The European
Pharmacopoeia in a Global
Context
May 17, 2010 | Beijing
Dr. Susanne Keitel
European Directorate for the Quality of
Medicines & HealthCare,
Council of Europe
TOPICS
 Role and History of the European
Pharmacopoeia / EDQM
 Working Principles
 Establishment of Monographs
 Revision of Monographs
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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The Council of Europe
• Founded on 5 May 1949 by 10 countries
• An international organization in Strasbourg which
comprises 47 countries of Europe.
• The primary aim of the Council of Europe is to create
a common democratic and legal area throughout the
whole of the continent, ensuring respect for its
fundamental values: human rights, democracy and
the rule of law.
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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The EDQM
The European Directorate for the Quality of Medicines & HealthCare
(EDQM), a Directorate of the Council of Europe (DG Social
Cohesion)
Our vision is to be a leader in protecting public health by establishing
high quality standards for:
• medicines for human and veterinary use, blood transfusion and
organ transplantation;
• the safe and appropriate medication;
• participating in programmes targeted towards the protection of
consumer health.
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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European Pharmacopoeia Convention
S.Almeling, 26/09/10 ©2010 EDQM, Council of Europe, All rights reserved
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Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
From the European Pharmacopoeia..
• 1964: Activities based on an International Convention from
the Council of Europe to promote free movement of
medicines in Europe
• Mandatory status reinforced in 1975 in the EU Regulations
(Directives) – with relevance for the EEA
• 1994: EU signs the EP Convention
• 1994: creation of the European Network for Official
Medicines Control Laboratories
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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..... To The EDQM
• 1994: creation of the procedure of certification for
active substances
• 2007: transfer of activities on blood transfusion
and organ transplantation
• 2008: transfer of activities on combating
counterfeits and healthcare activities
• 2009: transfer of activities on cosmetics and foodpackaging
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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The Ph.Eur. in the World
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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European Regulatory Network
European Union
European
Medicines Agency
EMA****
London
European Union
Council
Parliament
Commission
DG Health & Consumers
Brussels
Council
of Europe
Ph. Eur.**
European
Directorate
for the Quality
Certification***
Blood Transfusion of Medicines & HealthCare
Pharmaceuticals/
Pharm. care
Organ Transplantation
*OMCL :Official Medicines Control Laboratories
**Ph.Eur : European Pharmacopoeia
***Certification : Certification of Suitability of Monographs of the European
Pharmacopoeia
****EMA : European Medicines Agency
EDQM
Strasbourg
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
OMCL*
Network
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European Pharmacopoeia
• Protecting public health - one common compulsory standard
• THE official pharmacopoeia in Europe – complemented by
national pharmacopoeias for texts of interest to only one
Member State
• Mandatory at the same date in 36 Member States (CoE) and
the EU (decision of Ph. Eur. Commission).
• Legally binding quality standards for ALL medicinal products
in the EU, i.e. raw material, preparations, dosage forms,
containers must comply with the Ph. Eur. requirements when
they exist.
KEITEL©2010
EDQM,
All rights reserved
SusanneSusanne
Keitel ©2011
EDQM, Council
of Council
Europe,ofAllEurope,
rights reserved
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Parties Involved
 The European Pharmacopoeia Commission
 The National Pharmacopoeia authorities
 The Groups of Experts and Working Parties
 The EDQM / Technical Secretariat
 The Stakeholders
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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Ph. Eur. Commission
Decision making body of the European Pharmacopoeia
Up to 3 delegates for each
member country
1 delegate for each Observer
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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Role of the Ph.Eur. Commission
 To determine the general principles applicable to
the elaboration of the Pharmacopoeia
 To decide upon methods of analysis for that
purpose
 To define and adopt the work programme
 To recommend the implementation dates of the
Pharmacopoeia
 To appoint chairs and members of expert groups
and working parties
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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Observers to the Commission
• Admittance of Observers from :
– Member States of the CoE that are not part of
the Convention
– States that are not Members of the CoE
– International governmental organisations
Decided by unanimous vote of the
Commission
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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National Pharmacopoeia
Authorities
• Usually, the Secretariat of the National
Pharmacopoeia Commission, or if missing,
the National Competent Authority
– Appoint delegates to the Commission
– Nominate experts to groups of experts/working
parties
– Implement the European Pharmacopoeia
– Provide the necessary funding
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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The Groups of Experts
Currently 20 permanent Expert Groups and
48 Working Parties (more than 250 meeting days/year)
Task:
To draft and verify the monographs and general methods
Composition:
• Experts from universities, industries, licensing authorities and
Official Medicines Control Laboratories
• Up to one expert per member country, chosen on the sole basis of
his/her scientific competence
• Additional specialists, where needed
• Meet 2 to 3 times a year
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The Purpose of the
European Pharmacopoeia
• To promote public health by the provision of
recognised common standards. Such standards
are to be for the safe use of medicines by patients
and consumers.
• Their existence:
— facilitates the free movement of medicinal products
in Europe;
— ensures the quality of medicinal products and their
components imported into or exported from Europe.
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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The Principles
• Elaboration and approval of monographs and other texts
proceeds through an efficient and transparent, smoothrunning process, based on scientific co-operation
between the members of the various Groups of Experts
and Working Parties assigned by the European
Pharmacopoeia Commission, the governing body of the
Pharmacopoeia.
