New UK Medicines Licensing Rules Under the Windsor Framework

The Windsor Framework (WF) is a legal agreement between the United Kingdom (UK) and the European Union (EU). It adjusts the trade terms established by the Withdrawal Agreement and Northern Ireland Protocol when the UK left the EU in 2021. The EU and the UK agreed on the Windsor Framework in February 2023. It became effective on 1^st January 2025.  It is designed to address some of the practical complexities experienced with operating the Northern Ireland Protocol. The aim is to ensure a permanent solution to safeguarding supply and access for human medicines across all 4 UK countries (i.e. England, Scotland, Wales and Northern Ireland). As such, the Windsor Framework introduces new rules for medicines licensing by the MHRA.

 

The new rules for medicines licensing by the MHRA:

• The MHRA is again responsible for licensing medicines across the whole of the UK under the Human Medicines Regulations (HMR) 2012, as amended. Under the Northern Ireland Protocol, separate licences for Great Britain (GB) and Northern Ireland (NI) were established in 2021. However, a single UK Product Licence now replaces these separate licences.
• Changes agreed in the Windsor Framework apply to products that fall within the scope of the EU Centralised Procedure (CP). The MHRA already regulates medicines outside the CP’s scope, so they are not impacted by the licensing changes.
• Existing GB marketing authorisations (MAs) have automatically converted to UK-wide MAs but have retained the same PLGB licence number.
• EU centrally authorised products (EU CAPs) licensed by the European Commission are no longer valid for NI.
• Historical UK-wide MAs granted through decentralised or mutual recognition procedures (DCP/MRP) before EU Exit, where NI remains a Concerned Member State (CMS) in the EU procedure, are currently managed in alignment with the EU procedure.  This will continue unless there is a requirement for UK-specific changes.
• All medicines released to the UK market must carry a ‘UK Only’ label. This is to indicate they are not for sale in the EU.
• Serialisation features required in the EU under the Falsified Medicines Directive (FMD) no longer apply in NI.

 

Scope and Implementation of Licensing Changes

The Windsor Framework does not impact existing arrangements for clinical trials or medical devices. Combination products which are medicinal products, will also need to comply.

Throughout 2024, MHRA issued detailed guidance on the Windsor Framework. These guidances clarify UK requirements for key areas of medicines licensing, such as labelling and supply, and pharmacovigilance. MHRA continued to release updates through the final days of December 2024 and into January 2025.

This article provides a comprehensive overview of critical aspects of licensing in the UK under the Windsor Framework. It includes key clarifications issued by MHRA in the weeks before and after its implementation on 1^st January 2025.

 

Licensing

UK-Wide Licensing Changes

Implementing the Windsor Framework allows the MHRA to license all medicines across all of the UK under one UK-wide regime. This marks a return to the MHRA’s mandate before the UK’s exit from the EU. MHRA will grant most new MAs as “UKPL” licences covering the whole UK. The new MA number will have a PL prefix.

Existing PLGB MAs are now automatically valid for the whole UK, as MHRA takes responsibility for these medicines in NI. Thus far, MHRA have not required MA holders to implement a licence prefix change to reflect this territorial scope change.

 

Management of Existing Authorisations

The Windsor Framework does not affect existing UK-wide MAs granted by MHRA through EU collaborative assessment procedures (DCP/MRP) prior to the UK leaving the EU, where NI remains involved as a CMS. MA holders can continue to manage these MAs in alignment with the EU procedure.  However, if there are UK-specific changes, NI would withdraw from the EU procedure and MA holders would require a UK-wide MA.

 

PLNI Licensing and Transitional Arrangements

MA holders may continue to apply for a PLNI MA as part of a DCP/MRP. However, it is now not possible to hold both a PLNI and a UK-wide MA for the same product. MA holders had the option to withdraw NI from the DCP/MRP and request the MHRA to cancel the NI MA.  Without such a request, the MHRA cancelled the GB MA on 31st December 2024.

Finally, the CAP Bridging Mechanism and Northern Ireland MHRA Authorised Route (NIMAR) schemes are no longer be required. Nevertheless, the NIMAR remains in place in law. MHRA implemented these schemes to mitigate potential gaps in medicines availability in NI following the UK’s exit from the EU.

