Navigating Dual MHRA/EMA Pharmacovigilance Obligations Post-Windsor Framework

What Does the Windsor Framework Actually Mean for Your Pharmacovigilance System?

If your organisation holds marketing authorisations for medicinal products sold in the United Kingdom, including Northern Ireland, you are now operating under one of the most complex pharmacovigilance compliance landscapes in the world. Since 1 January 2025, the Windsor Framework has fundamentally reshaped how UK Marketing Authorisation Holders (MAHs) must manage their PV obligations, creating a dual regulatory environment where MHRA and EMA requirements apply simultaneously, but differently, depending on how each product is classified.

This is not a future compliance issue. It is live now. MAHs who have not yet aligned their pharmacovigilance systems, QPPV arrangements, PSMF structure, ICSR reporting workflows, and PSUR submission processes to the new framework are already operating with compliance gaps that MHRA inspectors are actively looking for.

This blog explains the Category 1 and Category 2 distinction, what it means across every core area of your PV system, and what actions organisations must take to achieve and maintain dual compliance.

Understanding the Core Change: Category 1 and Category 2 Products

The Windsor Framework categorises all UK-authorised medicines into two groups, and the category your product falls into determines almost every downstream PV obligation your organisation has.

Category 1 products are those that previously fell under the mandatory or optional scope of the EU Centralised Authorisation Procedure. From 1 January 2025, these products became UK national licences regulated entirely by the MHRA under UK Human Medicines Regulations (HMR) Schedule 12A. In PV terms, Category 1 products follow UK-specific requirements.

Category 2 products are all other medicines, including those previously authorised through national routes, Mutual Recognition Procedures (MRP), or Decentralised Procedures (DCP). These products continue to be governed by both Part 11 of the HMR and Commission Implementing Regulation (EU) No. 520/2012, meaning EU pharmacovigilance law still applies.

The practical consequence is that MAHs with large, diverse portfolios may now have products in both categories, each operating under a different legal framework within the same pharmacovigilance system.

ICSR Reporting: What Has Changed and Where the Risks Are

Individual Case Safety Report submission is one of the areas most directly affected by the Windsor Framework, and it is also one of the areas where compliance errors are most likely to occur without robust, documented procedures.

From 1 January 2025, the following applies to all MAHs regardless of product category:

• All UK ICSRs and serious non-UK ICSRs meeting MHRA reporting thresholds must be submitted 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 originating in Northern Ireland, country code XI must continue to be used when submitting to the MHRA

For Category 1 products, where an equivalent EU or EEA licence exists for the same active ingredient, the MAH must also submit all serious UK and other country reports to the EMA within 15 days, in line with EMA requirements.

For Category 2 products, ICSRs must be submitted to both the MHRA and the EMA as appropriate.

Two critical rules that prevent duplication errors:

• MAHs must not resubmit Northern Ireland ICSRs received from the MHRA to the EMA, as the MHRA already forwards these directly
• Where a case involves two distinct products with separate authorisations, duplicate reporting may apply and the individual case must be assessed against both sets of obligations

For organisations with mixed portfolios, maintaining separate, clearly documented procedures for Category 1 and Category 2 ICSR workflows is essential and is now a primary inspection focus.

PSUR Submissions: Different Routes for Different Categories

Periodic Safety Update Report submission requirements have diverged significantly between the two product categories under the Windsor Framework.

For Category 1 products:

• PSURs must be submitted directly to the MHRA
• If the same product also holds an EU authorisation, the MHRA will accept submission via the EU PSUR Repository, unless the MHRA requests otherwise
• UK-specific PSUR requirements may be imposed by the MHRA independently of EU timelines

For Category 2 products:

• PSUR submission to the MHRA is not mandatory if the report is available in the EU PSUR Repository, where the MHRA will access it directly
• Submission must follow the EU Reference Date (EURD) list for timelines unless the MHRA issues specific UK requirements
• Where no MHRA-specific timeline is published, organisations should default to EU EURD list dates

For PSMF Annex F, MAHs must include reporting metrics to the MHRA for Category 1 products and metrics to both the MHRA and the EMA for Category 2 products. Where an MAH holds both Category 1 and Category 2 products requiring EMA ICSR submission, the MHRA will accept EMA metrics for both types within the PSMF.

QPPV and NCP Requirements: What the New Legal Bases Mean Operationally

The Windsor Framework introduces distinct legal bases for the Qualified Person Responsible for Pharmacovigilance depending on product category, but the operational requirements remain essentially the same. The distinction matters for audit and inspection documentation, however, and MAHs must ensure their QPPV appointments are referenced correctly by category.

For Category 1 authorisations, the legal requirements for QPPV qualifications and responsibilities are set out in HMR Schedule 12A paragraph 10.

For Category 2 authorisations, the legal requirements are set out in Commission Implementing Regulation (CIR) Article 10.

