Good pharmacovigilance practice (GPvP)
Comply with good pharmacovigilance practice and prepare for an inspection.
Overview
Good pharmacovigilance practice (GPvP) is the minimum standard for monitoring the safety of medicines on sale to the public in the UK.
The MHRA inspects marketing authorisation holders (MAH) to determine whether they comply with pharmacovigilance (PV) obligations established in the UK. We have been conducting statutory GPvP inspections since 2003, and any UK MAH or marketing authorisation applicant (for any authorisation procedure) can be subject to GPvP inspection by the MHRA, which may also include any of their partners or service providers.
If pharmacovigilance activities are performed outside the UK, we may ask company personnel from other country sites to participate in an inspection at a UK site and/or may liaise with inspectorates in other regulatory agencies to perform an inspection at sites in their country or to share results from recent inspections, where confidentiality agreements are in place.
We may also conduct GPvP inspection of the PV system of used for UK authorised products in other territories.
Types of inspection
Inspections are typically scheduled by pharmacovigilance system, product or post-authorisation safety study, rather than by MAH. A pharmacovigilance system is defined as the system used by an organisation to fulfil its legal tasks and responsibilities in relation to pharmacovigilance and designed to monitor the safety of authorised medicinal products and detect any change to their risk-benefit balance.
If a group of associated MAHs share the same pharmacovigilance system, all MAHs may be included in the scope of a single inspection of that pharmacovigilance system. Conversely, if an MAH operates more than one pharmacovigilance system, we usually review these through separate inspections.
Routine national inspections
GPvP inspections are scheduled as part of our national inspection programme according to a risk-based approach, largely founded on the risk factors listed in EU statutory guidance (Good pharmacovigilance practice (GVP) Module III), as modified by the Exceptions and modifications to EU guidance on good pharmacovigilance practices that apply to UK MAHs and the licensing authority.
We usually notify the MAH of these inspections in advance.
For inspections that cover Category 2 products, the GPvP Compliance Team shares the list of planned and conducted UK national inspections with the European Medicines Agency (EMA) and this is made available to all EU member states.
If an inspection results in a critical finding it is likely the MAH will be subject to a triggered re-inspection within 12 to 18 months, with a focus on the actions that were agreed following the last inspection.
If no critical findings are identified, there is no specific timeline by which an MAH must be inspected again. We will decide the frequency of inspection using the risk-based approach. An inspection may take place at any time.
We may contact MAHs and ask for a copy of the UK-PSMF (Pharmacovigilance System Master File) as well as requesting other information such as a list of products with additional PV activities, copies of risk management plans (RMPs) or UK sales data. We can use this information to aid with risk assessment decisions, scheduling and planning activities. These requests may or may not result in an inspection notification being issued soon after.
If this information is required, the GPvP Compliance Team will contact the MAH directly.
Triggered inspections
We may perform a triggered inspection of an MAH in response to receiving specific risk information. For example, if we’re informed about possible GPvP breaches by:
- a whistleblower
- other MHRA departments
- another regulatory authority
We may send little or no notification of these inspections in advance.
Pre-authorisation inspections
The majority of MHRA GPvP inspections take place in the post-authorisation phase of the product life cycle. However, there are scenarios where pre-authorisation GPvP inspections of applicants for marketing authorisations are warranted. The objective of these inspections is to assess whether the applicant has the ability to comply with post-authorisation pharmacovigilance obligations.
Service provider inspections
Increasingly, MAHs are outsourcing all or some of their pharmacovigilance activities to contract service providers. Such activities conducted by these organisations on behalf of MAHs are subject to supervision by the MHRA, including by inspections.
Following a pilot programme of standalone service provider inspections, we concluded that a routine programme of inspections of pharmacovigilance service providers is not currently viable for the MHRA GPvP Compliance Team.
We continue to assess the activities performed by service providers in the context of MAH inspections. We may conduct standalone inspections of these organisations where we consider it necessary to evaluate the overall system and procedures implemented by a service provider based on risk information available to us.
Contracts with pharmacovigilance service providers should include provisions that cover the availability of data, documentation and appropriate support to the MAH and inspectors during a GPvP inspection.
Working with other regulators
We may share GPvP inspection reports that cover Category 2 authorised products with the EMA and EU/European Economic Area (EEA) member states.
