Following the news and updates from the MHRA and to ensure that all the involved parties can prepare for the new scenario, the Agency has published a guidance on QPPV including PSMF from 1 January 2021.
As you already are aware of, the United Kingdom (UK) left the European Union (EU) and the transition period after Brexit comes to an end this year. Following with the news and updates from the Medicines and Healthcare products Regulatory Agency (MHRA) – the UK’s standalone medicines regulator from January 1st, 2021 – and to ensure that all the involved parties can prepare for the new scenario, the Agency has published a guidance on qualified person responsible for pharmacovigilance (QPPV) including pharmacovigilance system master files (PSMF) from 1 January 2021.
From this date, the following legal obligations will apply to holders of UK marketing authorisations (MA). These include those that cover the whole of the UK, or are specific to Northern Ireland (NI) or to Great Britain (GB) (England, Wales and Scotland):
QPPV
- Must reside in the EU or the UK [regulation 182 of the Human Medicines Regulations 2012 (as amended) (MHRA)]
- Module I of Good Pharmacovigilance Practices (GVP) will be supplemented by the document ‘Exceptions and modifications to the EU guidance on good pharmacovigilance practices that apply to UK marketing authorisation holders’, which will be published in due course.
- For QPPV residing in the EU, a National contact person for pharmacovigilance (PV) in the UK shall be appointed.
- Reports to QPPV
- Has access to reports of suspected adverse reactions and PSMF
- Responds queries raised by the MHRA
- 12 months from 1 January 2021 to be appointed (further guidance will be published)
PSMF
- MAHs (with authorisations covering whole UK or specific to NI or GB) shall make the PSMF available upon request of the MHRA.
- PSMF must be located in the EU where the main activities are performed or at the site where the QPPV operates.
- Must be accessible from the UK.
- A single PSMF can be used for all UK authorised products (provided the PV systems is the same).
- PSMF number to be requested via MHRA Submissions Portal from 1 January 2021
- Changes in the details of the QPPV for the UK should be notified to the MHRA first before requesting an UK PSMF number.
PHARMACOVIGILANCE PROCEDURES
GVPs will remain in force but guidance notes will be published by MHRA.
GB (England, Wales, Scotland) → PV data (ICSRs, PSURs, RMPs, PASS) submitted to MHRA.
- All ICSRs (serious and non-serious) and serious ICSRs from other countries submitted via the new MHRA Gateway or/ ICSR Submission portal.
- QPPV Registration prior to 2021 (Residing in either UK or EU).
- MHRA needs to be notified of signals arising from any source (including standalone signals notified to the European Medicines Agency (EMA) or raised by EMA).
NI → Aligned to EU regulation. Respond and report to EU.
- Notify to EMA signals considered emerging safety issue
MA covering both GB and NI will need to report to both GB and EU!
Signals: MHRA will assess signals (identified by MHRA or highlighted internationally) and issue decisions.
Risk Management Plans (RMPs): MHRA will accept EU version of RMPs but specific information requests may be made.
- For CAPs the current approved version of the RMP should be included in the initiating sequence as part of the conversion process
Periodic Safety Update Reports (PSURs):
- EU format still accepted but additional info may be requested.
- EURD list to be followed until UK’s submission requirements and submission reference dates is developed.
- Submission dates after 1 January 2021 submitted to the UK and the EU (except for GB-only MAs and NI-only MAs)
- Single assessment process like submission (single PSUR for same substance).
- Products not currently included in the EURD list should submit PSUR (every 6 months for 2 years, then 1 year for the following 2 years, then every 3 years).
- Assessment fees will be charged (£890)
- PSURs submitted before 2021 but assessment not concluded → UK will assess considering info and EU decisions and may request further info.
- Assessment concluded but outcome not implemented → MHRA will be responsible
Post Authorisation Safety Studies (PASS):
Protocols and results submitted after 1 January 2021:
- Draft protocols submitted to MHRA prior to study start. (Also submitted to PRAC when concerning NI).
- Same applies for final study report (except when study was only conducted in the UK after MHRA request).
- Fee of £8309 for protocols or final report. Submission via Type II complex variation route (C.I.13).
Ongoing issues regarding PASS protocols after 1 January 2021:
- For UK authorised products where PRAC has either endorsed draft study protocol or an amendment to draft protocol, MHRA will accept the changes.
Ongoing issues with PASS final study reports after 1 January 2021:
- If no recommendations are made by EMA before 2021, the report should be submitted to the MHRA.
Safety Referrals:
MHRA will complete assessment of procedures started but not concluded before 2021, considering any decision made by the EU prior to 2021.
Major safety reviews:
- MHRA will conduct major safety reviews when concerns arise. Results and actions announced publicly but also notified to QPPV (different or additional contact for future correspondence can be nominated).
- Different fees available.
Post-authorisation measures:
- Post-authorisation obligations in place on 1 January 2021 will remain in place.
- For converted EU MAs, the current forms for PAMs can be used (same submission principles as for CAPs conversions). A copy of the application should be included in the data submission package.
- MHRA will conclude assessment of data submitted prior to 2021.
Implementation of outcomes from PSURs, PASS, Signal assessments and PAMs
- Amendment of product information → via variation procedure (same procedure as for EU if variation not submitted prior to 2021)
- Variation submitted but not concluded before 2021 → conclusion in line with outcome of procedure.
- MHRA will carry out assessment when no decision has been taken.
Asphalion, an International Scientific and Regulatory Affairs Consultancy, offers regulatory solutions in the UK and can ease your path through this transition, advising you each step of the way.
For further information or support on this topic, ASPHALION’s PV contact in the UK (Maria Molist) is always on hand to help you. Do not hesitate to contact us at london@asphalion.com
