Guidance

Pharmacovigilance following agreement of the Windsor Framework

Updated 11 March 2025

1. Overview 

This guidance is designed to provide information on the implementation of changes to pharmacovigilance for medicines authorised in the UK following the agreement of the Windsor Framework.  

These changes will be implemented from 1 January 2025.  

This guidance should be used in conjunction with the MHRA guidance on the Windsor Framework including UK-wide licensing for human medicines, and labelling and packaging guidance. This guidance should also be used to supplement the operational guidance in the MHRA’s existing guidance on pharmacovigilance procedures.  

2. Glossary of terms 

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

• 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 (PLGB): a product licensed by the MHRA that covers Great Britain (GB) only as the territorial application with PLGB as the MA number prefix

3. Legislative basis  

From 1 January 2025, all medicines approved in the UK will be licensed by the MHRA and authorised under the Human Medicines Regulation 2012 (as amended) (HMRs). 

​​​​​Products that fall within the mandatory or optional scope of the EU’s Centralised Procedure that, following the UK’s exit from the EU, were eligible for authorisation by the EC in NI (as a centrally authorised product (CAP)) will no longer be authorised in this manner. Instead, these products will be authorised UK-wide under UK requirements by the MHRA. These products will be known as Category 1 products under UK law and will be legally required to follow Part 11 of the HMRs for pharmacovigilance with further pharmacovigilance requirements outlined in Schedule 12A of the HMRs.  

Products that do not fall within this definition will be Category 2 products as shown in Table 1. These products will be authorised by the MHRA under the HMRs and will follow Part 11 for pharmacovigilance requirements. These products do not fall within scope of the changes to licencing arrangements agreed in the Windsor Framework and will therefore continue to follow the Commission Implementing Regulation (EU) No 520/2012 (CIR) where further pharmacovigilance requirements are stipulated. 

Table 1: Categorisation Criteria

UKMA (UK) Category 1	UKMA (UK) Category 2
Authorised products: Products that were authorised in the EU through the centralised procedure and subsequently grandfathered at the time of EU Exit.​ Or Are within the mandatory scope of the centralised procedure but authorised by the MHRA since 1 January 2021.  Or  Are within the optional scope of the centralised procedure but authorised by the MHRA since 1 January 2021, unless authorised by one or more member states through EU national procedures (including mutual recognition or decentralised procedures)	Authorised products: Products that do not fall within the mandatory scope of the centralised procedure ​ Or  In the case of the optional scope, products were authorised through national procedures.​  Or   Products were authorised prior to the introduction of the centralised procedure.
New applications for products that fall within the mandatory or optional scope of the centralised procedure This includes products authorised as conditional marketing authorisations.	New applications  for products that do not fall within Category 1 (products that do not fall within the mandatory or optional scope of the centralised procedure). This will not include products authorised as conditional marketing authorisations.
The generic, hybrid or biosimilar products of category 1 reference products. ​ For already authorised products, this will apply regardless of whether the centralised procedure was used for the generic, hybrid or biosimilar application.	The generic, hybrid or biosimilar products of Category 2 reference products.
These products will be authorised by the MHRA in accordance with UK law on a UK-wide basis.	These products will be authorised by the MHRA in accordance with UK law and applicable EU law[footnote 1] on a UK-wide basis.

Marketing authorisation holders (MAHs) will still be able to have a​n​ NI MA as outlined in the UK-wide licensing guidance. Pharmacovigilance requirements for NI MAs will be​ in​ line with those for Category 2 products.  

Additionally, the MHRA will retain the right to issue GB MAs, in exceptional circumstances, from 1 January 2025. These licences will not be available through application and will only be used in specific circumstances to safeguard the interests of patient’s health within the UK. These products would need to comply with Schedule 12A of the HMRs. The MHRA will ​​provide specific guidance in the event this type of licence is used. 

