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VMD Pharmacovigilance Requirements

Table of requirements for expedited reporting

Marketing Authorisation type Source Origin Adverse event type Target Timeline
All authorised products in the UK Any source UK All serious adverse events in animals, all human adverse reactions and any suspected transmission via a veterinary medicine of an infectious agent VMD Within 15 days
All authorised products in the UK* Any source Non-UK All serious and unexpected adverse events in animals, all human adverse reactions and any suspected transmission via a veterinary medicine of an infectious agent VMD Within 15 days

*All serious, unexpected adverse events occurring outside the UK relating to products authorised in the UK and identical products, for example, they may be authorised via authorities in other countries with different packaging and authorisation numbers but are identical in ingredients.

Frequency and timings of PSUR submissions

A PSUR should be submitted at least every six months after authorisation until the placing on the market. The PSUR covering this period during which the product is launched is considered the last of the six month PSURs to be submitted before ‘initial placing on the market’. The date of first launching always falls after the European birth date (EBD). Therefore, there are at least five 6-monthly PSURs for new marketing authorisations required.

Following the initial placing on the market, PSURs shall be submitted at the following intervals:

  • 6-monthly for the first 2 years
  • annually for the subsequent 2 years
  • thereafter at three-yearly intervals

PHARMACOVIGILANCE SYSTEMS

1.The Marketing Authorisation Holder (MAH)

The MAH must ensure that it:

  • has a suitable pharmacovigilance system in place
  • takes responsibility and liability for its veterinary medicines on the market
  • can take appropriate action, when necessary

A qualified person responsible for pharmacovigilance (QPPV) must be permanently and continuously at the disposal of the MAH. We strongly recommended that an MAH, or group of MAHs using a common pharmacovigilance system, appoint one QPPV responsible for overall pharmacovigilance of all veterinary medicines for which the company, or group, holds MAs within GB. This person is ultimately responsible for all aspects of the pharmacovigilance system of a company, or group.

The MAH must ensure that the QPPV can fulfil their responsibilities and activities by providing the following:

  • appropriate resources
  • documented procedures
  • communication mechanisms, including access to all sources of relevant information

The MAH must also implement mechanisms to keep the QPPV informed of:

  • emerging safety concerns, and
  • any other information affecting the evaluation of the benefit-risk balance of their veterinary medicines

This information may be from ongoing or completed clinical trials and other studies the MAH is aware of, including those carried out by organisations with whom the MAH has contractual arrangements and which may be relevant to the safety of the veterinary medicine.

The MAH must ensure that the QPPV has the authority to:

  • implement changes to the MAHs pharmacovigilance system to promote, maintain and improve compliance
  • provide input into the preparation of regulatory action in response to emerging safety concerns, for example, variations, urgent safety restrictions, and, if necessary, communication to the general public

The MAH should assess risks with potential impact on the pharmacovigilance system and plan for business contingency, including back-up procedures to cover, for example, non-availability of personnel, adverse event database failure, or failure of other hardware or software with impact on electronic reporting and data analysis.

2. The qualified person responsible for pharmacovigilance (QPPV)

The QPPV should be appropriately qualified, with documented experience in all aspects of pharmacovigilance so that they can be responsible for and perform the tasks of the post. If the QPPV is not a veterinarian, they should have access to a person qualified in veterinary medicine to help with the causality assessment of adverse event reports. MAHs must notify the VMD of changes to the name and contact details of the QPPV, including out-of-office hours details, or back-up procedures to ensure business continuity and continued fulfilment of pharmacovigilance obligations.

The QPPV:

  • oversees the establishment and maintenance of a pharmacovigilance system which ensures that information about all adverse events which are reported to any personnel of the MAH, is collected, collated and made accessible at one or more named locations
  • oversees the preparation for the VMD of the reports referred to in Part 8 of Schedule 1 of the VMR. Detailed guidance for the preparation of these reports is included in:
    • Adverse Event Reporting
    • Periodic Safety Update Reports
    • Post-Authorisation Safety Studies
  • oversees the conduct of continuous overall pharmacovigilance evaluation during the post-authorisation period
  • answers fully and promptly any request from the VMD for more information. This information, including volumes of sales or prescriptions of a veterinary medicine, aids the evaluation of the benefits and the risks of a veterinary medicine
  • provides us with any other information relevant to the evaluation of the benefits and risks of a veterinary medicine. This information may come from ongoing or completed post-authorisation safety studies, or from the actual use of a veterinary medicine. It may reveal evidence relating to the validity of the withdrawal period, or lack of expected efficacy or potential environmental problems

