14 January 2019 - Authored by:Jacqueline Bore
The MHRA has issued updated guidance on its plans for the regulation of medicines, medical devices and clinical trials in the event that the United Kingdom leaves the European Union on 29 March 2019 without any agreement on its future relationship with the EU and, therefore, without any transitional period. The guidance reflects responses to the government consultation conducted in the Autumn of last year and will be enacted into UK law in time for a no-deal exit by amendments to the relevant statutory instruments.
On marketing authorisation procedures, the proposals are:
• existing Community or centralised marketing authorisations granted by the EMA will be automatically converted into UK marketing authorisations;
• marketing authorisation holders will have one year to submit base line data to the MHRA in order to maintain these marketing authorisations;
• the MHRA will offer three new assessment procedures for products containing new active substances and biosimilars;
• the MHRA will target certain products to review based on a positive CHMP opinion. This assessment will be completed in 67 days so that the product could be available on the market in the UK at around the same time that the European Commission approves the grant of a marketing authorisation for the EU;
• otherwise industry can choose a full accelerated assessment route, for new active substances only, with a timeline of no more than 150 days;
• companies could also opt for a rolling review for new active substances and biosimilars which allows them to make applications in stages throughout a product’s development;
• the MHRA will work to lower the timetable for the existing national authorisation procedure from 210 days to 150 days.
On orphan medicinal products, the proposals are:
• orphan criteria will be based on the current EU criteria but will use the prevalence of the rare disease and the availability of satisfactory alternative treatment methods in the UK as well as the significant benefit of the product;
• compliance with the orphan criteria will be assessed at the same time as quality, safety and efficacy as part of the marketing authorisation procedure;
• there will be no pre-marketing orphan designation;
• 10 years market exclusivity from competition from similar products in the approved orphan indication will be retained;
• the initial application fee will be refunded at 100% for small and medium enterprises and at 10% for all other manufacturers.
On Paediatric Investigation Plans, the proposals are:
• compliance with a UK PIP or waiver will need to be demonstrated in all applications for marketing authorisations for new medicinal products and for applications for variations to include new indications, new routes of administration and new pharmaceutical forms for all products that are the subject of a supplementary protection certificate;
• the rewards will remain the same for compliance- a six month extension of a UK Supplementary Protection Certificate or a two year extension of orphan market exclusivity.
On data and market exclusivity, the proposals are:
• the periods of data and market exclusivity will remain the same as provided for in EU law but will begin from the date of authorisation in the EU or UK, whichever is earlier.
On legal presence requirements, the proposals are:
• a marketing authorisation holder should be established in the EU before the end of 2020;
• where the marketing authorisation holder is not established in the UK on exit day companies must put into place a UK based contact person within 4 weeks;
• a Qualified Person for Pharmacovigilance (QPPV) should be established in the UK on exit day but a temporary exemption will allow an EU based QPPV to assume responsibility until a QPPV who resides and operates in the UK can be established but this must be before the end of 2020;
• the holders of manufacturing licence must have a Qualified Person residing and operating in the UK in respect of products manufactured in the UK or imported from a third country not on an approved list ( i.e not EU or EEA countries).
On batch testing, the proposals are:
• the UK will continue to recognise QP certification from EU/EEA countries. All existing wholesale dealers will be permitted to purchase medicines that have been QP certified in the EU/EEA upon notification to the MHRA within 6 months of exit that they wish to continue this activity and the grant by the MHRA of a revised licence;
• there will be a new assurance system overseen by a Responsible Person for Import (RP-I) at each holder of a wholesale authorisation to ensure that any imported medicines have been QP certified. This will not require re-certification. Assurance regimes must be in place immediately on exit but companies will have two years to name a RP-I.
On packaging and leaflets, the proposals are:
• the industry will have until the end of 2021 to make necessary changes to packaging and leaflets e.g to substitute the UK marketing authorisation holders name and address, the UK licence number and information about the manufacturing site;
• the MHRA will accept proposals for packaging and leaflets in the English language that include information for other jurisdictions, for example, Ireland, so long as the information in all languages conveys the same message and complies with UK requirements;
• packs including the Falsified Medicines Directive safety features will still be accepted in the UK provided they are in line with other UK requirements. The legal obligations related to the Falsified Medicines Directive will be removed for actors in the UK supply chain as the UK will not have access to the EU central data base.
On abridged applications for generic medicinal products and biosimilars, the proposals are:
• the existing procedures in the UK will remain in place but it will not be possible to rely on a reference medicinal product only authorised in the EU and not also in the UK;
• UK marketing authorisations based on EU reference products or through mutual recognition or decentralised procedures completed before exit day will remain valid on exit.
