Transcript QANU Visitatie Master Drug Innovation, RUU Feb. 2007

The European
Pharmacopoeia,
Past, Present and Future
Moscow, March 2008,
Pharmsodruzhestvo 3rd International
Forum
 H. de Jong
Chair Ph.Eur. Commission (2007-2010)
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The Key Words
Harmony
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Harmonisation
Origins of the words:
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Latin: harmonica = concord of sounds
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Greek: harmos = joint
Joint, some meanings
A place of meeting for persons engaged
in some illicit operation
 In USA: a place illegally kept (usually by
Chinese) for opium smoking or illicit
drinking
 In Holland: a hand-rolled cigaret
containing « weed »
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Harmonisation, some meanings
Agreement in action, opinion, feeling
 Order of congrenuity of parts to their
whole or to one another
 Agreable sounds
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Harmonisation (ctd)
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Music:
- a combination of notes
- vertically represented
structure of a piece of
music
- the art or science
concerned with the
structure and
combination of chords
Harmonization (ctd)
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Collation of the material of parallel
narratives, especially the four gospels
Harmonisation perspectives:
From the Bible (the gospels) to the
opium kit (joint)
 Where the old Romans less criminal
than the classical Greeks ?
 Quo vadis ?
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Harmony in the Quality of
Medicines
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Where do we come
from ?
 First there were the
city pharmacopoeias
 Then National ones,
e.g. French, British,
Russian, ….
 Then…….?
Harmonisation a long story:
1865 German Pharmacists Associaton:
« Dream of an International
Pharmacopoeia »
 1893 APhA in Chicago presses for
uniform specifications for « potent
drugs »
 1906 First Intergovernmental
Convention: « International Formulary »
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Harmonisation
1908 Dutch Pharmacist’s Association
proposal for a permanent international
conference and association
 1911 Founding of FIP
 1912 First Assembly in Binnenhof, the
Hague
 1937 League of Nations 1st meeting of
Pharmacopoeial Experts
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Harmonisation
1948 WHO expert Committee on
Unification of Pharmacopoeias
 1951 Pharmacopoeia Internationalis 1st
Edition
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1964 Convention on the Elaboration of
a European Pharmacopoeia under the
aegis of the Council of Europe
Council of Europe Actions
Since the founding more than 170
European Treaties and Conventions
have been signed by the members,
replacing some 130 000 bilateral
treaties.
 Convention on the elaboration of
European Pharmacopoeia: European
Treaty Series No 50 of 1964
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European Pharmacopoeia
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In 1964, founding countries (8):
Belgium
France
Italy
Luxembourg
The Netherlands
United Kingdom
Fed Rep Germany
Switzerland
European Pharmacopoeia
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In 2008, the Convention has 37 members out
of 47 Member states of the Council of
Europe
 The EC is one of the signataries
 The Monographs and General
Prescriptions/Methods are applicable in the
Member States
 There are also 21 observers including WHO
Observers :
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WHO
Albania
Algeria
Australia
Belarus
Brazil
Canada
China
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Russian Federation
Georgia
Israel
Kazakhstan
Madagascar
Malaysia
Morocco
Moldova
Arab Rep of Syria
Observers :
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Senegal
 Tunisia
 Ukraine
 USA/FDA
« Missing countries, CoE »
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Andorra
Armenia
Azerbaijan
Liechtenstein
Monaco
San Marino
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A request from
Armenia to become
observer has just
been received
(19/3/2008)
Current scope:
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Approximately 2000 monographs
(active substances & excipients) and
General Chapters/Methods fully
Harmonised = Identical in the countries
of the Convention
Medicinal Products in Europe
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Starting with the Directive 65/65 EEC of 26
January 1965, via several (important)
modifications, leading to Directive
2001/83/EC of 6 November 2001, finally
adopted on 30 April 2004, now being
implemented.
