讨论 | ICH Q7 关于API成品放行中待检运输管理？

一直很困惑我这个原料药小QA的问题就是：“客户催货催的紧，我们的API是否可以在没有得到全部检验结果的时候就发运？是否可以设定一些制约条件，用于提前发运？想和同行的小伙伴们讨论一下。”

感谢齐力佳微信朋友群“LAO SUN”同志的来稿。

欢迎有更好处理意见的朋友，在留言区留言讨论哦！

带着以上问题，原料药小QA翻开了ICH Q7,原料药宝典，逐字学习理解了一下。试图为这个想法找一些法规依据。

我们先来看一段Q7原文：

10.       STORAGEAND DISTRIBUTION

10.2      DistributionProcedures

10.20    APIs and intermediatesshould only be released for distribution to third parties after they have beenreleased by the quality unit(s).  APIsand intermediates can be transferred under quarantine to another unit under the company’scontrol when authorized by the quality unit(s) and if appropriatecontrols and documentation are in place.

APIs和中间体在被质量部门放行以后，只能被分发至第三方。在经质量控制部门授权并有必要的控制措施和记录的情况下，待验中的API和中间体可以移交给属于该企业控制范围之内的另一部门。

APICHow to do 文件中有如下注释：

Theprocess of transfer underquarantine should be proceduralised. Quality unit of both sites need toapprove the shipment under quarantine and the receiving site cannot use thematerial before a CoA of the batch in scope is issued. Before shipment underquarantine the manufacturing batch record should be reviewed and approved bythe quality unit For more details see ICHQ7 Q&A Chapter 10, Storage andDistribution 1st question

待检运输应程序规定有必要的控制和记录。发出方和接收方的质量部门需要批准待检运输，并确保接收方在收到该批次COA前不会进行下一步处理。在待检运输前，应完成生产批记录审核。

2. Q. What does another unit exactlymean in the distribution procedure 10.2?

问：在分销规程中“另一个部门”的确切含义是什么？

Theintent there was to allow, company A with a manufacturing operation in onelocation to ship to another manufacturing operation in another location whenboth are operated under an effective quarantine control systems. It doesn'tnecessarily have to be two plants of the same company. It can besubcontractors. For example, if an intermediate was going out to a contractorwho is doing the next step and then being returned to you that would bepossible. That's why the term was used, 'under company control' asopposed to 'the same company'.

答：目的是允许下列情况，公司A 在一个地点制造操作，然后运输到另一个地点制造操作，两个地点都有有效的待检控制系统。这不一定是同一个公司的两个工厂，可以是分包者。例如，如果一个中间体转移到了一个分包者那里进行下步的反应，然后交换给你。这就是为什么使用那个术语，“在公司的控制下”而不是“相同公司”。

2015年ICH 关于Q7的问答（June 2015）中这么解释：

10. STORAGE ANDDISTRIBUTION  存贮和销售

10.1 What is meant by 'APIs andintermediates can be transferred under quarantine to another unit under thecompany’s control when...’and is this applicable to contract manufacturers?

“如果……API和中间体可以在受公司控制下在待检状态中以隔离的方式转移给另一个部门”是什么意思？它是否适用于合同生产商？

[ICH Q7, Section 10.20]states 'APIs and intermediates should only be released for distribution tothird parties after they have been released by the quality unit(s). APIs andintermediates can be transferred under quarantine to another unit under thecompany’s control when authorised by the quality unit(s) and if appropriatecontrols and documentation are in place’. The second sentence in [ICH Q7,Section 10.20] describes transport situations that are not considereddistribution. It provides for physical movement (transfer but not release) ofquarantined material to another unit. This unit can be on the same site,different site (within the same company), or a contract manufacturer (see finalparagraph below).

The goal of transfer underquarantine is to allow transportation and testing in parallel. Material that istransferred under quarantine is not to be used for further processing until alltesting and quality review is complete and the material is released by thequality unit as defined in [ICH Q7, Section 2.22].

This provision for transferunder quarantine is included in ICH Q7 for situations where a company isshipping APIs or intermediates from one unit to another and has both the needto expedite the shipping and the material management system in place to preventuse of the material before full release.

Examples of circumstanceswhere transfer under quarantine may be needed include extraordinary supplychain requirement(s) (e.g., short shelf-life), and materials with a lengthytimeframe for required test(s) (e.g., some microbiological tests, etc.).

Withappropriate oversight as described in [ICH Q10, Section 2.7], including awritten agreement as described in [ICH Q7, Section 16.12], and appropriateongoing controls, a contract manufacturer maybe considered a 'unit under thecompany’s control’. There is a joint responsibility by both parties to clearlyjustify and document the need to transfer the unreleased intermediate or API,and to ensure appropriate control is maintained to prevent use before fullrelease.

在【ICHQ7第10.20部分】中第二句说明了不作为销售的运输情况。在这种运输情况下可以将隔离的待检物料物理移动（转移但并不放行）给另一个部门。该部门可以是在同一个工厂、不同工厂（在同一个公司）、或者是合同生产商（参见以下最后一段）。

待检下转移的目的是让检测和运输同时进行。在根据【ICH Q7第2.22部分】要求完成所有检测、质量审核并由质量部门放行之前，待检下转移的物料不能用于进一步加工。

在ICHQ7中包括该待检下转移的条款是考虑了公司有时需要快速将API或中间体从一个部门转移至另一个部门，并且有一个物料管理体系来防止物料在放行前被使用。

需要在待检状态下转移的情况包括例如特殊的供应链要求（例如，货架期很短），物料检测需要很长时间（例如，一些微生物检测等）。

在具备【ICH Q10第2 7部分】所述的监管，包括【ICH Q7第16.12部分】所述的书面协议，以及适当的即时控制时，合同供应商可以当作是“在公司控制下的部门”。双方都有责任来清楚地论述和记录将未放行的中间体或API进行转移的必要性，保证维持适当的控制以免在全面放行前物料被使用。

根据上述规定和权威解读，同一个公司内部不同厂地或同一集团内的不同公司，在批生产记录审核完成之后，而检测结果没有出来之前，无疑是可以把API/IM转移到下一步骤的。

那么，如果与客户签订了质量协议，其中包括了如何进行待检运输，规定了双方的责任，是否也可以这么操作呢？药政法规当局能否接受这种操作？

即：为了节约等待成品检测的时间（5-10天），批记录审核完成后，QC检测，QA批准待检运输，仓库开始发运，客户在接到货物之后，根据QA的放行通知进行接收。如果检测结果不合格，那么客户会把货位退回来，或者进一步沟通其它操作。

补充问题：如果是中间体（非原料药），是否允许？

文章来源：LAO SUN