ARIM, Brexit, eCTD, EMA, Medical Devices, RIM Smart

Brexit and Health Products — Down to the Wire

As of this writing, The United Kingdom is expected to complete the Article 50 separation from the European Union — nicknamed Brexit — on March 29, just four weeks away. At this point, there is little expectation that the UK will remain in the trade union, or continue to use the regulations of the European Medicines Agency and the European Medical Device Directive (and the Active Implantable Device Directive and In Vitro Device Directive).

So what does this mean for companies that have products approved, or in process of approval, in Europe?

There are essentially four means of approval of medicinal products across Europe:

National Procedure (NP)

This is where a drug is approved in an individual country. You can gain approvals in multiple countries, but they’re considered separate and don’t influence each other. If there are products approved via the National Procedure no additional action is needed – you’re still valid in each country.

Mutual Recognition Procedure (MRP) and Decentralised Procedure (DCP)

This is a process where one country is selected as a Reference Member State to do the bulk of the review and the rest of the countries where you wish to market are called Concerned Member States. The difference between the two is that in a Mutual Recognition Procedure the Reference Member State has already issued an authorisation prior to the procedure, whereas a Decentralised Procedure has the first review done during the procedure.

At the end of this process, though, each country issues its own authorisation. The UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) has stated that products approved under a Mutual Recognition or Decentralised Procedure will be recognized as a National Procedure approval.

Similarly, there is little impact on the rest of the EU if a product is authorised using the MRP or DCP. The only issue is that of the Reference Member State for ongoing variations and periodic reporting. If the Reference Member State is the UK – and the UK is the Reference Member more often than any other country – The CMDh (Coordination Group for Mutual Recognition and Decentralised Procedures – Human) of the Heads of Medicines Agencies (HMA) requires that another country be selected as a reference member state prior to March 30, 2019.

Centralised Authorisation Procedure (CAP or CP)

The Centralised Authorisation Procedure requires a review directly by EMA, with assistance of one or two Rapporteur countries. This results in a single authorisation recognized by all of the EU (with mutual recognition by Iceland, Liechtenstein and Norway… but that’s another post).

MHRA has stated that they will issue an automatic National authorisation for all products currently authorised in the UK with the Centralised Procedure, unless companies opt out. The companies will then have a year to file a baseline submission to MHRA that will ‘roll up’ the history of the application. While companies are given a year, they can not file any variations to the product without the baseline being filed first. MHRA will continue to use the same eCTD Module 1 and Application Forms as Europe – no technical changes are expected.

Similar to the MRP/DCP, if the Rapporteur for a CAP is the UK, companies are expected to file a change of rapporteur in order to proceed with further changes to the product authorisation.

Other Impacts on Medicines

With the advent of Brexit, products moving between the UK and other parts of Europe will be considered an export/import situation.  The following administrative items must be established both in the UK and elsewhere in Europe:

  • Qualified Person for Pharmacovigilance (QPPV)
  • Pharmacovigilance Master File Location (PV MFL)
  • Site for Batch Release – the location where import or manufacturing inspection takes place

There may also be issues with customs delays importing across the UK border – many companies (drug company warehousing, pharmacies, hospitals) are stockpiling products in anticipation of such delays.

Medical Devices

Medical devices are authorised in Europe through the placement of a CE Mark indicating conformance with required directives and regulations. For the lowest-risk devices, this is done simply by self-declaring conformance. For higher-risk devices, this is done through a filling with a Notified Body, of which there are many, some specializing in certain kinds of devices.  Post Brexit, the EU will not recognize Notified Bodies in the UK for new CE Marks.

This is mitigated, though, as

  • Some of the UK-based bodies have already registered locations within the EU
  • Existing products do not need to be re-certified
  • The UK will continue to recognize medical devices with the European CE Mark at least through a transition period

Impact

Based on the information above, your company should already be working to prepare for the worst-case scenario of a no-deal Brexit. If a deal does materialize, there may still be mutual recognition between EU and the UK, but right now this is not expected.

Actions that should already be underway include:

  • Stockpiling supply for UK use for products produced elsewhere in the EU, or for EU use for products manufactured in the UK, in case there are customs delays.
  • Acknowledge the UK notice of ‘grandfathering’ centralized procedure authorisations
  • Update the Qualified Person for Pharmacovigilance, Pharmacovigilance Master File Location, Market Authorisation Holder and Batch Release Site to ensure that products can be sold and adverse experiences tracked both in the UK and EU.

Actions that should be planned now for later implementation:

  • Create Baseline submissions for the UK, for Centralised Procedure authorisations
  • Decide on the Notified Bodies that will be used for EU and UK certification of Medical Devices

IQVIA Can Help You Through This

The IQVIA RIM Smart system (formerly ARIM) can prepare the publications and track registrations for your medicinal and medical device products.  Our Global Regulatory Affairs service group can assist you with preparation of regulatory filings and advise on any other processes.  Please contact us for further information.

References

MHRA: How medicines, medical devices and clinical trials would be regulated if there’s no Brexit deal

MHRA: Further guidance note on the regulation of medicines, medical devices and clinical trials if there’s no Brexit deal

EMA: United Kingdom’s withdrawal from the European Union (‘Brexit’)

EMA: Practical guidance for procedures related to Brexit for medicinal products for human and veterinary use within the framework of the centralised procedure

CMDh: Questions and Answers related to the United Kingdom’s withdrawal from the European Union with regard to national authorised medicinal products for human use

CMDh:  CMDh procedural advice on changing the Reference Member State

Author: Joel Finkle

Joel became embroiled in electronic submissions when regulatory came downstairs and asked "Can we convert all our clinical study reports to WordPerfect format for the FDA reviewer?" and he didn't say, "No." Since then, he's been involved with custom CANDAs, PDF publishing, eCTD, document template automation, Regulatory Information Management, HL7's RPS, and the ISO IDMP standard. He joined ACUTA in April of 2017. He'd share some of his famous tomatillo salsa with you, but he can't carry it on airplanes.

One Commnet on “Brexit and Health Products — Down to the Wire

  1. Some additional information was released at the start of March:
    1) MHRA has released information on how to gain access to the MHRA gateway, to be used for submissions and vigilance reporting. https://www.gov.uk/guidance/making-submissions-to-the-mhra-in-a-no-deal-scenario
    2) They have also released information on how to transfer Marketing Authorisation Holder within the UK. https://www.gov.uk/guidance/medicines-marketing-authorisation-transfer-ownership

Leave a Reply

Your email address will not be published. Required fields are marked *