1 1 quality-principles
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Principles of quality control of registered medicines, non-registered medicines and
counterfeits of medical products
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
Jean-Marc Spieser, 23/09/09©2009 EDQM, Council of Europe, All rights reserved 2
ContentContent
• 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 3
The Council of EuropeThe 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 4
The Council of EuropeThe 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 5
Jean-Marc Spieser, 23/09/09©2009 EDQM, Council of Europe, All rights reserved 6
The European UnionThe European Union
Jean-Marc Spieser, 23/09/09©2009 EDQM, Council of Europe, All rights reserved 7
EDQM - Short History EDQM - Short History1964:
– 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 8
Short History 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 9
Progressive Transfer of ActivitiesProgressive 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 10
Ph.Eur.+ Eur. ObserversPh.Eur.+ Eur. Observers
Jean-Marc Spieser, 23/09/09©2009 EDQM, Council of Europe, All rights reserved 11
In the WorldIn the World
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European Directorate for the Quality of Medicines & HealthCare (EDQM) 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 13
European Directorate for the Quality of Medicines & HealthCare
European Directorate for the Quality of Medicines & HealthCare
Jean-Marc Spieser, 23/09/09©2009 EDQM, Council of Europe, All rights reserved 14
European Regulatory NetworkEuropean Regulatory Network
European AuthoritiesEuropean Union
Council of Europe
European UnionEuropean Union
Council ParliamentCouncil ParliamentCommissionCommission
DG EntrepriseDG EntrepriseBrusselsBrussels
EuropeanEuropean Medicines AgencyMedicines Agency
EMEALondonEMEALondon
EuropeanDirectorateEuropeanDirectoratefor the Qualityfor the Quality
of Medicines & HealthCareof Medicines & HealthCare
EDQMEDQMStrasbourgStrasbourg
Ph. Eur.**Ph. Eur.**
Certification***Certification***
OMCL*OMCL*NetworkNetwork
*OMCL :Official Medicines Control Laboratories**Ph.Eur : European Pharmacopoeia***Certification : Certification of Suitability of Monographs of the European Pharmacopoeia Organ TransplantationOrgan Transplantation
Blood TransfusionBlood Transfusion
PharmaceuticalsPharmaceuticalsPharmaceutical carePharmaceutical care
Jean-Marc Spieser, 23/09/09©2009 EDQM, Council of Europe, All rights reserved 15
Quality AssuranceQuality 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 16
Quality AssuranceQuality Assurance
As a general concept
QUALITYQUALITY
is manufacturedmanufactured and not only controlled
Jean-Marc Spieser, 23/09/09©2009 EDQM, Council of Europe, All rights reserved 17
Quality ControlQuality Control
QC PrinciplesQC 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 18
Quality ControlQuality Control
QC PrinciplesQC Principles• Working environment
QA/QMS in place Good reporting Procedures PTS Follow up and corrective actions Procedures in place Training
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RegulationsRegulations
• 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 20
RegulationsRegulations
A fully detailed registration dossier is filed based on:Quality – Production using appropriate process, suitable ingredients controlled and released by validated testsSafety - toxicology and pharmacologyEfficacy – clinical
Jean-Marc Spieser, 23/09/09©2009 EDQM, Council of Europe, All rights reserved 21
RegulationsRegulations
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
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RegulationsRegulations
• 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 23
ToolsTools
• 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 24
SamplingSampling
• 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 25
Non registered “medicines”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 26
Non registered “medicines”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 27
Non registered “medicines”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 28
COUNTERFEITED MEDICINESCOUNTERFEITED 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 29
COUNTERFEITED MEDICINESCOUNTERFEITED 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 30
COUNTERFEITED MEDICINESCOUNTERFEITED 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 31
COUNTERFEITED MEDICINESCOUNTERFEITED 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 32Thank you!Thank you!