UK MHRA Guidance on Pharmacovigilance Procedures: Key Requirements for UK Marketing Authorisation Holders

Pharmacovigilance for medicines authorised in the UK covers activities including safety information reporting, signal detection, risk management, periodic safety reporting, post-authorisation safety studies, safety reviews, post-authorisation measures, and safety communications.

The Medicines and Healthcare products Regulatory Agency (MHRA) has published Guidance on pharmacovigilance procedures to explain its approach to pharmacovigilance. The guidance was updated on 21 August 2026 to include further information on the EURD list.

The MHRA retains responsibility for pharmacovigilance across the UK, but requirements differ between Great Britain and Northern Ireland. For products authorised in Northern Ireland, EU pharmacovigilance requirements continue to apply alongside the UK requirements described in the guidance.

How Does Pharmacovigilance Work in the UK?

Marketing Authorisation Holders (MAHs) must submit relevant pharmacovigilance information to the MHRA according to UK requirements.

This includes:

• Individual Case Safety Reports (ICSRs)

• Periodic Safety Update Reports (PSURs)

• Risk Management Plans (RMPs)

• Post-Authorisation Safety Study (PASS) protocols and final reports

The MHRA assesses these submissions using relevant information and makes decisions reflecting UK clinical practice. The GVP modules and published guidance on exceptions and modifications to EU GVP requirements remain applicable.

MAHs must also notify the MHRA of information that could affect the benefit-risk evaluation of a product as soon as reasonably practicable. They are responsible for keeping product information up to date with current scientific knowledge and should monitor relevant MHRA, EMA and HMA outcomes affecting product information.

ICSR Reporting: What Needs to Be Submitted?

The MHRA requires the submission of UK ICSRs, including cases from Northern Ireland, for both serious and non-serious reports. Serious reports from other countries are also submitted through the MHRA Gateway and/or ICSR Submissions portal.

For products placed on the market in Northern Ireland, ICSRs continue to follow EU requirements through EudraVigilance. This includes serious reports from the UK and other countries and non-serious reports occurring in the EEA or Northern Ireland.

For regulatory purposes, Northern Ireland cases use the country code “XI” in the primary source country field. For reportable UK SUSARs, “GB” should be used.

Signal Detection: When Does a Safety Concern Become Important?

MAHs must have signal detection systems capable of cumulative signal detection across available data sources.

The MHRA does not require MAHs to conduct signal detection against the MHRA's own database because relevant UK data will be made available for inclusion in the MAH's systems. The MHRA assesses signals identified by itself as well as signals highlighted internationally.

MAHs must notify the MHRA of new information from other data sources when it affects the marketing authorisation, including relevant standalone signal notifications submitted to the EMA and signals raised by the EMA. Notification is not required once a signal is on the PRAC agenda.

Emerging Safety Issues: The 3-Working-Day Requirement

Once a signal or safety issue is established as meeting the definition of an emerging safety issue, the MHRA must be notified within 3 working days.

What Happens to a Validated Signal?

For UK-authorised products, MAHs should notify the MHRA once a signal has been validated. Validation should include analysis of available ICSR data and other relevant information, including whether the risk is already addressed in other UK-authorised products.

Depending on the outcome:

Situation	Action described in the guidance
New or changed risk requiring product information or RMP changes	Submit a variation
PSUR due within 6 months of signal assessment	Include the signal in the PSUR
Important risk included in a PSUR	Notify the MHRA separately
Signal cannot be confirmed or refuted	Standalone signal notification may be submitted
Refuted signal	Report in the PSUR

RMPs: Risk Management Can Change During the Lifecycle

A new RMP or update may be required at any point during the product lifecycle.

RMPs should continue to follow the EU template. Updates may be needed when new safety concerns arise or when there is a significant change to pharmacovigilance or additional risk minimisation activities.

Approved EU RMPs continue to be accepted. Where UK-specific information is required, a GB/UK-specific annex may be used.

For a new MA or procedure requiring a GB/UK RMP, an MAH may submit a GB/UK RMP or an approved EU RMP with a GB/UK-specific annex. Where differences are extensive, a standalone GB/UK RMP should be prepared using the EU RMP template.

RMP updates outside another regulatory procedure should be submitted through the appropriate variation procedure. RMP updates resulting from PSUR assessments should also use a variation procedure because the MHRA PSUR portal cannot accept RMPs.

Additional Risk Minimisation Measures

The MHRA oversees additional risk minimisation measures (aRMMs) required for UK-authorised products.

These measures should be submitted to the MHRA for agreement before implementation. Where educational materials are involved, the materials and their distribution details should also be submitted. Differences in the approach for Northern Ireland should be discussed with the MHRA where applicable.

PSURs: How Often Do They Need to Be Submitted?

PSUR format and content follow GVP Module VI and the associated exceptions document.

Where a PSUR must be submitted to both the MHRA and EU, the expectation is that the same PSUR will be submitted to both. UK-specific information relevant to the benefit-risk assessment should be included in an appropriate annex.