The QPPV should have oversight of the pharmacovigilance system in terms of structure and performance. They should be able to guarantee the pharmacovigilance system components and processes, either directly or through supervision. The oversight should include the functioning of the pharmacovigilance system, including:

  • quality control and assurance procedures
  • standard operating procedures
  • database operations
  • contractual arrangements
  • compliance data, for example in relation to the quality, completeness and timelines for expedited reporting and submission of PSURs
  • audit reports
  • pharmacovigilance training of personnel

The role of QPPV involves extensive tasks, depending on the size and nature of the pharmacovigilance system and the number and type of veterinary medicines for which the MAH holds MAs. The QPPV may delegate specific tasks, under supervision, to appropriately qualified and trained individuals, for example, an expert on the safety aspects of certain veterinary medicines. The QPPV must keep system oversight and overview of the safety profiles of all veterinary medicines. Such delegation should be recorded. In case of absence of the QPPV, an adequately qualified person must undertake their responsibilities.

3. Contractual Arrangements

A MAH may transfer pharmacovigilance tasks and functions, including the role of the QPPV, to another person or organisation. The MAH remains responsible for the quality and integrity of all pharmacovigilance tasks carried out. The MAH must have detailed and clearly documented contractual arrangements with the other persons or organisations involved. They must provide information on such arrangements to the VMD on request. The contracted person or organisation should carry out quality assurance and control and accept audit by or on behalf of the MAH.

MAHs who co-market separately authorised veterinary medicines, which are identical in all aspects apart from their invented names, must have arrangements that include measures to avoid the duplicate submission of adverse events to the VMD.

4. The detailed description of the pharmacovigilance system (DDPS)

All MAHs are required to have an appropriate system of pharmacovigilance in place. When applying for a Marketing Authorisation (M A), the Applicant should submit a Detailed Description of the Pharmacovigilance System (DDPS) in accordance with paragraph 2(3)(k), in Part 1 of Schedule 1 of the Veterinary Medicines Regulations and, where appropriate, a description of the risk management system. The DDPS should cover the Marketing Authorisation Application (M A A) in question, but where the details differ from the standard system, these particulars must be provided in a Product Specific Addendum.

The DDPS provides evidence that the MAH has the services of a qualified person responsible for Pharmacovigilance (QPPV), and the necessary means for the notification of adverse events (AE). It is important to remember that the MAH is ultimately responsible for ensuring that all pharmacovigilance obligations are fulfilled, even if pharmacovigilance activities are subcontracted. If a MAH uses a third party, for example a contractor, licensing partner or other company, for processing pharmacovigilance information, this must be explained in the DDPS.

The document should describe all the essential elements of an effective pharmacovigilance system, but should not include unnecessary information. Step-by-step descriptions of procedures must be laid out in written procedures, for example standard operating procedures (SOPs), and these may be requested at any time by the VMD for inspection or assessment. However, they should not be included within the DDPS; inclusion of unnecessary information leads to the need for variations should that information be changed or removed at a later date. Updates to the information provided in the DDPS should be made in accordance with current legislation.

The DDPS, including proof of the availability of the services of the QPPV and the proof that the MAH has the necessary means for the collection and notification of any adverse event, should be provided in Part 1 of the MAA.

A statement, signed by both a representative of the MAH and the QPPV, declaring the availability of the QPPV and that the MAH has the necessary means for the collection and notification of any adverse events occurring either in GB or occurring outside GB should be provided. The representative/person signing the DDPS statement on behalf of the MAH should have the authority to do so. The person signing on behalf of the MAH should not be the same person as the QPPV, unless there is no other suitable person in the MAH.

The DDPS should be version-controlled and dated to enable the tracking of updates and corrections. The document should include the following elements, as applicable, and be set out in a structured manner consistent with this list. Additional important elements pertinent to a specific situation should be added.

4.1 QPPV

The name and contact details of the QPPV should be provided in section 8.3 of the MAA form. Companies might, for example, use a 24-hour telephone number through which the QPPV or their back-up can be reached, diverting it to the appropriate person according to availability.

