under
control sufficient to assure that the identity,
strength, purity, and quality of a drug are as they
purport or are represented to possess.
每个生产企业应当判断是否已经对此获得了足够
的理解，即对其生产工艺提供一个高度保证，从
而证明其产品商业化销售的正当性。没有对生产
工艺的理解而仅注重于资质性的成果，不可能带
来对质量的充足保证。在工艺建立并确认后，生
产企业必须保证该工艺在其工艺生命周期内处于
受控状态，既使是在材料、设备、生产环境、人
员和生产工艺变更的条件下。
Manufacturers should use ongoing programs to collect and analyze product and process data to evaluate the state of control of the process. These programs may identify
process or product problems or opportunities for process improvements that can be evaluated
and implemented through some of the activities described in Stages 1 and 2.
制造商应该采用持续项目来收集和分析产品和工艺数据，以便评估工艺受控状态。这些项目可能确认工艺或者产品的缺陷，或者工艺改进的机会，这些问题或者机会可以通过阶段2和阶段3描
述的活动来评估和实施。
Manufacturers of legacy products can take advantage of the knowledge gained from the original process development and qualification work as well as manufacturing experience to continually improve their processes. Implementation of the recommendations in this guidance for legacy products and processes would likely begin with the activities described in Stage 3.
已有产品的制造商可以利用从原有工艺研发和确认工作中获得的知识，也包括制造经验来持续改进工艺。在本指南中，对于已有产品和工艺实施这些建议可以从阶段3描述的活动开始。
III. STATUTORY AND REGULATORY
REQUIREMENTS
FOR PROCESS VALIDATION
第三部分：工艺验证的法规和法规要求
III. STATUTORY AND REGULATORY REQUIREMENTS FOR PROCESS VALIDATION 第三部分：工艺验证的法规和法规要求 Process validation for drugs (finished
pharmaceuticals and components) is a legally
enforceable requirement under section
501(a)(2)(B) of the Act (21 U.S.C.
351(a)(2)(B)), which states the following:
对药品（制剂和组分）进行工艺验证是法案（21
U.S.C.351(a)(2)(B)）的501(a)(2)(B)部分的法定要
求，描述如下：
Process validation for drugs (finished
pharmaceuticals and components) is a legally
enforceable requirement under section
501(a)(2)(B) of the Act, which states the following:
III.工艺验证的法规和法规要求
药品(制剂与其成分)的工艺验证是食品、药品与
化妆品法之501(a)(2)(B)节规定的一个法定的、
强制性的要求，其规定如下：
A drug . . . shall be deemed to be adulterated . . . if . . . the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess. 某一药品…，如果在其生产、加工、包装或持有中所使用的方法、设施或管理控制不符合cGMP 要求，或未按照cGMP 要求来操作或管理，以便A drug . . . shall be deemed to be adulterated . . . if . . . the methods used in, or the facilities or controls used for, its manufacture, processing, packing, or holding do not conform to or are not operated or administered in conformity with current good manufacturing practice to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.
某一药品…，如果在其生产、加工、包装或持有中所使用的方法、设施或管理控制不符合cGMP 要求，或未按照cGMP 要求来操作或管理，以便保证
保证药品符合本法规所要求的安全性、鉴别、含量并符合其声称的质量与纯度特性，该药品将被视为伪劣药品。 药品符合本法规所要求的安全性、鉴别、含量并符合其声称的质量与纯度特性，该药品将被视为伪劣药品。 FDA regulations describing current good
manufacturing practice (CGMP) for finished
pharmaceuticals are provided in 21 CFR
parts 210 and 211.
FDA 法规描述的cGMP 即是21CFR 的210 与211
部分。
FDA regulations describing current good
manufacturing practice (CGMP) are provided
in 21 CFR parts 210 and 211.
cGMP 的第210 和211 部分对工艺验证进行了一
般性和特殊性的要求。
The CGMP regulations require that manufacturing processes be designed and controlled to assure that in-process materials and the finished product meet predetermined quality
requirements and do so consistently and
reliably. Process validation is required, in
both general and specific terms, by the
CGMP regulations in parts 210 and 211. The
foundation for process validation is provided in § 211.100(a), which states that “[t]here shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess...” (emphasis added). This regulation requires manufacturers to design a process, including operations and controls, which results in a product meeting these attributes. CGMP 法规要求制造工艺应该被设计和控制来确保中控物料和最终产品符合预先确定的质量要求，而且工艺被持续和有效的控制。 §211.100(a)提供了工艺验证的基础，其指出，“应当有设计的书面的用于生产与工艺控制的程序，用以保证其声称或代表拥有的药品鉴别、含量、质量和纯度”(重点强调)。该法规要求生产企业设计一个能使产品符合这些特质的工艺，包括操作与控制。
Process validation is required, in both general and specific terms, by the CGMP regulations in parts 210 and 211. The foundation
for process validation is provided in § 211.100(a), which states that "[t]here shall be written procedures for production and
process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess" (emphasis added). This regulation requires that manufacturers design a process including operations and controls that will result in a product meeting these attributes. Product quality in the context of process validation means that product performance is consistent from batch-tobatch and unit-to-unit. Many products are single-source or involve complicated processes to manufacture. Validation also offers assurance that a process is reasonably safeguarded from sources of variability affecting production output, the loss of which
can cause supply problems, thereby negatively affecting public health. §211.100(a)提供了工艺验证的基础，其指出，“应当有设计的书面的用于生产与工艺控制的程序，用以保证其声称或代表拥有的药品鉴别、含量、质量和纯度”(重点强调)。该法规要求生产企业设计一个能使产品符合这些特质的工艺，包括操作与控制。在工艺验证中产品质量意味着产
品性能在批与批之间、单位与单位之间是一致的。许多产品为单一来源或涉及复杂的生产工艺。验证还提供了另一种保证，即工艺被适度地保护，远离了可能会影响生产产量的变异性来源，产量
的损失可能会造成市场供应问题，进而影响到公众健康。
Other CGMP regulations define the various aspects of validation. For example, §
211.110(a), Sampling and testing of inprocess materials and drug products, requires
that control procedures “. . . be established to monitor the output and to validate
the performance of those manufacturing
processes that may be responsible for causing
variability in the characteristics of inprocess
material and the drug product” (emphasis
added). Under this regulation, even
well-designed processes must include inprocess
control procedures to assure final
product quality. In addition, the CGMP regulations
regarding sampling set forth a number
of requirements for validation: samples must
represent the batch under analysis (§
211.160(b)(3)); the sampling plan must result
in statistical confidence (§ 211.165(c) and
(d)); and the batch must meet its predetermined
specifications (§ 211.165(a)).
