Overview

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 (signalmanagement@mhra.gov.uk).

When a MAH becomes aware of an emerging safety issue, they should notify it in writing to the MHRA (signalmanagement@mhra.gov.uk).

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 PSUR

PSURs should be submitted through PSUR portal using 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.

Risk-benefit evaluations

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 (for example, reports on the marketing authorisation holder’s safety database)
active surveillance systems (for example, 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.

Exemptions

You do not need to submit routine PSURs if 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.

Fees

Find out more about the fees we charge at MHRA fees.

A fee 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 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.

Periodic Safety Update Reports (PSURs) for medicinal products