On October 9, the Medicines and Healthcare Products Regulatory Agency (MHRA) updated its guidance on “Pharmacovigilance Procedures in the Event the UK Leaves the EU Without a Deal.” The most up-to-date version can be found here. Some fairly substantial changes have been made, including the addition of two sections, on “Post-Authorisation Measures” and on “The Implementation of Outcomes of Referrals and Procedures Concerning PSURs, PASS, Signal Assessments and PAMs.” This note provides a brief summary of the changes made. Note that references to “Brexit” in this note are to a no-deal Brexit; it is currently envisaged that if Britain leaves the EU with a deal, there will be a period of implementation in which the status quo is maintained.
The update makes four broad changes:
1. Additional UK-Specific Steps: Many of the changes relate to information that will need to be passed to the MHRA, rather than just to the European Medicines Agency (EMA), post-Brexit. In particular:
- Signal Detection: Signals arising from data sources – including standalone signal notifications submitted to the EMA and signals raised by the EMA – must be notified by marketing authorisation holders (MAHs) to the MHRA, so it can make UK decisions for those signals. Emerging safety issues should be notified to the MHRA within three working days.
- Periodic Safety Update Reports (PSURs): The MHRA will assess all PSURs for products authorised in the UK and will now require UK-specific information relevant to the benefit/risk assessment to be included in a specific annex to any PSURs submitted post-Brexit. Whilst MAHs will not as a rule have to resubmit PSURs previously submitted to the EU PSUR repository, the MHRA may request this in some circumstances. The MHRA will issue the outcomes of its assessments shortly after the publication of the EU assessment.
- Post-authorisation Safety Studies (PASS): Category 1 and 2 (imposed) studies at EU level (though not category 3 (non-imposed) studies) that are a condition of a UK market authorisation should be submitted to the MHRA. The MHRA has stated that it will need to conduct its own assessment, taking into account the UK clinical perspective, although it will take into account the EU assessment.
2. Risk Management Plans (RMPs) and Post-authorisation Measures (PAMs):
- RMPs: RMPs for authorised products should continue to be submitted to the MHRA via a Type II variation procedure; updates to the approved RMP should be submitted via a Type IB procedure.
- PAMs: New guidance has been included for PAMs. All PAMs will remain in place post-Brexit and will need to be submitted to the MHRA. The current application form for PAMs should be used and submitted to the MHRA as a post-authorisation commitment. Where an assessment has not been concluded, but where data relating to a PAM has already been submitted pre-Brexit, the MHRA will conclude the assessment. Where an MAH’s evaluation of data suggests that an update to the product information is required, this should be submitted via a Type II variation application.
3. Variation Procedures: New guidance has also been added relating to the implementation of variation procedures where amendments are required as a result of the procedures set out in the guidance. Where a signal assessment, PSUR, PASS or PAMs procedure has been concluded pre-Brexit, and a variation is required but has not yet been submitted, the outcome will be implemented by the same procedure as for the EU (i.e., Type IA, Type IB or Type II). The UK will conclude variations in line with the outcome of the procedure, where the variation has been submitted but not finally processed in the UK pre-Brexit. Finally, where there has been no EU decision pre-Brexit, the MHRA will carry out its own assessment, with its outcomes published together with its advice on implementation. The UK outcome should be followed, and where a variation is required, the MAH will be notified regarding the type of variation required.
4. New Submission Portals: Reference to the new MHRA-Gateway and ICSR Submissions portal has also been added to the guidance. These portals should be used in the event of Brexit to submit any pharmacovigilance documents to the MHRA. Registration for these portals should be made as early as possible. Further, the MHRA has developed its own PSUR submission portal for use post-Brexit. It should be used to submit PSURs to the MHRA – though note that it should not be used to submit PSURs as part of the CTD lifecycle in the UK, nor as part of the initiating sequence in the conversion process for centrally-authorised UK market authorisations.