其它的cGMP 法规界定了验证的不同方面。例如，
第211.110(a)节中控物料与药品的取样和检测，
要求控制程序“…应该建立，以便监控产品的输
出并对有可能造成中控物料与药品特性变异的
那些生产工艺的性能进行验证”(重点强调)。该
法规建立了这样的要求，既使是精心设计的工艺
也必须包括中间工艺控制程序，以保证最终成品的质量。另外，CGMP法规设定了针对验证的一系列取样要求：需要分析的样品必须具有批次代表性（§211.160(b)(3)）；取样计划必须具有统计置信限（§ 211.165(c) 和(d)）；批次必须符合预先确定的标准（§ 211.165(a)）。
Other CGMP regulations define the various
aspects of validation. Section 211.110(a),
Sampling and testing of in-process materials
and drug products, requires that control procedures
“. . . be established to monitor the
output and to validate the performance of
those manufacturing processes that may be
responsible for causing variability in the
characteristics
of in-process material and the
drug product" (emphasis added). This regulation
establishes the requirement that even well-designed
processes must include inprocess
control procedures to assure final product quality.
其它的cGMP 法规界定了验证的不同方面。第
211.110(a)节中控物料与药品的取样和检测，要
求控制程序“…应该建立，以便监控产品的输出
并对有可能造成中控物料与药品特性变异的那些
生产工艺的性能进行验证”(重点强调)。该法规
建立了这样的要求，既使是精心设计的工艺也必
须包括中间工艺控制程序，以保证最终成品的质
量。
In addition to sampling requirements, the CGMP regulations also provide norms for establishing in-process specifications as an aspect of process validation. Section
211.110(b) establishes two principles to follow when establishing in-process specifications. The first principle is that “. . . in-process
specifications for such characteristics [of inprocess
CGMP regulations require that batch samples represent the batch under analysis (see, e.g., § 211.160(b)(3)) and that the sampling plan result in statistical confidence (§
211.165(c) and (d)) that the batch meets its predetermined specifications (§ 211.165(a)). Section 211.110(b) provides two principles to
follow when establishing in-process specifications.
material and the drug product] shall be consistent with drug product final specifications . . . .” Accordingly, in-process material should be controlled to assure that the final drug product will meet its quality requirements. The second principle in this regulation further requires that in-process specifications “. . . shall be derived from previous acceptable process average and process variability estimates where possible and determined by the application of suitable statistical procedures where appropriate.” This requirement, in part, establishes the need for manufacturers to analyze process performance and control batch-to-batch variability.10 除了取样要求，CGMP 法规也提供了建立中控标准的要求，这也是工艺验证的一部分。 cGMP 法规要求，批样品代表的是所分析的批号(参见§211.160(b)(3))，取样计划可带来统计上的信心(§211.165(c)与(d))，即该批符合其预定的规格标准(§211.165(a))。第211.110(b)提供了在建立中控标准时要遵守的两个基本原则，第一项，“中间物料的规格标准应该与最终产品的规格标准相一致”，相应地，对中间物料应当进行控制以确保成品能符合其要求的质量。本法规第二项原则进一步要求中控标准，“应该来自于先前可接受的工艺平均值及可能的工艺变量估计，而且应该用合适的统计方法进行确定”。这项要求，部分地确立了生产企业分析工艺性能并控制批与批之间变异的必要性。 注释10 The Agency further explains this principle in the preamble to the final rule on “Current Good Manufacturing Practice in Manufacture, Processing, Packing, or Holding” (43 FR 45013 at 45052, September 29, 1978) (available on the Internet at https://www.doczj.com/doc/4910842313.html,/cder/dmpq/ preamble.txt).
The first principle is that “. . . inprocess specifications for such characteristics [of in-process material and the drug product] shall be consistent with drug product final specifications . . . .” Accordingly, inprocess material should be controlled to assure that the final drug product will meet its quality requirements. The second principle in this regulation further requires that in-process specifications “. . . shall be derived from previous acceptable process average and process variability estimates where possible and determined by the application of suitable statistical procedures where appropriate.” This requirement, in part, establishes the need for manufacturers to analyze process performance and control batch-to-batch variability.77In the Federal Register of September 29, 1978 (43 FR 45013 at 45052), FDA published a final rule on “Current Good Manufacturing Practice in Manufacture, Processing, Packing, or Holding” (available on the Internet at https://www.doczj.com/doc/4910842313.html,/cder/dmpq/preamble.txt). In the preamble of the final rule, the Agency further explains this principle.
cGMP 法规要求，批样品代表的是所分析的批号(参见§211.160(b)(3))，取样计划可带来统计上的信心(§211.165(c)与(d))，即该批符合其预定的规格标准(§211.165(a))。第211.110(b)提供了在建立中控标准时要遵守的两个基本原则，第一项，“中间物料的规格标准应该与最终产品的规格标准相一致”，相应地，对中间物料应当进行控制以确保成品能符合其要求的质量。本法规第二项原则进一步要求中控标准，“应该来自于先前可接受的工艺平均值及可能的工艺变量估计，而且应该用合适的统计方法进行确定”。这项要求，部分地确立了生产企业分析工艺性能并控制批与批之间变异的必要性。 The CGMP regulations also describe and
define activities connected with process design, development, and maintenance. Section 211.180(e) requires that information and
The CGMP regulations also describe and
define activities connected with process design, development, and maintenance. Section 211.180(e) requires that information and
data about product quality and manufacturing experience be periodically reviewed to determine whether any changes to the estab-
lished process are warranted. Ongoing feedback about product quality and process performance
is an essential feature of process maintenance.
cGMP 法规中同样描述并定义了与过程设计、开发与维护相关的活动。第211.180(e)要求，产品质量与生产经验的资料和数据要进行定期审核，以确定是否与已经批准的工艺有任何变更。产品质量和工艺性能的持续反馈是工艺维护的本质特点。data about product performance and manufacturing experience be periodically reviewed
to determine whether any changes to the established process are warranted. Ongoing feedback about product performance is an essential feature of process maintenance.
cGMP 法规中同样描述并定义了与过程设计、开发与维护相关的活动。第211.180(e)要求，产品性能与生产经验的资料和数据要进行定期审核，以确定是否与已经批准的工艺有任何变更。产品性能的持续反馈是工艺维护的本质特点。
In addition, the CGMP regulations require
that facilities in which drugs are manufactured
be of suitable size, construction, and
location to facilitate proper operations (§
211.42). Equipment must be of appropriate design, adequate size, and suitably located
to facilitate operations for its intended use (§ 211.63). Automated, mechanical, and electronic equipment must be calibrated, inspected,
or checked according to a written
program designed to assure proper performance (§ 211.68).