 

Licensing of Category 1 and Category 2 Products

The changes to licensing arrangements agreed in the Windsor Framework only apply to those products that fall within the mandatory or optional scope of the EU CP. As a result, the Windsor Framework introduces the categorisation of UK medicines.

Medicines that fell or will fall within the scope of the EU CP are designated in UK law as “Category 1”​. ​Category 1 products include all medicines based on new active substances, orphan medicinal products, other innovative products and Advanced Therapy Medicinal Products (ATMPs). All products authorised through a conditional marketing authorisation (CMA) are Category 1 medicines. Category 1 also includes the generic, hybrid or biosimilar products of Category 1 reference products.

Medicines outside the scope of Category 1 are designated as “Category 2”. The Windsor Framework does not impact these medicines as the MHRA already regulated them. Consequently, applicable EU law on medicinal products continues to apply to Category 2 products after 1st January 2025. Category 2 products include generic, hybrid, or biosimilar products of Category 2 reference products.

Information on the category lists for licensed products is available on the MHRA website. New MA applications to MHRA must include the proposed category assignment where applicable. However, incorrect categorisation will not invalidate the application. MHRA will publish the categorisation of newly licensed products in the biweekly lists of new MAs.

Product categorisation impacts several regulatory compliance procedures, including those for pharmacovigilance, as described later in this review. MA holders need to understand reporting requirements for their UK MAs. Companies may have to adjust their systems to simultaneously manage the differing requirements for Category 1 versus Category 2 products.

 

Labelling

The Windsor Framework fundamentally distinguishes between medicines destined for the UK internal market and those entering the EU single market. All medicines placed on the UK market from 1^st January 2025 require ‘UK Only’ labelling on their outer packaging.  This requirement precludes onward movement of medicines licensed on a UK-wide basis into any part of the EU. It also ensures all medicines use the same packaging and labelling across the UK. “UK-only” labelling applies to all medicines. This includes Category 1 and Category 2, Prescription-Only Medicines (POM), Pharmacy (P), General Sales List (GSL) medicines, and parallel-imported products.

MA holders can add the “UK Only” statement via a sticker for 6 months only. After this, it must be printed directly onto the packaging.

 

Options for submission of updated artwork (including for stickering) to the MHRA:

• Self-certification notification, following which the MA holder can implement the change immediately (rather than waiting for formal approval). Usual fees for self-certification and guidance on bulk submissions apply.
• Self-certification without eCTD documentation followed by submission of the updated eCTD sequence including artwork by 31^st December 2025. Usual fees for self-certification and guidance on bulk submissions apply to both steps.
• Submission with any regulatory opportunity, where the artwork change is included with another application. However, in this scenario, MA holders must wait for formal approval for the procedure before implementing the labelling change.

 

Supply Chain Impact

To ensure continued supply of medicines to NI, MHRA will also accept identification of Manufacturing and Import Authorisation (MIA) holders (authorised for secondary packaging) within the self-certification submission.  The sole purpose must be to add ‘UK Only’ stickers to packs released before midnight 31^st December 2024.

As explained above, no new stock may be released to the UK market from 1^st January 2025 until the “UK Only” artwork change has been self-certified or approved by MHRA.  Notably, MA holders can no longer release joint EU/UK packs to the UK supply chain. Likewise, information relevant to NI must be removed from EU CAP packs per EU requirements). Shared inner packaging components, such as multi-lingual blister foils and joint leaflets, may continue to be used in the UK.  This is on the basis that the UK and EU licences remain aligned.

The stipulation for separate packs may create a significant issue for products supplied to meet the needs of ultra-rare conditions. MA holders should contact the National Supply Disruption Response and  the MHRA if they anticipate UK supply disruption.

 

Disapplication of FMD

From 1^st January 2025, the EU FMD no longer applies in NI. Safety features now fall under the terms of UK law.

This means that serialisation codes, included on a medicine’s outer packaging and registered with the European Medicines Verification Organisation (EMVO) for compliance with the EU FMD, are not permitted in GB or NI. MA holders must ensure serialisation codes are removed or covered on any new UK packs released from 1^st January 2025.

