The UK Medicines and Healthcare products Regulatory Agency ("MHRA") has published a raft of guidance on how various aspects of the UK regulatory regime for medicines will operate in England, Wales and Scotland (together Great Britain, "GB") and in Northern Ireland following the expiry of the Brexit transition period on 31 December 2020. The guidance includes clinical trials, marketing authorisations, importing, exporting and pharmacovigilance and is relevant to any business involved in the research, development or commercialisation of medicines in the UK.
The UK left the EU on 31 January 2020 and existing EU medicinal product legislation has continued to apply in the UK during the Brexit transition period under the terms of the EU-UK Withdrawal Agreement. When that period expires on 31 December 2020, the UK will leave the single market and the customs union to become a "third country".
At the expiry of the transition period, existing EU legislation will be automatically incorporated into UK domestic legislation as far as possible. Any EU legislation that takes effect after the expiry of the transition period will not automatically apply in the UK (unless the EU and UK agree a new trading relationship that provides otherwise, which is currently still under negotiation). For example, since the new EU Clinical Trials Regulation will take effect after the transition period has expired, it will not automatically be incorporated into UK legislation.
The MHRA guidance
From 1 January 2021, the MHRA will be the UK’s standalone medicines and medical devices regulator. As a result of the Northern Ireland protocol, different rules will apply in Northern Ireland than in GB; broadly, Northern Ireland will continue to follow the EU regulatory regime, but its national competent authority will remain the MHRA.
The new guidance will be given effect via the Human Medicines Regulations (Amendment etc.) (EU Exit) Regulations 2019 (the "Exit Regulations"). The Exit Regulations will also update existing UK legislation by, for example, by replacing references to EU databases and community marketing authorisation ("EU MAs") with newly established UK databases and UK marketing authorisations ("UK MAs").
A non-exhaustive list of key points from the various guidance documents is set out below.
- All sponsors, or their legal representatives, must be established in the UK or a country on the approved country list, which will include all EEA member states.
- Sponsors will need to appoint someone to maintain oversight of investigational medicinal product supply to GB clinical trials by the end of 2021.
- All existing EU MAs for centrally authorised products ("CAP") will automatically be converted into UK MAs free-of-charge on 1 January 2021. EU MAHs of CAPs can opt-out of this process if they wish. EU MAs of CAPs will remain valid for marketing products in Northern Ireland.
- UK MAHs will have until 1 January 2022 to submit essential baseline data. This data must follow the electronic Common Technical Document sequence and be submitted together with certain other related MA-specific information for each converted EU MA. In general, the MHRA will not consider any variations to converted EU MAs before the essential baseline data mentioned above has been submitted.
- UK MAs that were converted from EU MAs will be treated as if they were granted on the date the corresponding EU MA was granted and the periods of regulatory data protection and market exclusivity will be adjusted accordingly.
- UK MAHs of converted EU MAs will have until 1 January 2023 to transfer the UK MA to a UK-based entity and until 1 January 2024 to ensure that all stock released onto the GB market has updated packaging and product information.
- The position for applications for a centralised MA that are pending as of 1 January will depend on how far through the process the application is but will result in a separate UK MA.
- Advanced Therapy Medicinal Products ("ATMPs") and biosimilar products will be regulated in GB by the MHRA according to the same principles that previously applied. Northern Ireland will continue to follow the EU regulatory framework.
- There will be no pre-marketing authorisation orphan designation. Instead, the MHRA will review applications for orphan designation in parallel to the corresponding MA application. The criteria are essentially the same, but have been tailored for the GB market, i.e. the prevalence of the condition in GB (rather than the EU) must not be more than 5 in 10,000. Should an orphan designation be granted, the period or market exclusivity will be set from the date of first approval of the product in GB or EU/EEA, wherever is earliest.
- Goods "placed on the market" in the EU or UK before the expiry of the transition period may continue to circulate between these two markets. Medicines that have been certified by a Qualified Person ("QP"), released for sale or supply and for which there is an agreement or offer to transfer ownership to another legal entity before 11pm on 31 December 2020 will be deemed to have been "placed on the market".
Importing and exporting
- If a wholesale dealer already imports medicinal products from a jurisdiction on the approved country for import list (the "List") (which includes all EEA countries) prior to 1 January 2021, they can continue to do so provided that they notify the MHRA in writing of their intention to continue this activity by 30 June 2021 and nominate and name a Responsible Person (import) ("RPi") on their wholesale dealer authorisation ("WDA") by 1 January 2023.
- If a wholesale dealer does not already hold a WDA before 1 January 2021, in order to wholesale deal medicinal products they will need to apply for a WDA. The requirement to name an RPi on the WDA will apply immediately to all new licence applications made from 1 January 2021 which cover the importation of medicinal products from a country included on the List.
- The MHRA will retain responsibility for pharmacovigilance ("PV") across the UK from 1 January 2021. Products placed on the market in GB must adhere to the GB requirements, and products placed on the market in Northern Ireland will need to adhere to the EU requirements.
- The Good Vigilance Practices ("GVP") modules will remain in force in the UK, but the MHRA will publish a guidance note on the exceptions and modifications to the EU guidance on GVP in due course.
- UK MAHs will be required to operate a PV system for UK authorised products. They must have an appropriately qualified person responsible for PV ("QPPV") that resides and operates in the EU or the UK. If a UK MAH has an EU QPPV, they must nominate a "national contact person" for PV who resides and operates in the UK and reports to the QPPV by the end of 2021.
- UK MAHs must maintain and make available upon request a PV system master file ("PSMF") that describes the PV system for UK authorised products. The PSMF must be accessible electronically or physically from the UK at the same site at which reports of suspected adverse reaction may be accessed.
The MHRA has also published detailed guidance on comparator products in bioequivalence/therapeutic equivalence studies, exporting active substances manufactured in GB for use in EEA and Northern Ireland, handling of active substance master files and certificated of suitability, conditional MAs, paediatric products, converting parallel distribution notices to UK parallel import licences, traditional herbal medicinal products and homeopathic medicinal products, and further guidance is still to be published.
Guidance was also published by the MHRA on how medical devices will be regulated in the UK following the expiry of the transition period. For a summary of the changes to the regulatory framework applicable to medical devices, please see our earlier blog.