Good Pharmacovigilance Practice

The MHRA Pharmacovigilance Inspectorate is part of the Inspections and Standards Division of the MHRA. It assesses pharmaceutical companies’ compliance with UK and EU legislation relating to the monitoring of the safety of medicines given to patients.

It is one of the five inspectorates at the MHRA. The other four being:

  • Good Clinical Practice (GCP) Inspectorate
  • Good Distribution Practice (GDP) Inspectorate
  • Good Laboratory Practice (GLP) Inspectorate
  • Good Manufacturing Practice (GMP) Inspectorate

In this section you will find information regarding the working of the group, its responsibilities and powers as well as details of the inspection process.  We have presented the information in an easy to follow question and answer format but if you require any further information please do not hesitate to contact us.

News
The latest information from the Pharmacovigilance Inspectorate is available in the Good Pharmacovigilance Practice News section.

Frequently asked questions (FAQs)
The frequently asked questions section contains previous questions discussed at symposia, Pharmacovigilance Consultative Committee meetings and others received by the Pharmacovigilance Inspectorate.  All FAQs are available in the Frequently asked questions for Good Pharmacovigilance Practice section. Additional post-authorisation guidance is available on the EMEA website (external link).

What are the Regulators' expectation of Industry with regards to Good PV practice comments/guidance/ advisory notes posted in Q&A sections on the website of e.g. Human Medicines - EMEA Post-Authorisation Procedural Advice (external link) or Frequently asked questions for Good Pharmacovigilance Practice. 

  • Are MAHs expected the monitor these "Q&A" sites on a regular/ongoing basis?
  • Will the MHRA be inspecting MAHs against Good PV practice comments/guidance/advisory notes posted at these web sites?

With regards to the frequently asked questions section on the MHRA GPvP webpages these contain previous questions discussed at symposia, Pharmacovigilance Consultative Committee meetings and others received by the Pharmacovigilance Inspectorate. These FAQs have been compiled to provide all MAHs the opportunity to review previous questions the Pharmacovigilance Inspectorate has received. They aim to provide information on the expectation of the MHRA and additional clarification on existing legislative requirements and associated guidelines (e.g. Volume 9A) and do not include additional requirements that the MAH must comply with. They aim to educate the MAH on the current thinking on a specific topic and expectations on how existing requirements can be fulfilled. The FAQs are reviewed and updated regularly and it would be encouraged for MAHs to regularly review these. We have now implemented an e-mail alert service to notify subscribers when the GPvP webpages are updated.  Users can subscribe to the email alerting service via the Online services section of our website.

The MHRA is not the author of the EMEA post-authorisation guidance included on their website and therefore cannot specifically comment. However, upon review of these Q&As (in relation to pharmacovigilance) the objective seems similar to the MHRA webpages in which these provide clarification on existing legislative requirements and associated guidelines and do not introduce any new requirements that would be subject to inspection. With respect to centrally authorised products, the expectation is that the advice contained in the EMEA Q&As should be followed, unless the MAH can provide good justification for deviating from this advice.

What is pharmacovigilance?
Pharmacovigilance is the science of collecting, monitoring, researching, assessing and evaluating information from healthcare providers and patients on the adverse effects of medicines, biological products, herbals and traditional medicines with a view to:

  • Identifying information about potential new hazards
  • Preventing harm to patients.

The word is derived from the Greek pharmakon - drug, and the Latin vigilare - to be awake or alert, to keep watch.

What is the MHRA Pharmacovigilance Inspectorate Unit?
By conducting inspections at the sites of marketing authorisation holders, Pharmacovigilance Inspectors assess compliance with the requirements of legislation and guidelines relating to the monitoring of the safety of medicines used in clinical practice. Each Inspector has a statutory duty to assess compliance with medicines legislation and holds a warrant accordingly.

What does the Unit do?
The function of the Pharmacovigilance Inspectorate is to assess pharmaceutical companies’ compliance with UK and EU legislation relating to the monitoring of the safety of medicines given to patients. This is mainly achieved through carrying out inspections of UK Marketing Authorisation Holders (MAHs). These are the persons or organisations responsible for placing medicinal products on the market, usually pharmaceutical companies.
 
The inspection process
An outline of the inspection process is available below:
› Overview of the pharmacovigilance inspection process (28Kb)

Types of inspections
There are three types of inspections:

  1. Routine national inspections: these are scheduled inspections that UK MAHs undergo on a periodic basis. MAHs are notified of these inspections in advance. These inspections are generally systems-based, meaning that inspectors examine the systems and procedures used by a MAH to comply with existing EU and national pharmacovigilance regulations and guidance. 
  2. “For cause” national inspections: these are ad hoc inspections that are triggered as a result of, for example, safety issues, suspected violations of legislation relating to the monitoring of the safety of medicines, referrals by other Member States. In rare circumstances MAHs may not be notified of these inspections in advance.
  3. Committee on Human Medicinal Products (CHMP) requested inspections: the CHMP may request inspections of MAHs in association with specific centrally authorised products.  These can either be routine or triggered.  The general organisation and process for CHMP-requested pharmacovigilance inspections is described in Volume 9A, Part 1, Section 2.4.  The procedures for EU pharmacovigilance inspections requested by the CHMP can be found on the EMEA website (external link).