此外，cGMP 法规还要求生产药品的设施应当有合适的尺寸、材质以及布局以利于适当地操作(21CFR211.42)。设备必须是适当的设计，足够的尺寸，并适当地布局以方便其预定的操作用途(21CFR211.63)。自动化、机械以及电子设备必须根据书面程序进行校验、检查或核实以便保证其合适的性能。 In addition, the CGMP regulations require
that facilities in which drugs are manufactured
be of suitable size, construction, and
location to facilitate proper operations (21
CFR 211.42). Equipment must be of appropriate design, adequate size, and suitably
located to facilitate operations for its intended
use (21 CFR 211.63). Automated, mechanical, and electronic equipment must be calibrated, inspected, or checked according to a
written program designed to assure proper performance (21 CFR 211.68).
此外，cGMP 法规还要求生产药品的设施应当有合适的尺寸、材质以及布局以利于适当地操作(21CFR211.42)。设备必须是适当的设计，足够的尺寸，并适当地布局以方便其预定的操作用途(21CFR211.63)。自动化、机械以及电子设备必须根据书面程序进行校验、检查或核实以便保证其合适的性能。
In summary, the CGMP regulations require
that manufacturing processes be designed
and controlled to assure that in-process materials and the finished product meet predetermined quality requirements and do so
consistently and reliably.
总之，cGMP 法规要求应当对生产工艺进行设计和控制，以确保工艺中间物料与成品满足其预定的质量标准，而且应当一贯如此。In summary, the CGMP regulations require
that manufacturing processes be designed
and controlled to assure that in-process materials and the finished product meet predetermined quality requirements and do so
consistently and reliably.
总之，cGMP 法规要求应当对生产工艺进行设计和控制，以确保工艺中间物料与成品满足其预定的质量标准，而且应当一贯如此。
IV. RECOMMENDATIONS IV建议IV. RECOMMENDATIONS IV.建议
In the following sections, we describe general considerations for process validation, the recommended stages of process validation,
and specific activities for each stage in the product lifecycle.
在随后的部分，我们描述了工艺验证的一般考虑点、工艺验证的推荐阶段和产品生命周期中每个阶段的特定活动。
A. General Considerations for Process Validation
工艺验证的一般考虑A. General Considerations for Process Validation
A.工艺验证的一般考虑
In all stages of the product lifecycle, good
project management and good archiving that capture scientific knowledge will make the process validation program more effective
and efficient. The following practices should ensure uniform collection and assessment of information about the process and enhance
the accessibility of such information later in
the product lifecycle.
在产品生命周期的各个阶段，旨在捕捉科学知识的良好的项目管理与归档将使得工艺验证更加有效和高效率。这些惯例应确保统一收集并评估有关工艺信息，在后面的产品生命周期里加强利用这些资料。
W e recommend an integrated team
approach11 to process validation that
includes expertise from a variety of disciplines (e.g., process engineering, industrial pharmacy, analytical chemistry, microbiology, statistics, manufacturing,
and quality assurance). Project plans,
along with the full support of senior management, are essential elements
for success.
我们建议以整合团队的方式来进行工艺验证，其中包括来自于各不同的专门学科的专家，包括工艺工程、工业药学、分析化学、微生物学、统计学、生产和质量保证。项目计划，以及来自于高级管理层的全力支持，是必不可少的成功要素。In all stages of the product lifecycle, good
project management and good archiving that capture scientific knowledge will make the process validation program more effective
and efficient. These practices should ensure uniform collection and assessment of information about the process, reduce the chance for redundant information gathering and
analysis, and enhance the accessibility of
such information later in the product lifecycle.
在产品生命周期的各个阶段，旨在捕捉科学知识的良好的项目管理与归档将使得工艺验证更加有效和高效率。这些惯例应确保统一收集并评估有关工艺信息，减少多余信息的收集与分析机会，在后面的产品生命周期里加强利用这些资料。 · We recommend an integrated8team
approach to process validation that includes expertise from a variety of disciplines,
including process engineering,
industrial pharmacy, analytical chemistry, microbiology, statistics, manufacturing,
and quality assurance. Project
plans, along with the full support of senior management, are essential elements
for success.
我们建议以整合团队的方式来进行工艺验证，其中包括来自于各不同的专门学科的专家，包括工艺工程、工业药学、分析化学、微生物学、统计学、生产和质量保证。项目计划，以及来自于高
T hroughout the product lifecycle, various studies can be initiated to discover, observe, correlate, or confirm information about the product and process. All studies should be planned and conducted according to sound scientific principles, appropriately documented, and approved in accordance with the established procedure appropriate for the stage of the lifecycle. 在整个产品生命周期中，可以开展各种研究以便发现、观察、联想或确认有关产品和工艺的信息。所有研究应该按照可靠的科学原则进行策划、实施并妥善记录，并且应当按照在适当的生命周期阶段建立的书面程序进行审批。 T he terms attribute(s) (e.g., quality, product, component) and parameter(s) (e.g., process, operating, and equipment) are not categorized with respect to criticality in this guidance. With a lifecycle approach to process validation that employs risk based decision making throughout that lifecycle, the perception of criticality as a continuum rather than a binary state is more useful.
在这个指南中，没有对属性术语（例如质量、产品和组分）与参数术语（例如工艺、操作和设备）进行涉及关键性的分类。对于工艺验证采用以风险为基础的生命周期方法，在整个生命周期中，把关键性看作连续的比看作间断的更有用。 All attributes and parameters should be evaluated in terms of their roles in the process and impact on the product or in-process material, and reevaluated as new information becomes available. The degree of control over those attributes or parameters should be commensurate with their risk to the process and process output. In other words, a higher degree of control is appropriate for attributes or parameters
that pose a higher risk. The Agency recognizes that terminology usage can
级管理层的全力支持，是必不可少的成功要素。· Throughout the product lifecycle, various studies can be initiated to discover, observe, correlate, or confirm information about the product and process. All studies should be planned and conducted according to sound scientific principles, appropriately documented, and should be approved in accordance with the established procedure appropriate for the stage of the lifecycle.在整个产品生命周期中，可以开展各种研究以便发现、观察、联想或确认有关产品和工艺的信息。所有研究应该按照可靠的科学原则进行策划、实施并妥善记录，并且应当按照在适当的生命周期阶段建立的书面程序进行审批。 8 This concept is discussed in more detail in FDA’s guidance for industry, Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations, available on the Internet at https://www.doczj.com/doc/4910842313.html,/cder/guidance/ index.htm.
vary and expects that each manufacturer
will communicate the meaning
and intent of its terminology and categorization to
the Agency.
应该评估所有属性或参数对工艺的作用和对产
品或者中控物料的影响，重新评估的新信息也可
以使用。对那些属性或参数的控制力度应该和它
们对工艺的风险影响以及对工艺输出量的影响
相匹配。换句话说，对于产生较高风险的属性或
参数，实施较高程度的控制是合适的。FDA认为
术语使用在不同场合是不同的，期望每个制造商
和FDA进行关于术语定义和用途的交流。
Many products are single-source or involve
complicated manufacturing
processes. Homogeneity within a batch
and consistency between batches are
goals of process validation activities.
