Guidance on qualified person responsible for pharmacovigilance (QPPV) including pharmacovigilance system master files (PSMF)

The following legal obligations apply to holders of UK marketing authorisations (MA). These include those that cover the whole of the UK, or are specific to Northern Ireland or to Great Britain (England, Wales and Scotland), including Great Britain MAs granted to allow unfettered access from Northern Ireland.

• To operate a pharmacovigilance system for UK authorised products
• To have an appropriately qualified person responsible for pharmacovigilance (QPPV) that resides and operates anywhere in the UK or in the EU/EEA and is responsible for the establishment and maintenance of the pharmacovigilance system for UK authorised products
• To maintain and make available upon request a pharmacovigilance system master file (PSMF) that describes the pharmacovigilance system for UK authorised products. The PSMF must be accessible electronically from the UK at the same site at which reports of suspected adverse reactions may be accessed

Guidance on the QPPV for UK authorised products

For all UK MAs, including those that cover the whole of the UK or are specific to Northern Ireland or to Great Britain, the marketing authorisation holder (MAH) must have permanently and continuously at its disposal a QPPV who resides and operates anywhere in the UK or in the EU/EEA, and is responsible for the establishment and maintenance of the pharmacovigilance system (“the UK QPPV”). Where the QPPV is not in the UK, there will be a need for a national contact person for pharmacovigilance as set out below.

This is provided for by regulation 182 of the Human Medicines Regulations 2012 (as amended) (HMR).

For MAs that cover the whole of the UK or are specific to Northern Ireland, the legal requirements concerning the qualifications and responsibilities of the QPPV that are outlined in Article 10 of the Commission Implementing Regulation (EU) No 520/2012 (CIR) will remain unchanged.

For MAs that are specific to Great Britain, legal requirements concerning the qualifications and responsibilities of the QPPV are outlined in paragraph 10 of HMR Schedule 12A (inserted by the EU Exit Regulations 2019), which mirrors Article 10 of CIR.

Statutory guidance concerning the QPPV for UK authorised products is described in the Good Pharmacovigilance Practices (GVP) Module I. This guidance is supplemented by the Exceptions and modifications to the EU guidance on good pharmacovigilance practices that apply to UK marketing authorisation holders.

There is no temporary exemption as to the requirement to have a QPPV who resides and operates in the UK or the EU/EEA and is responsible for the pharmacovigilance system for UK authorised products.

National contact person for pharmacovigilance

If you choose to establish a QPPV who resides and operates in the EU/EEA, you must nominate a national contact person for pharmacovigilance who resides and operates in the UK and reports to the QPPV. This individual should have access to the reports of suspected adverse reactions referred to in regulation 187 of the HMRs and the PSMF for UK authorised products. The individual should be able to facilitate responses to pharmacovigilance queries raised by the MHRA, including via inspections.

There will be a temporary exemption in place which allows you 12 months from 1 January 2021 to appoint a national contact person for pharmacovigilance that resides and operates in the UK.

Once the national contact person for pharmacovigilance has been appointed, their details should be notified to the MHRA via the MHRA Submissions Portal. You should follow the instructions for submitting these details. You should receive a confirmation by email immediately upon completion of the form.

There is no requirement to appoint a deputy for the UK national contact person for pharmacovigilance, but for periods of extended absence greater than one month (such as maternity leave, long-term sick leave, etc.), it is expected that another individual is assigned as the national contact person for pharmacovigilance and their details should be notified to the MHRA within two weeks of the change. In practice, this means editing the existing details of the national contact person for pharmacovigilance that are saved in the MHRA Submissions portal.

Guidance on the PSMF for UK authorised products

For all UK national MAs, including those that cover the whole of the UK or are specific to Northern Ireland or to Great Britain, the MAH must maintain, and make available upon request of the MHRA, a PSMF that describes the pharmacovigilance system for UK authorised products (‘the UK PSMF’).

PSMF accessibility in the UK

All UK PSMFs must be accessible electronically at the same point in the UK from which the reports of suspected adverse reactions referred to in regulation 187 of the HMRs are accessible. This requirement applies from 1 January 2021.