UK PSUR frequency should continue to follow the EU Reference Date (EURD) list. If an active substance is removed from the list, the MAH should continue using the last frequency presented unless informed otherwise.

For actives or combinations not included on the EURD list, unless the MA specifies otherwise:

Period	PSUR frequency
First 2 years	At least every 6 months
Following 2 years	Once a year
Thereafter	Every 3 years

Products authorised under Article 10(1) or 10a do not require PSURs unless specific requirements are included in the MA.

GB vs Northern Ireland PSUR Submission

For Great Britain-only MAs, PSURs should be submitted through the MHRA PSUR portal.

For UK-wide or Northern Ireland-only MAs, PSURs should be submitted to the EU PSUR repository. Where the MHRA has access through that repository, separate MHRA submission is no longer required. The MHRA may request submission through its own portal in certain circumstances.

PASS: Post-Authorisation Safety Studies

The PASS requirements described in the guidance apply to non-interventional studies.

Where a PASS is an obligation or condition of the UK MA, the draft protocol should be submitted to the MHRA before the study starts. For Northern Ireland, the protocol should also be submitted to PRAC unless the study is conducted only in the UK at the MHRA's request.

For voluntary PASS, draft protocol submission is not specifically required unless the MHRA requests it for assessment. In that case, the protocol should be submitted as a Type II standard variation.

PASS Final Reports

Final reports for non-interventional PASS involving collection of safety data from patients or healthcare professionals should be submitted to the MHRA within 12 months of the end of data collection.

Applicable interim reports for PASS that are a condition of the UK MA should also be submitted. For Northern Ireland, applicable reports should additionally be submitted to PRAC unless the study was conducted only in the UK and not at PRAC's request.

Where PASS results affect product information, the changes should be submitted through a Type II variation.

Safety Referrals and MHRA Safety Reviews

UK products continue to participate in Union referral procedures for Northern Ireland.

For Northern Ireland, referral outcomes should be implemented through the relevant variation procedure. For Great Britain-only MAs, where an EU referral outcome needs to be reflected in the MA, the MAH should submit a Type II variation with the relevant referral documentation.

The MHRA may also conduct a major safety review where concerns could affect the positive benefit-risk balance.

The MHRA may also conduct other safety reviews in response to new safety signals or to support risk minimisation. The MHRA will provide the outcome and any wording that needs to be implemented.

Post-Authorisation Measures and Commitments

Post-authorisation measures and commitments in place on 1 January 2021 for converted EU MAs remain in place until fulfilled.

For MAs granted through the reliance route after that date, post-authorisation measures and commitments agreed for the EU MA also apply.

The guidance covers:

• Specific Obligations (SOB)

• Annex II Conditions (ANX)

• Additional pharmacovigilance activities in the RMP (MEA)

• Legally binding measures (LEG)

• Recommendations (REC)

Where information does not affect product information and is not submitted through another procedure, it can be submitted through the MHRA post-authorisation commitment route. Where it affects product information, an appropriate variation should be submitted.

EU Safety Outcomes and UK Product Information

MAHs should keep product information up to date with current scientific knowledge and continue monitoring EMA and HMA websites for relevant outcomes.

For UK MAs covering Northern Ireland, EU outcomes should generally be implemented unless otherwise advised.

For Great Britain-only MAs, MAHs are expected to follow EU outcomes and make the corresponding changes to the GB MA through the appropriate MHRA procedure. In exceptional circumstances, the MHRA may decide that a GB MA should not be updated in line with an EU decision and will inform the MAH within 14 days of publication of the EU outcome.

The reliance route can generally be used for implementing EU procedure outcomes for Great Britain-only MAs unless otherwise specified. However, reliance does not replace the MAH's pharmacovigilance obligations or responsibility to keep the MA current.

Safety Communications and DHPCs

The principles of GVP Module XV continue to apply to UK-authorised products.

The MHRA should be informed of planned safety communications as soon as possible, together with relevant documentation.

For Direct Healthcare Professional Communications (DHPCs), the content and communication plan must be agreed with the MHRA before dissemination in the UK.

Draft DHPCs should be sent to the MHRA for review. The final DHPC and communication plan should also be reviewed, and MAHs should wait for MHRA comments and agreement before UK dissemination.

Unfettered Access Route

For Great Britain-only MAs granted through the Unfettered Access route, pharmacovigilance obligations continue to apply.

MAHs must provide new information that may affect the terms of the MA or the product's benefit-risk balance, including relevant clinical trial information and data concerning use outside the MA terms.

Unless otherwise stated, the same data and submissions provided to the EU should also be submitted to the MHRA. These include:

• Serious suspectd adverse reactions

• Non-serious suspected adverse reactions occurring in the UK

• PSURs

• RMPs

• PASS protocols

• Final PASS study reports

• Other pharmacovigilance data submitted to the EU

For PSURs, the MHRA will accept copies submitted to the EU according to the EU frequency.

References

• Guidance on pharmacovigilance procedures — Medicines and Healthcare products Regulatory Agency (MHRA), updated 21 August 2026.