A summary Curriculum Vitae (CV) of the QPPV with the key information relevant to their role, including main qualifications, training and experience. If the QPPV does not hold a veterinary qualification, the QPPV should have access to a veterinary surgeon to assist with veterinary assessment of AE reports. Note that lists of scientific publications unrelated to pharmacovigilance issues should not be included.

A summary of the job description of the QPPV, detailing the roles and responsibilities for pharmacovigilance. Any pharmacovigilance roles that are delegated to other persons should be listed. Individuals should not be identified by name but by their position in the organisation. Note that roles and responsibilities not related to pharmacovigilance should not be included. Roles to be included:

  • establishment and maintenance of a pharmacovigilance system
  • ensuring the accurate recording of AEs
  • causality assessment of AEs
  • preparation of AE and Periodic Safety Update Reports (PSUR)
  • conducting continuous/ongoing/periodic pharmacovigilance evaluation
  • timely transmission of reports and provision of other information to the VMD, as required
  • training, including general pharmacovigilance and specific pharmacovigilance activities

A description of the back-up procedure to apply in the absence of the QPPV. If a specific deputy is identified, this should not be by name, but by their position in the organisation. Note that the VMD may request the name and contact details of a deputy separately. This information would not be part of the DDPS.

4.2 Organisation

Identification and location of the company units, or other organisations, where the principal pharmacovigilance activities are undertaken, in particular those sites where the main databases are located, where adverse events are collated and reported, and where PSURs are prepared and processed for reporting to the competent authority. To include:

  • the location and roles of each unit, for example, head office, local office, distributor/contractor etc., should be described, identifying which is responsible for data gathering, recording, assessment, reporting and archiving. Identification of affiliates may be made in a general sense, rather than affiliate-by-affiliate
  • reporting interactions and the position of the QPPV or local pharmacovigilance contacts within the organisation must be described. The MAH should clarify whether the QPPV is directly employed by the MAH or subcontracted

The description should explain how the pharmacovigilance system described applies to the proposed MAH, particularly if the pharmacovigilance system spans a number of differently named subsidiaries and their parent company, and any one of those companies may be the MAH for a particular MAA. MAHs should provide a brief description of the organisation of the companies/subsidiaries/affiliates that may fulfil the role of MAH and are directed by the pharmacovigilance system described. It should be clear that the MAH named in the MAA is governed by the pharmacovigilance system. The description should be written so that it can be applied to any MAA, whatever the authorisation procedure or whichever of multiple MAHs is the MAH for a particular MAA.

High level organisation charts providing an overview of the pharmacovigilance units and organisations and illustrating the relationships between them. The charts should show the main reporting relationships with management and clearly show the position of the QPPV within the organisation. Individual names of people should not be included here. Licensing partnerships are usually product specific and should be indicated in a product specific addendum, in the MAA for that product, unless a partnership is a consistent feature of the company’s organisation, across most products.

Flow diagrams indicating the flow of safety reports of different sources and types. These should indicate how reports/information are processed and reported from the source, to the point of receipt by the competent authority. These should be limited to the major processes.

4.3 Procedures in place, which are documented in writing

An essential element of any pharmacovigilance system is that there are clear, written procedures in place. The following list indicates topics that should usually be covered by these written procedures. The DDPS should indicate for which of these topics there are written procedures in place; if any topic is not covered, an explanation should be provided. Copies of written procedures or SOPs should not be included, nor should the specific titles, numbers or version dates of the SOPs. A procedure may cover one or more of the topics or one topic may have one or more procedures depending on its complexity and the organisation of the company. Care should be taken to ensure that quality control and review are appropriately addressed in the various processes, and reflected in the relevant procedures:

  • the activities of the QPPV and the back-up procedure to apply in their absence
  • the collection, processing; including data entry and data management, quality control, coding, classification, veterinary review and reporting of adverse events. The process should ensure that reports of different types and from different sources are captured:
    • organised data collection schemes, unsolicited, clinical trials, literature
    • GB and non-GB, veterinarians and other health care professionals, animal owners, sales and marketing personnel, and other MAH personnel, licensing partners, competent authorities, others
  • the follow-up of reports for missing information and for information on the progress and outcome of the cases
  • detection of duplicate reports
  • expedited reporting
  • electronic reporting
  • PSURs: The preparation, processing, quality control, review including veterinary review and reporting
  • global pharmacovigilance activities applying to all products: Continuous safety profile of authorised veterinary products:
    • signal detection and review
    • benefit-risk assessment
    • communication with the VMD and animal health care professionals regarding changes to the benefit-risk balance of products and requests for information
  • interaction between safety issues and product defects, specifically product defects that could lead to pharmacovigilance issues
  • responses to requests for information from the competent authority
  • handling of urgent safety restrictions and safety variations
  • meeting commitments to the competent authority in relation to a marketing authorisation
  • management and use of databases or other recording systems
  • internal audit of the pharmacovigilance system
  • staff training
  • archiving

Copies of the global and GB procedures should be available within two working days after receipt by the MAH of a request from the VMD. Any additional local procedures should be available to respond to specific requests.

4.4 Databases

A listing of the main databases used for pharmacovigilance purposes, for example, compilation of safety reports, expedited/electronic reporting, signal detection, sharing and accessing global safety information, and brief functional descriptions of these should be provided, including a statement regarding the validation status of the database systems.

The means by which pharmacovigilance data is recorded should be described, whether paper records, spreadsheets, a database developed in-house or a proprietary database. VMD are flexible as to whether a MAH has an electronic database, depending on the number of reports the MAH receives. However, we would prefer all MAHs to have some form of electronic storage for pharmacovigilance data, for example spreadsheets. Note that the description should be brief and technical specifications of the database should not be included. The person or group responsible for the operation and management of the database should be indicated.

A statement should be included regarding the compliance of the systems with the internationally agreed standards for electronic submission of adverse event reports. If the database is capable of assisting the compilation of safety reports and performing expedited and electronic reporting this should be described. The method of electronic reporting of cases occurring in both GB and outside GB should be indicated.

The MAH should describe the tools or approaches used for detecting signals.

It is also preferable that MAHs have databases for the control of submission of PSURs, for product information and for recording of sales information etc.

4.5 Contractual arrangements

Contractual arrangements with other persons or organisations involved in the fulfilment of pharmacovigilance obligations. Links with other organisations such as co-marketing agreements and contracting of pharmacovigilance activities should be outlined. The company should identify the major subcontracting arrangements it has for the conduct of its pharmacovigilance activities and the main organisations to which it has subcontracted these, in particular where the role of the QPPV, the electronic reporting of adverse events, the main databases, signal detection, or the compilation of PSURs is subcontracted.

A brief description of the nature of the agreements the company establishes with co-marketing partners and contractors for pharmacovigilance activities should be provided.

Since co-licensing or co-marketing arrangements are mainly product specific, any information on these may be provided in a product specific addendum, in the MAA. Likewise if subcontracting is product specific this should be indicated in a product specific addendum.

4.6 Training

Staff should be appropriately trained for performing pharmacovigilance related activities, taking into account their role within the company. This includes not only staff within the pharmacovigilance units but also staff who may receive or process safety reports, such as sales personnel, or field trial/clinical research staff. Describe the pharmacovigilance training given to all personnel, including contractors, who may be involved in pharmacovigilance. Personnel, should only be identified by their position in the organisation, not by name. Describe the type and frequency of training given, and the post holder who provides it. State where the training records of trainees and the CV and job description of the trainer are filed. Note that copies of personal training records should not be included in the DDPS.

4.7 Documentation

Provide a brief description of the locations of the different types of pharmacovigilance source documents, including archiving arrangements. Reference can be made to the organisation charts provided above.

Pharmacovigilance documentation should be stored securely. The location of documentation including original AE reports from the primary source, PSURs, Quality Control (QC) records relating to AE processing, SOPs and training records etc. should be identified. Also, the site where product sales figures can be accessed for pharmacovigilance should be identified. The length of time for which pharmacovigilance reports are archived should be indicated. The VMD would expect this to be at least for the life of the product plus some time to allow for expiry of the product. The VMD may request the identification of the post holders responsible for archiving, and a description of the validation and quality standards applied to archiving, but this should not form part of the DDPS.