Across both categories, the following rules apply:

• A UK QPPV must be appointed for all UK-authorised products and must reside and operate anywhere in the UK or the EU/EEA
• There is no temporary exemption from this requirement
• If the appointed QPPV is based outside the UK, a UK National Contact Person for Pharmacovigilance (NCP) must be nominated and reported to the MHRA
• The NCP must have access to suspected adverse reaction reports and the UK PSMF, and must be able to facilitate responses to MHRA queries including during inspections

For Category 2 products, MAHs must also 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). This is an additional obligation that does not apply to Category 1 products and is a frequent source of compliance gaps in mixed-portfolio organisations.

UK PSMF: Structure, Accessibility and Category-Specific Requirements

A UK PSMF is now required for all UK marketing authorisations regardless of product category or route of authorisation. This is non-negotiable and has been in effect since 1 January 2025.

Key PSMF requirements under the new framework:

• The UK PSMF must be electronically accessible from a single UK-based location
• A unique UK PSMF number must be requested from the MHRA for each pharmacovigilance system operated for UK-authorised products
• The PSMF must be up to date at the point it is sent to the MHRA
• The UK PSMF number will be invalidated if the electronic access address provided is not in the UK, and any submissions using an invalidated number will not be accepted

For Annex H of the UK PSMF, MAHs must now include the product category, either Category 1 or Category 2, for each product covered by the PSMF. This is a new structural requirement that many organisations have not yet implemented.

For organisations with both Category 1 and Category 2 products within a single pharmacovigilance system, the PSMF must clearly reflect both sets of obligations, with separate reporting metrics documented for each category in Annex F.

PASS, Safety Referrals and Signal Detection

Post-authorisation Safety Study obligations and safety referral implementation have also diverged under the Windsor Framework.

For PASS submissions:

• Category 1 products: draft protocols, significant amendments, and final study reports must be submitted to the MHRA only, unless the study is being conducted across multiple markets
• Category 2 products and NI MAs: draft protocols must be submitted to both the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) and the MHRA, unless the study is conducted exclusively in the UK at the MHRA’s request

For safety referrals:

• Category 1 products are no longer subject to EU referrals under Article 2001/83. However, MAHs retain full responsibility to keep the UK authorisation current with scientific knowledge and must evaluate any EU outcomes in the context of their UK licence
• Category 2 products and NI MAs remain fully subject to EU pharmacovigilance referrals, including Article 31 and urgent union procedures, and outcomes must be implemented in line with EU timelines
• Where an EU outcome should not be implemented in the UK in the interests of patient safety, the MHRA will notify MAHs within 14 days of the EU decision

For signal detection, the updated MHRA GVP exceptions and modifications guidance requires signal detection processes to incorporate MHRA-defined parameters and prioritise UK-focused risks, including data from UK-specific sources. For Category 2 products, EudraVigilance monitoring remains a component of signal management alongside UK-based surveillance.

What MAHs Must Do Right Now to Achieve Full Dual Compliance

The following actions are required for organisations that have not yet completed their Windsor Framework alignment:

• Confirm the Category 1 or Category 2 classification of every product in your UK portfolio by reference to the MHRA published Category 1 product list
• Map your current ICSR submission workflows against the category-specific requirements and update SOPs to reflect separate procedures for each category
• Review all PSUR submission routes and timelines, ensuring Category 1 and Category 2 obligations are separately documented and tracked
• Confirm your QPPV appointment is correctly referenced to the applicable legal basis by product category
• Appoint a UK NCP if your QPPV is based outside the UK and notify the MHRA accordingly
• Request a UK PSMF number from the MHRA Submissions Portal if you have not already done so
• Update your UK PSMF to include product category in Annex H and correct reporting metrics in Annex F
• Submit UK QPPV and UK PSMF details to the Article 57 database for all Category 2 products
• Update signal detection procedures to include MHRA-defined parameters and UK-specific sources
• Review all PV agreements with outsourced service providers to confirm dual-obligation coverage is included and documented
• Conduct a full internal PV audit against the MHRA’s updated Exceptions and Modifications to the EU GVP guidance, published in February 2025

How Quality and Vigilance Ltd Can Help

At Quality and Vigilance Ltd, we provide specialist pharmacovigilance compliance support to help MAHs navigate the complex dual-obligation environment created by the Windsor Framework. Our services directly relevant to post-Windsor Framework compliance include:

• Pharmacovigilance audits covering both MHRA and EMA compliance obligations, with specific focus on Category 1 and Category 2 product differentiation
• GVP compliance assessments aligned to the MHRA’s updated Exceptions and Modifications guidance and the February 2025 revisions
• EU QPPV and National QPPV or National Contact Person services for UK-authorised products
• PSMF review and restructuring to meet UK PSMF requirements including Annex F and Annex H updates
• ICSR processing support including intake, triage, data entry, QC, narrative writing, and regulatory authority submission to both MHRA and EMA
• PV system setup, maintenance, and ongoing compliance monitoring for mixed-portfolio MAHs
• SOP development and documentation review for dual MHRA/EMA submission workflows
• Inspection readiness support for MHRA pharmacovigilance inspections under the post-Windsor regulatory framework
• Training on GVP, MHRA-specific PV requirements, and Windsor Framework obligations for PV teams and MAH staff

Get in touch with our team to discuss your specific portfolio, QPPV arrangements, and PSMF structure, and to understand where your current pharmacovigilance system may have gaps under the new framework.