WHO Prequalification of Quality Control Laboratories

WHO Prequalification of
Quality Control Laboratories
Jitka Sabartova
WHO Prequalification of Medicines Programme
Objectives
• Increase the access to services of QCLs that
– Meet recommended standards for testing of
medicines, and
– Are committed to test medicines for UN agencies
• Contribute to capacity building of national QCLs
in developing countries (strengthening of health
systems)
– Technical assistance
– Trainings
– Guidelines
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Prequalification procedure
• Established in 2004 in cooperation with UN agencies
• Procedure published in 2004, revised in 2007 and 2011
• http://www.who.int/prequal/info_general/documents/TRS961/TRS961_Annex12.pdf
• Participation of a QC laboratory is voluntary
– Any laboratory (private or governmental) can participate
• Scope - chemical and microbiological testing (including LAL
test) of medicines (vaccines, biologicals not included)
• Based on the following principles
– Evaluation of information submitted by the laboratory
– On site inspection
– Monitoring of performance of prequalified laboratory
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Invitation for Expression of Interest
• Previous invitations limited to QC laboratories in Africa,
currently no regional limitation
• 3rd EOI published in September 2007
– http://www.who.int/prequal/info_applicants/eoi/EOIQCLabsV3.pdf
• Priority in the assessment is given to
– National QC laboratories and laboratories providing testing
services to the governments
– QC laboratories in areas where UN agencies identify the need
for quality testing
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Steps of the procedure
1. Expression of interest
− Currently free of charge
2. Submission of laboratory information file
− Guidelines for preparing LIF available
− Quality Manual can be submitted (amended as necessary)
3. Evaluation of submitted information
− Assessment of laboratory's potential to pass successfully the
inspection
• Compliance  WHO organizes an inspection
• Gaps  For a national QCL in a developing country, WHO may
organize a pre-audit/ technical assistance
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Steps of the procedure
4. Site inspection
− Planned and coordinated by WHO
• 2-3 days, external inspectors experienced in QC appointed (preferably from
MRA)
• Representative of MRA of the country where the QCL is located is invited
− Compliance with WHO recommended standards
• WHO Good Practices for Pharmaceutical Quality Control Laboratories
– http://www.who.int/prequal/info_general/documents/TRS957/GPCL_TRS957_Annex1.pdf
• WHO Good practices for pharmaceutical microbiology laboratories
– http://www.who.int/prequal/info_general/documents/TRS961/TRS961_Annex2.pdf
• WHO Good manufacturing practices – parts relevant to QCLs
– http://www.who.int/medicines/areas/quality_safety/quality_assurance/production/en/index.html
− Focus on the overall quality system in the laboratory and chemical
and microbiological testing, not on individual methods only
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Steps of the procedure
4. Site inspection (cont)
− Report communicated to the laboratory
• If corrective actions to be taken by the laboratory, final decision is made
after their evaluation
− Audit report from another authority (e.g. EDQM)
• Compliance with WHO standards is evaluated and WHO inspection may
not be necessary
• ISO accreditation encouraged and considered but does not cover GMP
aspects
− If compliant, laboratory is included in the published list and
WHOPIR is published
• Prequalification does not guarantee future contracts for testing for UN
agencies, competitive tendering usually organized
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Steps of the procedure
5. Monitoring after prequalification
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Re-inspections at a frequency based on risk assessment
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Evaluation of results from participation in proficiency testing
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WHO External Quality Assurance Scheme (EQAAS), ANSM network of
Francophone African countries
Brief report requested to be submitted annually
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At least once every 3 years
Summary of services provided to UN agencies, number of analysed samples,
methods used, complaints received
Changes with significant impact to the laboratory (key personnel, facility,
equipment) and update LIF
WHO may suspend or withdraw a laboratory from the list when
there is evidence of noncompliance
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Prequalified/interested QCLs
(February 2014)
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Prequalified QCLs
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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)
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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)
China, NIFDC (2012)
Portugal, Laboratorios Basi (2013)
Mexico, CCAYAC (2013)
India, Stabicon (2013)
Getz Pharma, Pakistan (2014)
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QCLs in the procedure
(February 2014)
