原料药合成的起始物料的供应商大家都是如何管理的

zhanghongle

求助：第一次接触原料药的起始物料的供应商管理，都是些工业试剂，请问大家都是如何操作的，是否需要进行现场审计，签订质量协议。

334352444

需要

快活王

需要，起始物料还是要去的，否则不放心。

ztzhang

起始物料API Starting material的定义可以参考ICH Q7：A raw material, 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 are normally of defined chemical properties and structure.一种原料，中间体或者原料药，用于某种API的生产，并进入该API的结构中，作为其重要结构片段。API起始物料可以是商品，可以从一个或者多个供应商处，通过合同或者商业协议采购得到，也可以是企业自己生产得到。通常来讲，API起始物料具有明确的化学性质和结构。
又根据Q7中对于GMP适用范围的规定，对于化学合成药物，从起始物料投入生产开始，就应该符合GMP。对于具体的API，其起始物料的定义应该是由生产企业在DMF中提出，一般是合成路线中API精制往前推2~3个步骤，然后通过相应的官方机构的批准。如果官方认为企业给出的起始物料不足，则还应该沿着合成路线往前推。
对于起始物料的供应商，应该给予重点的关注和评估，应与供应商签订质量协议，进行现场审计，在批准该供应商前，应完成生产评价（验证或者评估，确认使用该供应商生产的起始物料，不会影响API的生产和质量）。因为起始物料可能携带一些杂质，并残留至API，或者以杂质衍生物的形式残留至API，也可能携带一些溶剂（尤其是I类溶剂）至API。因此，需要在生产评价和现场审计时，对以上可能性进行评估，必要时，要进行分析方法的验证，确认可以检测到可能的杂质和溶剂残留，并制定相应的质量标准进行控制。

beiwei5du

All activities from receipt till approval or rejection of materials should be described in one or more procedures. Materials must be purchased against agreed specifications.
Companies should prepare a list of critical raw materials based on good scientific rational and impact on the quality of the API. Suppliers (manufacturers and/or agents if applicable) of critical materials should be evaluated and approved by the quality unit. The evaluation can be based on  
  historical experience with the supplier,
  on a questionnaire,  
  checking/comparing own analytical results (for e.g. three batches/shipments) with those on the suppliers Certificate of Analysis and / or  
  an audit done by a person authorized by the purchasing company
  use test
Audits are not mandatory as per current GMP and should be considered on a case by case basis for example if deviations are observed. Other useful information can include the reputation of the supplier within the industry and the availability of certificates such as ISO-9000 certificates.
The evaluation and approval process should be described in a procedure, taking into account some or all these possibilities. This includes the fact that the name and address of the manufacturer of a critical material must always be known. A change of the source (e.g .manufacturer or supplier)  of a critical material should be handled according to the Change Control procedure.

EVALUATION是必须的，至于audit是Q7A是没有强求的，但是一般情况下都会对critical materials进行audit,特别是API starting material