The guidance provides helpful clarity on key regulatory changes impacting life sciences companies in the event of a no-deal Brexit.
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published a significant volume of guidance documents on various aspects of the post-Brexit life sciences regulatory landscape in the UK, including in the event of a no-deal Brexit. The guidance provides helpful clarity to life sciences companies operating in the European Economic Area (EEA) and the UK, which continue to face significant uncertainty about how they will be impacted by Brexit — particularly given the ongoing risk of a no-deal Brexit. (For detailed analysis on how a no-deal Brexit scenario would impact life sciences companies, please see this prior Latham blog post.)
On 29 March 2017, the UK Prime Minister gave the European Council formal notification under Article 50 of the UK’s intention to leave the EU, setting the default withdrawal date for the UK’s withdrawal from the EU to 11 p.m. GMT on 29 March 2019. The UK Prime Minister requested an extension to the original withdrawal date in light of the UK Parliament’s failure to approve the withdrawal agreement agreed between the UK Prime Minister and the European Commission. On 21 March 2019, the European Council approved the UK government’s request, permitting an extension of the Article 50 period until either:
- 22 May 2019, if the UK Parliament approves the withdrawal agreement by the end of the week commencing 25 March 2019
- 12 April 2019, if the UK Parliament does not approve the withdrawal agreement by the end of the week commencing 25 March 2019, with this period capable of further extension by agreement between the European Council and the UK government, provided that the European Council expects the UK to indicate “a way forward” prior to 12 April 2019
UK Medicines Legislation After Brexit
On 23 January 2019, the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 and the Medicines for Human Use (Clinical Trials) (Amendment) (EU Exit) Regulations 2019 (which amend the UK Human Medicines Regulations 2012 (SI 2012/1916) and the UK Medicines for Human Use (Clinical Trials) Regulations (SI 2004/1031), respectively) were laid before Parliament.
These statutory instruments are due to come into force on the withdrawal date and will amend existing legislation to reflect the occurrence of Brexit.
Key amendments to the UK Human Medicines Regulations include changes to:
- Reflect the fact that the MHRA will act as a standalone regulator outside the EU network after the withdrawal date
- Permit the UK to recognise prescriptions from the EEA notwithstanding the UK’s withdrawal
- Permit regulations that temporarily modify the UK Human Medicines Regulations to address any serious shortages of medicines due to Brexit
- Incorporate EU guidance as it exists on the day prior to withdrawal date
Key amendments to the UK Medicines for Human Use (Clinical Trials) Regulations include changes to reflect the fact that the MHRA will act as a standalone clinical trials regulator outside the EU network after the withdrawal date, taking on new roles which were formerly performed by the European Medicines Agency (EMA).
To complement the above regulations, the MHRA has published, and continues to publish, a substantial amount of guidance that will apply from withdrawal date. The key changes include:
- New UK Assessment Routes: The MHRA has published details on three new assessment routes that will support the timely availability of new medicines for patients in the UK and enhance the development and availability of novel medicines in the event of a no-deal Brexit. These new assessment routes are: Targeted Assessment, Accelerated Assessment, and Rolling Review.
- Deadline for Opt Out of UK Marketing Authorisation Conversions: UK companies will have until 19 April 2019 to opt out of the conversion of their centrally authorised products to UK marketing authorisations (MAs). Holders of centrally authorised products will have a period of one year from the withdrawal date to submit certain required data and information in electronic common technical document (eCTD) format in connection with the MHRA’s ongoing regulation of these converted MAs. Holders of converted UK MAs will need to be established in the UK. Life sciences companies will have until the end of 2020 to fulfil this requirement.
- New Conditional Marketing Authorisation Scheme: In the event of a no-deal scenario, the UK will establish a new national conditional marketing authorisation scheme for medicinal products that fulfil an unmet medical need. The scheme will have the same eligibility criteria as the EU scheme.
- Ability to Opt In to UK Parallel Import Licenses: Holders of Parallel Distribution Notices have the opportunity to opt in to convert these notices to UK Parallel Import Licences by providing certain information and confirmations to MHRA within four weeks of the withdrawal date. Holders of Parallel Import Licences will need to be established in the UK within 21 months of the withdrawal date.
- New UK Orphan Product Incentives: In the event of a no-deal scenario, the UK will establish incentives for orphan products following the withdrawal date. In order for a drug to qualify, the prevalence of the condition in the UK must be not more than 5 in 10,000, or it must be otherwise unlikely that the marketing of the medicine for the UK would generate sufficient returns to justify the investment needed for the drug’s development. These requirements will substantially mirror the EU position. The incentives will include market exclusivity, full or partial refunds of marketing authorisation fees, and potential waivers from scientific advice fees. The market exclusivity period for UK orphan products will begin from the date of first approval in the UK or the EU/EEA. Market exclusivity periods for EU/EEA centrally approved orphan medicine marketing authorisations will continue.
- Changes to Reference Products for UK Biosimilars: UK biosimilar applications submitted after the withdrawal date will need to reference products that comply with Regulation 48 of the UK Human Medicines Regulations (as amended), including:
- Products authorised for at least eight years in the UK
- Products authorised by conversion from EU MAs
- Products that were opted out of conversion
- New Requirements for Holders of UK Wholesale Dealer’s Licences (WDLs): WDLs held on the withdrawal date will remain in force and will permit the importation of products from approved countries (initially EU/EEA countries). Holders of WDLs must appoint a Responsible Person for imports, which is a new role, the holder of which is required to implement a system for confirming that a Qualified Person certification has taken place when products are imported into the UK from approved countries.
- Transition Period for UK Qualified Person for Pharmacovigilance (QPPV) Requirement: As discussed in a previous Latham article, a UK-based QPPV will need to reside and operate in the UK for the sale of medicines in the UK. The updated MHRA guidance has clarified that QPPVs will have until the end of 2020 to comply with this requirement. In addition, a UK pharmacovigilance system master file (PSMF) will need to be located at single point in the UK from which reports of adverse reaction are accessible.
- New UK Artwork Registration Requirements: New artwork in relation to UK MAs must be registered within 21 months of withdrawal date. The MHRA will continue to allow multi-country and multi-language packs. MA holders will then have a further 12 months to ensure all stock released to market is in compliant packaging.
- New Requirements for UK Clinical Trials: UK clinical trials will require the sponsor or legal representative to be in the UK or a country on an approved list (which will initially include EU/EEA countries). Investigational Medicinal Products (IMPs) imported from countries on the approved list will continue to be allowed for one year from the withdrawal date, but after such date the supply of IMPs must be supervised by the holder of the UK Manufacturing and Import Authorisation for Investigational Medicinal Products who will be required to put in place an assurance system to check these IMPs have been Qualified Person certified in the EU or EEA.
The full suite of publications released by the MHRA can be found here.