Quality of procured medicines

Transcription

1 Quality of procured medicines What may go wrong Jitka Sabartova, Deus Mubangizi WHO Prequalification of Medicines Programme Copenhagen, Denmark, September 2013

2 PQP monitors medicines after prequalification Variations to the dossier of prequalified product Re-inspections (risk based planning, approx. 2 years) Re-qualification (5 years) Management of complaints Sampling and testing projects De-listing or suspension (if and when appropriate) 2

3 Independent quality control by procurers (1) Guarantee that the procured product Complies with specifications approved during prequalification Has been manufactured in the approved site Considerations on necessity/frequency of testing Based on defined QA policy and risk assessment Selection of a reliable laboratory WHO-prequalified ISO accredited Not always guarantees appropriate testing of medicines, e.g. investigation of out-of-specification result, appropriate qualification of equipment 3

4 Prequalified/interested QCLs (September 2013) 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, TÜV (2009) Canada, K.A.B.S. Laboratories (2010) Ukraine, CLQCM (2010) Ukraine, LPA (2010) Peru, CNCC (2010) Uruguay, CCCM (2010) Bolivia CONCAMYT (2010) Tanzania, TFDA (2011) India, SGS (2011) Belgium, SGS (2011) Netherlands, Proxy (2011) Portugal, INFARMED (2011) Brazil, FUNED (2011) Russia, FSBI-SCEEMP (2012) Belarus, RCAL (2012) Thailand, BDN (2012) NIFDC, China (2012) Laboratorios Basi, Portugal (2013) 4

5 QCLs in the procedure (September 2013) 5

6 Inspections / Pre-audits performed within QCL prequalification procedure 6

7 Independent quality control by procurers (2) Selection of specifications and methods to be used for testing Manufacturer's specifications and methods Procurer should ensure the availability Laboratory should perform method transfer Shelf-life specifications to be used Pharmacopoeia monograph Laboratory should perform appropriate verification Specifications and methods should be agreed with the supplier in advance Will avoid problems when non-compliant results are found 7

8 Independent quality control by procurers (3) When a non-compliant result is found Laboratory should investigate and exclude any error Manufacturer should be contacted WHO PQP should be informed prequalinspection@who.int Complaint procedure is initiated by inspectors Possible inspection and/or testing in an independent laboratory 8

9 Procurers may endanger quality Pushing price too low Quality has its price Number of rush orders results in Smaller batches, poor production planning, higher cost of materials (especially APIs), and increased cost of shipping (air freight instead of sea freight) Changing requirements E.g. labelling 9

10 WHO-Prequalification Programme Quality Monitoring Projects Objectives Monitor quality of medicines procured by UN agencies/ prequalified products Contribute to quality control of medicines Contribute to capacity building by cooperation with MRAs (strengthening of health systems) Sampling and testing projects a tool Importance of reliability of quality control laboratories used Prequalified laboratories, if available If not, laboratories for which the evidence of reliability is available 10

11 Principles Focus on HIV/AIDS, malaria, TB medicines Pre-established protocol with defined study objectives Selection of medicines and sampling sites based on risk analysis Cooperation with NMRAs in countries Discussion of protocol, preparation of national sampling plans, collection of samples Specifications and methods from major pharmacopoeias (Ph.Int., USP, BP) In case of non-compliant results, the respective NMRAs and manufacturers informed without delay Results discussed with MRAs before publication Publication of detailed report 11

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13 Quality survey of antiretrovirals in Africa (2007) Cooperation with NDRAs in Cameroon, DR of Congo, Kenya, Nigeria, Tanzania, Uganda and Zambia Monocomponent products (didanosine, efavirenz, lamivudine, nevirapine, stavudine, zidovudine), FDCs (lamivudine/zidovudine, stavudine/lamivudine, stavudine/lamivudine/nevirapine) 394 samples collected in official procurement and treatment centres, both private and public and tested according Ph.Int., USP, IP and inhouse laboratory methods Total failure = 1.8% 98.2% 1.8% Compliant Noncompliant 7 samples of 394 failed No critical deficiencies 53% PQed products 3 of 7 failing were PQed products 13

14 Quality survey of antimalarials in Africa (2011) Cooperation with NDRAs in Cameroon, Ethiopia, Ghana, Kenya, Nigeria, Tanzania ACTs and sulfadoxine-pyrimethamine 935 samples collected at all distribution levels including informal market and screened by Minilab 306 tested in laboratory according to Ph.Int., USP or laboratory method Total failure = 28.5% 16.9% 11.6% Compliant 71.5% Nonextreme deviations Extreme deviations Failure for PQed products 4% Failure for non PQed products 40% Failure rate (%) Cameroon 44 Ethiopia ACTs Ghana 56 Kenya SPs 8 0 Nigeria Tanzania 17 14

