Guidance

UK-wide licensing for human medicines: supplementary guidance

Published 31 January 2025

1. Overview 

The guidance on UK-wide licensing for human medicines provides information on the implementation of changes to the licensing of medicines for human use in the UK following the agreement of the Windsor Framework.  

This supplementary guidance addresses common queries about UK-wide licensing.   

2.  Glossary of terms  

For the purposes of clarity and consistency, this guidance uses the following definitions of key terms: 

• MA: marketing authorisation 

• IRP: international recognition procedure 

• UK-wide MA: a product licensed by the MHRA, across the whole of the UK (this may include MAs with a PL or PLGB prefix) 

• NI MA (PLNI): a product licensed by the MHRA that covers Northern Ireland (NI) only as the territorial application with PLNI as the MA number prefix  

• GB MA: a product licensed by the MHRA that covers Great Britain (GB) only as the territorial application (authorisations issued before 1 January 2025 with PLGB as the MA number prefix are now valid UK-wide - note that new MA numbers with a PLGB prefix will not be issued on or after 1 January 2025, PLGB MA numbers already issued continue to be used and the licences once granted will cover the whole of the UK from 1 January 2025 

• Union authorisation:  an MA issued by the European Commission for a product approved through the European Medicines Agency (EMA) centralised procedure 

• Centrally Authorised Product (CAP): a medicinal product authorised through a Union Authorisation issued by the European Commission and valid across the European Union 

3. Transitional arrangements  

From 1 January 2025, the MHRA will be responsible for regulating all medicines across the UK. Applications authorised via the EU centralised procedure will not be valid in the UK (NI) from this date. Therefore, a national MA application will be required to obtain UK-wide authorisation. Note that it will not be possible to submit a GB MA application from 1 January 2025.  

Authorisations and applications will be impacted as follows:  

3.1 Great Britain MAs (PLGBs) granted by the MHRA up to (and including) 31 December 2024  

GB MAs granted by the MHRA on or before 31 December 2024 were automatically converted to UK-wide authorisations on 1 January 2025, unless the GB MA was cancelled by the MA holder or the MHRA by 31 December 2024. MA holders will not be notified individually about this conversion.   

Product information that is separately approved for Northern Ireland through the EU centralised procedure will be superseded by product information approved for the UK-wide MA valid from 1 January 2025 (see section 5 on product information divergence from EU).   

The MA number including the PLGB prefix will not change after this conversion (see section 16: PLGB prefixes).  Communications have been issued to those involved in the medicines supply chain to advise them of this.    

MA holders with a GB MA and a NI MA for the same product should refer to Section 11.   

3.2 Pending applications submitted through the EU centralised procedures on or before 31 December 2024  

The outcome of initial and post-authorisation applications (variations and renewals) submitted via the EU centralised procedure that receive authorisation from the European Commission (EC) on or after 1 January 2025 will not take effect in Northern Ireland.  

3.3 Marketing authorisations (Union authorisations) granted by European Commission on or before 31 December 2024  

Authorisations (including any post-authorisation changes) issued by the EC on or before 31 December 2024 ceased to be valid in Northern Ireland from 1 January 2025.     

3.4 Pending GB MA applications submitted to the MHRA on or before 31 December 2024  

Initial and post-authorisation applications will follow the rules for existing authorised products set out in the guidance on UK-wide licensing. They will continue to be processed in accordance with national requirements and procedures in place on 31 December 2024. The outcome of the applications will apply UK-wide (see section 16: PLGB prefixes).      

3.5 UK-wide MA applications submitted up to and including 31 December 2024  

Initial and post-authorisation applications will continue to be processed in accordance with national requirements and procedures in place on 31 December 2024. There is no requirement to update the submitted application because of the Windsor Framework. The outcome of the application will apply UK-wide as now.  These applications will have a PL prefix, and that will be retained. 