Validation offers assurance that a
process is reasonably protected
against sources of variability that could
affect production output, cause supply
problems, and negatively affect public
health.
很多产品来源单一，或者涉及复杂的制造工艺。
工艺验证活动的目的是证明一批产品内部和在
批与批之间是均质的。验证还提供了另一种保
证，即工艺被适度地保护以避免可能会影响产品
产量的变异性来源，产量的损失可能会造成市场
供应问题，进而影响到公众健康。
注释11This concept is discussed in more detail in
FDA’s guidance for industry, Quality Systems
Approach to Pharmaceutical Current Good
Manufacturing Practice Regulations, available at
https://www.doczj.com/doc/4910842313.html,/Drugs/GuidanceComplianceR
egulatoryInformation/Guidances/default.htm.
B. Specific Stages and Activities of Process
Validation in the Product Lifecycle
B.产品生命周期里工艺验证的阶段与活动
The following subsections describe the
recommended
stages and specific activities.
下面的小节描述了建议的阶段与具体活动。
Stage 1– Process Design 阶段1-工艺设计Stage 1– Process Design 阶段1-工艺设计
Process design is the activity of defining the commercial manufacturing process that will
be reflected in planned master production
and control records. The goal of this stage is
to design a process suitable for routine commercial manufacturing that can consistently deliver a product that meets its quality attributes.
工艺设计是确定商业化工艺的活动，工艺将体现在预期的主生产记录和主控制记录上。这个阶段的目的是确定适用于例行商业化生产的工艺，可以持续的生产出符合质量属性的产品。
Building and Capturing Process Knowledge and Understanding
建立和捕获工艺知识与理解Building and Capturing Process Knowledge
and Understanding
a. 建立和捕获工艺知识与理解
Process design is the activity of defining the commercial manufacturing process that will
be reflected in the master production and
control records. The goal of this stage is to design a process suitable for routine commercial manufacturing that can consistently
deliver a product that meets its critical quality attributes. 工艺设计是定义商业化生产工艺的活动，这个工艺将反映在主生产和控制记录里。这个阶段的目标是设计一个适合于日常商业化生产的工艺，能够始终如一地生产出满足其关键质量属性的产品。
Generally, early process design experiments
do not need to be performed under the
CGMP conditions required for drugs intended
for commercial distribution that are manufactured during Stage 2 (process qualification)
and Stage 3 (continued process verification). They should, however, be conducted in accordance with sound scientific methods and
principles, including good documentation practices. This recommendation is consistent with ICH Q10 Pharmaceutical Quality System12. Decisions and justification of the controls should be sufficiently documented and Generally, early process design experiments
do not need to be performed under CGMP conditions. They should, however, be conducted
in accordance with sound scientific
methods and principles, including good documentation
practices. This recommendation
is consistent with ICH guidance for industry,
Q10 Pharmaceutical Quality System.9
Decisions and justification of the controls should
be sufficiently documented and internally
reviewed to verify and preserve their value
for use later in the lifecycle of the process
1.工艺验证系列：第一节--工艺验证概述及传统工艺验证 1.1.工艺验证的定义 工艺验证应当证明一个生产工艺按照规定的工艺参数能够持续生产出符合预定用途和注册要求的产品。 工艺验证可以有不同的验证方法，一般包括：传统工艺验证（前验证、同步验证）以及基于生命周期的工艺验证（工艺设计、工艺确认、持续工艺确认）。 工艺验证不应该是一次性的事情。鼓励药品生产企业采用新的工艺验证方法，即基于生命周期的方法，将工艺研发、商业生产工艺验证、常规商业化生产中持续工艺确认相结合，来确定工艺始终如一的处于受控状态。 1.2.工艺验证的一般原则 工艺验证的方法和方针应该有文件记录，例如，在验证总计划中规定。 采用新的生产处方或生产工艺进行的首次工艺验证应当涵盖该产品的所有规格。企业可根据风险评估的结果采用简略的方式进行后续的工艺验证，如选取有代表性的产品规格或包装规格、最差工艺条件进行验证，或适当减少验证批次。 工艺验证批的批量应当与预定的商业批的批量一致。 企业应当根据质量风险管理原则确定工艺验证批次数和取样计划，以获得充分的数据来评价工艺和产品质量。 企业通常应当至少进行连续三批成功的工艺验证。对产品生命周期中后续商业生产批次获得的信息和数据，进行持续的工艺确认。 企业应当有书面文件确定产品的关键质量属性、关键工艺参数、常规生产和工艺控制中的关键工艺参数范围，并根据对产品和工艺知识的理解进行更新。 工艺验证一般在支持性系统和设备确认完成后才可以开始。在某些情况下，工艺验证可能与性能确认同步开展。
用于工艺验证的分析方法已经过验证。 用于工艺验证批次生产的关键物料应当由批准的供应商提供，否则需评估可能存在的风险。 日常生产操作人员及工艺验证人员应当经过适当的培训。 工艺验证在执行前应进行适当的风险评估，以确定存在的风险点。 如企业从生产经验和历史数据中已获得充分的产品和工艺知识并有深刻理解，工艺变更后或持续工艺确认等验证方式，经风险评估后可进行适当的调整。 对于既有产品生产现场转移，生产工艺与控制必须符合上市授权，并符合当前对该产品类型的许可标准。如果需要的话，应提交上市授权变更。 对从一个场所转移到另外一个场所或者在相同场所的产品工艺验证，验证批的数目可以通过括号法减少。然而，现有的产品知识，包括以前的工艺验证内容，应该是合适的。如果合理，不同的规格、批量和包装量/容器类型的工艺验证的选择也可以使用括号法。 1.3.传统工艺验证 传统工艺验证的类型一般包括前瞻性验证、同步性验证。 前验证一般在药物研发和/或工艺研发结束后，在放大至生产规模后，成品上市前进行。前瞻性验证是正式商业化生产的质量活动，是在新产品、新处方、新工艺、新设备正式投入生产使用前，必须完成并达到设定要求的验证。 在对患者利益有很大的风险的例外情况，也可以在常规生产中进行工艺验证，即同步验证，例如，因药物短缺可能增加患者健康风险、因产品的市场需求量极小而无法连续进行验证批次的生产。然而，实施同步验证的决定必须进行论证，在验证总计划中进行记录，并由授权人员批准。因同步验证批次产品的工艺和质量评价尚未全部完成产品即已上市，企业应当增加对验证批次产品的监控。
