European Enforcement of Pharmacovigilance and Inspection Trends Is compliance possible within the EU? June 7, 2007 Dr. M.C. Koster CEO Vigilex Group

Europe 27 EU member states (per 1 January 2007) 3 European EFTA countries have chosen to follow the EU legislation & guidance for PV (Norway, Iceland and Liechtenstein) Together, these 30 countries are referred to as the EEA (European Economic Area)

Requirements for a MAH QPPV, residing within the EEA and permanently and continuously at his disposal Single QPPV for all products and responsible for: –overview of safety profile all products –establishment, maintenance/management of the PV system –oversight in terms of structure and performance of e.g. staffing, procedures, database(s), training, QC processes and QA activities –timeliness and correctness of expedited and periodic reports submitted –ongoing risk-benefit evaluation of all products –ensure any request from a competent authority is answered fully and promptly –must provide any information relevant to the evaluation of benefit and risk –Etc., Etc.

Requirements for a CA EC is the CA for pharmaceutical products authorised centrally and EMEA (European Medicines Agency) EC is the CA for pharmaceutical products authorised centrally and has the responsibility for the overall community system of PV; assisted by the CHMP and EMEA (European Medicines Agency) Individual MSs have other products when there is a Individual MSs have the responsibility for all other products when there is a marketing authorisation in their country (national procedures, including the mutual recognition and decentralised procedure) – –continually monitors the safety profile of the products available on its territory and takes appropriate action where necessary and monitors the compliance of MAHs; – –should ensure that MAHs implement, when appropriate, Risk Management Plans to effectively monitor and manage risks associated with the safety of their products; – –should ensure that PV data are shared between Member States and the Agency via EudraVigilance; –shall ensure, by repeated inspections, compliance with required activities

“If the law supposes that,” said Mr. Bumble,… “the law is a ass—an idiot. If that’s the eye of the law, the law is a bachelor; and the worst I wish the law is that his eye may be opened by experience.” CHARLES DICKENS, Oliver Twist, chapter 51, p. 489

Examples of obstacles 15 c-day deadline for expedited reports, but no sign off by CAs during the weekend or bank holidays Electronic reporting mandatory since November 2005; many CAs not ready yet Good PV staff is rare and so is a QPPV Volume 9A, containing a substantial number of changes, is in effect immediately Volume 9A will be regularly updated (225 pages), but changes are not marked Still countries requiring reports in national language

Examples of duplication Literature searches –MAHs are expected to maintain awareness of individual case reports in publications through accessing weekly a widely used systematic review and reference database –For a company wit 100 products this involves at average hours a week PSUR review for nationally authorised products, in principle, by 30 EEA countries Expedited reports could be sent all to the EudraVigilance database in stead of in a complex structure to individual MSs

Inspection trends A. Routine National inspection programs For centrally authorised products the CHMP will determine a program B. Targeted Triggered but without a specific concern Triggered but with a specific product or actual non-compliance Outcome of inspections are not predictable as findings vary per country and per inspector

Recipe for benefit to public health Reporting to EudraVigilance only Use resources better: –simplified PSURs for older products –simplify reporting for older products –No global & local literature searches by all companies Exempt PV from the strict data privacy Directive Abandon the macho behavior of individual countries Harmonise, Harmonise, Harmonise, Harmonise

QUESTIONS?