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1、,Prequalification Programme,Quality Control Laboratories,Olivier Gross,Jitka SabartovaPrequalification Programme:Priority Essential MedicinesHTP/PSM/QSM,UN Prequalification Programme for Priority Essential Medicines,Action plan of UN from 2001 for expanding access of priority medicines to patients w
2、ithHIV/AIDSMalariaTuberculosisReproductive healthPotentially other categories of productsAntiviral medicines efficacious for avian fluePaediatric formulations,UN Prequalification Programme for Priority Essential Medicines,WHO PQ Team working in co-operation with partners UNICEFUN Population Fund(UNF
3、PA)UNAIDSUNITAIDThe Global FundWorld BankAnti-malarial and anti-TB products:Roll Back Malaria and Stop TB(Global Drug Facility);HIV/AIDS Department,Elements of Prequalification Programme,Objective:To ensure quality,efficacy and safety of medicines procured using international funds(e.g.GFTAM,UNITAID
4、)Components:Evaluation of Quality,Safety and Efficacy of prioritised Essential medicines,inspections of manufacturers and monitoring of the products after their prequalificationPrequalification of quality control laboratoriesBuilding capacity of regulators,manufacturers and quality control laborator
5、ies,Prequalification of QC laboratories,Need to increase the access to QC laboratories thatmeet recommended standards for testing of medicinesare committed to provide a service of testing of medicines,including but not limited to HIV/AIDS,Tuberculosis and Malaria products to UN agenciesProcedure est
6、ablished in 2004Participation of a QC laboratory is voluntary,Procedure for assessing the acceptability,in principle,of quality control laboratories for use by UN agencies,Published in 2004(WHO TRS,No.917,Annex 4)Revision published in 2007(WHO TRS,No.943,Annex 5)Related documentsGood practices for n
7、ational pharmaceutical control laboratories(WHO TRS,No.902 Annex 3)WHO GMP:main principles for pharmaceutical products.In:Quality assurance of pharmaceuticals.A compendium of guidelines and related materials.Vol.2,2nd updated edition.Good manufacturing practices and inspection(Geneva,World Health Or
8、ganization,2007)Guidelines for preparing a laboratory information file(WHO TRS,No.917,Annex 5),Based on the following principles,Reliance on the information supplied by the national drug regulatory authorityGeneral understanding of the quality control activities of the laboratoryEvaluation of inform
9、ation submitted by the laboratoryAssessment of consistency in quality control through compliance with GMP(s)and WHO guidelines,Invitation for Expression of Interest,3rd EOI published in September 2007http:/www.who.int/prequal/info_applicants/eoi/EOI-QCLabsV3.pdfPrevious invitations limited to QC lab
10、oratories in Africa,currently no regional limitationPriority in the assessment will be given toNational QC laboratories and laboratories providing testing services to the governmentQC laboratories in areas where UN agencies identify the need for quality testingAny laboratory(private or governmental)
11、can participate,Steps of the procedure,Expression of interestSubmission of laboratory informationLaboratory Information File-LIF needed to get basic information on laboratorys activities and suggested scope of prequalificationA good LIF makes the procedure fasterGuidelines for preparing LIF availabl
12、eDocumentation and QA system,Personnel,Handling of samples,Materials,Premises,Equipment,Contract operations and activities,Out-of-specification investigation,Self-inspectionStability Testing,Microbiological testing,Water system,where applicable Quality Manual can be submitted(amended as necessary)Ev
13、idence of participation in proficiency testing schemes,Steps of the procedure,Screening of submitted laboratory informationFormal completenessAmendment requested,if necessaryEvaluation of the laboratory informationWHO carries out evaluation of LIFs to assess the laboratorys potential to pass success
14、fully the inspection If the LIF indicates that the laboratory would comply-WHO starts arranging an inspectionIf the LIF is not adequate WHOStarts arranging an inventory audit orAsks for more information orReturns the LIF,Steps of the procedure,Site inspection/inventory auditPlanned and coordinated b
15、y WHO(normally for 2-3 days)Experts appointed by WHO preferably from regulatory authority inspectorates,experienced in quality controlRequired to sign declaration of interest and confidentiality declarationCompliance with WHO recommended standardsGood Practices for National Pharmaceutical Control La
16、boratoriesGood Manufacturing Practices as recommended by WHO for such laboratoriesISO certification encouraged and consideredHowever,GMP aspects to be taken into account during inspection,Steps of the procedure,Site inspection/inventory audit(cont.)For the inspection representative(s)of the DRA of t
17、he country where the laboratory is located invitedInventory audit less formal,combined with discussions of problems and assessment of need of technical assistance,Steps of the procedure,Report and outcome of evaluationFinal Report in the established WHO format communicated to the laboratory and a co
18、py sent to the national DRAIf corrective actions to be taken by the laboratory,WHO postpone its final recommendations until the corrective action has been evaluated and found satisfactoryIn case of disagreement,possibility of an appealOwnership of the report lies with WHOResults of assessmentInforma
19、tion is sent to the laboratory and national DRAIf compliant,laboratory is included in the published list and WHOPIR is publishedThe list will be subjected to review at least once a year,Steps of the procedure,Re-evaluation after prequalificationOn-going monitoringRe-inspections at regular intervals(