Looking further afield, the we have memorandum of understanding agreements with other global medicines regulators such as USA, Canada and Australia. We share inspection-related intelligence and exchange inspection reports with them where requested. We have also conducted GPvP inspections in non-EU countries such as Japan, USA, Canada and India.
Preparing for a GPvP inspection
Inspection notification
The majority of GPvP inspections are announced and are typically scheduled on a quarterly basis. As part of the inspection notification, we will request the UK PSMF. You must acknowledge you have received the notification and provide details of the relevant contact person for future correspondence about the inspection.
If you have concerns about the authenticity of a notification, contact gpvpinspectors@mhra.gov.uk.
Pre-inspection documents
Before the inspection, the lead inspector will contact the MAH and Qualified Person for Pharmacovigilance (QPPV) and provide the draft plan as well as any specific requirements of the team. As well as the PSMF, inspectors may require supplementary information to confirm the scope of the inspection and to be well prepared. The lead inspector will explain how our document request system works.
MAHs will receive requests for documentation before the inspection and throughout. Where substantial document review is required before the inspection, inspectors may incorporate remote inspection time into the inspection plan.
We expect any documents listed in the UK PSMF to be readily available for inspection. This includes (but is not limited to):
- procedural documents such as standard operating procedures (SOPs), working instructions and guides
- outputs from pharmacovigilance activities such as safety review meeting minutes and documented product safety reviews
- audit risk assessments
- agreements in place with partners and service providers
Onsite inspections
To achieve the objectives for the inspection, inspectors will aim to be flexible with the plan and to accommodate changes, if possible. For onsite inspections, it is always preferable to conduct face-to-face interviews. However, the inspection team can accommodate interviews by telephone/videoconference if interviewees are unable to attend the site, provided facilities are adequate to support this. In this case, the MAH should inform the lead inspector if most of the personnel attending the inspection will not be on site, and where their location will be during the inspection.
If the MAH does not have a UK site and is using a vendor site or hiring office space for the inspection, they should ensure access throughout the inspection to:
- Wi-Fi and teleconference facilities (if required)
- printing and copying facilities
- all electronic documentation and systems, including the live safety database
The inspection will typically require the use of at least one main inspection room and the company may wish to have a ‘back-room’ for the preparation of document requests.
Remote inspections
Inspectors may conduct routine and triggered inspections remotely. They carry out these inspections through review of requested documents, including evidence to support pharmacovigilance activities and submissions. They supplement the document review with telephone/videoconference interviews using Microsoft Teams with relevant subject matter experts and written responses to specific queries.
Logistical aspects of the inspection, including timings and availability of specific subject matter experts and the UK QPPV for telephone/videoconference interview, are arranged with the inspected organisation before the inspection. An onsite inspection may be triggered following the remote inspection if we identify any significant non-compliance or concerns that require further investigation. If a remote inspection is scheduled, but the MAH is planning on bringing their staff together to the UK for the inspection, this should also be informed to the lead inspector.
Hybrid inspections
Occasionally inspections will take place in a hybrid manner: inspectors may conduct part of the inspection onsite at the MAH facilities and part of the inspection remotely. The lead inspector will communicate this clearly during the planning phase of the inspection.
A hybrid inspection may include some members of the inspection team being onsite while some are remote. Again, the lead inspector will communicate this thoroughly with the MAH to ensure provisions are in place to support both elements of the inspection.
Unannounced inspections
On rare occasions, inspections may take place unannounced. Under UK law, an inspector acting on behalf of the MHRA (as licensing authority) has the right, at any reasonable time, to enter premises (not limited to those of the MAH) to determine if there has been a contravention of the regulations laid out in SI 2012 No 1916 as amended (per Regulation 325) and the right to inspect information and documents relating the requirements for pharmacovigilance laid out in Part 11 of SI 2012 No 1916 (as per Regulation 327).
In other words, although rarely done, the MHRA GPvP inspectorate can arrive at and enter UK sites relating to the conduct of pharmacovigilance activities without notifying the MAH first. In this case, on arrival at site, the lead inspector will identify the most appropriate person on site as a point of contact and will explain the purpose and logistics of the inspection.
