How to submit your periodic safety update report report (PSUR) or periodic benefit risk evaluation report (PBRER)
You must submit a periodic safety update report (PSUR) for all approved medicinal products in the UK (unless they are covered by the derogation given in the Human Medicines Regulations 2012, as amended).
The PSUR is a periodic assessment of the risk-benefit balance of the product. You need to do this irrespective of the marketing status of the product (whether it is placed on the market or not). The PSUR provides an analysis of the safety, efficacy, and effectiveness of the product over its lifecycle.
Most information will likely be related to safety, but you should include information on any new limitations of the medicine and alternative treatment areas.
You must not wait for the PSUR submission to notify us of significant new information relating to the safety and efficacy of your product.
In line with GVP IX requirements, standalone notifications of signals should be sent to the MHRA (email@example.com).
When a MAH becomes aware of an emerging safety issue, they should notify it in writing to the MHRA (firstname.lastname@example.org).
When to submit your PSUR
If you have just been granted a UK Marketing Authorisation (MA) you usually need to submit your PSUR:
- every 6 months until the product is placed on the market
- every 6 months for the first 2 years after the product is placed on the market
- once a year for the following 2 years
At least initially the UK will continue to follow the European reference date (EURD) list so check this for the exact submission date relating to the active substance in your product, which overrides the general cycle above. The cycle may also be different if you were given specific conditions when you applied for your MA. Although these deadlines have been set, MHRA may request a PSUR at where appropriate.
Any PSUR, for a UK MA, with a submission deadline after 1 January 2021 will require a separate submission to the UK.
The EU versions of the PSUR can be submitted, but where the UK 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. How this is presented will depend upon the nature of the data to be included. A specific template is not available at this time.
If you cannot find the submission date for your active substance on the EURD list the standard PSUR cycle should be followed.
Data lock points (DLPs)
Your specific submission date is based on your ‘data lock point’ which is the cut off point for preparing your report (the end of the cycle). If your submission date is not on the EURD list, it will be:
- 70 days after your DLP if your PSUR covers a period of 12 months or less
- 90 days after your DLP if your PSUR covers a period of 12 months or more
You may be able to use some of the same modules in the development safety update report (DSUR) and or risk management plan in the PSUR to minimise duplication and improve efficiency. See appendix D in the ICH guidelines for more information.
How to submit your PBRER
Under legislation introduced in July 2012, the EMA has established a repository for the submission of PSURs in the EU. This repository also provides safe storage for associated assessment reports, additional data and comments. From 13 June 2016 it will be compulsory for all PSURs to be submitted to the repository. This will apply for all products including those only approved in the UK. From 13 June 2016 there will no longer be submission of PSURs to the MHRA or any other national competent authority.
The repository is now available and you can submit your PBRERs directly to the repository. Repository use will be mandatory from 13 June 2016. From this date all PSURs must be submitted to the repository even if the product is only authorised in the UK. Up until the 13 June you should also submit your PSUR to the MHRA using current procedures.
Further information on the repository, including how to register to use the submission tools can be found here.
PSURs should be submitted through MHRA Submissions. You can be given access to MHRA Submissions by a company administrator in your organisation.
How to prepare your PSUR
You should continue to submit one PSUR covering your medicinal products with the same active substance or combination of active substances according to the EURD list. This should include all:
- authorised indications
- routes of administration
- dosage forms and dosing regiments
This applies even if the products have different names.
You should only submit separate PSURs for different products with the same active substance if this was agreed when your MA was granted. For example when there are different formulations of the active substance with significantly different indications.
You should follow the ICH guidelines and the Good pharmacovigilance guidelines (GVP VII) to prepare your PSUR.
The PSUR should:
- critically examine information received since your last PSUR to see if there are new signals that have led to potential or current risks or update information on previous risks
- summarise any new information on the safety, efficacy and effectiveness of the product that could affect its risk-benefit balance
- provide an integrated benefit-risk analysis from the date of an interventional clinical trial (in any country) for all authorised indications - if you don’t know the date or you can’t access the information use the earliest applicable date for clinical developments as a starting point
- summarise any risk minimisation actions implemented or planned during the reporting interval
- outline plans for signal or risk evaluations including timelines and/or proposals for additional pharmacovigilance activities
You should also include the results of any new studies carried out on the safety of your product around off-label use, with a summary of their impact.
Efficacy, effectiveness and safety information of the product
To help demonstrate this in your risk-benefit evaluation you need to include sources. These may include:
- non-clinical studies
- spontaneous reports (e.g. reports on the marketing authorisation holder’s safety database)
- active surveillance systems (e.g. sentinel sites)
- investigations of product quality
- product usage data and drug utilisation information
- clinical trials, including research in unauthorised indications or populations
- observational studies, including registries
- patient support programs
- systematic reviews and meta-analysis
- marketing authorisation holders’ sponsored websites
- published scientific literature or reports from abstracts, including information presented at scientific meetings
- unpublished manuscripts
- licensing partners, other sponsors or academic institutions and research networks
- competent authorities (worldwide)
You can include other sources outside of those above to demonstrate the risks and benefits of the medicinal product.
You do not need to submit routine PSURsif your medicinal product falls under some articles in the European Commission’s directive (2001/83/EC), unless there’s a specific condition in your MA or it’s indicated in the EURD list. These are:
- article 10.1 generic (previously article 10.1 a ii)
- article 10.a - well established use (previously article 4.8ii)
- article 14 - homeopathic medicine
- article 16a - traditional herbal medicine
See the European Commission’s directive (2001/83/EC) for more information.
A fee of £890 will be payable for the assessment of PSURs for actives/ combinations currently listed on the EURD or future UKRD. There will be a reduction in fee to £445 for each PSUR where more than one Marketing Authorisation Holder is involved in the procedure.
Following assessment, we will publish the outcome of PSUR assessment procedures. No further fee will be payable for the amendment of the product information as a result of the assessment, updates will be made by a Type IA variation.