20、normally 3 years)Evaluation of results from participation in proficiency testing schemesWHO External Quality Assurance Scheme,AFSSAPS network of Francophone African countriesWHO may suspend or withdraw a laboratory from the list when there is evidence of noncompliance,Steps of the procedure,Monitori
21、ng of complaintsWHO will investigate complaints concerning the results of analysis or service provided by the laboratoryWritten report and where appropriate recommendations for action Copy of the report to the laboratory,manufacturer of the product and DRA of the country where the manufacturing site
22、 is locatedDRA could also be invited to participate in the investigation of the complaintCost recoveryWHO reserves the right to charge for the quality assessment procedure on a cost-recovery basis,Status of prequalification of QC LabsNovember 2007,4 QC laboratories prequalifiedSouth Africa,CENQAM-6/
23、2005South Africa,RIIP-7/2005Algeria,LNCPP-10/2005South Africa,Adcock Ingram 8/20072 QC laboratories near to PQ11 QC laboratories audited,corrective measures proposed6 QC laboratories expressed interest,but not send LIF yet,Frequent deficiencies and weak points(1),Quality systemSOPs not covering,not
24、properly maintainedNo quality responsibleNo or not enough self-auditsPersonnelNo qualification systemNot enough training,no training programmesResponsibilities and tasks not clearly definedon personal level,vague organizationPremisesToo small and unfitLimited and unfit storage areas(lot of cupboards
25、 etc.needed)No regular environmental(at least temperature)monitoringArchives not good,nor secured,Frequent deficiencies and weak points(2),Maintenance of the equipment No proper or only partial qualificationsDocumentation in general very deficientNot adequate training by the suppliers in the beginni
26、ngNo pre-maintenance programmeReference materials and reagents Maintenance system and records not efficient,nor clearNo working standards systemInstructions/methods No clear system as to which pharmacopoeial or manufacturers method to useValidations/verifications of methodsnot sufficient or non-exis
27、ting,Frequent deficiencies and weak points(3),Waste management Not properly organized Safety Fume hoods lacking or too fewNo or insufficient protection of the personnel(e.g.insufficient protective garments,no training,no safety sheets of the chemicals)No classificationnor proper storage of dangerous
28、 chemical materials(e.g.toxics,caustic/volatile reagents etc.),Technical assistance,Technical assistance provided to 5 national medicines quality control laboratories Assistance in implementation of quality systemAssistance in microbiological testing1 3 weeksCapacity building and technical assistanc
29、e provided to national QC laboratories out of the scope of the prequalification procedure,Training,Participation in Quality Assurance training of OMCLs organized by EDQMOctober 2005,5 participants from AFRO and EMROSeptember 2007,12 participants from AFRO,EMRO and EUROTrainings in Quality Assurance,
30、Quality Control and Ph.Int.under preparation November 2007,Morocco,40 participants from Francophone countries(AFRO,EMRO),cooperation with EDQMDecember 2007,Tanzania,40 participants from Anglophone countries(AFRO,EMRO)Trainings planned in 2008Market surveillance projects,Networking of African laborat
31、ories,Sampling and Testing(1),Survey of the quality of antiretroviral medicines circulating in selected African countriesCarried out in June-December 2005,report now finalized7 countries(Cameroon,DR of Congo,Kenya,Nigeria,Tanzania,Uganda and Zambia)Monocomponent products(didanosine,efavirenz,lamivud
32、ine,nevirapine,stavudine,zidovudine),FDCs(lamivudine/zidovudine,stavudine/lamivudine,stavudine/lamivudine/nevirapine)394 samples from official procurement and treatment centres,both private and publicTesting according Ph.Int.,USP,Indian Pharmacopoeia,validated in-house Swissmedic methods(laboratory
33、Swissmedic)Tests performed-Appearance,Labelling,Identification,Uniformity of mass(capsules/tablets),Dissolution/disintegration,pH(oral solutions-depending upon the matrix),Related substances,Content of each active ingredient,Sampling and Testing(2),Survey of the quality of antiretroviral medicines c
34、irculating in selected African countries-Findings,Very low failure of 1.8%,no critical deficiencies1 sample with broken tablets,2 samples insufficiently labelled,1 sample with higher content,1 sample failed to disintegrate in 30,2 samples lower dissolution53%prequalified productsIn 3 countries found
35、 non-registered products,mostly in private sector(12%of 394 samples)Positive effect of common efforts of NDRAs,WHO and others involved in prequalification and purchase policiesLimited to official distribution points and treatment centres around the capital cities,Sampling and Testing(3),Current acti
36、vitiesQuality survey of antimalarialsACTs,sulfadoxine-pyrimethamine in 9 African countriesQuality monitoring within UNITAID projectsPaediatric ARV FDCs,cotrimoxazol,second line ARVsDissolution of Coartem tabletsGeneric products containing nelfinavirEMS/MMS impurity,dissolutionMonitoring of quality o
37、f WHO prequalified productsVerification that WHO-prequalified products procured by agencies comply with the specifications approved within PQ processTesting on request from countriesArsuamoon tbl(co-blistered artesunate+amodiaquine),Guilin Pharma,China-from IndonesiaDiethylcarbamazine citrate tbl,Asian Pharmaceutical Company,Nepal from Nepal,Thanks for your attention,
