Brexit and drug approval in the UK: navigating regulatory changes

Since its departure from the European Union (EU) in 2020, the United Kingdom (UK) now operates independently in drug regulation under the International Council for Harmonization.

This shift offers the UK's regulatory agency, MHRA, an opportunity to establish itself as a significant player in the global regulatory landscape (Summerfield, 2020).

However, the complexity arising from the unique political and geographical aspects of the UK has hindered progress in implanting legislation related to Brexit and the pharmaceutical sector.

To address some of these challenges, the Windsor Framework has been introduced. Due to be implemented on January 1^st, 2025, the Windsor Framework for Northern Ireland (NI) aims to provide a long-term solution for supporting the supply of medicine into NI.

Importantly, it will facilitate the approval of medicines for the entire UK, thereby eliminating the applicability of the EU Falsified Medicines Directive to Northern Ireland. Questions have arisen regarding the impact Brexit has had on the regulatory landscape in the UK.

While there have been notable improvements in the authorization times for novel medicines and oncology drugs, there have also been significant delays and a lack of approvals overall.

This raises concerns about whether these challenges will diminish the UK’s appeal as a market for innovation (Meredith, 2023). With the initial implementation of Brexit, the European Medicines Agency (EMA) continued to approve novel and oncology drugs in NI.

However, this approach overlooked the fact that most drugs entered the UK as a whole and were then supplied to Northern Ireland via Great Britain (GB).

To address this issue of medicine flow, the EU made amendments to regulatory requirements affecting the movement of medicines from GB to NI. These amendments allowed the MHRA to maintain authorization of generic drugs under a single license for the UK.

This solution was considered temporary, as the challenge of novel and oncology drug approval by the EMA persisted. There was a risk of divergence for NI if the UK or EU laws changed (HM Government, 2023).

Additionally, the requirement for companies to comply with two different labeling requirements for NI and GB may have led some to refrain from registering their drug in NI, which would have adversely impacted patient access to medications in NI.

To address these concerns, the Windsor Framework was developed. The Framework aims to remove NI completely from the EU regulatory system, ensuring all approvals are eventually granted solely by the MHRA through UK-wide approval.

The Windsor framework enables medicines for the UK and NI to utilize the same packaging and labeling. After the January 1^st , 2025:

• New medicines intended for the UK market will be authorized by the MHRA and will be packaged with a prominent “UK only” label.
• These new medicines will only be eligible for sale within the UK, including Northern Ireland.
• Medicines entering Northern Ireland will no longer need to comply with the EU’s Falsified Medicines Directive, meaning they are no longer required to display the "safety features" as required by EU legislation on packaging for prescription drugs, including 2D barcodes and serialization numbers.
• Anti-tamper devices will remain mandatory on all medicine packaging for UK products authorized by the MHRA.

Legacy EU packaging will be acceptable until December 31^st, 2024, an extension of the previous deadline of December 31^st, 2023.

Products in existing EU packaging already on the market in the UK can remain in circulation until their expiry date (Medicines and Healthcare products Regulatory Agency, 2023).

Additionally, the “UK only” label can be applied using a sticker, which is applied by the marketing authorization holder, and certified by a Qualified Person, until June 30^th, 2025. However, after this deadline, the label must be printed onto the packaging.

The MAH must notify the MHRA of any artwork changes before December 31^st, 2024. This notification can be submitted alongside another application, except for Type 1A variations, and there will be no extra fee for the artwork change.

This submission should include a cover letter and form confirming that the labeling has been updated in accordance with the Windsor Framework requirements. It is advisable for the MAH to await approval of the procedure before implementing the artwork change.

Alternatively, a notification specifically related to the artwork change can be submitted to the MHRA. In this case, the changes to the artwork can be made after the application has been submitted. The implementation timeline for this route has been extended by six months, provided the artwork change is implemented before January 1^st, 2025 (Ridley, 2023).

While the Windsor Framework has addressed several challenges stemming from Brexit, it has overlooked veterinary medicines and medical devices (Teare, 2023).

In the case of veterinary medicines, the Veterinary Medicines Directive remains the regulatory authority for the UK, with Northern Ireland still subject to EU legislation.

A grace period until 2025 allows veterinary products to move freely from GB to NI. However, concerns arise regarding potential losses in veterinary medicines’ availability in NI due to batch testing requirements (British Veterinary Association, 2022).

Regarding medical devices, there are currently no updates to the requirement to adhere to EU law in Northern Ireland.