The PSMF needs to be permanently and immediately available for inspection at the stated location in the UK.

PSMF format, content and representation of pharmacovigilance systems

For MAs that cover the whole of the UK or are specific to Northern Ireland, the legal requirements concerning the format and content of the PSMF that are outlined in Chapter I of CIR will remain unchanged.

For MAs that are specific to Great Britain, legal requirements concerning the format and content of the PSMF are outlined in Part 1 of Schedule 12A of HMR, which mirrors Chapter I of CIR.

As the legal requirements concerning PSMF format and content are identical for MAs that cover the whole of the UK and Northern Ireland, and those that are specific to Great Britain, a single UK PSMF can be used for all UK authorised products. This is assuming that the pharmacovigilance system applied to all products is the same.

Statutory guidance concerning the PSMF for UK authorised products is described in GVP Module II. This guidance is supplemented by the Exceptions and modifications to the EU guidance on good pharmacovigilance practices that apply to UK marketing authorisation holders.

The UK PSMF must describe the global pharmacovigilance system and reflect the global availability of safety information for UK authorised products.

As per GVP Module II, there are different approaches to establishing a pharmacovigilance system. For example:

• MAHs can establish more than one pharmacovigilance system
• A pharmacovigilance system can be shared by several MAHs

The UK PSMF should be an accurate representation of the pharmacovigilance system that has been established and you must make sure that every pharmacovigilance system covering UK authorised products has been assigned a unique PSMF number by the MHRA.

How to request a UK PSMF number

All PSMFs that cover UK authorised products should be registered with the MHRA. You should request a unique UK PSMF number from the MHRA for each pharmacovigilance system that you are operating for UK authorised products. Where the pharmacovigilance system is shared by several MAHs, a single request for a UK PSMF number should be submitted to the MHRA.

A UK PSMF number can be requested via the MHRA Submissions Portal. You should follow the online instructions for requesting a UK PSMF number and you should receive the number by email immediately upon completion of the form. The address from which the PSMF can be electronically accessed must be in the UK. Your UK PSMF number will be invalidated if the address provided is not in the UK. Any submissions to the MHRA using an invalidated UK PSMF number will not be accepted.

The UK PSMF number will be sent to the UK QPPV email address as well as the email address you nominated on the UK PSMF number request form. If you have not received a confirmation email within three hours of submitting the form, please contact submissions@mhra.gov.uk. Please do not re-submit the form as this will cause delays in processing your request.

Once a UK PSMF number is assigned to a pharmacovigilance system it should remain unchanged, irrespective of how the system may change and evolve over time. You should not request a new UK PSMF number if there are changes to the pharmacovigilance system, including a change of UK QPPV.

You do not need to update the initial information that was provided in the online form at the time of requesting your UK PSMF number (e.g. QPPV telephone number, MAHs covered by the pharmacovigilance system, etc.). This information is solely for the purpose of generating and allocating a unique UK PSMF number at a specific point in time. You must maintain the pharmacovigilance system information for your UK licences via the submission of the appropriate variations to the MHRA. Guidance on this process is provided below.

Guidance for applicants for UK marketing authorisations

The material to accompany an application for a UK marketing authorisation includes a summary of the applicant’s pharmacovigilance system (SPS).

This must include the following elements:

1. proof that the applicant has at their disposal an appropriately qualified person responsible for pharmacovigilance who resides and operates in the EU or the UK,
2. the country (which must be either the UK or a Member State) in which the appropriately qualified person resides and carries out his or her tasks
3. the contact details of the appropriately qualified person
4. a statement signed by the applicant which says that they have the necessary means to fulfil the tasks and responsibilities listed in Part 11
5. a reference to the location where the pharmacovigilance system master file for the medicinal product can be accessed electronically, which must be in the UK

The SPS should also include the UK PSMF number.

The above is following HMR Schedule 8.

Guidance on the application process and on registering to make submissions via the MHRA Submissions Portal is available.

You should use Agency Activity Reference ID: G0001 – Initial Marketing Authorisation Application and Subactivity Text: H002 – “Original Submission”.