3.6 UK-wide MAs granted by the MHRA up to and including 31 December 2024  

Authorisations for UK-wide MAs granted by the MHRA up to and including 31 December 2024 will continue with UK-wide validity from 1 January 2025. These applications will have a PL prefix, and that will be retained. 

4. Category 1 and Category 2 

From 1 January 2025, medicines that were previously within scope of the EU centralised procedure are authorised under UK-wide MAs and no longer limited in territorial scope as GB MAs. Products not within this scope will be authorised UK-wide under UK and applicable EU law, as has been the case since 1 January 2021.  

To be clear which rules apply for UK authorisations, all new MA applications and existing products will be assigned to Category 1 or Category 2.  

For full details on the categorisation criteria, refer to the guidance on UK-wide licensing for human medicine. 

The following products will not be categorised:  

• NI-only MAs 

• traditional herbal registrations 

• homeopathic registrations through the simplified scheme 

• unlicensed medicines (including medicines supplied through the Early Access to Medicines Scheme) 

• parallel imports 

• investigational medicinal products  

View the MHRA lists of Category 1 and Category 2 medicinal products. The MHRA has assigned the allocated category of each product based on the criteria set out in the guidance on UK-wide licensing for human medicines updated on 30 August 2024.  

For any queries about the categorisation of a specific medicinal product, email RIS.NA@mhra.gov.uk with the email header ‘LICENCE CATEGORY’.  

From 1 January 2025, the categorisation of new products will be included in the lists of new marketing authorisations that are published every 2 weeks. When submitting MA applications via the Human Medicines portal, applicants must assign a category where applicable. Refer to the UK-wide licensing guidance and additional guidance in the MHRA submissions portal. The MHRA will assess the categorisation and correct it if necessary during the procedure. Incorrect categorisation will not lead to invalidation of the application. The final agreed category will be included in the grant letter. 

5. Product information divergence from EU  

MAs authorised in the EU via the centralised procedure are not valid in Northern Ireland from 1 January 2025. If the same product is authorised in GB on 31 December 2024, the MA will automatically convert to UK-wide validity on 1 January 2025. This means that the GB product information (summary of product characteristics and patient leaflet) applies UK-wide from 1 January 2025.  

There will be a period of overlap in the supply chain since EU packs that are qualified person (QP) certified before 1 January 2025 can continue to be supplied to patients in Northern Ireland until the product’s date of expiry.  

The MHRA does not expect MA holders to align the EU and GB product information before 1 January 2025. Differences in product information between the GB (to be UK-wide) MA and EU MA should be managed depending on the situation and the MHRA will take a pragmatic approach.  

MA holders should consider proactive communication to healthcare professionals in Northern Ireland where there are differences in product information between the EU and GB MA that will lead to a significant change of clinical practice, affecting patient safety in Northern Ireland. This may include significant differences in indications, contraindications or dosage. Follow current guidance on drafting direct to healthcare professional communications (DHPCs).  

Where new safety information has been included in the EU MA, it should be included in the GB MA or UK-wide MA via the variation process, as usual. The standard timelines of 3 to 6 months for implementation of updated materials continue to apply. 

Further details are available in the guidance on pharmacovigilance following agreement of the Windsor Framework. Contact safetyprojects@mhra.gov.uk for advice on managing the situation on a case-by-case basis.  

MA holders should also refer to the guidance on advertising and promotion following agreement of the Windsor Framework.

6. Reference medicinal products (RMPs) 

From 1 January 2025, only RMPs that are, or have been, authorised for at least 8 years in the UK (or GB before 1 January 2025) are valid and can be cited in UK-wide applications for generic, hybrid or biosimilar applications. European reference products are no longer permitted. This requirement applies to all national applications including those made through the IRP, Project Orbis and Access Consortium work-sharing initiative routes. 

Since the UK exit from the EU, the MHRA has expected national MA holders to update and maintain SmPCs/PILs (summaries of product characteristics/patient information leaflets) in line with the UK authorised innovator product. Where this is not possible, for example because the innovator product is no longer authorised in the UK, safety and other relevant product information updates to generics of EU reference products can be submitted via IRP variations.  