印刷中英文术语对照 Woodfree paper 書紙 Matt paper 啞粉紙 Glossy paper 光粉紙 1.GSM与LBS( pound)的转换： English paper grade to grammage conversion Grammage Paper Grade (LBS.) 44 gsm 30 lb. text 59 gsm 16 lb. bond, 40 lb. text 67 gsm 45 lb. text 89 gsm 24 lb. bond, 60 lb. text 104 gsm 70 lb. text 118 gsm 80 lb. text 148 gsm 67 lb. bristol, 100 lb. text 162 gsm 60 lb. cover 163 gsm 90 lb. index 176 gsm 65 lb. cover 178 gsm 80 lb. bristol 199 gsm 110 lb. index 216 gsm 80 lb. cover 219 gsm 100 lb. bristol 253 gsm 140 lb. index 263 gsm 120 lb. bristol
270 gsm 100 lb. cover 307 gsm 140 lb. bristol 308 gsm 170 lb. index 325 gsm 120 lb. cover 2.印刷品中英文对照 日历：calendar 台历：desk calendar 挂历：wall calendar 精装书: Case bound, hard bound, cloth bound, hardback, hardcover book 小册子:brochure 纸相架:Paper frame 纸板书: Board book 纸匣: paper tray 螺旋簿: spiral book 合订本：bound book 书芯纸印的封面。小册子的所有纸张（包括封面）采用同一类或相同克重的纸张，称为简装本（self-cover brochure）。 翻页书: flipbook 3.纸张中英文对照 铜版纸,又称涂布印刷纸:Coated Art Paper(or Board), Coated Woodfree; Art paper;Art printing pape;Copper printing paper 双铜纸: both sides coated art paper 亚粉纸: dull finished art paper,matt art paper
工艺验证方案 本公司产品XXXXX是非无菌原料药产品，为保证生产工艺在实际生产中的有效性和可靠性，故对其进行工艺验证，本工艺验证采用同步验证的方式。本生产工艺的验证是由质量管理部负责组织，生产技术部、设备工程部、生产车间及QC检验室有关人员参与实施。 本工艺验证方案参考了ICH Q7A的生产工艺验证的指导原则。 验证小组成员 方案制订 方案审核 方案批准
目录 1. 基本情况 (4) 1.1. 概述 (4) 1.2. 生产工艺 (4) 1.2.1. 生产工艺流程图 (4) 1.2.2. 生产工艺的详细描述 (4) 1.2.3. 关键工艺步骤和参数 (4) 2. 验证目的 (5) 3. 验证前提 (5) 3.1. 工艺环境包括公用系统情况 (5) 3.2. 工艺设备情况 (5) 3.3. 所用原辅料和包装材料情况 (5) 3.4. 所用文件的准备情况 (6) 3.5. 人员情况 (6) 4. 验证方案 (6) 4.1. 验证计划 (6) 4.2. 第一步反应（生产XXXXX粗品）的验证（应包括所有重点 考察的生产关键参数、结晶、离心、干燥） (6) 4.2.1第一步反应（生产XXXXX粗品）关键工艺参数验证 (6) 4.2.2第一步反应收率情况验证 (7) 4.2.3第一步反应中间体的质量情况验证 (7) 4.3. 粗品精制工序的验证 (8) 4.3.1溶解脱色验证 (8) 4.3.2 结晶工序验证 (8) 4.3.3 分离工序验证 (9) 4.3.4 干燥工序验证 (10) 4.3.5小批成品收率情况验证 (10) 4.3.6小批成品的质量情况验证 (11) 4.4批混合工艺的验证 (11) 4.4.1批混合工序关键工艺参数验证 (11) 4.4.2批混合效果的验证 (11) 4.5最终成品的质量情况验证 (12)
I. INTRODUCTION This guidance provides recommendations to applicants on submitting analytical procedures, validation data, and samples to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug products. 1. 绪论 本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用于支持原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。 This guidance is intended to assist applicants in assembling information, submitting samples, and presenting data to support analytical methodologies. The recommendations apply to drug substances and drug products covered in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), product license applications (PLAs), and supplements to these applications. 本指南旨在帮助申请者收集资料，递交样品并资料以支持分析方法。这些建议适用于NDA，ANDA，BLA，PLA及其它们的补充中所涉及的原料药和制剂。 The principles also apply to drug substances and drug products covered in Type II drug master files (DMFs). If a different approach is chosen, the applicant is encouraged to discuss the matter in advance with the center with product jurisdiction to prevent the expenditure of resources on preparing a submission that may later be determined to be unacceptable. 这些原则同样适用于二类DMF所涉及的原料药和制剂。如果使用了其它方法，鼓励申请者事先和FDA药品评审中心的官员进行讨论，以免出现这种情况，那就是花了人力物力所准备起来的递交资料后来发现是不可用的。 The principles of methods validation described in this guidance apply to all types of analytical procedures. However, the specific recommendations in this guidance may not be applicable to certain unique analytical procedures for products such as biological, biotechnological, botanical, or radiopharmaceutical drugs. 本指南中所述的分析方法验证的原则适用于各种类型的分析方法。但是，本指南中特定的建议可能不适用于有些产品所用的特殊分析方法，如生物药，生物技术药，植物药或放射性药物等。 For example, many bioassays are based on animal challenge models, 39 immunogenicity assessments, or other immunoassays that have unique features that should be considered when submitting analytical procedure and methods validation information. 比如说，许多生物分析是建立在动物挑战模式，免疫原性评估或其它有着独特特性的免疫分析基础上的，在递交分析方法和分析方法验证资料时需考虑这些独特的性质。Furthermore, specific recommendations for biological and immunochemical tests that may be necessary for characterization and quality control of many drug substances and drug products are beyond the scope of this guidance document. 而且，许多原料药和制剂的界定和质量控制所需的生物和免疫化学检测并不在本指南的范围之内。 Although this guidance does not specifically address the submission of analytical procedures and validation data for raw materials, intermediates, excipients, container closure components, and other materials used in the production of drug