The inspection
During an inspection the inspection team may:
- conduct site visits
- interview relevant personnel
- review documents
- carry out computer system reviews, including searching pharmacovigilance databases either by asking for access to a database or asking the MAH to provide a demonstration
The inspection team will ask for additional documentation during the inspection. They may also change the focus of the inspection if they suspect serious non-compliance.
The team and inspection duration
Inspection teams are comprised of between one and 4 inspectors, spending between 2 and 5 days on site or remotely. This can vary based on the type of products marketed by the company, the complexity of the pharmacovigilance system and the type of inspection (for example routine or, triggered).
Occasionally observers may also be present at our inspections. This may include representatives from the MHRA’s Safety and Surveillance (S&S) division and Enforcement Groups or other regulatory authority inspectorates.
We use the UK PSMF as a tool to determine the resource required to perform the inspection. However, this can be subject to change and inspections may be extended at short notice based on arising issues.
Extension to inspections may take the form of office-based review of documentation following the onsite inspection, or a return to the inspection site for additional days. We will communicate this to the MAH at the time, along with the rationale for extending the inspection and information on whether any additional inspection days will be subject to inspection fees.
Inspection conduct
Inspectors normally interview operational personnel who are involved in pharmacovigilance activities or activities associated with pharmacovigilance including regulatory affairs, and management of post-authorisation safety studies. We expect that the UK QPPV or delegate will be available during the entirety of the inspection.
If considered necessary, for example if we identify serious issues relating to a business area, it might be necessary to interview a senior executive, and we may request the senior executive(s) to attend the closing meeting.
The inspectors typically discuss issues with the MAH as they arise during the inspection to allow for clarification. For this reason, inspectors do not provide daily summaries or ‘wrap ups’ until the closing meeting at end of the inspection. At the closing meeting the inspector will provide verbal feedback and discuss any deficiencies and actions required after the inspection with the MAH.
Inspection fees
The MHRA will invoice the inspected party after the inspection.
Inspection outcomes
Grading of inspection outcomes
Deficiencies found during inspections are graded at 3 levels.
Critical
A deficiency in pharmacovigilance systems, practices or processes that adversely affects the rights, safety or wellbeing of patients or that poses a potential risk to public health or that represents a serious violation of applicable legislation and guidelines.
Major
A deficiency in pharmacovigilance systems, practices or processes that could potentially adversely affect the rights, safety or wellbeing of patients or that could potentially pose a risk to public health or that represents a violation of applicable legislation and guidelines.
Minor
A deficiency in pharmacovigilance systems, practices or processes that we would not expect to adversely affect the rights, safety or wellbeing of patients.
Routine inspection outcomes
Following the inspection, the lead inspector will hold a closing meeting to outline observations from the inspection and clarify logistics for the next stage of the inspection process.
There may be outstanding documentation to receive and to review following the inspection. The inspection report will be written, usually peer reviewed, and provided to the MAH within 25 working days of the closing meeting of the inspection or receipt of the last document, whichever comes last.
On receipt of the inspection report, the MAH has the opportunity to formally respond to the inspection report in writing, using the template and instructions provided. The responses should consist of:
- a root cause analysis
- a further assessment of the impact of each of the findings
- proposed corrective and preventative actions (CAPA) with associated deliverables and due dates
The MAH will have 25 working days to provide the responses to the lead inspector. See guidance for responding to inspection findings.
The lead inspector will review proposed actions and may request clarifications until satisfactory responses are agreed. This can take the form of written requests for clarification, discussions via teleconference or, less commonly, a face-to-face meeting.
Once agreed, the MAH will receive a final inspection report and the inspection will be closed. The lead inspector will typically work with the MAH to reach agreed actions that will bring the MAH’s pharmacovigilance system into compliance.
We expect that MAHs will share inspection reports with their service providers so that they may assess the impact of any inspection findings relating to their activities for the MAH across their wider client base and remediate where required.
If we consider inspection report responses and CAPA inadequate following the 2nd round of review by the inspector, we may refer the MAH to the GPvP Compliance Management Team (CMT) and may consider an early re-inspection.