Existing safety requirements under UK law remain unchanged e.g. inclusion of expiry date and batch number. MA holders may choose to apply a 2D barcode (including expiry date, batch number, Global Trade Item Number) and/or a serial number. MHRA encourage the use of anti-tamper packaging.

 

Qualified Person (QP) Release and Supply

From 1^st January 2025, all products released to the UK market must include “UK Only” labelling. Products must not carry EU FMD safety features. MA holders can no longer supply the NI market with EU CAPs.

Medicines already QP-released into the supply chain as of 1^st January 2025 can continue to be marketed in the relevant territory until their expiry without any relabelling or repackaging. This excludes medicines moved from NI to the EU/EEA or placed on the market in the EU/EEA.

 

Pharmacovigilance

As described above, product categorisation resulting from implementation of the Windsor Framework impacts pharmacovigilance requirements in the UK.

Category 1 products are legally required to follow Part 11 of the HMR 2012 for pharmacovigilance with further requirements outlined in Schedule 12A of the HMR 2012.

In contrast, Category 2 products also follow Part 11 of the HMR 2012 for pharmacovigilance requirements. However, they also continue to follow the European Commission Implementing Regulation (EU) No 520/2012 (CIR).

Although pharmacovigilance broadly aligns with current requirements, a few key aspects must be considered. The MHRA website provides further detail on the operation of pharmacovigilance under the Windsor Framework. An additional Q&A document is also available to support MA holders with common queries.

 

Qualified Person responsible for Pharmacovigilance (QPPV) and pharmacovigilance system master file (PSMF)

The MA holder must have a QPPV responsible to establish and maintain the pharmacovigilance system for all UK authorised products. This includes Category 1 and Category 2 products and PLNI and PLGB licenses. The QPPV can reside and operate anywhere in the UK or the EU/EEA. Where the QPPV does not reside and operate in the UK, MA holders require a national contact person for pharmacovigilance who resides and operates in the UK.

For all UK MAs, the MA holder must maintain a PSMF that describes the pharmacovigilance system for UK-authorised products. This is termed the “UK PSMF”.  For Category 1 and Category 2 products, details of the QPPV and UK PMSF must be provided to the MHRA.

In accordance with EU Regulation (EC) No 726/2004 Article 57(2), MA holders for Category 2 products and PLNIs must also submit information on the QPPV and the location of the PSMF to the Article 57 database.  EU legislation requires that the QPPV resides within the EU/EEA. Hence, for MA holders with UK QPPV / UK PSMF only, consideration of options to meet EU requirements is critical. For UK MA holders that did not have an EU QPPV at their disposal on 20^th April 2022, a UK QPPV is acceptable, in accordance with Directive 2022/642.

 

Individual Case Safety Reports (ICSRs)

MA holders must send all UK ICSRs (serious and non-serious) and serious non-UK ICSRs to the MHRA. The country code XI should be used for cases that occur in NI or the EEA. This requirement applies irrespective of licence category. The requirements for EMA reporting depend on the existence of an EU/EEA ​licence for the same active ingredient (shown below).

 

Overview of reporting requirements for ICSRs

	MHRA reporting	EMA reporting	EMA reporting
	All UK ICSRs and third-country serious ICSRs meeting MHRA reporting requirements	N​on-serious ICSRs (originating in NI)	Serious ICSRs (originating anywhere in the UK)
Category 1 – UK only licence	YES	n/a	n/a
Category 1 – UK and EU licence	YES	YES*	YES
Category 2 – UK only	YES	YES	YES
Category 2 – UK and EU licence	YES	YES	YES

^{*In line ​with ​EMA guidance Questions and answers to Stakeholders on the implications of Regulation (EU) 2023/1182 for centrally authorised medicinal products for human use (europa.eu)}

Source: Pharmacovigilance following agreement of the Windsor Framework – GOV.UK

 

Periodic Safety Update Reports (PSURs)

In most cases, MHRA will accept PSUR submission timelines in line with the EU. In the absence of a UK-specific requirement, MA holders should continue to follow the EU reference date (EURD).