工艺验证管理规定标准化管理处编码[BBX968T-XBB8968-NNJ668-MM9N]
工艺验证管理办法 1适用范围 本标准适用于本公司所有产品工艺验证。 2工艺验证的目的 通过工艺验证的有效实施，考察某一工艺过程是否能始终如一地生产出符合预定规格及质量标准的产品。为工艺规程定稿提供依据。 3职责 技术部：负责工艺验证方案的起草,并下发相关单位。 生产部：负责工艺验证方案的计划下达。 生产车间：负责工艺验证方案的组织实施。 质保部：负责按计划完成工艺验证方案中相关检验任务，确保检验结论正确可靠。并总结验证结果，向技术部提交验证产品的检测报告。 工艺员：负责工艺验证现场指导，解决验证现场问题,校对和调整、固化工艺文件。 技术负责人：负责审核工艺验证方案及报告。 技术副总：负责批准工艺验证方案及报告。 4内容
4.1验证小组成员 工艺员、生产部相关人员、检验员、质量员、生产车间相关人员。 4.2验证步骤 4.2.1制订验证计划 4.2.1.1由工艺员首先起草该工艺的验证计划，然后将验证计划交给验证小组讨论和 审批后分发至各责任部门。 4.2.1.2验证计划包括： 简介：简要说明验证对象信息、验证目的和拟采用的验证方法。 验证小组成员。 验证工作日程安排表（包括各验证项目的实施部门、责任人、实施日期及完成日期）。 4.2.2验证准备： 4.2.2.1负责验证现场的工装管理员提前半个工作日通知做好准备工作。 4.2.2.2工艺员负责提供现场验证的工艺文件。 4.2.2.3检验员负责准备好现场验证检测器具和质量文件。 4.2.2.4相关车间负责按验证计划准备好相应的工装设备、生产材料，并指派好验
管道及配件中英文对照 化工管道词汇翻译 1.1管子Pipe 管子(按照配管标准规格制造的) pipe 管子(不按配管标准规格制造的其他用管) tube 钢管steel pipe 铸铁管cast iron pipe 衬里管lined pipe 复合管clad pipe 碳钢管carbon steel pipe 合金钢管alloy steel pipe 不锈钢stainless steel pipe 奥氏体不锈钢管austenitic stainless steel pipe 铁合金钢管ferritic alloy steel pipe 轧制钢管wrought-steel pipe 锻铁管wrought-iron pipe 无缝钢管seamless (SMLS) steel pipe 焊接钢管welded steel pipe 电阻焊钢管electric-resistance welded steel pipe 电熔（弧）焊钢板卷管electric-fusion (arc)-welded steel-plate pipe
螺旋焊接钢管spiral welded steel pipe 镀锌钢管galvanized steel pipe 热轧无缝钢管hot-rolling seamless pipe 冷拔无缝钢管cold-drawing seamless pipe 水煤气钢管water-gas steel pipe 塑料管plastic pipe 玻璃管glass tube 橡胶管rubber tube 直管run pipe; straight pipe 1.2管件Fitting 弯头elbow 异径弯头reducing elbow 带支座弯头base elbow 长半径弯头long radius elbow 短半径弯头short radius elbow 长半径180°弯头long radius return 短半径180°弯头short radius return 带侧向口的弯头（右向或左向）side outlet elbow (right hand or left hand) 双支管弯头（形）double branch elbow 三通tee 异径三通reducing tee
201507 FDA行业指南：分析方法验证（中英文）（下） VII. STATISTICAL ANALYSIS AND MODELS 统计学分析和模型 A. Statistics 统计学 Statistical analysis of validation data can be used to evaluate validation characteristics against predetermined acceptance criteria. All statistical procedures and parameters used in the analysis of the data should be based on sound principles and appropriate for the intended evaluation. Several statistical methods are useful for assessing validation characteristics, for example, an analysis of variance (ANOVA) to assess regression analysis R (correlation coefficient) and R squared (coefficient of determination) or linear regression to measure linearity. Many statistical methods used for assessing validation characteristics rely on population normality, and it is important to determine whether or not to reject this assumption. There are many techniques, such as histograms, normality tests, and probability plots that can be used to evaluate the observed distribution. It may be appropriate to transform the data to better fit the normal distribution or apply distribution-free (nonparametric) approaches when the observed data are
印刷专业用语 纸料： 260g粉灰260g grey back MC board 300g粉灰300g grey back MC board 350g粉灰350g grey back MC board 350g单粉咭(白芯/灰芯)350g single side coated board (white liner/grey liner) 350g双粉咭(白芯/灰芯)350g both sides coated board (white liner/grey liner) 80g书纸80g W/F PAPER 80g色书纸80g color W/FPAPER 157g双粉纸157g art paper 157g哑粉纸157g matt coated paper 防潮纸Moisture Proof paper 铜板不干胶Raflacoat self-adhesive 双铜纸glossy paper/ coated art paper 双胶纸offset paper 轻涂纸Light Weight Coated Paper 无光铜版纸matt art paper 光面铜版纸gloss paper 灰底白板卡纸CCNB的全称是Clay Coated News Back 牛底白板纸板CCKB(Clay Coated Kraft Back) 白底灰芯纸板CCWB(Clay Coated White Back)
铜板卡纸/白芯粉咭SBS(Solid Bleached Sulphate) 合成纸Synthetic paper 根据表面涂布情况SBS又分为单粉咭C1S(coated one side)和双粉咭 C2S(coated two sides)。根据表面涂布效果分为Matte(哑光纸)和Glossy(光面纸)。 坑纸: BEE-flute (125g牛咭+110g芯纸) WE-flute (140g白牛咭+110g芯纸) B3-flute (125g牛咭+115g芯纸) A3-flute (175g牛咭+115g芯纸) K3-flute (250g牛咭+115g芯纸) W3-flute (140g白牛咭+115g芯纸) A3B9-flute (175g牛咭+115g芯纸+125g牛咭+110g芯纸)K3B9-flute (250g牛咭+115g芯纸+125g牛咭+110g芯纸)印刷 印油Transparent ink 印光油Gloss Varnishing 印哑油Matt Varnishing 印专色Printed in spot color 表面处理 磨光Calendaring 磨光吸塑油Blister-calendaring varnish 过光油Varnishing
