待检的API能放行给第三方（比如制剂厂家）吗？？

beiwei5du

各位蒲友：
想咨询一下待检的API在API厂家质量部门的控制下能否放行给第三方（比如制剂厂家，代理商)???
在Q7A中说道：待检的API可以在公司的控制下，在公司内部放行。
但在Q7A HOW TO DO 2015.08中却提到待检API可以在API厂家质量部门的控制下放行给第三方（当然有其他的要求：比如双方的同意，正式质量协议等文件中提及，第三方必须有相应的控制措施等等）。
而在有的网上http://www.gmpua.com/API/j.htm中写到：

Distribution under quarantine is only accepted when under the control of the manufacturer of the API or intermediate and not for transport to third parties.

The following examples are not considered as third parties

• Subcontractors (e.g. processing, milling, micronization, drying etc.)
• Warehousing (off site or at a subcontractors site)
• Processing at different sites of the same company
  

For subcontracted activities the formal quality agreement should cover this scenario as recommended in chapter 16 Research and Development.

感觉有一些矛盾，不知道如何理解。求指教！！！！顺便问一下,图片中的R&R of change是什么？？？？

xmango

单从上面看确实有矛盾的地方
但是无论如何放行肯定是不行的，原文用的是transport，跟release是有区别的

北重楼

不可以的，公司内部才可以；第三方不行

beiwei5du

北重楼 发表于 2016-6-7 10:56
不可以的，公司内部才可以；第三方不行

那你看一下HOW TO DO（就是最下面的图片） 为什么那样解释呢？？解释是错误的么？？？

beiwei5du

xmango 发表于 2016-6-7 11:37
单从上面看确实有矛盾的地方
但是无论如何放行肯定是不行的，原文用的是transport，跟release是有区别的

对，就是transport，这个说到重点，我没有表达清楚，

赵旭锋

也不点回答了
这里说一下个人见解
这个一看就知道不是针对国内GMP要求做的挥发，所以我们就不要管国内的要求了
待检的API可不可以发放给第三方（制剂厂家、代理上……）
其实按照现在流行的风险管理，只要能够保证待检的产品，生产企业能够保证其质量，并收发双方之间达成协议，并有制定双方都能接受的措施，防止不合格API用于制剂生产或者再次销售等等问题。
在待验期间放给下家是没有问题了。
当然了，这些放行，也应该是经过放行部门同意的才行。

冬冬珠宝

待检的可在公司内部放行，也是基于一定的风险评估以及产品长期的稳定性，若不合格可立马处理，减少可能带来的不良后果。对放于第三方，还是建议未出具结果前不放行，尤其是不稳定的产品。原文里已写了transport，更大程度上也是有意识的杜绝了产品放行后进入制剂生产可能带来的负面影响

cnosema

R&R of change

这里可能是指 roles and responsibilities change

beiwei5du

What is meant by ‘APIs and intermediates can be transferred under quarantine to another unit under the company’s control when...’and is this applicable to contract manufacturers? http://zhuyujiao1972.blog.163.com/blog/static/986947272015643227155/	[ICH Q7, Section 10.20] states ‘APIs and intermediates should only be released for distribution to third parties after they have been released by the quality unit(s). APIs and intermediates can be transferred under quarantine to another unit under the company’s control when authorised by the quality unit(s) and if appropriate controls and documentation are in place’. The second sentence in [ICH Q7, Section 10.20] describes transport situations that are not considered distribution. It provides for physical movement (transfer but not release) of quarantined material to another unit. This unit can be on the same site, different site (within the same company), or a contract manufacturer (see final paragraph below). The goal of transfer under quarantine is to allow transportation and testing in parallel. Material that is transferred under quarantine is not to be used for further processing until all testing and quality review is complete and the material is released by the quality unit as defined in [ICH Q7, Section 2.22]. This provision for transfer under quarantine is included in ICH Q7 for situations where a company is shipping APIs or intermediates from one unit to another and has both the need to expedite the shipping and the material management system in place to prevent use of the material before full release. Examples of circumstances where transfer under quarantine may be needed include extraordinary supply chain requirement(s) (e.g., short shelf-life), and materials with a lengthy timeframe for required test(s) (e.g., some microbiological tests, etc.). With appropriate oversight as described in [ICH Q10, Section 2.7], including a written agreement as described in [ICH Q7, Section 16.12], and appropriate ongoing controls, a contract manufacturer maybe considered a ‘unit under the company’s control’. There is a joint responsibility by both parties to clearly justify and document the need to transfer the unreleased intermediate or API, and to ensure appropriate control is maintained to prevent use before full release.
			“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第10.20部分】说，“API和中间体只能在经过质量部门放行后才可以销售发放给第三方。如果经过质量部门授权，并且具备适当的控制和文件记录，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”。在【ICH Q7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ICH Q7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。

beiwei5du

xmango 发表于 2016-6-7 10:49
单从上面看确实有矛盾的地方
但是无论如何放行肯定是不行的，原文用的是transport，跟release是有区别的