Non-routine inspection outcomes
Escalation to GPvP Compliance Management Team (CMT)
The GPvP CMT is a non-statutory group constituted to:
- coordinate and advise the GPvP inspectorate on compliance management issues following an inspection or detection from other intelligence sources
- make recommendations for referrals to IAG2 for action (see below)
- make recommendations for enforcement action
Cases considered by the GPvP CMT include:
- all critical inspection findings from MHRA GPvP inspections
- organisations that have not had critical findings but where there are major findings that are at high risk of developing into critical issues (for example, due to the management culture or a history of poor CAPA management)
- critical (or comparatively graded) findings arising from non-MHRA inspections, to assess any risk to UK public health and patient safety, compliance with national requirements and the need for specific UK remediation
- referrals of known or suspected non-compliance with pharmacovigilance obligations from internal or external sources
For MHRA GPvP inspections that have not initially resulted in a referral to the GPvP CMT, the lead inspector may refer the case to the CMT if they consider the responses to the inspection report inadequate despite requests for clarification.
Escalation to Inspection Action Group 2 (IAG2)
There are 2 inspection action groups (IAG) at the MHRA, IAG2 covers clinical trials of investigational medicinal products and the pharmacovigilance activities of MAHs and advises the directors of the Innovation and Compliance Group (I&C) and Safety and Surveillance (S&S), where appropriate.
Where recommended by CMT, cases will be referred to IAG2 for action or for information. IAG2 meets regularly to deal with ongoing business and to consider new referrals.
The criteria for making referrals to the IAG2 in relation to pharmacovigilance inspections include, but are not limited to:
- conditions that are likely to cause or lead to a significant risk to public health
- one or more unresolved critical deficiencies identified by an inspection
Early re-inspection has been the most common recommendation made by IAG2 to date. In most cases, adequate progress has been observed on re-inspection. In some cases, a further re-inspection has been required and a minority of cases have been referred back to IAG2 for consideration of other actions, which may include meetings with MAH senior representatives to discuss the issues and consequences of continued non-compliance.
The daily rate inspection fee includes preparation for, reporting and close-out of the inspection.
Inspections with critical findings or other significant non-compliance requiring referral to the GPvP CMT and/or IAG2 may require the inspector(s) to spend additional time beyond that covered by the daily rate overseeing the adequacy of the company’s CAPA and the company’s return to compliance.
For such inspections, an office-based inspection fee may be charged for this additional time spent by the inspector(s) on such activities (for example, reviewing CAPA plans, impact assessments and periodic CAPA status updates and corresponding with the company in writing or by teleconference).
Infringement notices
We may issue an infringement notice when we identify instances of serious or serious and persistent non-compliance with pharmacovigilance requirements.
Companies who have been issued an infringement notice.
| Company name | Date issued | Reason | Infringement notice | Status |
|---|---|---|---|---|
| Omega Pharma Limited | 9 October 2013 | Regulatory action | Closed: the MHRA has confirmed the measures set out in the infringement notice have been implemented successfully |
Inspection metrics
Annual pharmacovigilance inspection metrics dating back to 2009 are published on the MHRA website.
In addition, anonymised findings from MHRA pharmacovigilance inspections are presented at MHRA symposia and other conferences attended by inspectors. MHRA GPvP inspection reports are available on request under the freedom of information act.
Legislation and further guidance
CIR HMR Schedule 12A MAH communication
UK Human Medicines Regulations, Statutory Instrument 2012 No. 1916, Part 11 and Schedule 12A
Directive 2001/83/EC as amended
Regulation (EU) No. 726/2004 as amended
Commission Implementing Regulation (EU) No. 520/2012 as amended by 2025/1466
Good pharmacovigilance practices (GVP) - European Medicines Agency (EMA)
The process for pharmacovigilance inspections is described in the GVP module inspections
Updates to CIR 520/2012 – Information for UK marketing authorisation holders - GOV.UK
Contacts
The GPvP inspectorate welcomes ongoing feedback on the conduct of inspections. You can send feedback to the GPvP inspectorate mailbox: gpvpinspectors@mhra.gov.uk.
Updates to this page
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Updated to include link to CIR HMR Schedule 12A MAH communication
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Updated to reflect changes to regulations following brexit transition.
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Added a single line confirming that in a no-deal Brexit, the MHRA’s GxP risk-based inspection programmes will remain unchanged.
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Inserted "Preparing for an inspection" text
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Added a paragraph to the end of the Non-routine inspection outcomes section.
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Added additional information on what to expect from an inspection.
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Changed MHRA address.
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New section on compliance report requirements
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First published.