who prequalification programme milan smid, m.d., ph.d. prequalification programme: priority...
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WHO Prequalification WHO Prequalification ProgrammeProgramme
Milan Smid, M.D., Ph.D.Prequalification Programme: Priority Essential Medicines
WHO Prequalification Programme for Priority Medicines, Jakarta, October 20092 |
UN Prequalification Programme for Priority Essential MedicinesUN Prequalification Programme for Priority Essential Medicines
Action plan of UN from 2001 for expanding access of priority medicines to patients with
– HIV/AIDS
– Malaria
– Tuberculosis
– Reproductive health
– Influenza
– Acute diarrhoea
– Potentially other categories of products, if there is the need
WHO Prequalification Programme for Priority Medicines, Jakarta, October 20093 |
Elements of Prequalification ProgrammeElements of Prequalification Programme
Objective: To ensure quality, efficacy and safety of medicines procured
using international funds (e.g. GFTAM, UNITAID)
Components: Evaluation of Quality, Safety and Efficacy of prioritised Essential
medicines, inspections of manufacturers and monitoring of the products after their prequalification.
Prequalification of quality control laboratories. Building capacity of regulators, manufacturers and quality control
laboratories.
WHO Prequalification Programme for Priority Medicines, Jakarta, October 20094 |
How prequalification is organized?How prequalification is organized?
WHO manages and organizes the programme on behalf of the United Nations:
• provides technical and scientific support to assessment, inspections (GMP, GCP, GLP) and quality control (GPCL)
• involvement of qualified assessors and inspectors mostly from NRAs of ICH and associated countries and PIC/S inspectorates
• guarantees that international norms and standards are applied all through the process
• supports capacity of NRA in developing countries to evaluate, inspect and control the quality of medicines
• involvement of qualified assessors and inspectors from NRAs in developing countries
• by involvement of manufacturers from development countries into the project supports their capacity to produce according to international norms and standards
WHO Prequalification Programme for Priority Medicines, Jakarta, October 20095 |
How prequalification is organized?How prequalification is organized?
WHO PQT working in co-operation with partners
• UNICEF• The Global Fund to Fight AIDS, Tuberculosis and Malaria• UN Population Fund (UNFPA)• UNAIDS• World Bank
• Anti-malarial and anti-TB products: Roll Back Malaria and Stop TB (Global Drug Facility); HIV/AIDS Department
WHO Prequalification Programme for Priority Medicines, Jakarta, October 20096 |
Essential steps of PQ evaluation procedureEssential steps of PQ evaluation procedure
Need is specified and agreed by WHO treatment programmes Invitation for Expression of interest (EOI) is published Interested parties submit dossiersDossiers receive initial screeningFull dossiers are assessed Inspections are conducted at manufacturing sites and at CROsSamples are tested, if needed If outcome is positive, pharmaceutical product is listed on the
website, including product information (SPC, PIL), assessment report (WHOPAR) and inspection report (WHOPIR)
WHO Prequalification Programme for Priority Medicines, Jakarta, October 20097 |
Essential steps of monitoring of PQ productEssential steps of monitoring of PQ product
Variations to the dossier of prequalified product
Sampling and Testing
Reinspections
Requalification
De-listing or suspension (if and when appropriate)
WHO Prequalification Programme for Priority Medicines, Jakarta, October 20098 |
StandardsStandards
WHO standards as defined in WHO guidelines and International Pharmacopoeia are applied in prequalification process
If these not exist, ICH guidelines are applied
In case of need, guidelines of stringent regulatory authorities, which are involved in ICH process
WHO Prequalification Programme for Priority Medicines, Jakarta, October 20099 |
IExpression
of Interest
Compliance
Additional informationand data
Corrective actions
Compliance
Assessment Inspections
Steps in prequalification
Prequalification
Maintenance and monitoring
Product dossierSMF
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200910 |
Evaluation procedureEvaluation procedure Assessment of product dossiers
(Quality specifications, pharmaceutical development, production, control, stability, bioequivalence etc).
