III.B.7. Regulatory actions and sanctions

Under EU legislation, in order to protect public health, competent authorities are obliged to ensure compliance with pharmacovigilance obligations. When non-compliance with pharmacovigilance obligations is detected, the necessary action will be judged on a case-by-case basis. What action is taken will depend on the potential negative public health impact of the non-compliance(s), but any instance of non-compliance may be considered for enforcement action. Action may be taken by the Agency, the Commission or the competent authorities of the Member States as appropriate. As stated in Article 111(8) of Directive 2001/83/EC, where appropriate, the Member State concerned shall take the necessary measures to ensure that a marketing authorisation holder is subject to effective, proportionate and dissuasive penalties. Moreover Regulation (EC) No 658/2007 also empowers the Commission, to impose financial penalties on the holders of marketing authorisations to ensure the enforcement of certain obligations connected with marketing authorisations for medicinal products granted in accordance with Regulation (EC) No 726/2004.

In the event of non-compliance, possible regulatory options include the following, in accordance with guidance and, as applicable, rules set in legislation:

• education and facilitation: national competent authorities may communicate with marketing authorisation holder representatives (e.g. in a meeting) to summarise the identified noncompliances, to clarify the legal requirements and the expectations of the regulator, and to review the marketing authorisation holder’s proposals for corrective and preventive actions;
• provision of information to other competent authorities, the Agency or third country regulators under the framework of confidentiality arrangements;
• inspection: non-compliant marketing authorisation holders may be inspected to determine the extent of non-compliance and then re-inspected to ensure compliance is achieved;
• warning letter, non-compliance statement or infringement notice: these are non-statutory or statutory instruments in accordance with national legislation which competent authorities may issue stating the legislation and guideline that has been breached, reminding marketing authorisation holders of their pharmacovigilance obligations or specifying the steps that the marketing authorisation holder must take and in what timeframe in order to rectify the noncompliance and in order to prevent a further case of non-compliance;
• competent authorities may consider making public a list of marketing authorisation holders found to be seriously or persistently non-compliant;
• actions against a marketing authorisation(s) or authorisation application(s) e.g.
  • Urgent Safety Restriction; − variation of the marketing authorisation;
  • suspension or revocation of the marketing authorisation;
  • delays in approvals of new marketing authorisation applications until corrective and preventive actions have been implemented or the addition of safety conditions to new authorisations;
  • requests for pre-authorisation inspections;
• product recalls e.g. where important safety warnings have been omitted from product information;
• action relating to marketing or advertising information;
• amendments or suspension of clinical trials due to product-specific safety issues;
• administrative penalties, usually fixed fines or based on company profits or levied on a daily basis;
• referral for criminal prosecution with the possibility of imprisonment (in accordance with national legislation).