Summary – MHRA updated guidance on pharmacovigilance procedures

The United Kingdom (UK) formally left the European Union (EU) on 31 January 2020 and since that time has been in a transition ‘phase’. This transitionary phase, which is due to expire on 31 December 2020, has given pharmaceutical companies time to make the necessary changes to ensure that their centrally and nationally authorised medicines comply with EU law and can remain in the EU market, as well as to prepare those medicines authorised in the UK for compliance with UK law once the UK leaves the EU legal framework for the regulation of medicines.

The UK government has published updated guidance on pharmacovigilance procedures and the submission requirements for pharmacovigilance data effective from 1 January 2021. This guidance highlights those notable changes in the submission requirements of pharmacovigilance data and can be found here: https://www.gov.uk/government/publications/guidance-on-pharmacovigilance-procedures/guidance-on-pharmacovigilance-procedures

Summary Points:

General Approach to the operation of pharmacovigilance:

• The UK’s regulatory authority for medicines and medical devices (Medicines and Healthcare products Regulatory Agency or ‘MHRA’) retains responsibility for pharmacovigilance across the UK. There will be some amendments in requirements for products placed in the market in the UK with respect to Great Britain and Northern Ireland.
• The Marketing Authorisation Holder (MAH) for medicines authorised in Great Britain will be required to submit pharmacovigilance data to the MHRA, according to Great Britain requirements which includes UK and non-UK Individual Case Safety Reports (ICSRs), Periodic Safety Update Reports (PSURs), Risk Management Plans (RMPs), Post-Authorisation Safety Studies (PASS) protocols and final study reports.
• For medicines authorised to be sold or supplied in Northern Ireland, information will be submitted according to EU requirements, whereas for medicines which hold UK marketing authorisation (MA) covering both Great Britain and Northern Ireland information will be submitted in accordance with both UK and the EU requirements.

Actions for submitting and receiving ICSRs:

• The new MHRA Gateway or/ICSR Submissions portal will be used for submissions of all UK ICSRs (serious and non-serious) and serious ICSRs from other countries.
• For products placed on the market in Northern Ireland, ICSRs need to be submitted according to EU requirements to the Eudravigilance database including all serious reports from the UK and other countries and non-serious reports that occur in the EEA or in Northern Ireland. These cases are identified by using the country code “XI” in the field primary source country for regulatory purposes.
• For UK cases that relate to Northern Ireland which were initially submitted before 1 January 2021, the worldwide case ID should not be changed, however, in line with GVPmodule VI guidance when sending follow-up reports the organisations can change the safety report case ID if needed.
• The country code “GB” should be used for all reportable SUSARs occurring in the UK. Although it is possible for organisations to use the country code “XI” for SUSAR reporting, it will not be a requirement as reporting requirements between Northern Ireland and the rest of UK for clinical trial cases will not differ.

Signal Detection:

• As per the current EU Good Pharmacovigilance Practice (GVP) requirements, signal detection systems should be inbuilt for cumulative signal detection across all available data sources and the MHRA will make available UK data for inclusion in signal detection activities.
• Standalone notifications for signals identified as emerging safety concerns must be submitted to the MHRA within 3 working days, as well as EMA (for medicines authorised to be sold or supplied in Northern Ireland)
• The MHRA will carry out assessment of signals and issue decisions for both signals identified by the MHRA and those highlighted internationally.

Risk Management:

• The MHRA will continue to accept EU versions of the RMP, but any specific information requested will be provided in a specific annex.
• For EU products authorised under centrally approved procedure, the current approved version of the RMP should be included in the initiating sequence as part of the conversion process.

PSURs:

• The MHRA will continue to accept EU versions of the PSUR, but where the MHRA has made a specific request for information or where there is UK-specific information relevant to the benefit/ risk assessment this should be included in a specific annex.
• PSURs should be submitted to the UK (via the new eSubmission Portal) at the same time as submission to the EU (if applicable), PSUR assessment fees will be applicable, payable by the MA Holder(s).
• All PSURs, for products which hold UK MA, with the same active/combination, should be submitted as part of the same procedure. The content and format will remain the same as currently required in the EU, and the same PSUR will be submitted to the MHRA as to the EU.
• PSURs for UK MAs covering both Great Britain and Northern Ireland will be submitted to both the MHRA and EMA.
• Where the PSUR is for a product authorised by under UK MA with respect to both Great Britain and Northern Ireland, the EU single-assessment procedure will continue. Where the assessment has been concluded but the outcome not implemented before 1 January 2021, the MHRA will take the necessary steps to implement the outcome.
• PSURs for actives/combinations not currently on the EURD list and therefore not subject to the single assessment process should be submitted to the MHRA, at least six monthly during the first 2 years following placing on the market, once a year for the following 2 years and every 3 years after that

Post Authorization safety studies:

• For all PASSs that are non-interventional, that are either voluntary or a condition of the MA and which involve collection of safety data from patients/healthcare professionals, final study reports must be submitted to the MHRA for assessment within 12 months of the end of data collection.

Safety Referrals 

• For safety referrals started but not concluded before 1 January 2021, such as where a CHMP/CMDh opinion had not been reached, the MHRA will complete the assessment, where appropriate.

Major Safety Reviews

• 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.
• Fees will be incurred, payable by MA holder(s) for major safety reviews conducted by the MHRA.

Post-Authorisation Measures (PAMs)

• Post-authorisation obligations, including specific obligations, Annex II conditions, and additional pharmacovigilance activities in the RMP, legally binding measures or recommendations will remain the same.

Amendments to Product Information

• Where an amendment to the product information is required as a result of referrals/major safety reviews, or procedures relating to PSURs, PASSs, signal reviews or PAMs, the outcome will be implemented via a UK MA variation procedure.
• For ongoing reviews where no EU decision was made before 1 January 2021, the MHRA will carry out its own assessment where appropriate and the outcomes of assessments will be published together with advice on implementation