MA holders must submit PSURs for Category 1 products to MHRA (and to EMA if there is a corresponding EU licence). MHRA does not currently issue UK-specific PSUR assessment reports but has indicated that this aspect is under review. EU PSUR outcomes do not legally apply to Category 1 products. However, MA holders are obliged to maintain the UK MA up to date with current scientific knowledge. As such, MA holders should submit a variation application to the MHRA as necessary.

MA holders should submit PSURs for Category 2 products via the EU PSUR repository. MA holders do not need to make a separate UK submission. However, the MHRA would prefer to be notified by email of PSUR submission to the repository. MA holders may be requested to submit directly to MHRA if the PSUR is not accessible from the repository.

 

Signal Management/Safety referrals

Similarly to PSUR assessment reports, EU outcomes on safety referrals or signals do not legally apply to Category 1 products. However, MA holders must maintain UK product information with current scientific knowledge and submit variations to the MHRA accordingly.  MHRA requests that assessment reports continue to be shared where they are available.

 

Renewals

The Renewal application procedures also depend on the product category.

For Category 1 products, MA holders should submit renewal applications to MHRA. MA holders should continue to prepare the renewal application in accordance with current EU guidance for CAP products.

Renewal applications for Category 2 products should be submitted in line with EU requirements for DCP or MRP procedures. Renewal applications for standalone national UK-wide authorisations should be submitted to MHRA. MA holders should submit a cover letter and application form, but it does not require a consolidated dossier.

Renewal applications for CMAs should be submitted to MHRA and follow the same requirements as those for the EU.

 

Reference Medicinal Products (RMPs)

The Windsor Framework impacts the requirements for RMPs for generic applications and other abridged MA applications in the UK. Generic applications require an RMP that has been authorised in the UK for more than 8 years.

MA holders must provide clear evidence that a comparator product used in bioequivalence or therapeutic equivalence studies but not sourced from the UK market, is representative of the UK RMP. MHRA provides guidance on the level of evidence that would be acceptable. This includes source countries with similar scientific and regulatory standards as the UK, such as the EU/EEA and USA. Where the MA holder provides confirmation that the non-UK comparator product is identical to the UK RMP, MHRA do not require analytical data.  However, where this is not the case, the MA application should include bridging data from analytical studies.

 

Advertising and Promotion

MHRA issued guidance to MA holders on changes to the advertising and promotion of medicines due to the Windsor Framework.

Promotional materials for medicines must carry the product licence number. Materials for medicines previously authorised in NI under an EU CAP must be updated to the correct UK licence number. MA holders should also have assessed all NI promotional materials for products authorised under a CAP. This is to ensure that the content is consistent with the UK Summary of Product Characteristics (SPC) effective on 1^st January 2025. If the SPC diverged between NI and GB prior to 2025, existing NI materials may no longer be compliant.

MA holders must remove wording on GB materials indicating that the product has a GB MA.

 

Export

The MHRA published supplementary information about UK medicine exports. It aims to reassure international regulators about medicines with “UK only” labelling. These products can still be exported to territories outside the EU/EEA, in accordance with local import requirements. The MHRA confirms there have been no changes to its regulatory standards. The guidance presumably aims to protect the export market for UK medicines.

 

Summary

Implementation of the Windsor Framework ensures that medicines are approved and licensed on a UK-wide basis by the MHRA. UK medicines use the same packaging and labelling, and the requirements of the EU FMD have been disapplied. The Windsor Framework applies to medicines to which the CP would apply (defined in UK law as Category 1 medicines). Elements of EU medicines legislation still apply to those medicines not impacted by the Windsor Framework. UK law defines these medicines as Category 2 products. MA holders must understand the nuances of medicines licensing under the Windsor Framework. This will ensure compliance with UK and EU regulatory requirements.

 

Regulatory Support for MHRA Windsor Framework Licensing Guidance Updates

The MHRA updated guidance to reflect the Windsor Framework until the 31^st of December 2024 and post-implementation into 2025. DLRC has followed these developments and will continue to do so. Contact our regulatory experts to ensure that you are compliant with the new UK licensing rules. We have extensive experience in optimising UK regulatory strategy and submissions. DLRC are available to support both existing MA holders and medicines developers considering submission of an MA application in the UK. Get in touch to see how we can help you.