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Brexit: Picking a new Reference Member State. How?
11-12-2017

#Brexit: Picking a new Reference Member State. How?

In our previous Brexit blog we gave a broad overview of consequences that are on the horizon for the (bio)pharmaceutical industry. Especially professionals in Regulatory Affairs, Quality Assurance and Pharmacovigilance will be affected besides those working at EMA headquarters. Though nothing is certain yet we stipulated that, for the moment, the best advice may be to prepare for the worst: a hard Brexit. An important item on the list is to select a new Reference Member State (RMS).

Reference Member State

A reference member state is like a marriage; you stick with it for life; at least your product does. There are only two reasons to request a change of RMS. Usually, the Marketing Authorisation Holder (MAH) can request a change of RMS under exceptional circumstances, as described in the procedural advice by the CMDh. The other reason is (you probably saw this one coming) Brexit; or more specifically, the triggering of Article 50 by an RMS. To whom would this apply? All companies that have a marketed product for which the RMS for a Mutual Recognition Procedure (MRP) or Decentralised Procedure (DCP) is currently the UK. Seeing as how the UK is in second place (right after the Netherlands) for the total amount of new applications (MRP/DCP) and in third for finalized procedures (2017), a large number of companies will be affected.

Below you can see the new applications (started and finalised) from January 1st to June 30th this year as reported by the CMDh; click here for larger image.

So just a quick summary of an RMS’ role. They act as:

  • scientific assessor of a dossier
  • regulatory advisor to the applicant
  • moderator between applicant and CMS

The RMS provides regulatory and scientific advice as well as assessment reports, they decide on timetables, evaluate responses, organize and chair break-out sessions, refer to the CMDh, inform the EMA if there is no consensus after referral, inform applicant and Concerned Member State (CMS) after positive conclusion and prepare the final assessment report as well as the public assessment report.

It’s clear there’s ample motivation to do some research on the different Health Authorities (HA). What should you look for in a new RMS?? Some of the items to investigate prior to your selection could be.

Things to consider when picking a new RMS

Know your RMS

Previous experiences with an HA can be of major advantage. These connections often make sure procedures move along according to the set timetables without any unforeseen trouble because you understand their point of view, they speak the same language so to speak.  These professionals look out for and mitigate unforeseen delays due to their experience with that RMS; they are familiar with their workload, approach and the way they communicate.

Differences among Health Authorities

Although we’re all in the EU, every member state is responsible for their own day-to-day business. Though not limited to just Health Authorities, this is certainly the case here as well. Some might be better communicators, others more prone to act in a timely matter and others more inclined to be open to more pragmatic approaches. Companies are especially recommended to check the pass-through times and a backlog of a possible new RMS and are required to contact the Health Authority in advance to check their availability to take over as RMS for existing procedures. Besides there is also a difference in not every HA has extensive experience acting as an RMS at all.

It’s also worthwhile to see which of the current Member States are actively preparing for Brexit like the MEB in the Netherlands.

The Medicines Evaluation Board (MEB) is preparing for the partial takeover of extra work which arises due to Brexit. In this context continuity is paramount. For that reason, the Dutch government is investing € 2 million in extra capacity for the MEB in the coming years. Investments are also being made in reinforcing the European network by facilitating extra training opportunities.

 

Initiatives like these will most likely help assure a smooth transition to a new RMS.

RMS has experience in a therapeutic area

Some RMS have more experience than others in certain therapeutic areas. Are you a generic, you might want to check the originator’s RMS; which is often also the RMS for other generics. This is noticeable when an originator product goes off-patent because almost all generics manufacturers will tend to apply with this same RMS with which the original was registered. Or does a Health Authority have a special focus regarding specific therapeutic areas? Have they been involved in the development of certain guidelines? If the new RMS is going to be one of the current CMS, recall what the attitude towards the product was during a previous application. These are all questions worthwhile to investigate before making a final decision.

Location of the company

Though it might seem like an open door, avoiding language barriers and having the proper infrastructure in place is always a benefit to the daily business. As a matter of fact, the EMA itself is currently in the process of deciding on a new location for its headquarters (deadline 22nd November) and in a technical report by the agency they name several aspects that are deemed to be important factors weighing into the final decision.

It’s also strategic to choose your RMS according to your company’s EU affiliates; opening up the possibility of direct communication with the HA. Increased contact and the ease of face-to-face counsel can contribute positively. This is especially useful considering we’re working in a regulatory universe that seems to thrive mainly on communication through elaborate documents. Besides these advantages, it also allows affiliates to join the strategic conversation with HQ and to increase their visibility and experience.

Commercial reasons

Last but not least: financial gain. There are several commercial reasons to interact with a certain RMS; straight-forward aspects like fees charged by HAs, the market size of the RMS and are there key opinion leaders available?

Practicalities and recommendations

Some practicalities to keep in mind:

  • there can be no change of RMS during an ongoing procedure (of importance for timing/planning);
  • it is the obligation of the MAH to ensure that both the current RMS and the future RMS accept the change of RMS;
  • it is the responsibility of the MAH to supply to the new RMS if any dossier/ assessment reports or other relevant materials are missing or for any reason not already in possession of the new RMS.

And some summarizing recommendations:

  • an organisation should map their situation and set up reasonable timelines for the upcoming changes
  • budgets need to be adapted to higher (or lower) costs; HAs charge different fees for procedures
  • investigate possible RMS to your best ability or attract external advice
  • contact your HA of choice well in advance to prevent any unwelcome surprises

RMS overview

Finally, remember that these changes are imminent, possibly causing a rush on popular HA’s and thus proper planning is well-advised, to say the least.

Below you’ll find all possible member states that can be chosen as an RMS. There are, of course, differences in the amount and nature of applications these states have handled in the past and it would be far too elaborate to discuss all possible differences. So to this purpose, we’ve highlighted the ones that we’ve personally worked with up until today. Should you have any questions we invite you to contact us for some additional specific information.

And we always welcome any new topics regarding Brexit that you’d like to hear more about!

Blog by: Nick Veringmeier - Xendo

Austria

Belgium

Bulgaria

Croatia

Cyprus

Czech Republic

Germany

Denmark

Estonia

Spain

France

Greece

Hungary

Ireland

Italy

Latvia

Lithuania

Finland

Luxembourg

Malta

Netherlands, The

Poland

Portugal

Romania

Sweden

Slovakia

Slovenia

Iceland

Norway


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