Mitigation explainer: Pharmacovigilance
Explainer for the pharmaceutical industry on Pharmacovigilance requirements mitigations to bridge the gap between the implementation of the EU Regulation on veterinary medicines and the revised Veterinary Medicines Regulations as they have an effect in Great Britain (GB VMR).
Mitigations for Veterinary Medicines Regulations
EU Regulation 2019/6 will apply in the EU from 28 January 2022. We played an active role in developing and negotiating the Regulation when we were part of the EU and therefore agree with much of its content.
The GB Veterinary Medicines Regulation (VMR) is under review and will undergo a formal public consultation. Until such time that the revised GB VMR come into force, there will be what we call an “airgap” between both sets of legislation covering EU (NI) and GB.
We recognise that industry is set up to cover the region of Europe, which includes the UK, and its regulatory requirements. As an interim measure we have considered areas where we may bridge this gap between the EU Legislation and the current VMR, as they have an effect in GB, whilst still respecting both sets of legislation to reduce burdens to the industry and help facilitate the continued availability of veterinary medicines in NI and GB.
IMPORTANT: This is an interim measure and does not pre-empt or prejudice the outcome of the formal consultation on the GB VMR as we will take account of views from a wide range of stakeholders.
There are significant changes to pharmacovigilance requirements in EU Regulations 2019/6. Most notably the move from Periodic Safety Update Reports (PSURs) to place a greater reliance on signal detection, and the move from submitting the Detailed Description of the Pharmacovigilance System (DDPS) with each Marketing Authorisation in favour of a Pharmacovigilance System Master File (PSMF) approach.
Adverse event reporting
During the airgap Marketing Authorisation Holders (MAHs) are still required to comply with VMR 2013 and must submit all UK cases of serious, human and transmission of infectious agents adverse events within 15 days of becoming aware.
There is no requirement to submit all other UK adverse events to the VMD, but these must be recorded and can be submitted within 30 days if MAHs wish to follow the same processes as they would do for submission to the EU.
Causality assessments will no longer be required.
Serious adverse events
The definition used for serious adverse events by the VMD is taken from VICH GL24:
A serious adverse event is any adverse event which results in death, is life-threatening, results in persistent or significant disability/incapacity, or a congenital anomaly or birth defect. For animals managed and treated as a group, only an increased incidence of serious adverse events as defined above exceeding the rates normally expected in that particular group is considered a serious adverse event.
Northern Ireland reports
Adverse events cases occurring in Northern Ireland should continue to be reported to the VMD and should follow the recommendations of the GB pharmacovigilance guidance.
Third country reports
From 1 January 2022 MAHs are no longer required to submit non-UK cases to the VMD on an expedited or routine basis. This applies to both serious and non-serious adverse events. Data from third country adverse events must be kept by MAHs in their systems. We reserve the right to request these data when needed to assess the benefit:risk balance of a product.
If third country data are requested for particular products, we will ask for these in the form of line-listings and sales data. Submission deadlines for these ad hoc requests will be agreed between the MAH and VMD at the time.
Third country data will also be required as part of the PSURs submissions (see section below: PSURs during airgap).
Third country adverse events reported after 28 January 2022 will not be processed, and you will not receive an acknowledgement for these.
Format of the reports
We are currently updating our systems and we will notify you when the system is ready for MAHs to submit AERs using the VICH HL7 format. We are looking for companies to take part in testing the new schema format now. If you are ready for testing and wish to do so email adverse.events@vmd.gov.uk.
In the meantime, we will continue to use the current DEG xml format for both receiving and sending AERs.
You will not be able to upload xml files with VICH HL7 format through the VMDS AER system, but you can submit these via secure messaging.
Adverse event report reference number
From 28 January 2022 the format of worldwide case reference numbers is changing. These reference numbers will be known as the ‘Unique Adverse Event Report Identification Number’ (AERID) and made up of:
- country of occurrence code (3 characters)
- your MAHORGID (8 characters)
- remaining free text (up to 47 characters, which can include your routing ID)
For example: GBR-VMDDEFRA-ITCHFIX2022001
The 3-character country code and the 8-character MAHORGID should be used for all AERs. The remaining free text (up to 47 digits) can include the MAHs’ routing ID as required by the EMA for EU reporting.