4. Approach to the operation of pharmacovigilance 

Following the implementation of the​se​ arrangements​ from 1 January 2025​, pharmacovigilance requirements will remain broadly in line with current requirements. However, there will be aspects of pharmacovigilance which will be impacted depending on whether the product is Category 1 or 2. 

Information on the different requirements for Category 1 and Category 2 (and NI MAs) in specific areas is included below.  

5. Actions for submitting individual case safety reports (ICSRs)  

5.2 MHRA reporting 

From 1 January 2025, all MAHs, irrespective of licence ​c​ategory, must send all UK ICSRs and serious non-UK ICSRs which meet the MHRA reporting requirements to the MHRA via ICSR Submissions or Gateway within current specified timeframes (15 days for serious reports, 90 days for non-serious reports). 

For cases in respect to NI the country code XI should continue to be used to send ICSRs to the MHRA. 

5.3 EMA reporting 

For Category 1 products, where a company has an EU ​or EEA ​licence for the same active ingredient, the MAH will be required to submit all serious UK and other country reports to the EMA within 15 days and submit all non-serious ICSRs originating from NI in line with EMA requirements. 

Where a​n​ MAH does not hold a licence in the EU or an EEA state for Category 1 products, they will not be required to submit ICSRs to the EMA. 

For Category 2 products (and NI MAs), the MAH must submit all serious UK and other country reports to the EMA within 15 days. In addition, the MAH must submit all non-serious ICSRs originating from NI, or which occur in an EEA state to the EMA within 90 days. 

To avoid duplicate ICSRs, MAHs should not submit ICSRs from NI which have been received from the MHRA as these ICSRs are sent directly to the EMA from the UK Health Authority. 

A summary of the requirements is specified in Table 2. 

Table 2: 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)} 

6. Periodic safety update reports (PSURs)   

The MHRA is able to set UK-specific submission requirements for PSURs for Category 1 products in the same way as for products currently authorised via a GB MA (before 1 January 2025). These requirements can be set at the time of authorisation or post-authorisation. However, in most circumstances, PSUR submission timelines will be in line with the EU and in the absence of a UK-specific requirement, MAHs should continue to follow the EU reference date (EURD) list.  

PSURs for Category 1 products should be submitted via the MHRA PSUR portal. 

PSURs for Category 2 products (and NI MAs) should be submitted via the EU PSUR Repository and, where appropriate​,​ will be subject to the EU single assessment process.  MAHs do not need to make a separate PSUR submission to the MHRA for a Category 2 product (or NI MA). However, in circumstances where the PSUR cannot be accessed from the EU PSUR Repository, MAH’s may be requested to submit a PSUR directly to the MHRA. 

A summary of the requirements is included in Table 3. 

Table 3: Overview of PSUR submission requirements 

	Submission to MHRA PSUR portal	Submission to EU PSUR repository
Category 1 – UK only licence	YES	N/A
Category 1 – UK and corresponding EU licence	YES	YES
Category 2 – for UK only and UK and EU licence	Not required*	YES

^{*Provided the MHRA can access the PSUR from the EU PSUR Repository.} 

7. Post authorisation safety studies (PASS)  

For Category 1 products, draft protocols, and significant amendments (for ​C​ategory 1 and 2 studies), and final study reports for all studies should continue to be submitted to the MHRA in line with the current guidance for GB MAs.  

For Category 2 products (and NI MAs), the draft study protocol should be submitted to the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) as well as to the MHRA and this also applies to significant amendments to the draft protocol (unless the study is only being conducted in the UK at the request of the MHRA, where submission is only required to the MHRA). 

8. Safety referrals 

From 1 January 2025, Category 1 products will not be subject to EU referrals (under Article 2001/83). However, it is the MAH’s responsibility to keep the authorisation up to date with current scientific knowledge. The MAH should consider how any new information affects their UK authorisation and make necessary changes via the appropriate variation submitted to the MHRA.  

