Guidance

Overall Pharmacovigilance Evaluation and Safety-Related Regulatory Action

Updated 8 June 2022

Applies to England, Scotland and Wales

1. Overall Action

The MAH and the VMD must keep up to date with all relevant information in order to fulfil the following responsibilities:

• ensuring that all sources of information are screened regularly to identify potential signals
• ensuring that appropriate action is taken in response to new evidence which impacts on the benefit-risk balance
• keeping health-care professionals and animal owners informed on changes to authorised veterinary medicine information

2. Overall Evaluation

Signals of possible unexpected adverse reactions or changes in severity, characteristics or frequency of expected adverse reactions may arise from any source. Rarely, even a single report of an unexpected adverse reaction may contain sufficient information to represent a signal on or establish a potential causal association with the suspected veterinary medicine and impact on the benefit-risk balance.

The responsibilities of the MAH, and in particular of the QPPV, are provided in Pharmacovigilance Systems, including Risk Management and Compliance and Inspections.

It is the responsibility of the QPPV to provide the VMD with any information relevant to the evaluation of benefits and risks afforded by a veterinary medicine, including appropriate information on post-authorisation safety studies, lack of expected efficacy, information regarding the validity of the withdrawal period or potential environmental problems arising from the use of the veterinary medicine.

The MAH is obliged to immediately inform the VMD of any prohibition or restriction imposed by the National Competent Authority (NCA) of any country in which the veterinary medicine is marketed and of any other new information which might influence the evaluation of the benefits and risks of the product concerned. A comprehensive report evaluating the issue and considering the risks in the context of the benefits should be submitted at the earliest opportunity, and no later than the date agreed between the MAH and the VMD, and should also be included in the relevant PSUR.

3. Principles of Benefit-Risk Assessment

The benefit-risk assessment of a veterinary medicine is a complex process based on the intended use and the indications of that product in respect to its overall safety. The assessment should describe and objectively compare the benefits and risks of the veterinary medicine to evaluate the benefit-risk balance. The reasoning leading to the conclusion should be explained and discussed in a critical manner.

4. Optimising the Benefit-Risk Balance

The MAH should aim to optimise the safe use and the benefit-risk balance of an individual veterinary medicine. Where necessary, the benefit-risk balance may be improved either by increasing the benefits, for example including further explanation of how best to use the product, or by reducing the risks by risk mitigation measures, for example by contraindicating the use in animals particularly at risk, reducing dosage, or introducing precautions for use. When proposing measures to improve the benefit-risk balance of a veterinary medicine, their feasibility under normal conditions of use should be taken into account. If dose reduction is considered as a method of risk minimisation, the impact of dose reduction on efficacy should be carefully evaluated.

The following types of management actions may be necessary and may be initiated by the MAH or by the VMD:

• intensified pharmacovigilance surveillance and post-authorisation safety studies
• variation of marketing authorisations in respect of the indication, dosing recommendations, contraindications, warnings and precautions for use or information about adverse reactions or other sections of the product literature
• direct provision of important safety information to veterinarians and other health-care professionals and animal owners, for example through letters, bulletins, via electronic media etc
• urgent Safety Restrictions: urgent safety restrictions may be taken by MAHs in the event of risk to human or animal health or to the environment. If the MAH takes an urgent safety restriction, the MAH shall immediately inform the VMD. Urgent Safety Restrictions may also be initiated by the VMD
• suspension or withdrawal of the marketing authorisation of a veterinary medicine, in the event that the overall benefit-risk balance is considered unfavourable and proposed risk minimisation measures are considered inadequate. Veterinarians and other health-care professionals and animal owners/the general public should be informed as appropriate

Such actions may be taken voluntarily by MAHs. However, it is recommended that any such intended measure be discussed at an early stage with the VMD.

5. Communication

A Marketing Authorisation Holder (MAH) must notify the VMD before, or at least at the same time as they publicly release information about pharmacovigilance concerns. This information may take the form of letters, bulletins or electronic means, such as emails.

They must present the information objectively and must not be misleading. Ideally, allow the VMD to review the information, prior to release.

The VMD undertakes to inform vets, other health-care professionals and the public of the results of evaluation of safety concerns, having assessed the impact of such information and having also informed the MAH.

6. Freedom of Information requests made to the VMD

The VMD is committed to follow the legislation relating to freedom of information requests including our commitment not to disclose information where that information is properly covered by one of the FOIA’s exceptions. We will deal with data requests on a case by case basis and will consult with the data ‘owners’ where necessary. The VMD will seek the views of those that provided us with the data on what harm will fall if we disclose the information and decide if it’s likely to be actual and reasonably foreseeable on the basis of the MAH’s case.

The final decision on whether we withhold the information rests with the VMD. However, we will take MAH’s views into account when we make this decision.