最近又看到一下，感觉还是有点困惑。
https://www.ouryao.com/forum.php? ... 0%CA%BC%CE%EF%C1%CF

Q: A batch of an API has been released before all testing and final approval was completed. How do I handle this in the certification of the final product?

问：一批原料药在所有检测和最终批准完成前即被放行。我在对制剂成品出具证书时要怎么办？

A: Within the EU shipment of unapproved API is not be acceptable under EU law. For shipments outside of the EU the local laws would have to be checked. It would be necessary to check what is stated in the API producer’s SOP with reference to shipping unapproved material and whether that contravened any regulatory laws. The quality agreement between the API producer, the contract manufacturer and the MA holder should also be looked at to see if there is any reference to the movement of unapproved material being acceptable. It is not good practice to ship unapproved materials and as such this should have been picked up by the quality person releasing the API. Further, a deviation should have been raised and a full investigation carried out as to the root-cause. In addition the contract manufacturer should have quarantined this material on receipt and also raised a deviation to find out what went wrong. If this was a one-off incident and not a fundamental break down of the API’s manufacturers and/or the contract manufacturers Quality System, then as long as the API was formally approved, you should reference the deviation report and as long as everything else was in order, certify the final drug product. However, if this incident was part of a systematic failure of the Quality System would recommend not to certify the drug product as the potential for other GMP non-conformances would be too great. The follow-up to the deviation could involve an audit of the API producer initiated by the MA holder.

答：根据欧盟法律，在欧盟境内发运未经批准的原料药是不能被接受的。如果是发生在欧盟境外，则要检查当地法律是否允许发运。需要检查原料药生产商的SOP中关于发运未经批准物料的条款，看是否违反了法规规定。要查看合同生产商和上市许可持有人与原料药生产商之间的质量协议，看看是否有条款规定未经批准的物料转移是可以接受的。发运未经批准的物料是不好的方式，因此需要由原料药放行质量人员进行挑选。另外，要启动偏差程序，进行全面调查，找出根本原因。还有，合同生产商要在接收时暂扣该物料，也需要启动偏差调查找出是什么地方出问题了。如果这只是一次性的偶然事件，而不是原料药生产商或合同生产商的质量体系基础崩溃，则只要该原料药经过了正式批准，你可以引用偏差报告，只要保证其它所有事情都正常，就可以批准最终制剂。但是，如果该事故是一个质量体系系统性的失效事件，则建议不要批准制剂，因为潜在的其它GMP不符合性可能是很严重的。在偏差跟踪时，上市许可持有人可以启动对原料药生产商的现场检查。

yc20160802

待检的API不能放行给第三方（比如制剂厂家）。

yc20160802

yc20160802 发表于 2016-9-6 09:13
待检的API不能放行给第三方（比如制剂厂家）。

这里谈到的是中间体不是API.

似睡骄杨

不能，只能内部使用，Q7a中有明确规定。

safsaf

北重楼 发表于 2016-6-7 10:56
不可以的，公司内部才可以；第三方不行

待验的原料药未完成全部检验项目、未完成全部审核放行流程就放行和销售给第三方，确实违背GMP理念。
实际执行过程中，特殊情况，如需在待验产品完成全部项目检验和审核放行前紧急发货，需要有控制客户或用户在完成全部项目检验和审核放行前不销售或不使用的措施。

safsaf

似睡骄杨 发表于 2018-5-24 14:32
不能，只能内部使用，Q7a中有明确规定。

之前做原料药，为节省运输时间，偶尔会在待验产品完成检验和审核放行前紧急发货。
紧急发货前，需要与客户书面沟通，经客户书面同意。在完成检验和审核放行前，客户不得用于生产。如完成全部项目检验和审核放行则书面通知客户结果，如检验不合格和不放行则书面通知客户退货。

safsaf

赵旭锋 发表于 2016-6-7 14:31
也不点回答了
这里说一下个人见解
这个一看就知道不是针对国内GMP要求做的挥发，所以我们就不要管国内的 ...

同意，待验的API可以放行和销售给第三方客户