今天看ICH Q7A，里面有一句话：生产厂商要定义并用书面文件说明原料药的生产从何处开始的理论依据。
自己搞不懂，应该如何定义？如果自己定义，那定义生产的起始原料在工序中的位置越往后不是越好吗？
请教一下各位大侠！
你的理解不对.
看下面的资料:
1-An API starting material is a raw material, an intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API starting material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in-house. API starting materials normally have defined chemical properties and structure.
译文=“原料药的起始物料”是指一种原料、中间体或原料药，用来生产一种原料药，或者以主要结构单元的形式被结合进原料药结构中。原料药的起始物料可能是在市场上有售、能够通过合同或商业协议从一个或多个供应商处购得，或由生产厂家自制。原料药的起始物料一般来说有特定的化学特性和结构。
2-The company should designate and document the rationale for the point at which production of the API begins. For synthetic processes, this is known as the point at which API starting materials are entered into the process. For other processes (e.g., fermentation, extraction, purification), this rationale should be established on a case-by-case basis. Table 1 gives guidance on the point at which the API starting material is normally introduced into the process.
译文:生产厂商要指定并用书面文件说明原料药的生产从何处开始的理论依据。对于合成工艺而言，就是“原料药的起始物料”进入工艺的那一点。对其他工艺（如：发酵，提取，纯化等）可能需要具体问题具体对待。表1给出了原料药的起始物料从哪一点引入工艺过程的指导原则。
上面是Q7的内容,下面是指南注释的内容:
Guidance on How To Define API Starting Materials
． Follow the guidance given in ICH Q7A and involve technical, quality and regulatory departments in agreeing the definition of the API Starting Materi-als. Where possible use the same definition of API starting material in regu-latory filings and in defining the steps for which the GMP requirements of ICH Q7a apply.
． Further guidance on How To Define the API Starting Materials and regula-tory strategy is given in the article:
“The Active Pharmaceutical Ingredients Starting Material (APISM) and other materials in API manufacture: Scientifically-based principles for the Common Technical Dossier” by Helga Möller and Chris Oldenhof, Drug Information Journal, Volume 33, Number 3, 1999, pages 755 – 761.
See also Eudralex Vol. 2b, page 162 (“Validation of the process should be carried out…for steps of the manufacturing process which are critical for the product”)
． The API Starting Material Decision Tree, developed by CEFIC/APIC and FIP, is the central feature of this guidance (see table at the end of the chap-ter).
． Where the proposed API Starting Material is close to the API itself ensure that details on the synthetic process and analytical controls used to manufac-ture the API Starting Material are available in case these would still be (justi-fiably) requested by the regulators. Where the API Starting Material is a commercial molecule the requirement to provide these details (if needed for confidentiality reasons: directly to the authorities only) may be included in the commercial contract.
． Similarly, Change Control requirements should be defined in the commercial contract for supply of API Starting Materials. Any significant changes to the synthetic route, analytical controls or specifications by the manufacturer of the API Starting Materials in general needs notification to and acceptance by the API manufacturer.
． While API Starting Materials do not require to be manufactured to the GMP requirements defined in ICH Q7a, manufacturers of intermediates and / or API’s should have a system for evaluating the suppliers of critical materials (Reference Q7a Section 7.11). Appropriate qualification of API Starting Ma-terial suppliers is required.
． Companies should consider redefining the API Starting Material for well-established products. This offers the opportunity to reduce the overall GMP requirements for early manufacturing steps and to shift the focus to be on the control of the critical synthetic steps starting from the redefined API Starting Materials. Any proposed re-definitions to API Starting Materials should of course be agreed with the regulatory authorities. The FDA have already indi-cated their willingness to reduce the filing requirements for certain well es-tablished "Qualified Products", including those relating to the final API syn-thesis steps.
下面是一个决策树,仔细研究就会发现起始物料具有如下特征:
1-具有一定的具体结构,而且结构是组成最后API的主要成分.
2-理化性质和杂质性质比较清除.
3-商业化可得或者有委托加工商.
4-如果还是不能确定,请和欧盟或者FDA药政当局协商,但是技术会议需要花钱.