UK Category 2 products (and NI MAs) will be subject to EU pharmacovigilance referrals (including Article 31 and urgent union procedures) and the outcome should be implemented in line with EU timelines. MAHs should submit the relevant documentation to the MHRA and may be requested to submit additional information regarding the procedure to the MHRA. In exceptional circumstances where the outcome of an EU safety referral does not align with patient safety in the UK, the MHRA will inform the relevant MAHs of the action to take as soon as possible, usually within 14 days of publication of the EU decision. 

9. UK-specific actions 

Where there are concerns regarding a medicine or class of medicines that are authorised in the UK, the MHRA may conduct a major safety review to review the available data and consider what regulatory action may be needed. We will also conduct safety reviews for UK products in circumstances where a major safety review does not apply, this may be in response to a new safety signal or support effective risk minimisation. 

Where any UK-specific action impacts on products authorised via the Mutual Recognition Procedure or the Decentralised Procedure (MRP/DCP) and that action is not aligned with the mutual recognition position, MAHs will be required to withdraw from the procedure.  

The resultant purely national, UK-wide MA will then be managed as a standalone UK authorisation.  

Implementation of this approach is in line with current procedures and is not affected by the implementation of the arrangements for human medicines under the Windsor Framework. 

10. Implementation of EU outcomes 

MAHs for Category 2 products (and NI MAs) need to continue to implement the outcome of relevant EU procedures including those for PSUR single assessments and pharmacovigilance referrals in line with EU timelines. There is no legal requirement for an outcome of an EU procedure to be implemented for a Category 1 product. However, in line with their obligations to keep the marketing authorisation up to date with current scientific knowledge, irrespective of the category of the product, MAHs should continue to monitor the EMA and the MHRA websites and make changes to the authorisation as appropriate. For Category 1 products, the terms of the authorisation may be different from those for the EU product and therefore implementation of any EU outcome should be considered in the context of the terms of UK authorisation.  

In circumstances where the outcome of an EU outcome should not be implemented in the UK in the interests of UK patient safety, the MHRA will inform MAHs of the action to take as soon as possible, usually within 14 days of the publication of the EU decision. 

11. UK qualified person for pharmacovigilance (QPPV)  

​​​Following the implementation of the arrangements ​for human medicines ​under the Windsor Framework on 1 January 2025, no changes to the UK requirements of the UK QPPV are anticipated. The legislative reference for a product may change if a product is subject to HMR schedule 12A rather than CIR due to product category allocation. The requirements for both category 1 and category 2 products are stipulated below: 

• for Category 1 authorisations, the legal requirements concerning the qualification and responsibilities of the QPPV will be outlined within HMR Schedule 12A paragraph 10 
• for Category 2 authorisations the legal requirements concerning the qualifications and responsibilities of the QPPV as stated in CIR Article 10 will continue to apply

The HMR schedule 12A requirement mirrors that of the CIR and therefore no differences exist in practical terms. 

The following table sets out the requirements for a UK and EU​​​/EEA​ QPPV for each of the UK licensing categories. The UK QPPV can be the same person as the EU QPPV. Where the UK QPPV resides in the EU/EEA a UK National Contact Person must be appointed.  

Table 4: UK and EU​​​/EEA​ QPPV requirements

	UK QPPV	EU-QPPV	EU-QPPV
	Can reside in EU/EEA or UK	Must reside in EU/EEA	Can reside in UK or EU/EEA
Category 1 – UK only licence	YES	No	No
Category 1 – UK and EU licence	YES	YES	No
Category 2 – UK only	YES	Subject to EU directive*	Subject to EU directive*
Category 2 – UK and EU licence	YES	YES	No

^{*Publications Office (europa.eu)}

12. UK national contact person (for pharmacovigilance) (NCP) 

Following the implementation of the arrangements ​for human medicines ​under the Windsor Framework on 1 January 2025, there are no changes to the requirement to operate an NCP within the UK.  

