Changes: The new EU procedure

The Pharmacovigilance Working Inspectors Group (PWIG) and the Pharmacovigilance Risk Assessment Committee (PRAC) have adopted a new EU procedure on the management of pharmacovigilance inspection findings which may have an impact on the robustness of the benefit-risk profile of the relevant medicinal products. The new EU procedure came into effect on 1 June 2014.

The aim of the recent changes is to enhance cooperation between individuals and entities involved in those inspections. This includes inspectors, Pharmacovigilance assessors, the PWIG and PRAC.

The new procedure is proposed to supplement the existing post inspection actions which already exist in the EU.

Impact of the benefit-risk profile

The new procedure specifically concerns the steps taken following inspection findings impacting the benefit risk profile applied in connection with medicinal products. The findings which could have an impact are situations where the benefit-risk profile has been altered, or where deficiencies in the pharmacovigilance system have been identified. This consequently could have an impact on the products’ safety profile.

Steps to be taken:

First step:

Corrective and preventative measures undertaken by Market Authorisation Holder (MAH) (a follow-up assessment may be considered to assess the implementation).

Second step:

Inspectors to assess corrective and preventative measures and to assess improvement during re-inspection. Any impact assessment produced by MAH should be referred to an assessor at competent authority level in the EU to consider whether additional follow-up actions are necessary.

Third step:

A PRAC representative or a pharmacovigilance assessor must be notified on the inspection findings if: (1) the inspector and assessor agree that they have identified serious failings during the inspection; and (2) there is likely to be an impact on the benefit-risk profile or failings have led to a delay in introducing risk minimisation measures. The PRAC representative or a pharmacovigilance assessor is responsible for assessing the corrective and preventative measures to be taken by MAH.

The PRAC representative or the pharmacovigilance assessor may determine that follow-up inspections, and the requirement for Periodic Safety Update Report submissions, would be insufficient in order to safeguard patients from risk. In such circumstances, the PRAC representative or the pharmacovigilance assessor must escalate inspection findings to PRAC for an assessment of whether the safety profile of the medicinal product is appropriate. Following the assessment by PRAC recommendations or enforcement action may be taken against the MAH.

Under the new procedure the following findings must be escalated to PRAC:

  • findings which may challenge the established benefit-risk profile of the medicinal product or may have resulted in significant delays in introduction of appropriate risk-minimisation measures;
  • findings related to the non-reporting of Individual Case Safety Reports data in significant volumes which may affect one or more medicinal products; and
  • findings which may result in enforcement actions against the MAH.

Inspections and product labelling:

Where inspections identify failings in the labelling of products, either on the product characteristics or information to be given to patients, then the inspection finding must be shared with all EU Member States that are effected by the failings and EU action may be taken.

The main aim of the revised procedure is to harmonize EU pharmacovigilance inspections and enhance cooperation of all parties involved in such inspections. Entities involved in inspection activities will need to ensure full consideration is given to the procedure to ensure they meet the requisite EU standards of the new procedure.