In some circumstances non-UK sites may be subject to inspection if they are involved in monitoring the safety of medicines marketed in the UK/EU.  This can be at a national level or EU level.

Actions required by MAHs following notification of an inspection
Following notification of the intent to perform a Pharmacovigilance inspection it is recommended that the MAH contacts the lead inspector (either by e-mail or via the main MHRA switchboard - contact details below) as a precautionary measure to ensure the notification is genuine, due to the potential for impersonation of MHRA staff.

MAHs are required to complete and submit a Summary of Pharmacovigilance Systems (SPS) document (696Kb) before the Inspection takes place. The SPS provides information to assist both the MAH and the Inspectorate in preparing for the inspection.  Additional documents may also be requested as appendices to the SPS.

The inspections themselves consist of site visits during which interviews, document and computer system reviews (including searches of any pharmacovigilance databases) are performed.

Grading of inspection findings
Deficiencies found during Inspections are graded in one of three ways:

  • Critical: a deficiency in pharmacovigilance systems, practices or processes that adversely affects the rights, safety or well-being 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 well-being of patients or that could potentially pose a risk to public health or that represents a violation of applicable legislation and guidelines.
  • Other: a deficiency in pharmacovigilance systems, practices or processes that would not be expected to adversely affect the rights, safety or well-being of patients.

› Some common inspection findings and current areas of concern that have been identified during recent inspections, together with some examples (386Kb)

Inspection report and Company response process
Once the inspection has been completed, an inspection report is prepared by the lead inspector, usually within 30 days of either the last site visit, or receipt of the last document requested, which ever is later. It should be noted that the factual matter contained in the inspection report relates only to those things that the inspection team sees and hears during the inspection process. The inspection report is not to be taken as implying a satisfactory state of affairs in documentation, premises, equipment, personnel or procedures not examined during the inspection.

The MAH is requested to provide responses to inspection findings within 30 days of the report being issued.  Guidance on responding to inspection findings is available below:
› Responding to inspection findings (393Kb)

Referral to Pharmacovigilance Inspection Action Group (PIAG)
Critical findings are routinely referred to the MHRA’s Pharmacovigilance Inspection Action Group (PIAG).  This is a non-statutory, multi-disciplinary group constituted to advise the Director, Inspection and Standards, the Director, Post Licensing and the Director, Licensing on any recommendation for referral or enforcement action appropriate to the Divisions, which arises from non-compliance detected during pharmacovigilance inspections. PIAG provides advice in cases where critical findings are identified during inspection and/or serious non-compliance is identified that could affect the rights, safety or well-being of patients.

What rights do inspectors have?
Inspectors have rights conferred under the Medicines Act 1968 sections 111(1 to 3) and 112 (1 to 4 and 7) as well as subordinate legislation applying the Act. These include the right to enter any premises covered by the Act to carry out inspections, take samples, require the production of books and documents, and to take copies of, or copies of entries in, such books and document and seize and detain substances, articles and documents. It is a criminal offence under section 114 (2 and 3) of the Medicines Act 1968 to obstruct an Inspector during the conduct of an inspection covered by the Act.

How is the inspectorate organised?
An organogram for the Pharmacovigilance Inspection Unit is available below:
› Organogram for the Pharmacovigilance Inspectorate Unit (338Kb)

Who does the unit report to?
The Inspectorate reports to Gerald Heddell, Director of the Inspection and Standards (I&S) Division.

Mr Heddell is a member of the MHRA’s Executive Board which reports to Department of Health Ministers via the MHRA’s Agency Board.

Where is the unit located?
The unit operates from two locations:

  1. Pharmacovigilance Inspectorate Unit, MHRA, 2 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW, telephone 01707 299130, fax 01707 376649
  2. Pharmacovigilance Inspectorate Unit, MHRA, Market Towers, 1 Nine Elms Lane, London, SW8 5NQ, telephone 020 7084 2606, fax 020 7084 3519

Fees
Organisations who are Marketing Authorisation Holders (MAHs) are charged a fee when they undergo pharmacovigilance inspections. From 1 April 2008 the fee structure for inspections has changed to a fee calculated on the basis of the time inspectors spend on site – a daily fee. The daily fee rate was part of this year’s fees consultation (MLX 344).

The current level of fees payable and additional information on how the fees will be calculated can be found in our 'Fees for licensing medicines' section.

Organisations that are not MAHs, but are involved in drug development and hold a clinical trial authorisation (CTA) are not currently subject to pharmacovigilance inspections. However, they are subject to Good Clinical Practice (GCP) Inspections.

Links
(The MHRA is not responsible for the content of external internet sites)

Contact for further information
For further information on this part of our site, please contact either:

  1. Pharmacovigilance Inspectorate Unit, MHRA, Market Towers, 1 Nine Elms Lane, London, SW8 5NQ, telephone 020 7084 2606, fax 020 7084 3519  or e-mail info@mhra.gsi.gov.uk
  2. Pharmacovigilance Inspectorate Unit, MHRA, 2 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW, telephone 01707 299130, fax 01707 376649 or e-mail info@mhra.gsi.gov.uk


Page last modified: 26 September 2008