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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The Principles
• Experts give of their time, expertise and experience
to produce the highest-level quality standards
available to the public, standards that are
continually revised in line with scientific
developments. This co-operation between experts
from regulatory authorities and official government
laboratory scientists, academia and industry
represents the pinnacle of scientific co-operation to
produce a high standard of technical monographs
and chapters.
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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The Principles
• Furthermore, the technical requirements
adopted by the Pharmacopoeia Commission
are based upon a unanimous decisionmaking process – each Member State of the
Pharmacopoeia Commission has the right to
veto, should they choose to exercise it.
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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Contents of the Ph. Eur.
More than 2200 monographs
Fats
dosage forms
Herbals
Radiopharm.
Human
vaccines
Vet. Vaccines
Plastics
Chemicals
Blood deriv.
Antibiotics
Gases
homeopathy
biologicals
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Basis for Monographs
• Monographs must take account of all currently
approved products
• Approved specification(s) are the main basis
backed up by batch data
• Draft monographs are checked by regulatory
authorities at Pharmeuropa stage
• Close collaboration between European
Pharmacopoeia and European Licensing Authorities
defined in EU Pharmaceutical Legislation (e.g.
Directive 2001/83/EC)
• Policy for monograph development is given in the
Technical Guide for the Elaboration of Monographs
(available on web site)
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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Creation or Revision of a Text
Request of creation / revision
Approval by
the
Commission
Allocation to
a Working
Procedure
Publication
Text
approved by
the
Commission
Overall timescale:
2-3 years
Assignment
to a Group
of expert
Public
enquiry
Creation /
revision of
the text by
the Group
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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Notification of National
Monographs
• According to the Guide for Work, delegations must notify
the Commission of any creation/revision of National
Monographs that may be within the scope of the Ph. Eur.:
– Information is sent by the NPA to the Secretariat.
– Proposals are then distributed by the Secretariat to all
delegations.
– Item added to the work programme:
• If at least 2 delegations are interested,
• If the text is within the scope of the Ph. Eur.
• If no delegation is opposed to it.
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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New Monographs
• Addition to programme depends on:
– therapeutic importance
– extent of use
– number of countries in which product is approved
– known quality problems
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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Revision: Why?
• Impact of globalisation: new sources (may) have new
impurity profiles
• Revision requests from European Licensing Authorities
or the EDQM Certification Division (CEP)
• New quality issues arise
• Analytical methods change: more convenient methods,
more powerful methods, more reliable methods
become available
• International harmonisation (PDG, ICH, VICH)
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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How Standards Are Regularly Reviewed
and Revised To Stay ‘State of The Art’
Increased demand for
Generic and Biosimilar
products
Developments in
Regulatory
Environment
e.g. Guidelines,
ICH Q8/Q9/Q10/Q11, REACH
e.g. New sources
Need to regularly
review and update
Ph Eur texts _
need to create
new texts
Scientific / technical
evolutions
New risks to
Public Health
e.g. Genotoxic impurities,
TSE, contamination/
falsification (heparins)
e.g. Fast LC, NIR, PAT,
new molecules, new
therapies e.g. CT
Developments in
Manufacture and
Globalisation
e.g. continuous
manufacturing, changed
routes of synthesis
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Pharmeuropa
• is the European Pharmacopoeia Forum containing draft
monographs and texts for public comment
• 4 issues per year
• 4 comment deadlines per year
• As of Jan 2012, i.e. Pharmeuropa 24.1, will be paperless and
free
• Texts will be published on ongoing basis, while comment
deadlines will stay as before
• Trial period (both online and print available):
– 23.3 and 23.4 access for ANPs
– 23.4 access for general public
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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Publication and Implementation
• The text is first published in Pharmeuropa for
information and posted on the EDQM website.
• Ph. Eur. texts are implemented usually 1 year
after adoption by the Commission and about 6
months after publication.
• Ph. Eur.: 3 supplements per year and 1 new
edition every 3 years.
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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Reference Standards
• Most monographs require at least one reference
standard
• The reference standard underpins the quality standard
• Established and monitored by the EDQM Laboratory
• Produced and distributed by the Reference Standards
Division
2200 reference standards
• Since 2010, EDQM is also responsible for WHO’s ICRS
portfolio
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
ouncil of Europe, All rights reserved
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Ph. Eur. International Activities
• 36 European Member States and EU
• 22 observer countries and WHO
• MoU‘s and Confidentiality Agreements
with NIFDC, FDA, TGA....
• Pharmacopoeial Discussion Group (PDG)
• Collaboration in the establishment of
reference standards
• ....
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Key Documents
• Convention on the Elaboration of a European
Pharmacopoeia http://www.edqm.eu/medias/fichiers/1964_PhEur_Convention_English.pdf
• Protocol to the Convention on the Elaboration of a
European Pharmacopoeia
http://www.edqm.eu/medias/fichiers/1994_Protocol_PhEur_English.pdf
• Rules of Procedure of the European Pharmacopoeia
Commission http://www.edqm.eu/medias/fichiers/Rules_of_Procedure_of_the_European_Pharmacopoeia_C.pdf
• Guide for the Work of the European Pharmacopoeia
http://www.edqm.eu/medias/fichiers/PAPHSG_10_42_DEF_Guide_for_the_work_of_the_Europea.pdf
• Code of Practice for the Work of the European
Pharmacopoeia
http://www.edqm.eu/medias/fichiers/Code_of_Practice_for_the_Work_of_the_European_Phar.pdf
Susanne Keitel ©2011 EDQM, Council of Europe, All rights reserved
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