工艺验证管理细则 1. 本细则规定了工艺验证的范围,基本任务，主要验证内容和验证程序。 2. 本细则适用于本公司产品工艺验证。 3. 工艺验证范围：凡需批量生产的新产品，在样件试制鉴定后批量生产前,均需进行小批试生产工艺验证。 4. 工艺验证的基本任务： 通过小批试生产，考核工艺文件和工艺装备的合理性和适应性，以保证今后批量生产中产品质量稳定，精益成本，达到顾客要求并符合相关国家法律法规要求。 5. 主要验证内容： 5.1工艺文件是否齐全； 5.2工艺规定的特征参数是否达到设计要求； 5.3关键特殊工序是否明确； 5.4设备及工艺装备能否满足产品质量要求； 5.5量检具的配备率及检测能力是否满足生产技术质量要求； 5.6产品质量达到规定要求的情况。 6. 验证程序： 6.1制定验证实施计划，验证实施计划的内容应包括：主要验证项目；验证的技术准备；组织措施和时间地点的安排。 6.2验证前的准备： 6.2.1生产部门负责下达验证计划并做好试生产的全部材料或毛坯准备； 6.2.2技术部门负责提供验证所需的工艺文件和有关资料； 6.2.3相关生产车间提供所需的全部设备、工艺装备，并做好试生产准备； 6.2.4质检部门做好检查准备。 6.3实施验证： 6.3.1验证时必须严格按工艺文件要求进行试生产； 6.3.2验证性的试生产件数量为：一般情况，总体尺寸≤100×100时=10 ~ 30件；总体尺寸＞100×100 ~ ≤500×500时=5－20件；总体尺寸＞500×500以上时约
3－10件；较大型覆盖件、成本较高的产品应根据情况临时按排试生产数量。6.3.3验证过程中，有关工艺和工装设计人员必须经常到生产现场进行跟踪考察，认真听取生产操作者的合理化意见，对有助于改进工艺、工装的建议要积极采纳，发现问题及时进行解决，并要详细记录问题发生的原因和解决措施。 6.4验证总结与鉴定： 6.4.1验证总结： 试生产验证结束后，技术部门应填写工艺验证书，其内容包括： ①试生产件的名称图号、验证内容、数量、时间； ②工艺文件的准备情况、特征参数是否达到设计要求； ③设备和工艺装备的准备情况、工装设备是否满足产品质量要求； ④量检具的配备率及检测能力是否满足生产技术质量要求； ⑤关键特殊工序是否明确； ⑥产品质量达到规定要求的情况； ⑦质检部门填写产品验证记录表； ⑧验证结果分析：其内容包括验证情况及结果分析和改进意见； ⑨验证结论：内容包括对今后批量生产的意见和建议。 6.4.2验证鉴定： ①一般产品有企业技术主要负责人主持召开由各相关科室及生产车间参加的工艺验证鉴定会，根据工艺验证总结和各方面的意见，确定该产品工艺验证是否合格，能否进行批量生产。对作出鉴定结果的验证书，参加鉴定会的成员应在验证书会签栏签名。鉴定合格的产品，由质检部门发出合格产品通知单。鉴定不合格的产品，由技术部门组织整改，整改后进入下一轮验证程序。 ②对被纳入主机厂验证计划的重要产品，在通过本企业鉴定后,还需要报主机厂,主机厂下达验证计划的主管部门组织验收,根据主机厂相应主管部门发出的产品试制鉴定通知，质检部门通知生产部门对验收合格的产品组织批量生产。验收不合格的，由质检部门通知技术部门组织整改，整改后进入下一轮验证程序。 编制：批准：
美国FDA分析方法验证指南中英文对照 美国FDA分析方法验证指南中英文对 照 I. INTRODUCTION This guidance provides recommendations to applicants on submitting analytical procedures, validation data, and samples to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug products. 1. 绪论 本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用 于支持原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。 This guidance is intended to assist applicants in assembling information, submitting samples, and presenting data to support analytical methodologies. The recommendations apply to drug substances and drug products covered in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), product license applications (PLAs), and supplements to these applications. 本指南旨在帮助申请者收集资料，递交样品并资料以支持分析方法。这些建议适 用于NDA，ANDA，BLA，PLA及其它们的补充中所涉及的原料药和制剂。 The principles also apply to drug substances and drug products covered in Type II drug master files (DMFs). If a different approach is chosen, the applicant is encouraged to discuss the matter in advance with
工艺验证管理制度示范文 本 In The Actual Work Production Management, In Order To Ensure The Smooth Progress Of The Process, And Consider The Relationship Between Each Link, The Specific Requirements Of Each Link To Achieve Risk Control And Planning 某某管理中心 XX年XX月
工艺验证管理制度示范文本 使用指引：此管理制度资料应用在实际工作生产管理中为了保障过程顺利推进，同时考虑各个环节之间的关系，每个环节实现的具体要求而进行的风险控制与规划，并将危害降低到最小，文档经过下载可进行自定义修改，请根据实际需求进行调整与使用。 1. 工艺验证由生产技术科和质管科两个部门共同负 责。 2. 工艺验证应达到预期的质量效果，能证明新工艺更 合理更有效。 3. 对工艺验证过程中出现的问题应采取措施及时解 决。 4. 工艺验证后应由验证部门记录或出具报告。 5. 有以下情况之一的应进行工艺验证： a ) 主要原料改变时； b ) 增加或减少工序时； c ) 有新设备加入时； d ) 采用新的工艺方法时；
e ) 产品结构改变时； f ) 新产品试产时； g ) 相应法规规定时。 请在此位置输入品牌名/标语/slogan Please Enter The Brand Name / Slogan / Slogan In This Position, Such As Foonsion
管材、管件、阀门、接头、管道特件、紧固件、垫片、密封、工程材料等中英文对照 化工管道设计技术英语词汇(1－2－3) 1 管道组成件 Piping component 1.1 管子 Pipe 管子(按照配管标准规格制造的) pipe 管子(不按配管标准规格制造的其他用管) tube 钢管 steel pipe 铸铁管 cast iron pipe 衬里管 lined pipe 复合管 clad pipe 碳钢管 carbon steel pipe 合金钢管 alloy steel pipe 不锈钢 stainless steel pipe 奥氏体不锈钢管 austenitic stainless steel pipe 铁合金钢管 ferritic alloy steel pipe 轧制钢管 wrought-steel pipe 锻铁管 wrought-iron pipe 无缝钢管 seamless (SMLS) steel pipe 焊接钢管 welded steel pipe 电阻焊钢管 electric-resistance welded steel pipe 电熔（弧）焊钢板卷管 electric-fusion (arc)-welded steel-plate pipe 螺旋焊接钢管 spiral welded steel pipe 镀锌钢管 galvanized steel pipe 热轧无缝钢管 hot-rolling seamless pipe 冷拔无缝钢管 cold-drawing seamless pipe 水煤气钢管 water-gas steel pipe 塑料管 plastic pipe 玻璃管 glass tube 橡胶管 rubber tube 直管 run pipe; straight pipe 1.2 管件 Fitting 弯头 elbow 异径弯头 reducing elbow 带支座弯头 base elbow k半径弯头 long radius elbow 短半径弯头 short radius elbow 长半径180°弯头 long radius return 短半径180°弯头 short radius return 带侧向口的弯头（右向或左向） side outlet elbow (right hand or left hand) 双支管弯头（形） double branch elbow
包装印刷中英文专业术语大全 刀版die plate 菲林printing film/artwork 数码印刷digital printing 印前工序prepress process 包装种类 包装盒 packaging 天地盖盒lid and base box 彩盒color printing box 储物盒storage box 展示盒display stand 翻盖盒/可折叠盒folding paper box 珠宝盒Jewelry box 茶叶盒tea box 鞋盒shoe box 盒Box 纸盒 paper box 硬纸盒rigid paper box 瓦楞纸盒corrugated paper box 木盒Wooden Box 铁盒Iron Box 塑料透明盒 Plastic Transparency Box 苯乙烯盒 Styrol Box 礼盒presentation box 礼品盒gift box 展示盒showing box