Teams of professionals from national Drug Regulatory Authorities (DRA): Including Brazil, China, Canada, Denmark, Estonia, Finland, France, Germany, Hungary, Indonesia, Malaysia, Philippines, Spain, South-Africa, Sweden, Switzerland, Tanzania, Uganda, UK, Zimbabwe ...
Copenhagen assessment week
• 8 to 20 assessors together during one week at least every two months at UNICEF in Denmark
• Every dossier is assessed by at least four assessors. • An assessment report is issued - signed by assessors• Letter summarizing the findings and asking for clarification and
additional data if necessary is sent first by e-mail to the applicant followed by surface mail
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200911 |
Assessors participating in PQ assessment (all visits in 2001-2008, share of the WHO regions)
Assessors participating in PQ assessment (all visits in 2001-2008, share of the WHO regions)
34196
151
12
1
0 EURO
AMRO
AFRO
WPRO
SEARO
EMRO
In total 603 participations
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200912 |
Inspections:Inspections:
Team of inspectors for each inspectionWHO PQ inspector plus PIC/S member country plus local
country inspector (observer)Some cases – capacity building (recipient country)Preparation includes SMF, product information, inspection
reports, complaints etcAPIs, Finished products Clinical studies: Mostly Bioequivalence studies (generic
products
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200913 |
Prequalification assessmentPrequalification assessment
Innovator products• Accepted, if approved by stringent authorities like US FDA and
EMEA • Based on availability of assessment reports, WHO Certificate of
Pharmaceutical Product (CPP), batch certificate• Continuous update on product changes after prequalification
• Confidence in scientific expertise of well-established RAs
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200914 |
Alternative regulatory pathways
USA FDA tentative approvals linked to PEPFAR– Included in WHO PQ List – Confidentiality agreement with US FDA in place
EU Article 58– For products exclusively to be used outside EU
Canadian Access to medicines scheme– WHO cooperation with the above mentioned– Confidentiality agreement in preparation
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200915 |
Prequalification assessmentPrequalification assessment
Multisource products Assessment • Quality: information on starting materials and finished product,
(API details, specifications, stability data, formulation, manufacturing method, packaging, labelling etc.)
• Interchangeability with reference product (efficacy and safety): Report of bio-equivalence, biovaiwer or clinical study demonstrating interchangeability with reference product
• Inspection of manufacturers and CROs• Laboratory analysis in case of need
Monitoring after prequalification
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200916 |
Simplified assessmentSimplified assessment
Prequalification of Multisource (generic) Finished Pharmaceutical Products approved by Stringent Regulatory Authorities
– Assessment report (waived for anti-TB or antimalarial medicines with 30 years of therapeutic experience - including 15 years in ICH region)
– 5 years of continuous manufacturing experience
– last Annual Product Report
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200917 |
Prequalification assessmentPrequalification assessment
Combined products, new dosage forms, new indications
Assessment • May require safety and efficacy data
Monitoring after prequalification
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200918 |
Outcomes of PQ procedureOutcomes of PQ procedure
Information in public domain: http://who.int/prequal/
Lists of PQ medicinal products WHOPAR (SPC, PIL, labelling) WHOPIR (both FPP and API) Notices of Concern and Suspension Information on progress of assessment procedure and
inspections Supportive documents: WHO guidelines, description of PQ
procedure
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200919 |
www.who.int/prequal/www.who.int/prequal/
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200920 |
Same principals applied in prequalification as valid for national regulatory approvals by stringent authorities
Same principals applied in prequalification as valid for national regulatory approvals by stringent authorities
Benefits prevail the risks at a time of regulatory approval and nothing indicates that benefits will not prevail also during use of product in normal medical practice
– Available data about quality (Dossier)– Available data about efficacy and safety or interchangeability (Dossier)– Available data are credible and were eticaly obtained
• Good practices (GLP, GCP, GPhVP, …)– Existing reassurance about production in stable quality and quality assurance
mechanisms• GMP
– Way of use of medicine characterized for physicians and patients • Data sheets, SPCs, PILs, package labeling
