The basics to understand what the European PV modules are and what they entail.

1. 1
PV MODULES:
WHAT ARE THEY?
WHY ARE THEY IMPORTANT FOR THE
USA?
PRESENTED BY:
VASKA TONÉ

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

3. Centralized Procedure
http://ec.europa.eu/health/authorisation-procedures-centralised_en.htm
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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

4. 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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5. DeCentralized Procedure
http://ec.europa.eu/health/authorisation-procedures-decentralised_
en.htm
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 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).

6. EU Pharmacovigilance
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 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

7. EU Pharmacovigilance
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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.

8. EU Pharmacovigilance
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 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.

9. EU Pharmacovigilance
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 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.

10. EU PV Modules
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 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

11. EU PV Modules
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 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.

12. EU PV Modules
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 Modules VIII – X are Product or Population Specific Considerations
 Module VIII – Post‐Authorization Safety Studies
 Module IX – Signal Management
 Module X – Additional Monitoring

13. EU PV Modules
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 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

14. 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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15. Module II – PV System Master Files
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 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.

16. Module IV – PV Audits
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 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.

17. Financial Impact
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 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

18. WHEW – That was LONG…..
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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