Prequalification of
Quality Control Laboratories
WHO Quality Monitoring Projects
Jitka Sabartova
Prequalification Programme: Priority Essential Medicines
HSS/EMP/QSM
Prequalification of QC laboratories
 Need to increase the access to QC laboratories that
– meet recommended standards for testing of medicines
– are committed to provide a service of testing of medicines, including but not
limited to HIV/AIDS, Tuberculosis and Malaria products to UN agencies
 Procedure established in 2004 for QC laboratories in Africa
– In cooperation with UNICEF, UN Population Fund (UNFPA), UNAIDS and with
the support of the World Bank
– UNITAID and The Global Fund - partners
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QCLs Prequalification Procedure
 Participation of a QC laboratory is voluntary
– Any laboratory (private or governmental) can participate
– Free of charge
 3rd Invitation for Expression of Interest published in
September 2007
– Without regional limitation
– http://www.who.int/prequal/info_applicants/eoi/EOI-QCLabsV3.pdf
 Priority in the assessment is given to
– National QC laboratories and laboratories providing testing services to the
government
– QC laboratories in areas where UN agencies identify the need for quality testing
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Based on the following principles
 General understanding of the quality control
activities of the laboratory
– Evaluation of information submitted by the laboratory
 Assessment of consistency in quality control
through compliance with WHO standards
– Inspection of the quality system implemented by the
laboratory
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QCLs Prequalification Procedure
(1)
September 2009
QCLs Prequalified
Prequalified QCLs:
QCLs Interested
35
30
25
24
24
20
15
22
16
10
5
10
8
8
3
3
11
3
0
2004
2005
2006
2007
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2008
Sep-09
 South Africa,
RIIP+CENQAM (2005)
 Algeria, LNCPP (2005)
 South Africa, Adcock
Ingram (2007)
 Morocco, LNCM (2008)
 Kenya, NQCL (2008)
 India, Vimta Labs
(2008)
 France, CHMP (2008)
 Vietnam, NIDQC (2008)
 Kenya, MEDS (2009)
 Singapore, HSA (2009)
 Singapore, TÜV (2009)
QCLs Prequalification Procedure
(2)
September 2009
National QCLs
Other QCLs
QCLs interested
26
9
20
18
16
QCLs prequalified
5
14
12
10
8
6
14
1
4
2
0
5
AFRO
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EMRO
1
3
EURO
1
2
SEARO
3
WPRO
Inspections / Pre-audits performed
10
9
4
8
7
6
5
Pre-audits
5
6
4
6
1
6
3
2
3
1
3
1
1
0
2004
2005
2006
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2007
2008
Sep-09
Inspections
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Monitoring after prequalification
 Re-inspections at regular intervals
•
•
Normally 3 years
2 re-inspections performed
 Brief report to be submitted annually
•
•
•
•
Summary of services provided to UN agencies, number of analysed samples, methods used,
complaints received
Brief details of proficiency testing
Changes to key personnel, facility, equipment or other significant impact to the laboratory
Update of LIF, in case of changes with significant impact on LIF content
 Evaluation of results from participation in proficiency testing
•
WHO External Quality Assurance Scheme, AFSSAPS network of Francophone African countries
 WHO may suspend or withdraw a laboratory from the list when there is
evidence of noncompliance
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Participation in WHO
External Quality Assurance Scheme (1)
 Non-commercial laboratories involved in prequalification procedure
were invited
 WHO - Phase 4, 06/2007 - 01/2009
– Water content by Karl Fischer (Oxytetracycline dihydrate)
• 3 of 10 labs unacceptable results
– Dissolution testing (Isoniazid tablets, UV)
• 2 of 18 labs unacceptable results
– HPLC assay (zidovudine/lamivudine FDC)
• 2 of 18 labs unacceptable results for both assays
– Titration (quinine dihydrochloride injection)
• 2 of 18 labs unacceptable results
– Polarimetry (glucose)
• 2 of 12 labs unacceptable results
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Capacity building
 Technical assistance provided to 8 national medicines QC laboratories
– Focus on implementation of quality system and microbiological testing, inventory audits
 Trainings in Quality Assurance, Quality Control and Ph.Int. under
preparation (2007)
– Morocco, 44 participants from 16 Francophone countries (AFRO, EMRO), cooperation with EDQM
and AFSSAPS
– Tanzania, 46 participants from 23 Anglophone countries (AFRO, EMRO, PAHO/AMRO)
 Seminar on rational sampling and testing in quality control of medicines
(2009)
– Kenya, 45 participants from 21 countries (AFRO, EMRO, WPRO)
 Participation in EDQM Quality Assurance training for OMCLs
– 2005, 5 participants from AFRO and EMRO
– 2007, 12 participants from AFRO, EMRO and EURO
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WHO Prequalification Programme
monitoring of medicines quality
 Policy
– To monitor quality of medicines procured by UN agencies/
prequalified products
– To contribute to quality control of medicines, if requested by
Member States