Marketing authorisation applications for Northern Ireland only (PLNIs) will need to continue to comply with EU requirements for RMPs and therefore these applications are not required to cite a UK RMP.  

7. Demonstrating or justifying that a non-UK comparator product is representative of the UK reference medicinal product 

Comparator products (CPs) used in bioequivalence (BE), pharmacokinetic (PK) and therapeutic equivalence (TE) studies supporting abridged applications should be representative of the UK RMP supporting the application. If the CP is not sourced from the UK market, the applicant can provide evidence that it is representative of the UK RMP.  

Evidence from physico-chemical testing of 3 batches of each product is usually required to provide the bridge between the two products. However, in cases where the UK RMP and the non-UK CP have a recent shared regulatory history, applicants may be able to justify representativeness without further batch testing.   

This utilises the principle that post-authorisation changes to products that have more than a minor impact on quality have been reviewed by the relevant regulatory authorities to ensure that they do not impact on the safety, efficacy or overall balance of benefit and risk. 

Justification based on evidence of shared regulatory history will be considered where the comparator product is: 

• a centrally authorised product that has, until 31 December 2024, been authorised for Northern Ireland 

•  a product authorised through MRDC procedures where Northern Ireland is or was a concerned member state (CMS)  

This will not normally be acceptable for complex products or those that exhibit a higher inherent batch-to-batch variability. 

Applicants should refer to the detailed guidance on comparator products in bioequivalence/therapeutic equivalence studies.  

8. Applications for established medicines for which there is no UK reference medicinal product 

Applications for established medicines for which a valid RMP authorised in the UK cannot be established will need to be submitted under a different legal basis, for example, a well-established use application (regulation 54 of Human Medicines Regulations) or a full mixed dossier application (regulation 50 of Human Medicines Regulations).   

9. Well established use 

National MA applications can be accepted under the legal basis of well-established use (Regulation 54 of the Human Medicines Regulations 2012).  

In accordance with Regulation 54 it is possible to replace results of pre-clinical and clinical trials by detailed references to published scientific literature, if it can be demonstrated that the active substances of a medicinal product in the claimed therapeutic indication have been in well-established medicinal use in the UK or EU for at least 10 years, with recognised efficacy and an acceptable level of safety.  

The Windsor Framework does not alter Regulation 54. Therefore, after 1 January 2025, it is still possible to accept applications based on demonstration of well-established medicinal use in the EU for at least 10 years.  

This legal basis is an option in cases where there is no identifiable UK reference medicinal product to cite in a generic or hybrid application. Although well-established use applications usually involve established medicines, it is possible to use this legal basis for a product that would be a new active substance in the UK if there is sufficient evidence of its use in the EU. Evidence can include both licensed and unlicensed use. 

10. Mutual recognition procedure (MRP)/decentralised procedure (DCP) 

For existing UK-wide MAs granted through MRP/DCP before 1 January 2021 where NI remains a CMS in the EU procedure, these can continue to be managed in alignment with the EU procedure, unless there is a requirement for UK-specific changes.  

In that situation NI will have to be withdrawn from the procedure and the existing UK-wide MA will then be managed as a standalone UK-wide MA in order to implement the UK-specific changes. Alternatively, the licence can be converted to a NI-only MA.   

11. Applications for Northern Ireland-only MAs 

It is possible to apply for an NI MA on or after 1 January 2025 but the MHRA will only accept applications using the EU MRP/DCP with NI included as a CMS in these procedures.   

NI can continue to be maintained as a CMS in existing procedures. However, it will not be possible for a MA holder to simultaneously hold a PLNI and a UK-wide MA for the same product. If an MA holder currently holds a UK-wide MA and seeks a PLNI through the MRP or the DCP, the UK-wide MA will need to be cancelled.  