箱Case 纸箱Carton 外箱master carton 瓦椤纸箱Corrugated Carton 旧瓦椤纸箱Old Corrugated Carton (O．C．C．) 木箱Wooden Case 板条箱Crate 木条箱Wooden Crate 竹条箱Bamboo Crate 胶合板箱Plywood Case 三层夹板箱3--Ply Plywood Case 镀锡铁皮胎木箱Tin Lined Wooden Case 集装箱Container 袋Bag(Sack) 布袋Cloth Bag 草袋Straw Bag 麻袋Gunny Bag／Jute Bag 旧麻袋Used Gunny Bag／Old Gunny Bag 新麻袋New Gunny Bag 尼龙袋Nylon Bag 聚丙烯袋Polypropylene Bag 聚乙烯袋Polythene Bag 塑料袋Poly Bag 塑料编织袋Polywoven Bag 纤维袋Fibre Bag 玻璃纤维袋Glass Fibre Bag 玻璃纸袋Callophane Bag 防潮纸袋Moisture Proof Pager Bag 乳胶袋子Emulsion Bag 三层牛皮纸袋3=ply Kraft Paper Bag 锡箔袋Fresco Bag 特大袋Jumbo Bag
管件中英文对照(2007-07-15 11:42:00) 等径直通equal coupling 异径直通reducing coupling 内牙直通 female coupling 外牙直通 straight tube with outside 90等径弯头 90 equal elbow 45等径弯头 45 equal elbow 外牙弯头 male elbow 内牙弯头 female elbow 等径三通 equal tee 异径三通 reducing tee 内牙三通female tee 外牙三通 male tee 管帽cap sch代表压力 lr长半径或1倍半 大小 SIZE 数量 QTY 碳钢弯头 Carbon Steel Elbow 不锈钢弯头 Stainless Steel Elbow 高压弯头 High-Pressure Elbow 同心异径管 Concentric Reducers 偏心异径管 Eccentric Reducers 高压异径管 High-pressure Reducers 不锈钢等径三通 Stainless Straight Tee 碳钢等径三通 Carbon Straight Tee 不锈钢等径四通 Stainless Straight Cross 高压三通 High-pressure Tee 锻制三通 Forged Tee
异径接头 Template 管帽 Caps 法兰flange 长径和短径弯头 long and short radius elbows 同心和偏心异径接头 concentric and eccentric reducers 等径和异径三通 straight and reducing outlet tees 大小头 CONCENTRIC REDUCER Tee Equal 相等的三通 等径三通Straight Tee 异径三通Reducing Tee 等径四通Straight Cross 90°短半径弯头90°SS Elbow (SR) 90°长半径弯头90°SS Elbow (LR) 高压厚壁弯头Thickness Elbow U型管Return Bend 盲法兰Blank Flange 弯管Bends 翻边stub ends 异径接头reducers 公称通径 nominal diameter 外径(mm) outside diameter 中心距至端面的距离 center to end 理论重量(kg/pcs) approx weight description 类种 Standard标准 Design类型 Material材质 双丝头 Nipple 短节 SWAGE NIPPLE
1 II. 背景 (2) III. 分析方法的类型 (3) A. 法定分析方法 (3) B. 可选择分析方法 (3) 3 C. 稳定性指示分析 (3) IV. 对照品…………………………………………………………………………… 4 A. 对照品的类型 (4) B. 分析报告单 (4) C. 对照品的界定 (4) V. IND 中的分析方法验证 (6) VI. NDA, ANDA, BLA 和PLA 中分析方法验证的内容和格式 (6) A. 原则 (6) B. 取样 (7) C. 仪器和仪器参数 (7) D. 试剂 (7) E. 系统适应性实验 (7) F. 对照品的制备 (7) G. 样品的制备 (8) H. 分析方法 (8) L. 计算 (8) J. 结果报告 (8) VII. NDA，ANDA,BLA 和PLA 中的分析方法验证 (9) A．非法定分析方法 (9) 1．验证项目 (9) 2. 其它分析方法验证信息 (10) a. 耐用性 (11) b. 强降解实验 (11) c. 仪器输出/原始资料 (11) 3．各类检测的建议验证项目 (13) B．法定分析方法 (15) VIII. 统计分析………………………………………………………………………… 15 A. 总则 (15)
C. 统计 (16) IX. 再验证 (16) X. 分析方法验证技术包：内容和过程…………………………………………… 17 A. 分析方法验证技术包 (17) B. 样品的选择和运输 (18) C. 各方责任 (19) XI. 方法……………………………………………………………………………… 20 A. 高效液相色谱(HPLC) (20) B. 气相色谱(GC) (22) C. 分光光度法，光谱学，光谱法和相关的物理方法 (23) D. 毛细管电泳 (23) E. 旋光度 (24) F. 粒径相关的分析方法 (25) G. 溶出度 (26) H. 其它仪器分析方法 (27) 附件A：NDA，ANDA，BLA 和PLA 申请的内容 (28) 附件B：分析方法验证的问题和延误 (29) 参考文献…………………………………………………………………………………… 30 术语表……………………………………………………………………………………… 32 This guidance provides recommendations to applicants on submitting analytical procedures, validation data, and samples to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug products. 1. 绪论 本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用于支持 原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。 This guidance is intended to assist applicants in assembling information, submitting samples, and presenting data to support analytical methodologies. The recommendations apply to drug substances and drug products covered in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), product license applications (PLAs), and supplements to these applications.
管理制度编号：LX-FS-A37370 工艺验证管理制度标准范本 In The Daily Work Environment, The Operation Standards Are Restricted, And Relevant Personnel Are Required To Abide By The Corresponding Procedures And Codes Of Conduct, So That The Overall Behavior Can Reach The Specified Standards 编写：_________________________ 审批：_________________________ 时间：________年_____月_____日 A4打印/ 新修订/ 完整/ 内容可编辑
工艺验证管理制度标准范本 使用说明：本管理制度资料适用于日常工作环境中对既定操作标准、规范进行约束，并要求相关人员共同遵守对应的办事规程与行动准则，使整体行为或活动达到或超越规定的标准。资料内容可按真实状况进行条款调整，套用时请仔细阅读。 1. 工艺验证由生产技术科和质管科两个部门共同负责。 2. 工艺验证应达到预期的质量效果，能证明新工艺更合理更有效。 3. 对工艺验证过程中出现的问题应采取措施及时解决。 4. 工艺验证后应由验证部门记录或出具报告。 5. 有以下情况之一的应进行工艺验证： a ) 主要原料改变时； b ) 增加或减少工序时； c ) 有新设备加入时；
d ) 采用新的工艺方法时； e ) 产品结构改变时； f ) 新产品试产时； g ) 相应法规规定时。 请在该处输入组织/单位名称 Please Enter The Name Of Organization / Organization Here