– To contribute to capacity building by cooperation with NDRAs
 Sampling and testing projects – a tool for fulfilling the policy
 Prequalified laboratories or laboratories for which the
evidence of reliability is available
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Sampling and testing projects
Entry
information
Plan
Quality concerns,
complaints/defects,
signals, inspections
PQ procedures
Actions
Reports
Inspections
Assessment
PhV
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+updates
Conduct
of projects
P1
P2
P3
…
Quality monitoring projects (1)
 Quality monitoring of medicines funded by UNITAID (2008/9)
– Strengthening of quality control of medicines as close to patients as possible, in
cooperation with NDRAs (capacity building)
– Framework protocol supplemented by country specific sampling plans
– Assessment product information compliance with national requirements
(Labelling and PIL)
– Pilot phase
• Paediatric and second line ARVs (abacavir, didanosine, efavirenz, tenofovir,
tenofovir/emtricitabine, lopinavir/ritonavir, lamivudine, stavudine, nevirapine, zidovudine,
lamivudine/stavudine, lamivudine/zidovudine, lamivudine/stavudine/nevirapine) + co-trimoxazole
•
•
•
•
•
Kenya, Tanzania, Uganda and Zambia
Testing in MHRA (UK), AFSSAPS (France), NICPBP (China)
Pharmacopoeial specifications – Ph.Int., USP, IP, manufacturers' methods
383 samples from 24 manufacturers, majority prequalified and registered in the country
3 samples non-compliant, no critical failure
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Quality monitoring projects (2)
 Quality survey of antimalarial medicines (2008/9)
– ACTs (most sold and recommended by national guidelines), sulfadoxine-pyrimethamine, oral
dosage forms
• Artemether/lumefantrine, artesunate/amodiaquine (both co-blistered and FDCs),
sulfadoxine/pyrimethamine, sulfamethoxypyrazine/pyrimethamine
– In 6 African countries (Cameroon, Ethiopia, Ghana, Kenya, Nigeria, Tanzania)
– Collection of samples
• At all levels of distribution chain (private and public) and informal market, throughout the countries
• 936 samples collected by NDRAs in cooperation with WHO country offices
– Testing
• Screening by GPHF-Minilab
• 305 samples then tested in RIIP, South Africa / USP (Ph.Int., USP, laboratory in-house method)
• 67 non-compliant samples, range of quality problems, including absence of API in 2 samples
– Assessment of quality of product information (Labelling and PIL)
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Quality monitoring projects (3)
 Quality survey of antituberculosis medicines (2009)
– Eastern Europe and NIS
• Countries with high multidrug-resistant TB and extensively drug-resistant TB
• Armenia, Azerbaijan, Belarus, Kazakhstan, Ukraine, Uzbekistan
– Close cooperation with NDRAs and WHO EURO regional office
– First- and second-line anti-TB medicines to be collected close to patients
• Rifampicin capsules, Isoniazid tablets and injection, Rifampicin/Isoniazid tablets
• Kanamycin powder for injection, Ofloxacin tablets and solution for infusion
– Testing in OMCLs of Austria and Luxembourg, in EDQM, SGS (Belgium)
according to Ph.Int. / USP
– Comparative dissolution study of Rifampicin capsules and Rifampicin/Isoniazid
tablets at Goethe University, Germany
– 360 samples planned to be collected
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Quality monitoring projects (5)
 Comparative dissolution study of Coartem tablets (2007)
– Artemether / lumefantrine innovator - problems with dissolution reported
– 5 batches manufactured in different manufacturing sites and collected in Tanzania,
tested in RIIP, South Africa
– Dissolution profiles compared to the mean of all data  SIMILAR
 Generic products containing nelfinavir (2007)
– Triggered by Roche worldwide withdrawal of Viracept
– Test on EMS/MMS impurity using Roche method
– Samples of finished product from Cipla, Hetero, GPO Thailand and of API from
Matrix, Hetero collected from manufacturers, as well as from markets, tested in
Swissmedic
– All samples ≤ 0.5 ppm
– For the purposes of Ph.Int. monograph dissolution tested
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Testing
 Testing on request from countries/UN agencies
– Artesunate+Amodiaquine tablets (co-blistered), Guilin Pharmaceuticals,
China – request from NGO in Indonesia
– Diethylcarbamazine citrate tablets, Asian Pharmaceutical Company, Nepal
– request from Ministry of Health in Nepal
– Praziquantel tablets, Merck, Mexico – cooperation with WHO procurement
and Neglected Tropical Diseases - Schistosomiasis control project
– Artesunate tablets, Guilin Pharmaceuticals, China – request from WPRO
– Miltefosin capsules, Popular Pharmaceuticals, Bangladesh - request from
Ministry of Health in Bangladesh
– Rifampicin capsules and Clofazimine capsules, Sandoz, India cooperation with WHO procurement and Neglected Tropical Diseases –
Leprosis elimination project
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Thanks for your attention
prequallaboratories@who.int
www.who.int/prequal
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