““How to do” Document ：Interpretation of the ICH Q7a Guide”原文可见
可下载学习。
决策树如下：
自己搞不懂，应该如何定义？如果自己定义，那定义生产的起始原料在工序中的位置越往后不是越好吗？
请教一下各位大侠！
你的理解不对.
看下面的资料:
1-An API starting material is a raw material, an intermediate, or an API that is used in the production of an API and that is incorporated as a significant structural fragment into the structure of the API. An API starting material can be an article of commerce, a material purchased from one or more suppliers under contract or commercial agreement, or produced in-house. API starting materials normally have defined chemical properties and structure.
译文=“原料药的起始物料”是指一种原料、中间体或原料药，用来生产一种原料药，或者以主要结构单元的形式被结合进原料药结构中。原料药的起始物料可能是在市场上有售、能够通过合同或商业协议从一个或多个供应商处购得，或由生产厂家自制。原料药的起始物料一般来说有特定的化学特性和结构。
2-The company should designate and document the rationale for the point at which production of the API begins. For synthetic processes, this is known as the point at which API starting materials are entered into the process. For other processes (e.g., fermentation, extraction, purification), this rationale should be established on a case-by-case basis. Table 1 gives guidance on the point at which the API starting material is normally introduced into the process.
译文:生产厂商要指定并用书面文件说明原料药的生产从何处开始的理论依据。对于合成工艺而言，就是“原料药的起始物料”进入工艺的那一点。对其他工艺（如：发酵，提取，纯化等）可能需要具体问题具体对待。表1给出了原料药的起始物料从哪一点引入工艺过程的指导原则。
上面是Q7的内容,下面是指南注释的内容:
Guidance on How To Define API Starting Materials
． Follow the guidance given in ICH Q7A and involve technical, quality and regulatory departments in agreeing the definition of the API Starting Materi-als. Where possible use the same definition of API starting material in regu-latory filings and in defining the steps for which the GMP requirements of ICH Q7a apply.
． Further guidance on How To Define the API Starting Materials and regula-tory strategy is given in the article:
“The Active Pharmaceutical Ingredients Starting Material (APISM) and other materials in API manufacture: Scientifically-based principles for the Common Technical Dossier” by Helga Möller and Chris Oldenhof, Drug Information Journal, Volume 33, Number 3, 1999, pages 755 – 761.
See also Eudralex Vol. 2b, page 162 (“Validation of the process should be carried out…for steps of the manufacturing process which are critical for the product”)
． The API Starting Material Decision Tree, developed by CEFIC/APIC and FIP, is the central feature of this guidance (see table at the end of the chap-ter).
． Where the proposed API Starting Material is close to the API itself ensure that details on the synthetic process and analytical controls used to manufac-ture the API Starting Material are available in case these would still be (justi-fiably) requested by the regulators. Where the API Starting Material is a commercial molecule the requirement to provide these details (if needed for confidentiality reasons: directly to the authorities only) may be included in the commercial contract.
． Similarly, Change Control requirements should be defined in the commercial contract for supply of API Starting Materials. Any significant changes to the synthetic route, analytical controls or specifications by the manufacturer of the API Starting Materials in general needs notification to and acceptance by the API manufacturer.
． While API Starting Materials do not require to be manufactured to the GMP requirements defined in ICH Q7a, manufacturers of intermediates and / or API’s should have a system for evaluating the suppliers of critical materials (Reference Q7a Section 7.11). Appropriate qualification of API Starting Ma-terial suppliers is required.
． Companies should consider redefining the API Starting Material for well-established products. This offers the opportunity to reduce the overall GMP requirements for early manufacturing steps and to shift the focus to be on the control of the critical synthetic steps starting from the redefined API Starting Materials. Any proposed re-definitions to API Starting Materials should of course be agreed with the regulatory authorities. The FDA have already indi-cated their willingness to reduce the filing requirements for certain well es-tablished "Qualified Products", including those relating to the final API syn-thesis steps.
下面是一个决策树,仔细研究就会发现起始物料具有如下特征:
1-具有一定的具体结构,而且结构是组成最后API的主要成分.
2-理化性质和杂质性质比较清除.
3-商业化可得或者有委托加工商.
4-如果还是不能确定,请和欧盟或者FDA药政当局协商,但是技术会议需要花钱.
““How to do” Document ：Interpretation of the ICH Q7a Guide”原文可见
可下载学习。
决策树如下：