1 1 quality-principles

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


The Council of EuropeThe Council of Europe

– Founded in 1949– Development of European common and democratic

principles – 47 member countries– Strasbourg


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


The European UnionThe European Union


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


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”)…


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


Ph.Eur.+ Eur. ObserversPh.Eur.+ Eur. Observers


In the WorldIn the World


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


European Directorate for the Quality of Medicines & HealthCare

European Directorate for the Quality of Medicines & HealthCare


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


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


Quality AssuranceQuality Assurance

As a general concept

QUALITYQUALITY

is manufacturedmanufactured and not only controlled


Quality ControlQuality Control

QC PrinciplesQC Principles

• Laboratory of high quality

Good equipment: validated, regularly maintained

Good reagents Good operators


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


RegulationsRegulations

• Medicines are submitted to very strict regulations

• Each individual preparation requires a Marketing Authorisation (MA)



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



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



• 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


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


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


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??



• 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



• 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


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



• How to combat these products- Through multisectorial surveillance

- Forensic analysis- Custom vigilance- Police controls



• 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



• Simple comparative tests

• Then sophisticated– HPLC using different detectors, coupled with mass spectrum

• Usefulness of network

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Documents

edqm council of europe

networkjeanmarc spieser

europejeanmarc spieser

observers jeanmarc spieser

world jeanmarc spieser

traceable jeanmarc spieser

good quality medicines

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