PV MODULES:WHAT ARE THEY?

WHY ARE THEY IMPORTANT FOR THE USA?

PRESENTED BY:

VASKA TONÉ

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European Union http://europa.eu/about-eu/countries/

EU Made up of 28 countries as of July 2013 Each country has to implement the EU Directives into local

government regulations Not all countries have implemented every directive and many are

behind in implementing the PV Directives Marketing Applications are usually done through a centralized

procedure: Regulation (EC) No 726/2004

NOTE: There are specific requirements regarding which products MUST be registered via the centralized procedure but there are many products that do not need to be registered centrally

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Centralized Procedurehttp://ec.europa.eu/health/authorisation-procedures-

centralised_en.htm

What is the Centralized Procedure? Regulation came into operation in 1995 Allows applicants to obtain a marketing authorization that is valid

throughout the EU Application is sent directly to the European Medicines Agency, to be

assessed by the Committee for Medicinal Products for Human Use (CHMP)

A rapporteur and a co-rapporteur are designated by the competent EMA scientific committee who liaises between the CHMP and the applicant

Evaluation process is 210 days

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Centralized Procedure

The Agency sends to the CHMP its opinion and assessment report, together with annexes containing: the summary of product characteristics (SPC) (Annex 1); the particulars of the MAH responsible for batch release, the

particulars of and the manufacturer of the biological active substance and the conditions of the marketing authorization (Annex 2);

the labelling and the package leaflet (Annex 3)

AH-HA! Finally the PV portion!

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DeCentralized Procedurehttp://ec.europa.eu/health/authorisation-procedures-

decentralised_en.htm The Decentralized Procedure is for applicants who wish to market a

product in various EU countries and for which the product has not yet received an approval in any EU country.

The decentralized procedure was introduced by Directive 2004/27/EC

An identical application for marketing authorization is submitted simultaneously to the CAs of the Reference Member State (the country making the scientific evaluation of the application) and of the Concerned Member States (where the product will be marketed).

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EU Pharmacovigilance

The company that HOLDS the marketing authorization must continuously collect data and conduct PV

The company that has developed the product in the USA might not be the MAH in the EU. It may be a licensing or marketing partner. Safety information must be shared usually through a Safety Data Exchange Agreement (SDEA)

The MAH must report continual PV information and inform the EMA about any emerging concern about the benefit-risk balance of the product

Companies are open to inspection of their PV systems

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EU Pharmacovigilance

The EU has three (3) bodies that help regulate products in the EU: The Competent Authority (CA) in each Member State: equivalent of

the FDA in each European country – also can be called the Health Authority (HA).

The European Commission (the body approving the authorization (aka registration) of the product.

The European Medicines Agency (“The Agency”) responsible for releasing regulations/EU Directives and requests for inspections.

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EU Pharmacovigilance

New pharmacovigilance legislation (Regulation (EU) No 1235/2010 and Directive 2010/84/EU) was adopted by the European Parliament and European Council in December 2010; it did not become effective until 2012!, and MANY member states have yet to enact it into local regulation

The legislation was the biggest change to the regulation of human medicines in the European Union (EU) since 1995.

It has significant implications for applicants and holders of EU marketing authorizations.

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EU Pharmacovigilance

The EMA is responsible for implementing much of the new legislation, with the PV legislation being amended was in October 2012 but doesn’t apply until October 2013.

The legislation is actually known as the Good Pharmacovigilance Practices (GVP) and consists of both requirements and procedures.

These are the new PV MODULES, are constantly being updated and revised or amended/improved for clarity.

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EU PV Modules

The PV Modules are similar to Guidance Documents in the USA but are ALSO adopted into Regulation by the Member States

These modules specify the detailed requirements that all companies who have received marketing authorization for their products in Europe must follow. As each module is adopted by the EU it replaces the relevant

sections of Volume 9A of the Rules Governing Medicinal Products in the EU, which was the authoritative PV “manual”

Modules I – VII are related to PV processes & procedures Modules VIII – X are related to Product or Population Specific

Considerations Modules XI – XVI are related to Benefit-Risk and Risk Minimization

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EU PV Modules

Modules I – VII are procedures/processes Module I – PV systems and their quality systems Module II – PV System Master File Module III – PV Inspections Module IV – PV System Audits Module V – Risk Management Systems Module VI – Management and Reporting of Adverse Reactions Module VII – Periodic Safety Update Reports

Modules I, II & IV are very important for US auditors.

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EU PV Modules

Modules VIII – X are Product or Population Specific Considerations Module VIII – Post‐Authorization Safety Studies Module IX – Signal Management Module X – Additional Monitoring

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EU PV Modules

There are to be an additional 4 modules released in 2013 but up to 16 total Modules, Module XI – Public Participation in PV Module XII – Continuous pharmacovigilance, ongoing benefit-risk

evaluation, regulatory action and planning of public communication Module XIV – International Cooperation Module XV1 – Risk-minimization measures: selection of tools and

effectiveness indicators

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Module I – PV System & Quality System

MAHs are required to have a quality system in place which covers their PV activities, and documentation of the system will be necessary.  Quality principles need to be routinely applied, particularly for:• Resource management• Staff training• Procedural documentation• Quality control• Monitoring• Improvement• Audits

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Module II – PV System Master Files

Summary information only concerning the EU qualified person for pharmacovigilance (QPPV) and the location of a pharmacovigilance system master file will be contained in marketing authorizations. 

Full descriptive information about the PV system will have to be contained in a PSMF, which should be made available to the requesting Competent Authority.

There is a clear requirement for an adequate pharmacovigilance system as a condition of marketing authorization.

Marketing authorization applicants should be aware that the PSMF may be requested for review during the application process, and an inspection may be conducted to establish the adequacy of the (proposed) PV system before authorization is granted.

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Module IV – PV Audits

Audits of the PV system (including the quality system) will have to be: Conducted on a regular basis, ideally once every two years, Have enough resources to do the audits Will have to include:

Internal PV System (HQ, global and local affiliates) PV Vendors & possibly Reg Affairs vendors License/Marketing Partners

The new Regulation contains the legal basis for the conduct of pre-authorization inspections, and there is also a clear requirement for an adequate pharmacovigilance system as a condition of marketing authorization. 

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Financial Impact

Financial penalties to MAHs in Europe were introduced in 2007. Non-compliance penalties can be imposed of up to 5% of total EU annual turnover.  Non-compliance includes:• Not Maintaining up to date product information• Not providing data requested by an agency• Maintaining a comprehensive pharmacovigilance system• Not Submitting a PV System Master File (PSMF) at agency request• Not having a risk management system• Not recording or reporting Individual Case Safety Reports (ICSR)• Not submitting the PSUR• Not Notifying the agency of public communications, such as Dear Doctor

letters• Not Collating and assessing pharmacovigilance dates• Not having an EU QPPV

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WHEW – That was LONG…..

ANY QUESTIONS???

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Contact Information:

Vaska Toné

President & CEO

Email: vaska.tone@lavapharm.com

Phone: +1-951-240-5635

www.lavapharm.com

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