1. Prequalification of Quality Control Laboratories WHO Quality Monitoring Projects Jitka Sabartova Prequalification Programme: Priority Essential Medicines HSS/EMP/QSM

2. EMP Departmental Meeting | 15.10. 2009, Geneva 2 |2 | 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

3. EMP Departmental Meeting | 15.10. 2009, Geneva 3 |3 | 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 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

4. EMP Departmental Meeting | 15.10. 2009, Geneva 4 |4 | 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

5. EMP Departmental Meeting | 15.10. 2009, Geneva 5 |5 | QCLs Prequalification Procedure (1) QCLs Prequalification Procedure (1) September 2009 Prequalified QCLs:  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)

6. EMP Departmental Meeting | 15.10. 2009, Geneva 6 |6 | QCLs Prequalification Procedure (2) QCLs Prequalification Procedure (2) September 2009

7. EMP Departmental Meeting | 15.10. 2009, Geneva 7 |7 | Inspections / Pre-audits performed

8. EMP Departmental Meeting | 15.10. 2009, Geneva 8 |8 |

9. 9 |9 |

10. 10 | 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

11. EMP Departmental Meeting | 15.10. 2009, Geneva 11 | 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

12. EMP Departmental Meeting | 15.10. 2009, Geneva 12 | 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

13. EMP Departmental Meeting | 15.10. 2009, Geneva 13 | 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

14. EMP Departmental Meeting | 15.10. 2009, Geneva 14 | Sampling and testing projects Conduct of projects Plan +updates P1 P2 P3 Actions Reports Inspections Assessment PhV Entry information Quality concerns, complaints/defects, signals, inspections PQ procedures …

15. EMP Departmental Meeting | 15.10. 2009, Geneva 15 | 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

16. EMP Departmental Meeting | 15.10. 2009, Geneva 16 | 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)

17. EMP Departmental Meeting | 15.10. 2009, Geneva 17 | 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

18. EMP Departmental Meeting | 15.10. 2009, Geneva 18 | 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

19. EMP Departmental Meeting | 15.10. 2009, Geneva 19 | 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

20. EMP Departmental Meeting | 15.10. 2009, Geneva 20 | Thanks for your attention prequallaboratories@who.int www.who.int/prequal