4.8 Quality management system

Provide a brief description of the quality management system, making cross-reference to the elements provided under the above sections. Particular emphasis should be placed on organisational roles and responsibilities for the activities and documentation, quality control and review, and for ensuring corrective and preventive action.

A brief description of the responsibilities for quality assurance auditing of the pharmacovigilance system, including where appropriate auditing of sub-contractors, should be provided.

Note that, although it may be helpful, there is no requirement for certification to a particular standard. During the assessment of the DDPS additional information or assurance about the Quality Management system may be requested by the VMD, but it should not form part of the DDPS.

4.9 Supporting documentation

The MAH should ensure that the pharmacovigilance system is in place and documented. An essential feature of a pharmacovigilance system is that it is clearly documented to ensure that the system functions properly, that the roles and responsibilities and required tasks are clear to all parties involved and that there is provision for proper control and when needed change of the system.

4.10 Product specific addendum

Whilst not part of the main system description, this should be provided, if appropriate, in an Annex to the MAH DDPS. Risk management systems or post-authorisation requirements should be included here if appropriate. Where appropriate, a brief description should be given of the nature of any agreements for sub-contracting and co-marketing/co-licensing, specifying regulatory responsibilities and pharmacovigilance activities.

The MAH should identify precisely how the normal system is amended to accommodate the specific product.

5. Risk management

GB legislation requires applicants/MAHs to provide the VMD with a description of risk management systems, when appropriate, in accordance with paragraph 2(3)(k), Part 1 of Schedule 1 of the VMR.

The risk management system is defined as a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicinal products, including the assessment of the effectiveness of those activities and interventions.

It is recognised that at the time of authorisation, information on the safety of a medicinal product is relatively limited. This is due to many factors including the limited representation of target animals, for example the number of animals, age, breeds etc, used in the pre-clinical and clinical development of the product. Risks of many potentially affected subpopulations remain to be identified during the clinical use of the product.

A veterinary medicine is authorised on the basis that in the specified indications, at the time of authorisation, the benefit-risk is judged positive for the target population, the user, the consumer of food from food producing animals as well as the environment. However, not all actual or potential risks are identified when an initial marketing authorisation is granted. Planning of pharmacovigilance activities will be improved if it were more closely based on product specific issues identified from pre- or post-authorisation data and from pharmacological principles.

Risk management is defined as the process, distinct from risk assessment, of weighing policy alternatives, considering risk assessment and other factors relevant to ensure quality, safety, including environmental safety, and efficacy of the veterinary medicine. Risk management should include, if needed, risk mitigation measures.

1. Monitoring of compliance by the VMD

Compliance monitoring relates to activities carried out by the VMD to ensure that a system of pharmacovigilance is in place within MAHs. Methods used include examination of the DDPS, written procedures and safety reports, and monitoring prompt responses to requests for information. Deficiencies identified during compliance monitoring may lead to an inspection request. The aim of this process is to support companies to achieve compliance before regulatory action becomes necessary.

1.1 Qualified Person for Pharmacovigilance

The VMD will maintain a list of QPPVs. This list will include business address and contact details, including out of hours contact. MAHs should inform the VMD promptly of any changes in the name or contact details of the QPPV. Failure to inform the VMD of QPPV changes may be considered as non-compliance.

1.2 Availability of pharmacovigilance data

The VMD will monitor, through assessment of the DDPS and when inspections are carried out, that pharmacovigilance data are collated and accessible by the MAH at least at one location.

1.3 Change in the evaluation of the benefit-risk balance of a product

One of the key responsibilities of MAHs is to immediately notify the VMD of any change in the balance of benefits and risks of their products. Any failure to do so may pose a significant threat to public or animal health. Any evidence of failure to notify such changes will result in consideration of enforcement action by the VMD.

