On 4 January 2019, the UK Government finalised further guidance on the topic of how the UK would regulate medicines, medical devices and clinical trials in the event of a “no-deal” Brexit. This guidance document follows on from a technical notice published on 23 August last year (the “Medicines Notice”) and takes into account responses from a public consultation which took place in October 2018. The purpose of the updated guidance (the “Updated Notice”) is to provide greater clarity on regulatory procedures. This legal update provides a high-level summary of the Updated Notice.
1 Medicinal products: converting CAPs into UK MAs
The Medicines & Healthcare products Regulatory Agency (“MHRA”) previously suggested a process of “grandfathering”, meaning that all centrally authorised products (“CAPs”) would be automatically converted to UK marketing authorisations (“MAs”). This process is elaborated on in the Updated Notice, which explains that market authorisation holders (“MAHs”) would have one year from EU Exit to provide the MHRA with full baseline data for CAPs that are converted into UK MAs. However, the MHRA would accept a “basic” baseline data set initially, enabling variations and other post-authorisation submissions to be processed.
2 MA assessment procedures
2.1 In conjunction with the current 210-day assessment route for national MAs, the MHRA has announced a suite of proposals relating to new assessment procedures for products containing new active substances (“NAS”) and biosimilars:
2.1.1 a targeted assessment for NAS and biosimilars products submitted to the European Medicines Agency (“EMA”) that have received a positive opinion from the Committee for Medicinal Products for Human Use (“CHMP”). The MHRA has committed to assessing the same data within 67 days from the submission of the application, provided the MHRA can obtain all relevant information and CHMP assessment reports;
2.1.2 a full accelerated assessment procedure for NAS only, which would benefit from a reduced timeframe of 150 days; and
2.1.3 a “rolling review” procedure for NAS and biosimilars, meaning that staged applications can be made throughout a product’s development in order to better manage development risks.
2.2 The MHRA has committed to working with industry to identify workable solutions to expedite the national assessment timeframe and has specifically targeted a 30-day reduction from 210 days to 180 days.
3 Orphan medicines
3.1 Post-Brexit, there would be a UK orphan designation system for products for rare diseases. This would be based on the current EU criteria but tailored for the UK. For instance, the prevalence of a disease in the UK population, availability of satisfactory alternative treatments in the UK, and the significant benefit of a product would all be relevant factors.
3.2 Orphan designation in the UK would also be assessed and granted at the same time as the MA application, rather than prior to it as is the case in the EU. Moreover, where orphan status is granted, SMEs would receive relief in the form of a fully refunded initial MA application fee (10% for other manufacturers) and a fee waiver for variations in the first year after MA is granted.
3.3 Orphan market exclusivity is a critically important incentive to stimulate ongoing research and development for orphan products. The MHRA proposes to retain this 10-year exclusivity period with the sublte but significant distinction that the exclusivity period would begin following grant of a UK orphan MA.
4 Paediatric Investigation Plans (“PIPs”)
The MHRA acknowledges that decisions in relation to paediatric matters, such as agreeing a PIP and granting waivers and deferrals, are currently made at EU level, as are assessments of compliance with PIPs. In the event of a no-deal Brexit, this decision-making power would be taken on by the MHRA with respect to UK MA applications. The MHRA states that the same rewards for PIP compliance would be available, i.e. 6-month extension of a UK Supplementary Protection Certificate (“SPC”) or two years’ additional market exclusivity for orphan products.
5 Free scientific advice to SMEs
The MHRA has stated that it would not charge UK-based SMEs for scientific advice, in order to help retain research and development in the UK.
6 Product labelling
The MHRA has specified an industry grace period until the end of 2021 to update administrative details such as the name and address of the MA holder on packaging and leaflets for products already on the UK market.
7 Medical devices
7.1 In the event of a no-deal Brexit, all classes of medical device, active implantable medical devices, in vitro diagnostic medical devices (“IVDs”) and custom-made devices would need to be registered with the MHRA before being placed on the UK market. There would be a grace period of up to 12 months in order to give manufacturers time to comply.
7.2 Once the Medical Devices Regulation (“MDR”) and In Vitro Diagnostic Devices Regulation (“IVDR”) fully apply in the EU (from May 2020 and May 2022 respectively) the UK would mirror “key elements” of the new requirements within that legislation. This would mean the individual registration of all products.
7.3 If the device manufacturer is not established in the UK, the device would need to be registered by a "UK Responsible Person" established in the UK with a UK registered address.
8 Clinical trials
8.1 The current legislation governing clinical trials has been in force since 2004, but suffered from a number of operational deficiencies resulting in increased associated costs, administrative burdens and delays. To combat these issues, the Commission embarked upon legislative reform with the intention of enhancing the attractiveness of the EU as a destination for global research and development. A new legislative framework in the shape of the Clinical Trial Regulation (“CTR”) No. 536/2014 was introduced on 16 April 2014.
8.2 Though the CTR entered into force on 16 June 2014, it will not start to apply until the EU portal and database achieve full functionality. It is also subject to an independent technical audit, which has been repeatedly delayed since 2017. The CTR will become applicable six months after the Commission publishes notice of this confirmation.
8.3 In addition, Article 98 of the CTR provides for a three year transition period from the date it starts to apply. The exact timeframe is therefore dependent on these various conditions being met, and so may well be after the date of UK exit.
9 Conclusion: remaining uncertainty
9.1 Despite the clarification that the Updated Notice provides, there remains uncertainty over the situation regarding pending and future applications. For instance, for medicines it is not clear whether or not MA Applicants would need to submit an EU application followed by a separate UK application.
9.2 In addition, the MHRA has expressly stated that regulatory data protection (“RDP”), SPC extensions and orphan exclusivity would be retained and would reflect the existing EU approach, albeit the relevant date for ‘starting the clock’ would be based on the date of either an EU or UK MA, whichever comes first. It is notable that the CJEU has previously wrestled with similar issues, most recently in the Astellas Pharma case. It therefore remains to be seen whether the European Commission would accept the validity of MAs granted by a non-EU country (i.e. the post-Brexit UK) for the purposes of calculating RDP.
9.3 A substantial practical burden for industry would be that MA Applicants would need to have a UK legal representative and Qualified Person for Pharmacovigilance (“QPPV”) in place as of exit day. The concern is that this would result in significant time, cost and resource burdens for those who do not already have a UK presence.
9.4 For medical devices, manufacturers would need to appoint both an EU and a UK authorised representative if they intended to access both markets. It is also worth noting that the UK Government is only proposing compliance with the “key elements” of the MDR and IVDR, as opposed to full regulatory alignment. This statement therefore leaves some ambiguity as to whether the UK may choose to depart from certain provisions.
9.5 Despite the central EU portal, UK trials would need to implement a separate procedure if they sit outside of the EU. However, it remains unclear how this would work in practice.
The Updated Guidance highlights that there remains a great deal of uncertainty around the trajectory of Brexit and its impact on this sector. Indeed, one notable deletion from the earlier Medicines Notice is of the introductory remark stating that a no-deal scenario was “unlikely”. Nevertheless, the Updated Notice also evidences that the MHRA and UK Government have been working closely to strategise the best options for the safe and effective UK regulation of medicines and medical devices, irrespective of the Brexit outcome.
As is clear from the Updated Notice, additional Government guidance on issues such as the “grandfathering” of MAs; MA assessment routes; change of ownership applications; UK QPPV requirements; and the Responsible Person for Import role will be published in the coming months. Those working in the life sciences sector should therefore continue to plan for a no-deal Brexit in order to mitigate the risks that this scenario would impose.