 Annex I: Analytical, pharmacotoxicological
and clinical standards and protocols in
respect of the testing of medicinal products
Annex I
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Introduction and general principles article
(5):
« With respect to the quality part (chemical,
pharmaceutical and biological) of the dossier,
all monographs including general
monographs and general chapters of the
European Pharmacopoeia are applicable »
Annex I (continued)
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Standardised marketing autorisation
dossier requirements, article 3.2 Content:
basic principles and requirements section (4):
« All the procedures and methods…..state of
scientific progress…..shall be validated. In
case of test procedures included in the
PhEur, give appropriate detailed reference to
monograph(s) and general chapter(s) »
Annex I (continued):
Section (5):
« The monographs of the PhEur shall be
applicable to all substances,
preparations and pharmaceutical forms
appearing in it. In respect of other
substances, each Member State may
require observance of its own national
pharmacopoeia »
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Annex I (continued)
Section (6):
« In case where starting and raw
materials, active substance(s) or
excipient(s) are described neither in the
PhEur nor in the pharmacopoeia of a
Member State , compliance with the
monograph of a third country
pharmacopoeia can be accepted…….
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Annex I (continued):
….In such cases, the applicant shall
submit a copy of the monograph
accompanied by the validation of the
analytical procedures contained in the
monograph and by a translation where
appropriate »
Conclusions :
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When there is a PhEur text : apply
 When there is no PhEur text, check if national
text exists
 When no PhEur and no national text, look for
third country e.g. BP, PF, Ph Helv, JP,
USP…..and validate
 Harmonisation of Pharmacopoeias and
Regulatory Acceptability of its outcomes very
important
Worldwide Harmonisation
The WHO Pharmacopoeia
Internationalis
 The USP, JP, PhEur collaboration in the
Pharmacopoeial Discussion Group
(PDG) since 1989 in liaison with the
International Conference on
Harmonization (ICH)
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International Harmonisation
Ingredients
History
Environment
Law
Language….
C.A. Johnson FIP Congress
Dublin 1975
2007 NEWS
A New Building in Strasbourg
New meeting rooms
Certificate of Suitability to the
PhEur « recognised » by Canada
Kazakhstan observer and……
Croatia, new edition
A new Director: Dr.Susanne Keitel
successor to Dr. Agnes Artiges
A New Edition, applicable
01/01/2008 (now already at 6.2)
Global Harmonisation (Ph.Eur.
JP, USP
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ICH Q4B Pharmacopoeial
Interchangeability Guideline. Step 4 signed
in Yokohama November 1, 2007
 9 of 11 General Chapters (Q6A) signed –off,
2 ongoing
 10 other general chapters signed off, 7
ongoing
 Excipient Monographs: 36 signed off, 26
ongoing
Harmonisation of General Methods
(ICH Q6 and PDG)
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Dissolution
Disintegration
UDU
Tests for micro-org.
Microbial enumer.
Limits for non sterile
Bacterial endotoxins
Color (instrumental)
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Extractable volume
 Particulate
contamination
 Residue on ignition
 Sterility testing
Harmonisation of General Methods
PDG
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Analytical sieving
Bulk Density and
Tapped Density
Conductivity
Gas pycnometric
density of solids
Powder flow
Tablet friability
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Heavy metals
Inhalation products
Optical microscopy
Powder fineness
Specific surface
area (powders)
Porosimetry (by
mercury intusion)
Harmonisation of General Methods
PDG
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Laser diffraction
measurement of
particle size
 X-ray powder
diffraction
 Water-solid
interaction
 Thermal analysis
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Uniformity of
delivered dose of
inhalations
 Microcalorimetry
 Density of solids….
Harmonisation of General Methods
PDG Biotech Products
Amino acid determination
 Capillary electrophoresis
 Isoelectric focussing
 Protein determination
 Peptide mapping
 Polyacrylamide gel electrophoresis
 Glycan mapping
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New observers to the PhEur
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Russian Federation
 Kazakhstan
 Belarus
 Moldova
Important current topics :
Chromatographic separation techniques
 Quantification of impurities
 Potential genotoxic impurities
 Functionality related characteristics for
excipients
 Biologicals/biosimilars
 Traditional medicines (China, India…)
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Thank You