Quality of procured medicines - World Health Organization · PDF fileQuality of procured medicines What may go wrong ... MEDS (2009) •Singapore, TÜV ... •India, SGS (2011) •Belgium,

Quality of procured medicines

What may go wrong Jitka Sabartova, Deus Mubangizi

WHO Prequalification of Medicines Programme

Copenhagen, Denmark, 23-25 September 2013

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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)

Copenhagen, Denmark, 23-25.9.2013

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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 17025 accredited

• Not always guarantees appropriate testing of medicines, e.g. investigation of out-of-specification result, appropriate qualification of equipment


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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)


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QCLs in the procedure (September 2013)


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Inspections / Pre-audits performed within QCL prequalification procedure


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• 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


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• When a non-compliant result is found – Laboratory should investigate and exclude any error

– Manufacturer should be contacted

– WHO PQP should be informed

• Email: [email protected] • Complaint procedure is initiated by inspectors • Possible inspection and/or testing in an independent

laboratory


mailto:[email protected]

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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


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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


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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


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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 in-house laboratory methods

• 7 samples of 394 failed • No critical deficiencies • 53% PQed products • 3 of 7 failing were PQed products 98.2%

1.8% Total failure = 1.8%

Compliant

Non-compliant


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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

• Failure for PQed products 4% • Failure for non PQed products 40%

Total failure = 28.5%

71.5%

16.9%

11.6% Compliant

Non-extremedeviationsExtremedeviations

32

44

0 0

27

56

8

0

63 67

0

17

0

10

20

30

40

50

60

70

Failu

re ra

te (%

)

CameroonEthiopia

GhanaKenya

Nigeria

Tanzania

ACTs SPs


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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

None of 38 samples of WHO-prequalified products failed

Total failure = 11.3%

88.7%

10.3%

1.0%Compliant

Non-extremedeviationsExtremedeviations

10 107

23

4

13

0

5

10

15

20

25

Failure rate (%)

Armenia

Azerbai

jan

Belarus

Kazakhs

tan

Ukraine

Uzbekis

tan


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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 (www.theglobalfund.org/en/activities/amfm)

• 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


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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) – 87.4 – 95.3% 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


SUBSTANDARD, SPURIOUS, FALSELY LABELLED, FALSIFIED AND COUNTERFEIT

(SSFFC) MEDICAL PRODUCTS

Global Surveillance and Monitoring Project

Michael Deats, SFFC Project Manager

[email protected]


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PROJECT OBJECTIVES

Scale • Quantity • Value

Scope • Medicines • Vaccines • Diagnostics

Extent • Geographic

coverage

Harm • Public

Health

Improve the quantity and quality of data concerning SSFFC medical products


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1. METHODOLOGY - RAPID ALERT FORM


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2. METHODOLOGY - DATABASE

Incident

Classification

Health Analysis and Impact

Dissemination and exchange

Risk Assessment

Suspect Product


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Cambodia Croatia Georgia Indonesia Kyrgyzstan

Malaysia Philippines Russia Ukraine Vietnam

3. METHODOLOGY - PILOT STUDY


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4. METHODOLOGY - PROGRAM DEPLOYMENT

Planned Workshops 2013

Current Participants


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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


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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


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Published information - Drug Alerts www.who.int/medicines/publications/drugalerts

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Falsified batches of Postinor 2 in African countries

• No active ingredient

• 150 000 doses discovered by NAFDAC at Lagos airport

• Cooperation with the manufacturer

• Falsified batches found also in 2011/12 in Ghana, Kenya, Angola

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Falsified batches of Coartem in Western and Central Africa

• No active ingredient

• Discovered by a pharmacist in Cameroon

• Cooperation with the manufacturer and NMRAs


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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


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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


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Thanks for your attention

[email protected] [email protected] www.who.int/prequal


Documents

Quality of procured medicines - World Health Organization · PDF fileQuality of procured medicines What may go wrong ... MEDS (2009) •Singapore, TÜV ... •India, SGS (2011) •Belgium,