欧洲QP协会问答： 临床研究用药品相关问题（转自Julia博客）

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IMP-related questions 临床研究用药品相关问题

Q: Manufacturing of tablets for a phase I and for a phase II study: is it possible to release and/or submit an IMPD or similar documentation without microbiological quality as a lot release parameters for tablets in phase I or IIa? (tablets do not contain any component that would have a high total viable aerobic count by origin). 一期和二期研究中所用的片剂生产：是否可能放行和/或提交IMPD或类似的文件，而不将微生物质量（片剂不包括任何可能具有较高TVAC来源的成份）包括在一期或IIa期片剂批放行参数中？

A: Especially for IMPs manufactured the first time it should be proved that the microbial quality is satisfactory, since usually only limited experience and only little validation data are available. Although the compounds are unlikely to be "contaminated", contamination may happen during manufacturing. Often the raw materials used for the manufacture are not tested for their MB status.

答：在IMP生产中，特别是第一次应证明微生物质量是令人满意的，因为一般仅具有有限的经验，只有少量的验证数据。尽管成分不可能被“污染”，但在生产过程中可能会发生污染。通常生产所用的原料并不需要测试其MB状态。

One approach could be to test at least the first 3 lots of a manufacturing sequence for MB status.

可以考虑一种方法，即至少检测前3个连续生产批中的MB状态。

Independent of what is mentioned in the IMPD (and accepted by authorities), the QP keeps the final responsibility for the batch and should be able to justify her/his release decision. If the QP decides to release without MB testing, we would strongly recommend to perform a risk analysis of the release decision.

与IMPD（被药监部门所接受）中提到的独立不同，QP保留有其对批次的最终责任，应可以做出其放行决定。如果QP决定在没有MB测试的情况下放行，我们会强烈推荐对放行决定进行风险分析。

Q: Is it true and do the health agencies/ inspectorates accept that a company can import medicine from outside the EU and use it as an IMP in a clinical trial inside the EU without performing reanalysis within the EU? Is there a reference in the respective legislation? 是否药监部门/检查员接受一个公司从EU以外的地区进口药品，并在EU内的临床试验中用作IMP，而不在EU内进行再次分析？是否有相关的法规引文？

A: That is indeed correct, Clinical trial Material (CTM) imported from a non-EU country into the EU does not need to be reanalysed/retested in Europe. This is covered in the Directive 2001/20/EC Article 13 (Manufacture and import of investigational medicinal products), at the end of paragraph 3:

答：这还真是对的，从非EU地区进口临床试验材料（CTM）到EU内是不需要在欧洲进行再次分析/检测的。这在2001/20/EC第13条（生产和进口临床药品）第3段结尾有说明。

“Insofar as the provisions laid down in (a), (b) or (c) are complied with, investigational medicinal products shall not have to undergo any further checks if they are imported into another Member State together with batch release certification signed by the qualified person”

根据条款中（a）(b)(c)中规定，如果临床研究药品是进口至另一个成员国，随货发送批放行证明，并由QP签署，则不需要经过任何进一步检查。

In this article the QP certification act is described as well. In summary it mentions that the QP should certify that the CTM is compliant with:

在该条中也说明了QP出具证明的活动。总而言之，它提到了QP应证明CTM符合：

European (or equivalent ) GMPs 欧洲（或等同的）GMP要求 The product specification file 产品质量标准文件 The IMPD (Investigational Medicinal Product Dossier)
• IMPD（临床试验药品文档）
  

Remark: 注
-the IMP QP can always decide to reanalyse/ retest the imported CTM. Important to know is that this is not mandated by the EU HAs

IMP的QP也可以决定对进口的CTM进行再次分析/检测。但重要的是这并不是EU HA的强制义务。

Q: Should a QP audit CROs and investigators or can a QP rely on GCP-auditors of the own company? QP应否审计CRO公司和临床研究机构，还是说QP可以信赖他自己公司的GCP审计员？

A: The QP can rely on the information provided by the GCP auditors.

答：QP可以信赖GCP审计员提供的信息。

Q: When IMPs are imported from outside the EU; how could I set up a working relationship as a contract QP when it comes to liability and insurance? 当IMP从EU以外进口时，在讨论连带责任和保险时，我要怎么来订立合同作为合同QP工作？

A: As a contract QP you are a “normal” contracting party (i.e. just like any other service provider for the company but with the specific legal responsibilities and risks of a QP) and therefore no employee of the company. That means that you are not covered by any of the insurance programmes which companies usually provide for their employees (e.g. D&O insurance). As a result, you should mention that fact – and the related legal risks – during your contract negotiations with the company.

答：作为合同QP，你是一个“正常”的合同方（即，就像其它给公司提供服务的一方一样，但是具有特定的法律责任和作为QP会有风险），因此不是公司的雇员。这表示你不会被包括在任何的保险计划中，一般公司会给他们普通员工提供一定的保险（例如D&O保险）。这样，你应该在与公司讨论合同内容时谈到这个情况----及相关的法规风险。

Ideally, there should be an indemnification clause in the service contract providing for that ‘the company indemnifies the contract QP from any and all third party claims related to the services which the contract QP may perform under the service contract’. If your current contract does not contain such provision, you should ask the company to sign an amendment with aforesaid clause.

理想的做法是，在服务合同中有一个赔偿条款，“公司应负责赔偿QP根据服务合同提供相关服务给任何第三方时与服务相关的索赔”。如果你现在的合同没有包括这类条款，你应该要求公司签证一份补充条款，加入上述内容。

You can also ask the company to get yourself explicitly included in its D&O insurance contract (some insurers may actually be ready to do so because of the specific situation of the contract QP).This inclusion could be the first part of the contractual provision, followed by the indemnification clause mentioned above.

你也可以要求公司清楚说明将你包括在其D&O保险合同中（有些保险人实际可以这样做，因为合同QP是比较特定的情形）。这可以包括在合同条款的第一部分，在上述赔偿条款之后。