Cases from Northern Ireland should use the GBR country of occurrence code.
If you do not have a MAHORGID, or are unsure if you have one or not, email adverse.events@vmd.gov.uk for help before submitting your report.
PSURs during airgap
To comply with VMR 2013 MAHs will still need to submit the PSURs for their products.
The information provided within these PSURs will have to comply with the provisions of VMR 2013. To ensure compliance with these requirements, MAHs are strongly recommended to follow the GB PSUR template or VICH GL29 format and read VMD guidance on PSURs
Third country data will still have to be included in your PSURs as per current requirements.
The dates and deadlines for the submission of PSURs have not changed. MAHs will have to submit the PSURs following 6 months, 1 year or 3 years after their last data lock point (DLP), depending on the situation of each product, but you can align your PSUR submission dates with your EU submission dates.
Aligning your PSUR and EU submission dates
Once the EMA has published the due dates for the annual benefit-risk assessment conclusion of the signal detection analysis, MAHs might wish to align their submissions dates for products that are authorised both in the UK and the EU. To do this, you will have to notify the VMD by email to psur.submissions@vmd.gov.uk and provide justification about why you want to change your submission dates in the UK. Your PSUR will still have to include all the information collected since the DLP of your last PSUR submitted to the VMD, including information from third country adverse events and sales data.
MAHs will also be able to change the PSUR cycle of their marketing authorisations to be in line with the annual benefit-risk assessment provided to the EU. For those on a 3-yearly cycle, you can voluntarily submit on an annual basis at the same time as EU signal detection submission. For those products on a 6-monthly schedule, you can request to move to annual submission.
Moving to Signal Management System
For products with a DLP after 28 January 2022, after submission of a PSUR during the airgap, MAHs may wish to move on to the new Signal Management System in a similar way as they would do in the EU. If so, you will need to notify the VMD by sending a “closing” PSUR. The change to the Signal Management System should be specifically mentioned in a cover letter included in the closing PSUR submission.
Once you decide to move on to the new Signal Management System, all adverse events occurring in the UK will need to be reported to the VMD. Serious, human and transmission of infectious agents AEs will have to be sent to the VMD within 15 days, and all other AERs are expected to be sent within 30 days, after becoming aware of the event. MAHs moving on to the Signal Management System will have to provide an annual benefit-risk assessment conclusion of the signal detection analysis carried out during the year. More information will be provided in due course about submissions to the VMD of this annual benefit-risk assessment.
You do not have to move on to the new Signal Management System and can continue to send PSURs as you do now. However, please be aware that following the revision of the VMR 2013, it is probable that this system will need to be implemented in the future by all MAHs.
Contents of the closing PSUR
The content and format of a closing PSUR should be the same as normal PSURs but you must specifically mention that you intend to change to the Signal Management System in a cover letter included in the closing PSUR submission.
PSURs and renewals
MAHs will no longer need to submit PSUR with their renewal applications.
DDPS and PSMF
MAHs can choose to continue with the current DDPS requirements or provide a Pharmacovigilance System Master File (PSMF) summary in its place. The full PSMF will need to be available for inspection. The format for the GB PSMF is largely the same as will be for the EU PSMF. Specific information can be found in the Requirements for PSMF and the PSMF summary
Using your EU PSMF for UK/GB marketing authorisations
MAHs will be able to use their EU PSMF for their UK/GB marketing authorisations. However, additional information will need to be provided regarding specific aspects of the GB processes that might be different than those followed in the EU, such as PSUR submissions or deadlines for submissions of serious adverse events. Specific information can be found in the Requirements for PSMF and the PSMF summary.
Variations to DDPS/PSMF
MAHs can switch from their DDPSs to the PSMF without the need to submit variations. MAHs wishing to do so, should inform VMD at a.tout@vmd.gov.uk and adverse.events@vmd.gov.uk and submit their PSMF summary.
For MAHs that continue with a DDPS, if you submit a variation application for any reason, we will consider whether we can apply a reduced fee to cover all changes rather that a flat fee for each product. This will be considered on a case-by-case basis.