Prequalification ofPrequalification of Quality Control LaboratoriesQuality Control Laboratories

WHO Quality Monitoring ProjectsWHO Quality Monitoring Projects

Jitka Sabartova

Prequalification Programme: Priority Essential Medicines

HSS/EMP/QSM

EMP Departmental Meeting | 15.10.2009, Geneva2 |

Prequalification of QC laboratoriesPrequalification 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

EMP Departmental Meeting | 15.10.2009, Geneva3 |

QCLs Prequalification ProcedureQCLs 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

EMP Departmental Meeting | 15.10.2009, Geneva4 |

Based on the following principlesBased 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

EMP Departmental Meeting | 15.10.2009, Geneva5 |

QCLs Prequalification ProcedureQCLs Prequalification Procedure (1) (1)September 2009

QCLs Prequalification ProcedureQCLs Prequalification Procedure (1) (1)September 2009

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2004 2005 2006 2007 2008 Sep-09

QCLs Prequalified QCLs Interested 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)

EMP Departmental Meeting | 15.10.2009, Geneva6 |

QCLs Prequalification ProcedureQCLs Prequalification Procedure (2)(2)September 2009

QCLs Prequalification ProcedureQCLs Prequalification Procedure (2)(2)September 2009

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AFRO EMRO EURO SEARO WPRO

QCLs interested QCLs prequalified

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National QCLs Other QCLs

EMP Departmental Meeting | 15.10.2009, Geneva7 |

Inspections / Pre-audits performedInspections / Pre-audits performedInspections / Pre-audits performedInspections / Pre-audits performed

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2004 2005 2006 2007 2008 Sep-09

Pre-audits

Inspections

EMP Departmental Meeting | 15.10.2009, Geneva8 |

EMP Departmental Meeting | 15.10.2009, Geneva9 |

EMP Departmental Meeting | 15.10.2009, Geneva10 |

Monitoring after prequalificationMonitoring 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

EMP Departmental Meeting | 15.10.2009, Geneva11 |

Participation in WHOExternal Quality Assurance Scheme (1)

Participation in WHOExternal 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

EMP Departmental Meeting | 15.10.2009, Geneva12 |

Capacity buildingCapacity 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

EMP Departmental Meeting | 15.10.2009, Geneva13 |

WHO Prequalification Programmemonitoring of medicines quality

WHO Prequalification Programmemonitoring 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

EMP Departmental Meeting | 15.10.2009, Geneva14 |

Sampling and testing projectsSampling and testing projects

Conduct of projects

Plan+updates

P1 P2 P3

Actions Reports

InspectionsAssessment

PhV

Entryinformation

Quality concerns,complaints/defects ,

signals, inspectionsPQ procedures

…

EMP Departmental Meeting | 15.10.2009, Geneva15 |

Quality monitoring projects (1)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

EMP Departmental Meeting | 15.10.2009, Geneva16 |

Quality monitoring projects (2)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)

EMP Departmental Meeting | 15.10.2009, Geneva17 |

Quality monitoring projects (3)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

EMP Departmental Meeting | 15.10.2009, Geneva18 |

Quality monitoring projects (5)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

EMP Departmental Meeting | 15.10.2009, Geneva19 |

TestingTesting

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

EMP Departmental Meeting | 15.10.2009, Geneva20 |

Thanks for your attentionThanks for your attentionThanks for your attentionThanks for your attention

prequallaboratories@who.int www.who.int/prequal