12. Northern Ireland MHRA Authorised Route (NIMAR) 

NIMAR continues to be available following implementation of the Windsor Framework. However, as the MHRA is implementing a UK-wide licensing scheme from 1 January 2025, the MHRA anticipates that the use of NIMAR will be significantly reduced. Relevant updates to the existing NIMAR guidance will be made where the existing guidance interacts with the Windsor Framework. 

13. Place of establishment for MA holder from 1 January 2025  

The requirement on the place of establishment of the MA holder is not changed by the Windsor Framework. Therefore, from 1 January 2025, the MA holder can continue to be established in the UK or European Union in accordance with Regulation 49 of the Human Medicines Regulations (2012) unless the application is made through the Unfettered Access Procedure (UAP).    

In the case of an application made through UAP the MA holder must be established in Northern Ireland.   

14. Application routes 

In addition to the direct national route, a UK MA can be applied for via the: 

• International Recognition Procedure (IRP) 

• Project Orbis or  

• Access Consortium work sharing initiative 

The guidance on UK-wide licensing for human medicines explains how UK-wide licensing operates for all applications from 1 January 2025, including those submitted through IRP, Project Orbis and the Access Consortium work-sharing initiative.   

The requirements for reference medicinal products and comparator products apply irrespective of application route and IRP reference regulator (see sections 6 and 7).  

15. Biosimilars  

From 1 January 2025, UK-wide biosimilar applications should conform to Regulation 53B of the Human Medicines Regulations 2012, and only UK reference medicinal products (RMPs) can be cited in the application form. For further details on the choice of reference product for the comprehensive comparability exercise, refer to the guidance on the licensing of biosimilar products. 

Biosimilars will be designated as the same category as the RMP. In most cases this is expected to be Category 1.  

16. PLGB prefixes  

From 1 January 2025, the MHRA regulates medicines through UK-wide marketing authorisations (MAs). Medicines authorised before that date will retain their current MA number (including the prefix even if that is a PLGB prefix). Any UK-wide authorisation issued on or after this date will have an MA number with a PL prefix, unless an MA number with a PLGB prefix was requested at the time of application before 1 January 2025.   

From 1 January 2025, the MA number prefix does not denote the territorial scope of the licence, apart from medicines authorised in NI only through MRP/DCP, which retain the PLNI prefix.  

From 1 January 2025, it is not possible to request an MA number with a PLGB prefix.   

17. Medical devices 

There are no changes to the regulation of medical devices. For medicine-device combination products, the medicines element follows the arrangements for medicinal products as set out in guidance on UK-wide licensing for human medicines.  

UK-wide authorisations for combination products which contain co-packaged medicines and medical devices will need to continue to follow the EU legislation for medical device components.   

18. Paediatric requirements 

All MHRA regulatory submissions (MA applications or variations) which trigger paediatric requirements must have an agreed or adopted UK paediatric investigation plan (UK-PIP) and relevant MHRA compliance checks, or a full product specific waiver or MHRA confirmation of a class waiver. This is irrespective of category or regulatory route (direct national, Access, Project Orbis or IRP). The MHRA expects most regulatory submissions that trigger paediatric requirements to be for Category 1 products which are regulated under UK law.   

Category 2 products will be regulated under UK and applicable EU law. For regulatory submissions of Category 2 products that are subject to paediatric requirements, an EU-agreed PIP must also be in place unless a waiver is granted.  

The MHRA advises developers of Category 2 products are to align the UK-PIP and EU-PIP where possible. Confirmation of equivalence of the UK-PIP and EU-PIP will form part of the MHRA compliance check and obviate the need to include the EU-PIP in the MHRA regulatory submission of a Category 2 product. 

For further details, refer to the guidance on: 

• Procedures for UK Paediatric Investigation Plan  

• Format and content of applications for agreement or modification of a Paediatric Investigation Plan 

19. Further contact information  

For further information, contact ris.na@mhra.gov.uk