MRA与FDA---对QP有什么影响？

The MRA with FDA - any Consequences for the QP?

MRA与FDA---对QP有什么影响？

On 2nd March 2017, the US FDA and the European Medicines Agency (EMA) informed that they concluded a so-called MRA (Mutual Recognition Agreement). As a consequence, a manufacturing site would be inspected by the local competent authority only (or other inspectorates not covered by an MRA). FDA inspections in the EU or EU inspections in the USA should then only be performed in exceptional cases. The MRA will start coming into force in November 2017.

2017年3月2日，美国FDA和EMA通告说他们达成所谓MRA（互认协议）。其结果就是，生产场所将仅由本国药监机构进行检查（或MRA未覆盖的其它检查机构）。FDA在EU的检查，或EU在美国的检测应该只有在例外情况下才会进行。MRA将从2017年11月开始实施。

What else is important for the Qualified Person (QP)?

对于QP来说还有什么重要的？

The removal of the importation testing requirement

进口检测要求的取消

Will testing continue to be required on importation into some Member States and not others reflecting accession timelines?

是否一些成员国仍会要求对进口药品进行检测，而另一些成员国则会执行正式加入的时间表？

There is a statement in Article 19 "Entry into force": "Notwithstanding paragraph 1, Article 9 [Batch testing] of this Annex shall not apply until the date on which all the EU Member State authorities for human pharmaceuticals listed in Appendix 2 have been recognized by the FDA." So nothing will change after November 1st in this regard because not all Member States have been accessed by FDA until then. Import testing needs to be performed until all Member States have been found equivalent. After implementation of this part of the agreement, the Qualified Person will be relieved of the responsibility for carrying out the controls laid down in Article 51 paragraph 1 of Directive 2001/83/EC and in Article 55 paragraph 1 of Directive 2001/82/EC with the following provisions:

在第 19条“生效”中是这样说的：“尽管如此，但本附录第一段第9条【批检测】在FDA认可列于附录2的所有EU成员国人药药监局之前不适用”，因此，在11月1日之后其实并不会有什么变化，因为FDA到彼时并无法认可所有成员国。进口检测在所有成员国被认为具有等同性之前仍需执行。在实施该协议的该部分之后，QP将不需要承担责任实施法令2001/83/EC第1段第51条，以及2001/82/EC第1段第55条所要求的以下控制：

• The product was manufactured in the United States
• 药品在美国生产
• The respective controls have been carried out in the United States
• 相应的控制已在美国实施
• Each batch is accompanied by a batch certificate (in alignment with the WHO certification scheme), issued by the manufacturer certifying that the product complies with requirements of the marketing authorisation and signed by the person responsible for releasing the batch
• 每个批次均随货有一份批证书（符合WHO认证计划），由生产商签发用以证明药品符合MA要求，并由负责放行批次的人员签字
  

GMP Certificates  GMP证书

At present marketing authorisation applications to EU authorities that list medicinal product manufacturers located in the USA are required to submit proof of the holding of an Establishment Licence issued by the FDA [Art. 8.3(k)/12.3(m) of Directive 2001/83(2)/EC] and a EU GMP certificate issued to the site. But, with full implementation of the MRA, those EU GMP certificates will not be issued anymore. And the FDA does normally not issue GMP certificates. Therefore an alternative approach will be needed (issuing of GMP certificates is not part of the current FDA system but work is ongoing to find a suitable alternative).

目前，交给EU药监的MA申报会列出美国的生产商清单，这些场所需要提交证据证明持有FDA签发的场所证书[Art. 8.3(k)/12.3(m) of Directive 2001/83(2)/EC]，并且该场所持有一份EU GMP证书。但是，随着MRA的全面实施，这些EU GMP证书就不再要签发了，并且FDA通常不会签GMP证书。因此，将会需要有一个别的替代方法（签发GMP证书并不是目前FDA体系的一部分，但目前双方仍在努力寻找一个适当的替代方法）。

GMP Audits  GMP审计

The holder of the manufacturing authorisation is responsible for the supplier qualification, but in fact the supplier qualification and respective audits are one of the tasks of the Qualified Person (which can be delegated) as defined in Annex 16 of the EU GMP Guidelines. The QP of the marketing authorisation holder is responsible for certifying the drug product for the market place and is being held accountable to ensure that all aspects of the supply chain have been taken into account under the appropriate GMPs. Audits will still be an essential part of this process. Another essential part is the verification of available GMP certificates. Here, the QP needs to see what will be available in future and what information can be used in the absence of an EU GMP certificate.

MA持有人对供应商确认承担责任，但实际上根据EU GMP指南附录16中的要求，供应商确认和相应的审计是QP的任务之一（可以委托）。MA持有人的QP承担责任认证药品上市，并负有责任确保供应链的所有各方面问题均在适当GMP条件下受到考虑。审计仍会是此流程的一个必需部分。另一个必需部分是核查持有的GMP证书。这里，QP需要查看未来有些什么，在没有EU GMP证书情况下哪些信息可以利用。

Quality Defects 质量缺陷

Quality defects also seem to cause some challenges. Although the two-way alert system from the original 1998 MRA is considered operational, it seems that this does not appear to be working optimally. The new MRA provides an opportunity for relevant experts in the EU and the FDA to discuss and agree on operational requirements.

质量缺陷貌似也会引发一些挑战。尽管自1998年MRA开始，双向警示体系被认为可运行，但貌似运行情况不乐观。新的MRA为EU和FDA的相关专家提供了一个讨论运行要求和达成一致的机会。

So in future the QP needs to have an eye on what is available to qualify manufacturing sites in the US in the absence of a GMP certificate. Also testing of imported materials still needs to be performed until the MRA is fully implemented.

因此未来QP需要察看在没有GMP证书的美国生产场所确认所需内容。还有，进口物料仍需要进行测试，直到MRA全面实施。

The MRA and other  international developments and their possible impact on GMP, manufacturers and especially QPs will also be discusses at this year's QP Forum in Budapest.

MRA和其它国际发展以及其对GMP、生产和尤其是QP可能的影响还将在本年度的QP论坛中讨论。