Where the company has a UK QPPV residing in the EU, a UK NCP shall need to be nominated and informed to the MHRA. 

MAHs should continue to follow the guidance outlined in the existing NCP guidance within the guidance on qualified person responsible for pharmacovigilance (QPPV) guidance pages.  

13. UK Pharmacovigilance System Master File (PSMF)  

Following the implementation of the arrangements for human medicines under the Windsor Framework on 1 January 2025, a UK PSMF will be required for all UK marketing authorisations regardless of the route of authorisation.  

There will be no changes to the operational implementation of the UK PSMF; however, the current legislative reference for a product may change if a product is now subject to HMR schedule 12A rather than CIR due to product category. The following legislation will apply:  

• For Category 1 authorisation​s​, the legal requirements concerning the format and content of the PSMF as outlined in HMR Schedule 12A Part I. 
• For Category 2 authorisations, the legal requirements concerning the format and content of the PSMF as outlined in Chapter I of the CIR will continue to apply. 

The HMR requirement mirrors that of the CIR and therefore no differences exist in practical terms. 

14. Notification of QPPV and PSMF to Extended EudraVigilance Medicinal Product Dictionary (XEVMPD) 

Following the implementation of the arrangements for human medicines under the Windsor Framework, Category 1 products should continue to follow the existing notification requirements.  

For Category 2 products, in addition to notifying the UK QPPV and UK PSMF details to the MHRA, MAHs must submit information on the UK QPPV and the location of the UK PSMF to the Article 57 database in accordance with Regulation (EC) No 726/2004 Article 57(2). 

15. Traditional herbal (THR) and homeopathic (NR and HR) medicinal products 

UK herbal (THR) and homeopathic (HR) medicinal products should continue to use the existing relevant pharmacovigilance guidance and procedures.  

Where homeopathic products are licensed via a homeopathic marketing authorisation (UK-wide NR) in accordance with the UK National Rules Scheme, these products will fall within Category 2 and are expected to follow the relevant pharmacovigilance guidance as outlined on this page.  

16. Guidance for packs already released to the market  

The MHRA guidance on UK-wide licensing for human medicines and the guidance on labelling and packaging confirm that QP-certified packs can continue to be supplied to patients until the product’s date of expiry in the territory for which the product was valid for supply prior to 1 January 2025. 

For packs QP-certified when the EU CAP licence was valid in NI, the EU CAP will cease to have validity in NI from 1 January 2025. The corresponding GB MA will have UK-wide validity.  

There will be a period of overlap where QP-certified packs of the EU CAP are present in the supply chain. It is the responsibility of the MAH to manage potential differences in licences if they are submitting variations.  

Where there are safety updates to the product information, including the label, the standard timelines of 3-6 months for implementation of updated materials continue to apply. MAHs should update the electronic medicines compendium accordingly, if applicable.  

MAHs should manage any differences in safety information between the EU CAP and GB MA via the variation process, taking into account the ​MHRA​ timelines for approval of variations. MAHs should contact the MHRA as soon as possible, at safetyprojects@mhra.gov.uk if a delay in approval of any application is affecting the production of updated materials. 

MAHs only need to communicate with healthcare professionals where there is significant difference in safety information between the EU CAP and GB MA that would impact on the clinical management of patients. Where MAHs believe that this applies they should contact the MHRA at safetyprojects@mhra.gov.uk and we will give advice on managing the situation on a case-by-case basis. 

17. Further information 

For further information, read our Q&A or use the following contacts:

• for general information on pharmacovigilance, please contact vigilanceservice@mhra.gov.uk 
• for any queries about pharmacovigilance compliance, please contact gpvpinspectors@mhra.gov.uk 
• for anything else, please email our Customer Services Centre at info@mhra.gov.uk or telephone 020 3080 6000

1. As amended by EU Regulation 2023/1182 and Directive (EU) 2022/642 ↩