5 th Pharmacovigilance Forum GLC Switzerland - still a special country? Tips for an successful Pharmacovigilance Inspection Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 2 nd March 2017 Berlin Vers 1 valid 2014-11-26
The views expressed in this presentation are purely personal views from individuals and do not represent any official view of a company or any department thereof. Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 2
Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 3
EU CH Area 4.5 Mio km² 41'285 km² Member States/Cantons Active spoken languages Inhabitants 28 23 500 Mio 26 4 8 Mio Currency Regulatory Authority regulatory medicines 1999: Euro 10 currencies in addition EMA London, National Competent Authorities (NCAs) 1798: Right of coinage is regulated by the cantons 1803: Swiss Francs (CHF) Swissmedic Bern Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 4
>65000 reports in 2015 Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 5
Reporting Duties EU CH domestic cases! Fatal / Life threatening CT Post marketing 7d 15d 7d 15d SUSAR CT 15d 15d Serious expected and unexpected post marketing 15d 15d Non serious unexpected post marketing 90d 60d Non serius expected post marketing 90d - Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 6
EU PSUR/ PBRER Module VII, ICH E2C step 4 Continuous evaluation of benefit to risk Overview of Signals (Module VII B5.15, ICH 3.15) Signal and Risk evaluation (Module VII B5.16, ICH 3.16) CH Swissmedic wants to receive the PSUR yearly for the first 5 years, when there is no special risk, no new indication, new application form, new dose (Art 17.2 VAM, 16.1 HMG). Thereafter no PSUR has to bs submitted. Old PSUR format is accepted. Not for known active ingredients Exceptions: Changes which may influence the safety profile of the drug trigger a restart of the reporting period of the PSUR. The PSUR timing is handled quite restrictively RMP is submitted together with the PSUR/PBRER Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 7
EU CH EURD list http://www.ema.europa.eu/ema/pages/includ es/document/open_document.jsp?webconte ntid=wc500133159 PSUR Repository http://esubmission.ema.europa.eu/index.htm No additional information needed International rhythm is accepted (on request) No bridging reports Naming convention: PSUR Swissmedic requests Summary Tables of important case s as fatal cases, serious, serious unlisted, medically confirmed, total cases, reference with page number Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 8
EU GVP Module Module I Pharmacovigilance systems and their quality system Module II Pharmacovigilance system masterfile (rev.1) Module III Pharmacovigilance inspections Module IV Pharmacovigilance audits Module V Riskmanagement systems (rev.1) Module VI Management and reporting of adverse reactions to medicinal products(rev.1 draft) Module VII Periodic safety update report (rev.1) Module VIII Post-authorisation safety studies, incl. Addendum IMS requirements for information transmission of NIS (rev.1) Module IX Signal Management Module X Additional Monitoring Module XI Public participation in pharmacovigilance (QIV/2014 QI/2015) Module XV- Safety communication Module XVI- Risk Minimization Measures. Selection of tools and effectiveness measures Module XVI Addendum Educational Material CH Art. 59.2, 16 HMG Art. 35, Art 16, Art 30 VAM Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 9
Art. 59.2 Art. 58.3 59 1-3 HMG 35 1-2 VAM Risk Minimization triggering action (update SmPC ) Risk with the assessment of safety actions (domestic or international) Unexpected increase in frequency 15 cd riskmanagement@swissmedic.ch Individual Case Safety Reports (only domestic): serious, cluster or unexpected Signal (Suspected) Serious expected, unexpected, SUSAR 15 cd Non serious unexpected 60 cd CT death, life-threatening 7 cd vigilance@swissmedic ch Risk followed by immediate action 5 cd Significant potential risk of harm 15 cd Slight potential causing harm 6 months Adaptation of leaflet (nonurgent) Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 10
EU CH GVO Module V (Risk Management System) ICH Wird akzeptiert Required ICH E2 State of the art in science and technology as far as not otherwise defined in Swiss legislation and ordinance SM can consider EU guidance documents or Approval with requirements is possible GVP Module V (Risk Management System) RMP CTD Module 1.8.2 Safety Specification PV Plan Risk Minimisation is accepted, format according to ICH is accepted Timing and content comparable with the EU EU format is accepted US format (Risk Evaluation and Mitigation Strategy) is not accepted Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 11
isk Minimisation (3) Signals, Safety Actions, worldwide measures of the authorities EU Have to be reported to EMA/NCAs when they are product related CH Important New Safety Signal report immediately (Art 59 HMG) Worldwide findings and assessments, which could influence the basis of evaluation -> report immediately (Art 35,36 VAM) Set-up of risk minimization measures Signal: Possible relationship with the medication not yet known PRAC recommendati on on measures for all EU member states The Swiss affiliate has to be informed about risk minimisation measures from abroad in order to fulfill the obligation to keep Swissmedic informed and give them the opportunity to ask the Swiss affiliate to implement the same measures Swissmedic wants to be informed Critical evaluation of the problem RMP associated with changes of the overall benefit/risk assessment Educational Material / Measurement of success of the measures of risk minimisation Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 12
Risk Management Plan Special measures EU For all new drug applications RMP GVP Module Template http://www.ema.europa.eu/ema/index.jsp?curl =pages/regulation/document_listing/document _listing_000360.jsp&mid=wc0b01ac058067a 113 May demand additional monitoring for special products -Black triangle (monthly update of products which are concerned: http://www.ema.europa.eu/docs/en_gb/docum ent_library/other/2013/04/wc500142453.pdf -PASS CH RMP updates have to be submitted together with the PSUR/PBRER Contact: riskmanagement@swissmedic.ch For new active substances, Biotech products, Biosimilars, vaccines, new herbal products, expanded indication, new user group, upon request ICH guidelines ICH@ema.europa.eu Not needed for known active substances, even if they are used in a new combination Approval with requirements Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 13
Swissmedic Inspection Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 14
What was highly appreciated in our inspection - It was highly appreciated that the EU QPPV attended the PV inspection in Switzerland although this is not required by local law - All documents have been provided during the inspection - All documents were provided in electronic form and not as paper copy - Having a PSMF available is not mandatory for Switzerland, however it was asked for - Pregnancy cases with the company drug are considered to be serious by Swissmedic. As this is only the case in Switzerland, we found a possibility to report the case as serious, but enter the data as non serious in our database - Case assessment for ICSR - E2B connectivity with local stop in order to fill in the Swiss specific labelling/ assessment Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 15
Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 16
Questions? Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 17