Information on the QPPV and PSMF for UK authorised products should be entered in section 2.4.4 of the electronic application form (eAF). You should note the following:

• if the QPPV for UK authorised products resides and operates in the UK, the checkbox entitled “The above-mentioned qualified person resides and operates in the EEA” can remain unchecked.
• the UK location where the PSMF can be accessed from does not need to be registered in the Article 57 database, therefore the associated checkbox can remain unchecked.

For UK licence applications via mutual recognition or decentralised procedures, the UK SPS should be included in module 1.8.1 as a standalone file or alternatively under a UK subfolder.

Notification of QPPV and PSMF details to the MHRA by existing holders of UK marketing authorisations

This guidance replaces the previous requirement to submit a Type IA(IN) variation and an accompanying eCTD sequence followingto updatesmake these changes. This has been simplified and only an update notification is required, there is no requirement to submit an eCTD sequence. This guidance applies from 11 May 2023

The summary of Pharmacovigilance System (sPS) is a signed declaration by both the QPPV and the MAH. It contains the MAH details (i.e. Company name and address), the QPPV details (i.e. QPPV name and Contact address), the location in UK where the PSMF can be accessed and the UK QPPVPSMF information.number. NewThe procedureseCTD place holder for the sPS is module 1.8.1.

Changes have now been designedmade to simplifythe processesway MHRA should be notified of updates to notifythe QPPV and PSMF details by licence holders.

Module 1.8.1 of the MHRAeCTD product lifecycle will only need to be updated when the PSMF is replaced or a new PSMF is registered. The registration or replacement of thesea typesPSMF will still require a new UK PSMF number. All new Marketing Authorisation application will continue to require the inclusion of changes.a ThissPS guidanceunder appliesmodule from1.8.1. 11When Maythe 2023.PSMF is replaced because of a change of ownership, the new MAH must include a copy of the new sPS under module 1.8.1 of the COA dossier. A Type IA C.I.8.a variation will no longer be required when a new PSMF is introduced or replaced because of a Change of Ownership.

The following changes to the SPSsPS will no longer require the submission of a Type IA variation to update the SPSsPS but can be submittedupdated via ana Updatenotification Notification:update:

• The UKChanges to the MAH details (i.e. Company name and address) as specified in the sPS
• The QPPV details (i.e. UKdetails (i.e. QPPV name, addressname and contactContact details)address)
• The location in UK where the UKthe PSMF can can be electronically accessed.

To make these changes, a UK only SPSsPS Update Notification, covering the affected product licences (PL)), under a unique pharmacovigilance system, mustneeds to be submitted to the UK to register these changes. changes. An updated eCTD sequence is not required. There is currently no fee for SPSsPS Update Notifications. A Notification of Acceptance letter will be issued once finalised on our systems. SPSsPS Update Notificationsnotifications will be processed within 30 days of receipt of the notice.application.

How to make a SPSsPS Update Notification

All notificationsapplications to update the SPSsPS are required to be submitted as an SPSsPS Update Notification via the the MHRA Submissions Submissions Portal immediately followingsoon implementation,after thisimplementation: * would be expected to be submitted within 14 days. The notification should be made within the following links in the portal:

• Agency Activity Reference ID G0109: Summary of Pharmacovigilance System Update Notification - UK-QPPV-PSMF
• * Subactivity Text: H002 – “Original Submission” must be selected.

You must submit your SPSsPS Update Notifications outside of the eCTD product lifecycle, in collections of no more than 25 25 PLs and and you should submit no more than one collection in a single package.

Documentation you need to supply:

You mustshould supply the following documentation for ana SPSsPS Update Notification:

1. Cover letter (in PDF format) detailing the changes being made.
2. SPS-Update-Notification-formsPS-Update-Notification-form (in Excel format). Please Please download a copy from here and and complete sections A,A B and C.B.