On parallel imports, the proposals are:
• medicinal products that are the subject of a marketing authorisation in another EU Member State, including Community marketing authorisations, will continue to be able to be imported under a parallel import licence if they can be shown to be essentially similar to a product that has been granted a UK marketing authorisation;
• parallel import licence holders will need to be established in the UK. Companies have until 31 December 2010 to effect this change if they are currently established in the EU/EEA but must have a UK based contact person within 4 weeks of exit;
• holders of parallel distribution notices issued by the EMA in respect of centrally authorised products will automatically be issued with a parallel import licence if the UK is listed as a destination country in the notice.
On the recognition of prescriptions, the proposals are:
• the UK will continue to recognise prescriptions (as private prescriptions to be dispensed at no cost to the NHS) from all EU/EEA countries so long as the prescriber is of equivalent professional status to a profession that is eligible to prescribe in the UK.
On the certification of batches of immunological medicinal products or a medicinal product derived from human blood or plasma, the proposals are:
• the UK expects to be able to put in place mutual recognition agreements with third countries such as Switzerland and Israel to recognise Official Control Authority batch release batch testing conducted in those countries;
• for countries where there is no mutual recognition agreement, and this will include the EEU /EEA in the event of no-deal, the MHRA will require UK certification of batches by NIBSC but certificates issued by EEA/EU countries before exit will remain valid. Certificates issued by EU/EEA countries after exit will be taken into account in deciding whether to make a paper based assessment or require additional testing.
There are also proposals for a revised fee schedule.
On conformity of products, the proposals are:
• the MHRA will continue to allow medical devices to be placed on the UK market that are in conformity with the applicable EU Directive. Devices must carry a CE mark and be the subject of a valid CE certificate from a Notified Body if required;
• the UK will continue to recognise certificates issued by UK Notified Bodies after exit and such devices that are the subject of such certificate may continue to be placed on the market in the UK after exit;
• the UK will continue to accept labelling in the English language which includes information for other jurisdictions such as Ireland so long as the information complies with all UK requirements.
On clinical investigations, the proposal is:
• the UK will continue to recognise existing regulatory and ethics clinical investigation approvals.
On the market surveillance of devices, the proposal is:
• the MHRA will continue to perform market surveillance of medical devices on the UK market and will be able to take a decision over the marketing of a device in the UK regardless of the position of the European Regulatory Network (the EU/EEA, Switzerland and Turkey) or any decision of the CJEU.
On the new EU Regulations relating to medical devices, the proposal is:
• the UK will have a regulatory system in place on 30 march 2019 which will mirror all the key elements of the new Medical Devices Regulation, the in vitro diagnostic Regulation which will be brought into force in line with the transitional timetable being followed by the EU for full application of these Regulations.
On the registration of medical devices on the UK market, the proposals are:
• all medical devices, including in vitro diagnostic, active implantable and custom made devices, will need to be registered with the MHRA prior to being placed on the market after exit. There will be grace periods for compliance with the new registration process, their length being related to the class of the device;
• where the device manufacturer is not established in the UK, registration of a product with the MHRA must be undertaken by a UK responsible person established in the UK and with a UK registered address.
The proposals for clinical trials are:
• the UK will continue to recognise existing approvals;
• the UK will require the sponsor or legal representative of a clinical trial to be in the UK or a country on an approved list. The list will initially include all EU/EEA countries. Separate registration of a UK contact point will not be not required;
• the new EU Clinical Trials Directive will not be incorporated into UK law on exit day as it will not yet be in force in EU law but, once it is in force in the EU, the UK will re-align with those parts of the legislation that are within its control.
• the UK will recognise QP certification done in any EU/EEA country for investigational medicinal products and will not require re-certification;
• all importers of investigational medicinal products into the UK will require a manufacturer’s licence and will require to have in place an assurance system to check that the investigational medicinal products have been certified in the EU or EEA. Clinical trial sponsors will have 12 months to commence compliance with the new regime;
• sponsors will be required to submit all UK relevant suspected unexpected serious adverse reaction reports to the MHRA via UK based IT systems;
• the UK’s ability to participate in multinational trials will not change.
• the MHRA will work towards a system allowing a single application and a single ethics decisions for clinical trials conducted in the UK.
• in the short term those running trials should continue to use existing international registries to publish information about clinical trials. Ultimately, the UK will have its own specific hub for information about clinical trials that will give UK patients and researchers a single reference point for all UK trials.