1.4 Expedited adverse event reporting

Requirements for expedited reporting of adverse events are given in Adverse Event Reporting. Methods available to the VMD for monitoring of compliance with expedited reporting of adverse events include:

  • monitoring adverse event reports received from MAHs against other sources to determine complete failure to report
  • monitoring the time between receipt by MAH and submission to the VMD to detect late reporting
  • monitoring the quality of reports. Submission of reports judged to be of poor quality may result in the follow-up procedures of MAHs being scrutinised
  • monitoring that all adverse events that are kept electronically comply with the requirements for electronic reporting set out in Adverse Event Reporting
  • checking PSURs to detect under-reporting, for example of expedited reports
  • checking interim and final reports of post-authorisation safety studies to ensure that all qualifying serious animal reports and human reactions have been submitted within 15 calendar days
  • at inspection there may be a review of a sample of reports on the MAH database to assess the quality of data, determine whether the relevant reports have been expedited, and to confirm that procedures are in place to follow up reports

1.5 Periodic Safety Update Reports (PSURs)

PSURs provide an opportunity for MAHs to review the safety profile of their products and ensure that the Summary of Product Characteristics (SPC) and other product information are up to date. They also provide the VMD with a valuable source of pharmacovigilance data. For these reasons the VMD places great importance on compliance with periodic reporting. Non-compliance may include:

  • non-submission: complete non-submission of PSURs, submission outside the correct cycle or outside the correct time frames, non-restart of the cycle of submission when necessary
  • incorrect format of the document: report not in accordance with Periodic Safety Update Reports
  • omission of information required by Periodic Safety Update Reports, particularly in the following sections of the report:
    • update of regulatory competent authority or MAH actions taken for safety reasons
    • changes to the SPCs
    • animal exposure, including sales volume and numbers treated
    • PSUR line listing
  • poor quality reports: poor documentation of adverse events or insufficient information provided to perform a thorough assessment in the section covering the narrative review of the individual case histories on basis of the line listing of individual reports, new safety signals not or poorly assessed in the section for overall safety information, misuse not highlighted, absence of standardised veterinary terminology
  • SPC: where unauthorised changes have been made to the SPC since the submission of the last PSUR
  • previous requests from the VMD not addressed: submission of a report where previous requests from the VMD have not been addressed, for example, close monitoring of specific safety issues

1.6 Requests for information from the VMD

No fixed time frames are laid down in UK legislation or guidelines for responding to a request for information from the VMD. This reflects the fact that the appropriate time frame will depend mainly on the urgency of the pharmacovigilance issue and its potential impact on public or animal health. The VMD will ensure that requests for information from MAHs have a clear deadline when needed and this deadline should be appropriate to the complexity and urgency of the issue. The VMD will liaise with MAHs regarding the appropriate deadline, as required. Failure of MAHs to provide the necessary information/data within the deadline may be considered as non-compliance.

1.7 Submission of safety variations

UK legislation and guidelines do not specify deadlines for submission of safety variation applications. As with responding to requests for information from the VMD, deadlines for submission of safety variations will depend on the urgency and potential public or animal health impact of the pharmacovigilance issue. The VMD will ensure that requests for safety variations have a clear deadline and this deadline should be appropriate to the complexity and urgency of the issue. The VMD will liaise with MAHs regarding the appropriate deadline, as required. Failure of MAHs to submit the variation application within the deadline may be considered as non-compliance.

1.8 Post-Authorisation Safety Studies

Because of the objectives of post-authorisation safety studies there is considerable potential for safety signals to arise or changes in the balance of risks and benefits of products to be identified. Therefore, expedited reporting and submission to the VMD of interim and final study reports from such studies has an important role in protecting public or animal health. Where appropriate, the VMD will scrutinise protocols prior to the initiation of post-authorisation safety studies. The VMD checks that relevant adverse event reports are expedited from those studies and monitors the submission of interim and final study reports. Guidance on post-authorisation safety studies is available in Post Authorisation Safety Studies.

2. Pharmacovigilance Inspections

The VMD inspects all marketing authorisation holders (MAH) to ensure that they have the personnel, systems and facilities in place to comply with their pharmacovigilance obligations. Any MAH with a product authorised in the UK can be subject to a pharmacovigilance inspection by the VMD, which may also include any of their partners or service providers. If pharmacovigilance activities are performed outside the UK, the VMD may ask company personnel from other country sites to participate in an inspection at a UK site.

Inspections outside the UK will be included in the inspections programme whenever this is considered appropriate.

2.1 Types of inspection

Pharmacovigilance inspections are scheduled according to the VMD’s risk-based approach, largely based on the nature of the products, extent of use, number of products on the UK market, previous inspection history and additional risk factors such as:

  • the MAH has recently been or is involved in a merger or takeover process
  • the MAH has changed their system significantly, for example, new database system, contracting out of reporting activities etc

Inspections will generally be routine but can also be targeted to MAHs suspected of being non-compliant.

