More Related Content Similar to 1 1 quality-principles Similar to 1 1 quality-principles (20) 1 1 quality-principles1. Principles of quality control of
registered medicines, non-
registered medicines and
counterfeits of medical products
Jean-Marc Spieser,
Head of Department of Biological Standardisation, OMCL
Network & HealthCare (DBO),
EDQM/ Council of Europe, Strasbourg
2. Content
• EDQM – General Background
• Legal environment of registered medicines
• Tools available for the quality control of registered medicines
• The case of non-registered medicines and their vast
environment
• How to control non-registered products
• Counterfeits of medical products
• How, why, and where it happens
• How to control it
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 2
3. The Council of Europe
– Founded in 1949
– Development of European common and democratic
principles
– 47 member countries
– Strasbourg
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 3
4. The Council of Europe
– Founded in 1949
– Development of European
common and democratic
principles
– 47 member countries
– Strasbourg
European Convention on Human Rights
(protection of individuals) &
European Court of Human Rights
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 4
6. The European Union
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 6
7. EDQM - Short History
1964:
– Convention on the Elaboration of a European
Pharmacopoeia signed by 8 Member States
1992:
– 1st co-operation contract with the EU Commission on the
Biological Standardisation Programme
1994:
– European Community signs the Convention
– CEP – Implementation of the “Certification of Suitability
scheme”
– Official Medicines Control Laboratory (OMCL) – Creation of
the Network
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 7
8. Short History
Change of name: the Secretariat of the
European Pharmacopoeia becomes the
European Department (and later
“Directorate”) for the Quality of Medicines
(and later “& HealthCare”)…
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 8
9. Progressive Transfer of Activities
2007 – Blood Transfusion and Organ
Transplantation
2008 – Pharmaceuticals and Pharmaceutical
Care (general pharmaceutical
activities)
2009 – Cosmetics and Food Packaging
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 9
11. In the World
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 11
12. European Directorate for the Quality of
Medicines & HealthCare (EDQM)
Mission: to contribute to the basic human right
of access to good quality medicines
and healthcare
Health is a social human right indispensable
for the exercise of all other human rights, for
prosperity and democratic stability of people
in Europe
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 12
13. European Directorate for the Quality of
Medicines & HealthCare
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 13
14. European Regulatory Network
European Authorities
European Union
European Union
European
Council Parliament Medicines Agency
Commission EMEALondon
DG Entreprise
Brussels
Council
of Europe Pharmaceuticals
EuropeanDirectorate Ph. Eur.**
Pharmaceutical care
for the Quality
*OMCL :Official Medicines Control of Medicines & HealthCare
Laboratories Blood Transfusion Certification***
**Ph.Eur : European Pharmacopoeia
***Certification : Certification of Suitability EDQM
of Monographs of the European
Pharmacopoeia Organ Transplantation Strasbourg OMCL*
Network
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 14
15. Quality Assurance
Quality is obtained through the combination of:
• Definition and concept of the product based on development
work
• Good manufacturing processes steadily under control
- starting, in-process and final controls
- continuous optimisation
- VALIDATED controls of the final product based on
suitable and appropriate limited testing (necessary and
fully sufficient),
All the above should be totally traceable
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 15
16. Quality Assurance
As a general concept
QUALITY
is manufactured and not only
controlled
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 16
17. Quality Control
QC Principles
• Laboratory of high quality
Good equipment: validated, regularly
maintained
Good reagents
Good operators
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 17
18. Quality Control
QC Principles
• Working environment
QA/QMS in place
Good reporting
Procedures
PTS
Follow up and corrective actions
Procedures in place
Training
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 18
19. Regulations
• Medicines are submitted to very strict
regulations
• Each individual preparation requires a
Marketing Authorisation (MA)
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 19
20. Regulations
A fully detailed registration dossier is filed
based on:
Quality – Production using appropriate
process, suitable ingredients controlled and
released by validated tests
Safety - toxicology and pharmacology
Efficacy – clinical
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 20
21. Regulations
All information and documentation
compiled by producers and/or authorised
importer are filed to Health Authorities in
accordance with legal procedures and
assessed by experts using defined rules
Official Authorisation
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 21
22. Regulations
• The product is continually assessed
throughout its lifetime:
Inspections
Controls
through laboratory testing
Pharmacovigilance
If non-conformities are found administrative, legal
and/or financial penalities
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 22
23. Tools
• The MAA: QA part
• CTD part
• Pharmacopoeias such as National Pharmacopoeias, International
Pharmacopoeias, Ph. Eur., USP
- General Chapters
- Individual Monographs
• Guidelines/ aide mémoire for inspections, sampling
• Literature/ data
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 23
24. Sampling
• Ensure representativity
- withdrawn by authority or mandated persons
- not by manufacturer
- define place where samples are taken, how and how much
• Ensure good storage
- temperature
- humidity
- transportation
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 24
25. Non registered “medicines”
• Traditional origin
- Mostly oral and very restricted data available
- Origin not always traceable but should be
- How to control the claims and attributes given to these
products
- What to control, which criteria and indicative parameters
• Legal environment??
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 25
26. Non registered “medicines”
• Controls
- Based on visual recognition of the substance or the plant
- If plant is chopped or ground use of of organoleptic
properties, microscopic aspect and basic wet chemistry(test
tube ) assays
- Important to verify that the right species is there
- Need of specialists
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 26
27. Non registered “medicines”
• Controls
- Based on traditional knowledge
- Sometimes described in literature bust mostly oral
- No official standards but need to develop it in known
recognised compendia
- Be carefull on adulterated, counterfeits
- ILLEGAL
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 27
28. COUNTERFEITED MEDICINES
• By definition not known
• When and where it will happen
- ILLEGAL of course by defition
- 2 basic areas attacked
- Blockbusters, expensive, well known, attractive…….organised crime
- Local , smallsmugglers for small quantities of every possible things
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 28
29. COUNTERFEITED MEDICINES
• How to combat these products
- Through multisectorial surveillance
- Forensic analysis
- Custom vigilance
- Police controls
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 29
30. COUNTERFEITED MEDICINES
• To start with
– Visual check of packaging very important
• Followed by analysis
– Simple and more and more sophisticated
• Need to have comparator
– Reference substance(s)
– Authentic samples
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 30
31. COUNTERFEITED MEDICINES
• Simple comparative tests
• Then sophisticated
– HPLC using different detectors, coupled with mass spectrum
• Usefulness of network
Jean-Marc Spieser, 23/09/09
©2009 EDQM, Council of Europe, All rights reserved 31