EMA and Brexit Yet Again: Part 3

2018年10月2日
Bart Cobert

医薬品安全監視、医薬品安全性および規制関連業務に関する執筆者・専門家

As previously noted, the Brexit and EMA saga continues. In my last post, I covered the EMA perspective. Here I will discuss in depth the current lack of a Brexit agreement between the UK and the EU.

 

No Brexit Agreement between the UK and EU

Finally, on August 23 of this year, the UK issued three documents covering many fields of business if there is no agreement between the UK and EU before March 29, 2019 and no extension. The first is a guidance (that is, high level) and covers medicines and devices. The second is a detailed guide on technical information on human and veterinary medicines.  The third is a detailed guide on clinical trials in the UK.

The first one touches on PV and other related areas:  “How medicines, medical devices and clinical trials would be regulated if there’s no Brexit deal.” Nothing on devices is noted in this post, so see the document for such information.

 

Key points on PV and other issues:

  • “If there’s ‘no deal’, the MHRA will have primary responsibility for the conduct and oversight of all pharmacovigilance activities in relation to UK MAs, certificates of registration and traditional herbal registrations. The details of our approach will be subject to consultation.

 

  • Sharing of common systems, and formal exchange and recognition of data submitted for regulatory activities between the UK and EU countries would The MHRA already holds its own database of Individual Case Safety Reports (ICSRs), so will not require historical information from MAHs.

 

  • In future, for medicines sold in the UK, MAHs will be required to submit pharmacovigilance data (UK and non-UK ICSRs and PSURs (Periodic Safety Update Report)) directly to the MHRA.

Comment: UK PV will be done by the MHRA and ICSRs, PSURs and all other issues will be adjudicated in the UK for the UK as far as we know now.  Whether an arrangement with the EMA (e.g. for PRAC) is done remains to be seen.  This will impose duplicate work on the companies and a significant increase in work for the MHRA.

 

  • UK participation in the EMA would cease and the UK MHRA would take on these functions. This would require new legislation by parliament.

 

  • The 2004 EU regulations remain in force modified under the UK’s “EU withdrawal act”. The new EMA clinical trials regulation 536/2014 will not be in force in the UK. The UK will try to align with this regulation subject to parliamentary approval and will not be in force on March 29, 2019.

 

  • “The EU (Withdrawal) Act will ensure that existing EU rules are converted into UK law at the moment of exit, with changes where necessary to make sure the rules work in the UK. Where this is needed, we’ll give adequate time for business to implement any new requirements.”

 

  • To ensure such that centrally approved (CAP) medicines will continue to be authorised for use in the UK, all CAP MAs will automatically be converted into UK MAs on March 29, 2019. The MHRA will communicate with all such MA holders before this “grandfathering” date. Some data from the MA holders may need to be communicated to the MHRA.

 

  • New initial marketing applications for the UK must have a submission to the MHRA which will do a “streamlined” national assessment to “ensure that patients can access new and innovative medicines at the same time as EU patients.” The UK will no longer be a part of the EU centralized, mutual recognition and decentralized procedures. Existing medications that received a UK MA via the mutual recognition or decentralized procedure will be unaffected.

 

  • For MA applications underway as of March 2019, the EU approval will not be valid in the UK. The application will need to be submitted to the MHRA for review. For some procedures an extended transition period may be put in place.

 

  • Generics in the UK: As the MHRA will not have access to the data submitted to the EU, new generic applications will need to be based on reference products that have been authorized in the UK. Existing MAs for generics with a reference product authorized in the UK will remain valid.

 

  • Currently a Qualified Person for PV (QPPV) is required and this will continue after March 2019. “The Qualified Person for Pharmacovigilance (QPPV) should be established in the UK on day one, although those without a current UK presence will have until the end of 2020 at the latest to do so, but would nevertheless be required to make arrangements for providing the MHRA with access to the relevant safety data related to UK Marketing Authorisations (MAs) at any time. Companies may choose to have the EU QPPV take on responsibility for UK MAs until the UK QPPV can be established. A variation should be submitted to the MHRA to change QPPV. Exact details of this will be consulted upon”.

Comment: This is tricky. Companies need a UK QPPV in the UK. If one is based in the UK already this sounds fine. If not, the UK company has until December 31, 2020 to establish one in the UK. Companies can have the EU-based QPPV continue to function for the UK till establishment of a QPPV in 2020. The trick here is that the UK-based QPPV will no longer be accepted by the EU and he/she must be in the EU. What will happen if the UK-based QPPV moves to the EU from the UK is unclear.

 

  • Orphan and pediatric medicines will have details worked out to encourage development after withdrawal. Details to follow.

 

  • Labeling, packaging and leaflets: The MHRA will continue to accept proposals in English that include information from other countries (such as Ireland) as long as the information complies with UK requirements. The MHRA will be “pragmatic” they say.

 

  • Clinical trials are largely done nationally now and this will continue. Some changes will occur and need to be worked out.

 

Bottom Line

We are slowly beginning to get information and a bit of clarity on what will happen after March 31, 2019, though there is a lot of kicking the can down the road. It seems that there may be an implementation period running from March 2019 to December 31, 2020 during which some of the EU requirements will continue to apply in the UK in regard to pharmaceuticals. On the other hand, the UK has issued information should there be no agreement with the EU (“no deal”).

The high level framework is being put in place for this period. The current EU law will be transposed into UK law so that it continues to apply during the implementation period. Some broad agreements have been discussed and agreed upon in regard to continuing PV, GMP, some inspections, etc. as is more or less.

But the devil is in the details and they have not yet been worked out, particularly for PV.  There will be an added burden on the companies and perhaps an even heavier one on the MHRA.

What is less clear is what happens if these laws are changed by the EU/EMA during this period. Will the changes also apply in the UK (if yes, automatically or not)?  We seem to know that a QPPV can still sit in the UK with the PV Master File. How this will play out if the rapporteur or “leading authority” is in the EU remains to be seen.

 

So we don’t yet know how PV will really be done after March, 2019.

More to follow.  Watch this space.

 

 

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