2.2 Routine inspections

The MAH is notified of these inspections in advance. These inspections may be requested with one or more specific veterinary medicines selected as examples for which specific information can be traced and verified through the various processes, in order to provide practical evidence of the functioning of the pharmacovigilance system of the MAH and their compliance with their regulatory obligations.

Where the pharmacovigilance system of a MAH has not been inspected previously, an inspection of the system will be performed within four years of placing the first veterinary medicine on the UK market. Where the system has previously been inspected, re-inspection will take place at intervals. If no critical findings are identified the frequency of inspection will be decided using the risk-based approach.

If an inspection results in a critical finding it is likely the MAH will be subject to a triggered re-inspection within 12 months, with a focus on the actions that were agreed following the last inspection. Targeted inspections Targeted inspections may be conducted when triggers are identified and the VMD determines that inspection is the appropriate course of action. Triggers which may result in a targeted inspection include:

  • delays in carrying out or failure to carry out specific obligations or follow-up measures relating to the monitoring of product safety, identified at the time of the marketing authorisation
  • delays in expedited or periodic reporting
  • incomplete reporting
  • submission of poor quality or incomplete PSURs
  • inconsistencies between reports and other information sources
  • change in risk-benefit balance
  • failure to communicate change in risk-benefit balance
  • previous inspection experience
  • information received from other authorities
  • poor follow-up to requests for information from the VMD
  • product withdrawal with little or no advance notice to the VMD

The above are examples and other issues may trigger a targeted pharmacovigilance inspection. The presence of a trigger will not always lead to an inspection.

It is anticipated that the majority of triggered inspections will be announced. However, on occasions, it may be appropriate to conduct unannounced inspections or to announce an inspection at short notice.

2.3 Remote inspections

Routine and targeted inspections may be conducted by inspectors remotely. These inspections are conducted through a combination of review of requested documents, including evidence to support pharmacovigilance activities, and a method for interviews with relevant personnel. Logistical aspects of the inspection will be arranged with the MAH prior to the inspection. Should any significant issues be identified, that cannot be adequately reviewed during the remote inspection, it may be necessary to schedule an on-site inspection of the MAH’s pharmacovigilance system.

2.4 Inspection conduct

Inspection requests are prepared by the Pharmacovigilance Inspector. As part of the inspection notification a number of documents will be requested. You must acknowledge you have received the notification and provide the requested documentation within the timeframe stated in the letter. Details of the relevant contact person for future correspondence about the inspection should be provided. If this is not the QPPV they should be made aware by the MAH of the inspection and be contactable during the inspection.

The inspection team will ask for additional documentation during the inspection.

The MAH should ensure access to WIFI and teleconference facilities, if required, throughout the inspection; as well as prompt access to printing and copying facilities, and access to all electronic documentation and systems including the safety database.

At the closing meeting the inspector will provide feedback and discuss any deficiencies and actions required after the inspection with the MAH.

Each inspection will result in an inspection report. The inspection report will be made available to the MAH. Where an inspection reveals non-compliances the MAH will be required to prepare a remedial action plan to correct the non-compliances and avoid recurrence. The MAH may be required to provide evidence of the progress and completion of the action plan. There may be re-inspection at an appropriate time to verify the progress and success of these remedial actions.

The results will be used to help MAHs improve compliance and may also be used as a basis for enforcement action.

3. Regulatory Action

When non-compliance with pharmacovigilance regulatory obligations is detected, the necessary action will be judged on a case-by-case basis. The action taken will depend on the potential negative public or animal health impact of non-compliance but any instance of non-compliance may be referred for enforcement action.

In the event of non-compliance, regulatory options include the following:

  • MAHs may be assisted to comply with the legislation through the provision of advice and guidance
  • non-compliant MAHs may be inspected to determine the extent of non-compliance and then re-inspected to ensure compliance is achieved
  • a formal warning may be issued reminding MAHs of their pharmacovigilance regulatory obligations
  • an Improvement Notice may be issued
  • a Variation of the MA may be requested
  • the MA may be suspended
  • the MA may be revoked

VMDS - Overview

VMDS - Adverse Event Reporting