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1、5 9 i% g1 w$ M R+ C6 y! i7 |4 EQ8 (R1) Pharmaceutical development Revision 1) N1 qQ; J8 1 O* T- pQ8(R1) 药物开发 修订1$ K# z B2 f/ q |1. Introduction+ E$ 9 D1 k1 s% T5 f. SThis guidance is an annex to ICH Q8 Pharmaceutical Development and provides further clarification of key concepts outlined in the core
2、 guideline. In addition, this annex describes the principles of quality by design (QbD). The annex is not intended to establish new standards;however, it shows how concepts and tools (e.g., design space) outlined in the parent Q8 document could be put into practice by the applicant for all dosage fo
3、rms. Where a company chooses to apply quality by design and quality risk management (ICH Q9, Quality Risk Management), linked to an appropriate pharmaceutical quality system, then opportunities arise to enhance science- and risk-based regulatory approaches (see ICH Q10, Pharmaceutical Quality System
4、s)., C h6 M- N3 - 5 # I# 1介绍$ f! e/ u: K# / S本指南是ICH Q8 药物开发这个指南的补充，对Q8中所述的关键概念作了进一步的阐述。此外， 本补充描述了设计质量（Quality by design, QbD）的原则。该补充旨不在于建立新的标准，但表明了Q8 指南中所述的的概念和工具（如，设计空间）是如何能被所有剂型的申请者应用实施的。当一公司选择将设计质量和质量风险管理（ICH Q9， 质量风险管理）与适宜的药物质量体系相联接的话，则提高基于科学和基于风险的法规体系的机会出现了。（见ICH Q10， 制药质量体系）! ay* Z/ B4 T0 U1.
5、1. Approaches to Pharmaceutical Development4 E: oI3 i6 O6 o2 XIn all cases, the product should be designed to meet patients needs and the intended product performance. Strategies for product development vary from company to company and from product to product. The approach to, and extent of, develop
6、ment can also vary and should be outlined in the submission. An applicant might choose either an empirical approach or a more systematic approach to product development. An illustration of the potential contrasts of these approaches is shown in Appendix 1. A more systematic approach to development (
7、also defined as quality by design) can include, for example, incorporation of prior knowledge, results of studies using design of experiments, use of quality risk management, and use of knowledge management (see ICH Q10) throughout the lifecycle of the product. Such a systematic approach can enhance
8、 the process to achieve quality and help the regulators to better understand a companys strategy. Product and process understanding can be updated with the knowledge gained over the product lifecycle.* e, K) E6 , y6 d& g1.1. 药物开发的方法( f# . I8 l; e- I& Vo& ! E无论在何种情况下，产品都应被设计成符合患者的需求，符合拟定的产品性能。产品开发的策略
9、因公司而异，也因产品而异。产品开发的方法和程度也各不相同，这些均应在申请文件中得以概述。申请人会选择基于经验的方法，或更系统的方法用于产品开发。这些方法的对比说明见附录1。 更系统的开发方法（也被定义为设计质量）可以包括，如，整合现有知识，运用实验设计进行研究的结果，运用质量风险管理和在整个产品生命周期内运用知识管理（见ICH Q10）。这样的系统方法可以加强达到质量的工艺，并有助于监管者更好地理解公司的战略。产品和工艺理解能通过产品生命周期中获得的知识得以更新。1 m& M$ E2 e7 i z8 YA greater understanding of the product and its
10、 manufacturing process can create a basis for more flexible regulatory approaches. The degree of regulatory flexibility is predicated on the level of relevant scientific knowledge provided in the registration application. It is the knowledge gained and submitted to the authorities, and not the volum
11、e of data collected, that forms the basis for science- and risk-based submissions and regulatory evaluations. Nevertheless, appropriate data demonstrating that this knowledge is based on sound scientific principles should be presented with each application. r8 H3 V- X* y L更好的产品及其生产工艺理解能为更灵活的法规体系建立基础
12、。法规灵活度是能根据注册申请中提供的相关科学知识水平来预定的。形成基于科学和基于风险的申请文件和法规评审的基础的是获得并递交至官方机构的知识，而不是收集到的资料。但，论述这些知识是基于充分的科学依据的适宜资料应当呈现在每个申请文件中。2 N0 KN# v* 4 _Pharmaceutical development should include, at a minimum, the following elements:7 c. a: D$ M/ $ b, S9 F* Defining the target product profile as it relates to quality, s
13、afety and efficacy,considering e.g., the route of administration, dosage form, bioavailability, dosage, and stability! B9 O0 z5 rm* Identifying critical quality attributes (CQAs) of the drug product, so that those product characteristics having an impact on product quality can be studied and control
14、led% 9 _8 b; 4 U4 q4 Y* Determining the quality attributes of the drug substance, excipients etc., and selecting the type and amount of excipients to deliver drug product of the desired quality) w8 q+ l5 a3 s2 K4 l* Selecting an appropriate manufacturing process1 i: N6 R+ ( k: t BW* Identifying a co
15、ntrol strategy9 M; 6 Z% K% h- C4 u( w药物开发应，至少包括下列要素:6 I2 D6 R0 p9 A1 f6 J4 $ C Z7 D( X* 确定目标产品的质量，安全和功效相关概况，需考虑，如用药途径，剂型，生物利用度，剂量和稳定性。3 n- N8 q K9 U4 J3 |* 确定药物关键质量属性，以使对产品质量有影响的产品特性能得以研究和控制。! M U/ j* X F0 G* 确定药物活性成分，赋形剂等的质量属性，并选择赋形剂的类型和量以使药品达到理想的质量。$ V; Q$ Z+ : X0 r, ?* 选择适宜的生产工艺。 E+ Y3 N+ a1 d5 d
16、9 L* 确定控制策略0 R- y) u- r fk) X9 e6 V a7 W vAn enhanced, quality by design approach to product development would additionally include the following elements:0 W6 C7 |; t 0 8 ( E1 ) W- B- b* A systematic evaluation, understanding and refining of the formulation and manufacturing process, including:0 w- t, h( X: p. h6 # f# go Identifying, through e.g., prior knowledge, ex