15 Quality survey of anti-tb medicines in NIS (2011) Cooperation with NDRAs in Armenia, Azerbaijan, Belarus, Kazakhstan, Ukraine, Uzbekistan Rifampicin, Isoniazid, Rifampicin/Isoniazid, Ofloxacin, Kanamycin 291 samples collected at hospitals, dispensaries, pharmacies and tested according to Ph.Int. or USP Total failure = 11.3% 10.3% 1.0% 88.7% Compliant Nonextreme deviations Extreme deviations None of 38 samples of WHOprequalified products failed Failure rate (%) Armenia Azerbaijan Belarus Kazakhstan Ukraine Uzbekistan 13 15

16 Survey of the quality of antimalarials supplied within AMFm project Affordable Medicines Facility malaria Innovative financing mechanism to expand access to ACTs managed by GFATM ( In 2012 two articles questioned quality of PQed products supplied within AMFm Artemisinin component allegedly below 75% Complaint procedures initiated by PQP inspectors with manufacturers No non-compliance found 3 out of 12 suspect batches independently sampled and tested before shipment within GFATM QA policy and found compliant 16

17 Survey of the quality of antimalarials supplied within AMFm (2) To verify quality of AMFm medicines sampling & testing project organized Sampling In Ghana, Nigeria, Uganda, in cooperation with NMRAs At points where delivered by manufacturers and at pharmacies Testing According to manufacturers' methods and specifications approved in prequalification, Ph.Int. monograph for artemether/lumefantrine tablets 54 samples produced by 6 manufacturers collected in countries 4 samples with the content of artemisinin component below 90% (the lowest 86.4%) Investigation with manufacturers on-going 4 samples obtained from R.Bate (2 remaining tablets per sample) % of artesunate, tested 3-4 months after expiry 1 retention sample of an allegedly substandard batch collected at a manufacturer 97.4% of artesunate, tested 3 months after expiry 17

18 SUBSTANDARD, SPURIOUS, FALSELY LABELLED, FALSIFIED AND COUNTERFEIT (SSFFC) MEDICAL PRODUCTS Global Surveillance and Monitoring Project Michael Deats, SFFC Project Manager 18

19 PROJECT OBJECTIVES Scale Quantity Value Scope Medicines Vaccines Diagnostics Improve the quantity and quality of data concerning SSFFC medical products Extent Harm Geographic coverage Public Health 19

20 1. METHODOLOGY - RAPID ALERT FORM 20

21 2. METHODOLOGY - DATABASE Incident Risk Assessment Suspect Product Health Analysis and Impact Dissemination and exchange Classification 21

22 3. METHODOLOGY - PILOT STUDY Cambodia Croatia Georgia Indonesia Kyrgyzstan Malaysia Philippines Russia Ukraine Vietnam 22

23 4. METHODOLOGY - PROGRAM DEPLOYMENT Planned Workshops 2013 Current Participants 23

24 Outcomes Significantly improve our knowledge Which medical products, therapeutic categories and dosage forms Which Regions / Sub regions / Freight routes Scientifically tested methods to identify harm caused Enable evidence based policy making Incentivise reporting Build capacity for Countries and sub regions most negatively affected Establish the root causes and shape policy to prevent SSFFC Protect Public Health Increase vigilance in countries and global 'pinch points' Focused market surveillance Increased and improved screening and laboratory analysis Timely and wide publication of International Drug Alerts 24

25 High Level Statistics 76 Incidents 143 Different Batches of medical products 98 Different Medical Products 65 Active Pharmaceutical Ingredients Reported from 27 Member States 11 Incidents involved serious adverse reactions 7 Cases involved fatalities 4 WHO Drug Alerts 25

26 Published information - Drug Alerts 26

27 Falsified batches of Postinor 2 in African countries No active ingredient doses discovered by NAFDAC at Lagos airport Cooperation with the manufacturer Falsified batches found also in 2011/12 in Ghana, Kenya, Angola 27

28 Falsified batches of Coartem in Western and Central Africa No active ingredient Discovered by a pharmacist in Cameroon Cooperation with the manufacturer and NMRAs 28

29 Contaminated Dextromethorphan API Dextromethorphan cough syrup killing 60 people in Pakistan All death cases seemed to be linked to drug addiction Medicine contained also high percentage of levomethorphan (potent opiate) API manufacturing quality failure 29

30 Contaminated Isotab More than 107 deaths and 450 severe ADRs with isosorbide mononitrate manufactured in Pakistan Clinically resembled Dengue fever Passed quality control testing Forensic investigation revealed pyrimethamine in toxic quantities 30

31 Thanks for your attention 31