Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH

2nd March 2017 Berlin Vers 1 valid 2014-11-26

Switzerland - still a special country?

Tips for an successful Pharmacovigilance Inspection

5th Pharmacovigilance Forum GLC

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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

3 Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH

Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 4

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 1999: Euro 10 currencies in addition

1798: Right of coinage is regulated by the cantons 1803: Swiss Francs (CHF)

Regulatory Authority

regulatory medicines

EMA London, National Competent Authorities (NCAs)

Swissmedic Bern

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>65000 reports in 2015

Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH

Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 6

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 7

EU CH 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)

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 8

EU CH

EURD list http://www.ema.europa.eu/ema/pages/includes/document/open_document.jsp?webContentId=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 9

EU CH

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

Art. 59.2, 16 HMG Art. 35, Art 16, Art 30 VAM

Signal (Suspected)

10

• Significant potential risk of harm ≤ 15 cd

Individual Case Safety Reports (only domestic): serious, cluster or unexpected

Serious expected, unexpected , SUSAR ≤ 15 cd

Non serious unexpected ≤ 60 cd

CT death, life-threatening ≤ 7 cd

Risk with the assessment of safety

actions (domestic or international)

Unexpected increase in frequency ≤15 cd

Risk Minimization

triggering action

(update SmPC…)

Art. 58.3 59 1-3 HMG 35 1-2 VAM

• Risk followed by immediate action ≤ 5 cd

Art. 59.2

riskmanagement@swissmedic.ch

vigilance@swissmedic ch

• Adaptation of leaflet (non-urgent)

• Slight potential causing harm ≤ 6 months

Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH

GVO Module V (Risk Management System) Wird akzeptiert

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EU CH

ICH 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)

is accepted, format according to ICH is accepted

RMP CTD Module 1.8.2 Safety Specification PV Plan Risk Minimisation

Timing and content comparable with the EU

EU format is accepted

US format (Risk Evaluation and Mitigation Strategy) is not accepted

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isk Minimisation (3) EU CH

Signals, Safety Actions, worldwide measures of the authorities

Have to be reported to EMA/NCAs when they are product related

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

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

Signal: Possible relationship with the medication not yet known

PRAC recommendation on measures for all EU member states

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

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EU CH

Risk Management Plan

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=WC0b01ac058067a113

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

Special measures

May demand additional monitoring for special products

-Black triangle (monthly update of products which are concerned: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2013/04/WC500142453.pdf

-PASS

Approval with requirements

Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 14

Swissmedic Inspection

Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH 15

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

- Having a PSMF available is not mandatory for Switzerland, however it was asked for

- All documents have been provided during the inspection

- 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

- All documents were provided in electronic form and not as paper copy

- Case assessment for ICSR - E2B connectivity with “local stop” in

order to fill in the Swiss specific labelling/ assessment…

16 Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH

Questions?

17 Dr. Doris Taeschner, Boehringer Ingelheim (Schweiz) GmbH