– Lack of knowledge is be properly manged• Pharmacovigilance, risk management programmes
– Evaluations and inspections follow WHO and/or ICH standards
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200921 |
Difference between PQP and national approval procedures
Difference between PQP and national approval procedures
Only certain categories of products are accepted
Voluntary - no direct legal implications
Free of charge (yet)
Assessment and inspections done by multinational teams
Assessment and inspection outcomes are publicly available, no negative conclusions and findings published (yet)
Issues of IPP fully in responsibility of applicant / manufacturer
Definitive negative conclusions exceptional
Technical assistance and regulatory support possible
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200922 |
Prequalified priority essential medicinesPrequalified priority essential medicines(July 2009)
Prequalified priority essential medicinesPrequalified priority essential medicines(July 2009)
164
80
1112
6
10
11
10
0
50
100
150
200
250
Combination
Mono-component
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200923 |
0
50
100
150
200
250
HIV/AIDS Tuberculosis Malaria
Prequalification procedures
HC assessment
FDA assessment
Innovators
Multisourceproducts
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200924 |
194
33
1
6899
11
11
11
12
12 16
India
France
South Africa
UK
Germany
Switzerland
USA
Canada
Spain
Netherlands
China
Australia
Morocco
Pakistan
Countries where prequalified medicines are Countries where prequalified medicines are manufactured manufactured (July 2009)
Countries where prequalified medicines are Countries where prequalified medicines are manufactured manufactured (July 2009)
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200925 |
Prequalification of Quality Control Laboratories
Prequalification of Quality Control Laboratories
Invitation for expression of interest issued by WHO
Laboratory Information File submitted by interested QCLs
If needed, technical assistance is provided
Inspection is organised
Currently 10 QCLs is prequalified, 25 in process of prequalification (mostly from Africa)
More information PQP website
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200926 |
QCLs Prequalification ProcedureQCLs Prequalification Procedure (1) (1)June 2009
QCLs Prequalification ProcedureQCLs Prequalification Procedure (1) (1)June 2009
83
10
3
16
3
22
8
24
10
25
0
5
10
15
20
25
30
35
2004 2005 2006 2007 2008 Jun-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, HAS (2009)
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200927 |
Contribution of PQ to capacity buildingContribution of PQ to capacity building
Organization of trainings– general and problem specific (HIV/AIDS, TB and antimalarial
products, pediatric dosage forms, BE, BE/BCS, GMP)
– Trainings of NRA staff and manufacturers frequently combined
Involvement of assessors from NRAs into PQ assessment
Involvement of inspectors from NRAs into PQ inspections
3 months rotations of experts from NRAs in WHO HQ – PQT
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200928 |
4
9
4
11
4
0
2
4
6
8
10
12
14
16
2006 2007 2008
Trainings organized or supported by PQP
PQP supported
PQP organized
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200929 |
Topics of training workshops2006-2008
Topics of training workshops2006-2008
8
10
53
3
4
42
Prequalification advocacyPrequalification requirementsGood manufacturing practiceQuality controlBioequivalence/BCS and GCPAssessment of medicinesPharmaceutical developmentPQ general
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200930 |
165
198
103
57
263
301
568
0
100
200
300
400
500
600
700
2007 2008
Participants in trainings organized or supported by PQP
Others
QCL staff
Regulators
Manufacturers
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200931 |
Technical AssistanceTechnical Assistance
Provision of expert consultants to– Manufacturers – Quality control laboratories– Regulators
Assistance focuses on – GMP, GCP or GLP compliance– Regulatory guidance
Assistance is separated from the assessment / inspections and may be followed by specific trainings
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200932 |
Technical assistances organized by WHO PQP 2006-2008Technical assistances organized by WHO PQP 2006-2008
2
1
3
2
10
3
8
0
2
4
6
8
10
12
14
2006 2007 2008
REG
GPCL
GCP
GMP
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200933 |
Conditions for provision of technical assistance
Conditions for provision of technical assistance
Manufacturers:Participation in the prequalification programme,Found to be capable and willing to improveLocation in a developing country
Products: Inclusion in the list of expression of interestHigh value for Public Health purpose Poor representation on the Prequalification list.
WHO Prequalification Programme for Priority Medicines, Jakarta, October 200934 |
Thank you for attention