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Areas of frequently found deficiencies
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SOPs not covering all laboratory activities, change control
Internal audits, complaints, corrective and preventive actions
Personnel - qualification, responsibilities, training programme, authorisation
Premises - monitoring of storage conditions; controlled access
Equipment – qualification, maintenance (not scheduled, not documented)
Reference substances - use not documented, traceability to primary standards
Reagents - labelling, stock management, water quality not regularly verified
Records – traceability of results
Back-up of electronic data
Verification of validated analytical methods (pharmacopoeial, manufacturers')
Procedure for atypical and out-of-specification results
Subcontracting tests
Safety procedures – waste management, material safety data sheets, storage of
dangerous chemicals
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Capacity building
• Technical assistance provided to national medicines
QCLs in developing countries
– 36 since 2006 (11 in 2013)
– Focus on implementation of quality system, microbiology testing
• Training
– Training in HPLC (organized with ANSM in March 2013, Tunisia)
– Workshops on laboratory quality control of reproductive health products
(organized with UNFPA in November-December 2011 - Tanzania and
Namibia; February 2012 – Ghana; November 2012 – Thailand, February
2013 - Fiji)
• External Quality Assessment Scheme for National Drug
Quality Control Laboratories
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Potential benefits of PQ for QCLs
• Possibility to provide testing services to UN agencies and
other organizations - financial profit
• Recognition as being WHO listed laboratory
• Facilitated discussions with manufacturers/customers in
case of non-compliant results
• Learning process improving the standards of laboratory
work
• In case on a national QCLs in a developing country,
possibility to be assisted by WHO expert consultants and
participate in WHO organized trainings
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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, if requested by MSs
– 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 MRAs
– 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 inhouse laboratory methods
Total failure = 1.8%
1.8%
Compliant
98.2%
Noncompliant
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7 samples of 394 failed
No critical deficiencies
53% PQed products
3 of 7 failing were PQed
products
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Quality survey of antimalarials in Africa
• 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
ACTs
Total failure = 28.5%
SPs
70
63
56
Compliant
16.9%
71.5%
Nonextreme
deviations
Extreme
deviations
Failure rate (%)
60
11.6%
50
44
40 32
27
30
17
20
8
10
• Failure for PQed products 4%
• Failure for non PQed products 40%
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Quality survey of anti-TB medicines in NIS
• 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%
1.0%
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Compliant
Nonextreme
deviations
88.7%
Extreme
deviations
• None of 38 samples of WHOprequalified products failed
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Failure rate (%)
10.3%
20
13
15
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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 project (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
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Survey of the quality of medicines identified by the
UN Commission on Life-Saving Commodities for
Women and Children
• UN Commission strategy
– Increasing access to and appropriate use of medicines and medical
devices that effectively address major avoidable causes of death during
pregnancy, childbirth and childhood – 13 neglected commodities defined
– Recommendation 4 - By 2015, at least 3 manufacturers per commodity
are manufacturing and marketing quality-certified and affordable
products in each of EWEC countries
• Objectives of the survey
– Identify products of good quality or the quality of which can be improved
in short period of time
• Quality of identified products will be verified through inspections and dossier evaluation
– Evaluate quality of products currently available at the first level of
distribution chain
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Survey of the quality of medicines identified by the
UNCoLSC
• Countries selected for sampling
– 10 countries in Africa and Asia (Burkina Faso, Kenya, Madagascar, Nepal, Nigeria,
Tajikistan, Tanzania, Uganda, Vietnam, Zimbabwe)
• Products and specifications
Oxytocin inj
Ph.Int. Betamethasone suspension for USP
inj (Na phosphate+acetate)
Magnesium sulfate inj
Ph.Int. Dexamethasone inj
BP
Gentamycin inj
BP
Amoxicillin dispersible tablet
USP
Procaine benzylpenicillin
powder for inj
BP
Zinc sulfate dispersible tablet
or syrup
USP
Ampicillin powder for inj
BP
Levonorgestrel tablet
BP
Ceftriaxone powder for inj
BP
Mifepristone tablet
Manuf.
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Thanks for your attention
[email protected]
www.who.int/prequal
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