The SPSsPS (in PDF format)format), shouldwhich be a single document and must include the following elements.

information:

1. proof

   a. Proof that the applicant has at their disposal ana appropriately qualified person responsible for pharmacovigilance whoand residesa statement signed by the applicant to the effect that the applicant has the necessary means to fulfil the tasks and operatesresponsibilities listed in the EUPart 11 HMR or 2012. A signed sPS by both the UK,

2. QPPV and the MAH will suffice.

   b. The country (which must be either the UK or a Member State) in which the appropriately qualified person for pharmacovigilance resides and carries out their histasks.

   c. orContact her tasks

3. the contact details of the appropriately qualified person
4. a statementfor signedpharmacovigilance who byresides the applicant which says that they have the necessary means to fulfil the tasks and responsibilitiesoperates listed in Partthe 11EU ofor the HumanUK.

   d. MedicinesA Regulation 2012 as amended

5. a reference to the location where the pharmacovigilancePSMF system master file for the medicinal product can be accessed, accessed electronically, which must be in the UK

UK.

The SPS shoulde. alsoUK include the UK PSMF number. number

Failing to supply all required documentation and information may lead to a rejection of the notification, SPS changes, which will require you to make a resubmission addressing all discrepancies.

A Notificationnotification of Acceptanceacceptance letter will be issued when we have made the changes on our system.

Please note that any eCTD sequence submitted will be discarded as it is not required as part of this process.

Changes to the UK PSMF numberContact

ChangesGeneral queries relating to the UKQPPV, PSMF (andand associatedestablishment information) for product licences (PLs) made due to change of ownershippharmacovigilance systems mayfor beUK submittedauthorised asproducts partshould of the Change of Ownership (COA) dossier or may be submittedsent following grant of the COA application: (whether this has resulted in a change to the UK PSMF number or not)gpvpinspectors@mhra.gov.uk.

1. If

   Queries yourelating wish to submit the changes to the UK PSMF number forshould a PL as part of a COA application, a copy of the updated SPS may be includedsent under module 1.8.1 of the COA dossier. This update should also include information regarding changes to the UK QPPV details and UK location of the UK PSMFUKPSMFadmin@mhra.gov.uk.

   Queries Anyrelating subsequent changes to thesubmission UK PSMF number or other details of theType SPSIA followingvariations grant of the COA should be notifiedsent to thevariationqueries@mhra.gov.uk

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   mail@ccra.org.uk

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Notification of QPPV and PSMF details to XEVMPD

From 1 January 2021, for products in respect of Northern Ireland (UK-wide and Northern Ireland-only MAs), in addition to notifying the QPPV and PSMF details to the MHRA, you must submit information on the UK QPPV and the EU location of the UK PSMF to the Article 57 database in accordance with Regulation (EC) No 726/2004 Article 57(2).

Pharmacovigilance requirements for UK authorised products webinar recording, which took place on 13 January 2020. This webinar was part of a series of Brexit and post-transition guidance webinars:

Pharmacovigilance requirements for UK authorised products webinar recording, which took place on 13 January 2020:

Post transition: Pharmacovigilance requirements for UK authorised products webinar recording, which took place on 22 October 2020:

Pharmacovigilance requirements for UK authorised products webinar recording, which took place on 22 October 2020.

This webinar was part of a series of EU Exit and post-transition guidance webinars.

Contact

General queries relating to the QPPV, PSMF and establishment of pharmacovigilance systems for UK authorised products should be sent to gpvpinspectors@mhra.gov.uk

Queries relating to the UK PSMF number should be sent to UKPSMFadmin@mhra.gov.uk

Queries relating to submission of Type IA variations should be sent to variationqueries@mhra.gov.uk

For further information, please email our Customer Services Centre at info@mhra.gov.uk or call 020 3080 6000. You can also email vigilanceservice@mhra.gov.uk with urgent questions. Alternatively, contact your Trade Association by emailing:

• Association of the British Pharmaceutical Industry (ABPI): regulatory@abpi.org.uk
• British Generic Manufacturers Association (BGMA): info@britishgenerics.co.uk
• BioIndustry Association (BIA): regulatory@bioindustry.org
• Clinical & Contract Research Association (CCRA): mail@ccra.org.uk
• Ethical Medicines Industry Group (EMIG): info@emig.org.uk
• Health Food Manufacturers’ Association (HFMA): pennyviner@btconnect.com
• The National Pharmacy Association (NPA): independentsvoice@npa.co.uk
• Proprietary Association of Great Britain (PAGB): regulatory@pagb.co.uk