To register a medical device in Northern Ireland, it must be registered with the MHRA and comply with EU market requirements under either the EU Medical Device Regulation or the EU In Vitro Diagnostics Regulation. Medical devices moving from GB into NI are considered imports into the EU and must comply with EU regulations as a result.

This creates a challenge of having to comply with both the MHRA and EMA rules and further checks during import (Osborne Clarke, 2022). New authorizations via the EU centralized procedure will no longer be accessible for NI.

However, medications previously approved through this procedure and available in Northern Ireland can remain on the market until their shelf life expires, provided they are not repackaged or relabeled. The UK is obliged to provide evidence that these drugs will not reach the EU market (Schofield, 2023).

Mutual recognition and decentralized routes of approval were still acceptable in the UK until January 1^st, 2024.

In relation to pediatric investigation plans (PIP), the MHRA is aiming to maintain alignment with the EMA Pediatric Committee (PDCO) opinion but retains the right to diverge if necessary.

The UK will conduct comprehensive UK PIP assessments before going forward. EU PIPs that have had a completed EMA decision before 2021 do not require resubmission to the MHRA (MHRA, 2020).

Despite uncertainties surrounding medical devices and veterinary medicines, the MHRA hopes to maximize Brexit freedoms to foster innovation.

It also intends to build on pre-existing collaborations via the frameworks and pathways discussed above, to accelerate approval times, and improve UK patients’ access to cutting-edge medicinal products.

Ellie McDermott is a Regulatory Executive at G&L Healthcare Advisors.

References:

British Veterinary Association (2022). British Veterinary Association warns ‘costly bureaucracy’ and ‘onerous regulation’ of veterinary medicine in Northern Ireland risk to animal welfare, public health and agricultural economy. [online] British Veterinary Association. Available at: https://www.bva.co.uk/news-and-blog/news-article/british-veterinary-association-warns-costly-bureaucracy-and-onerous-regulation-of-veterinary-medicine-in-northern-ireland-risk-to-animal-welfare-public-health-and-agricultural-economy/ [Accessed 26 Jul. 2023].

HM Government (2023). The Windsor Framework: A new way forward CP 806. [online] Available at: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1138989/The_Windsor_Framework_a_new_way_forward.pdf.

Medicines and Healthcare products Regulatory Agency (2023). Windsor Framework medicines announcement. [online] GOV.UK. Available at: https://www.gov.uk/government/news/windsor-framework-medicines-announcement#:~:text=It%20will%20ensure%20that%20medicines [Accessed 26 Jul. 2023].

Meredith, S. (2023). How Has Brexit Affected Drug Regulatory Decisions in the UK? [online] Medscape UK. Available at: https://www.medscape.co.uk/vie... [Accessed 26 Jul. 2023].

MHRA (2020). Procedures for UK Paediatric Investigation Plan (PIPs). [online] GOV.UK. Available at: https://www.gov.uk/guidance/procedures-for-uk-paediatric-investigation-plan-pips [Accessed 26 Jul. 2023].

Osborne Clarke (2022). The UK medical devices regime and the impact of the Northern Ireland Protocol. [online] www.osborneclarke.com. Available at: https://www.osborneclarke.com/insights/uk-medical-devices-regime-and-impact-northern-ireland-protocol [Accessed 26 Jul. 2023].

Schofield, I. (2023). EU Adopts New Rules On UK-Wide Approvals For Novel Drugs. [online] Pink Sheet Citeline Regulatory. Available at: https://pink.pharmaintelligence.informa.com/PS148296/EU-Adopts-New-Rules-On-UK-Wide-Approvals-For-Novel-Drugs [Accessed 26 Jul. 2023].

Summerfield, J. (2020). UK post-Brexit regulation of medicines from 1 January 2021. [online] www.engage.hoganlovells.com. Available at: https://www.engage.hoganlovells.com/knowledgeservices/news/uk-post-brexit-regulation-of-medicines-from-1-january-2021/ [Accessed 26 Jul. 2023].

Teare, I. (2023). The Windsor Framework - what does it mean for life sciences? [online] www.mills-reeve.com. Available at: https://www.mills-reeve.com/insights/blogs/life-sciences/february-2023/the-windsor-framework-what-does-it-mean-for-life-s [Accessed 26 Jul. 2023].

Ridley, D. (2023). Post-Brexit Windsor Framework: Start Submitting ‘UK Only’ OTC Medicines Packs To MHRA. [online] HBW Insight. Available at: https://hbw.citeline.com/RS154158/Post-Brexit-Windsor-Framework-Start-Submitting-UK-Only-OTC-Medicines-Packs-To-MHRA [Accessed 20 Dec. 2023].