1. UN Prequalification Programme
Milan Smid
WHO Prequalification of Medicines Programme
WHO Expert Committee on Specifications, Oct 2010

2. UN Prequalification Programme for Priority Essential Medicines
Action plan of UN from 2001 for expanding access to selected priority medicines
Objective:
To ensure quality, efficacy and safety of medicines procured using international funds (e.g. GFTAM, UNITAID) to serve patients in developing countries
Components:
Evaluation of Quality, Safety and Efficacy of prioritised Essential medicines (FPPs and APIs), 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, Beijing, P.R. China, DIA, May, 2011

3. Potential benefits for manufacturers
Participation in tender procedures organized by international procurers and financial profit
Recognition as being WHO listed company
Facilitated registration in some recipient countries
Reduction of inspections from recipient countries
Possibility to be assisted by expert consultants (GMP, dossier)
Learning process improving company's chance to succeed with submissions to SRAs
Recognition of prequalified APIs
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

4. Reported Procurement information http://www. theglobalfund
Over 1, 400 million* US of transactions reported in the PQR system
Products/Manufacturers distribution
ARV
Anti-malarial
anti-TB
Branded: 34%
Branded: 70%
Branded: 22%
Generic: 66%
Generic: 30%
Generic:78%
Sophie Logez, GFATM, March 2011
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011
WHO Expert Committee on Specifications, Oct 2010 4

5. GFATM Quality Assurance Policy for Pharmaceuticals (since 2009)
Quality Criteria
For all products
Authorization for use in the recipient countries
For ARVs, anti-TB and anti-malarial products
WHO Prequalified or authorized by a Stringent Regulatory Authorities; or
Recommended for use by an Expert Review Panel: Only If <2 WHO PQed or SRA authorized products available
Clinical Criteria
Medicines listed in WHO or national or institutional Standard Treatment Guidelines
Monitoring Quality
Monitoring quality of products all along the supply chain
Systematic random quality control testing
Recipients report testing results to Global Fund + +
Sophie Logez, GFATM, March 2011
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011
WHO Expert Committee on Specifications, Oct 2010 5

6. Availability and capacity
Increasing demand
Malarial ,TB, and opportunistic infection medicines of assured quality
Lack of sources for some product formulations, such as:
Artemisinin-based combinations: DHA PP
Artemisinin-based single-ingredients: artesunate inj, suppositories
Anti-TB products: all second/third line TB, streptomycin
ARVs: heat stable formulations for Lop/r, Ata/r
Pediatric formulations for all diseases: flexible solid oral forms, FDCs
Strengthening National Regulatory Authority capacity and regulatory networking and harmonization
Sophie Logez, GFATM, March 2011
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

7. COUNTRIES RECEIVING COMMODITIES…US$1.1Billion UNITAID funds
HIV / AIDS
51 recipient countries
Malaria
29 recipient countries
Tuberculosis
76 recipient countries
> US$600 mil
> US$300 mil
> US$200 mil
- Cross cutting programs: US$109 m for PQ of drugs & diagnostics and transversal programs
Lorenzo Witherspoon, UNITAID, March 2011
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011
WHO Expert Committee on Specifications, Oct 2010

8. Categories of medicines invited
Primary categories of medicines:
HIV/AIDS
Malaria
Tuberculosis
Later added:
Reproductive health
Influenza
Acute diarrhoea
Potentially other categories of products, if there is the need (neglected diseases)
Prequalification also applicable for APIs
Published in invitations for Expression of Interest (EOI) on Prequalification website
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

9. 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 developing countries into the project supports their capacity to produce according to international norms and standards
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

10. Essential 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 dossiers
Dossiers receive initial screening
Full dossiers are assessed
Inspections are conducted at manufacturing sites and at CROs
Samples 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, Beijing, P.R. China, DIA, May, 2011

11. Essential steps of monitoring of PQ product
Variations to the dossier of prequalified product
Sampling and Testing
Reinspections
Requalification
Management of complaints
De-listing or suspension (if and when appropriate)
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

12. Steps in WHO prequalification I
Expression
of Interest I
Product dossier
SMF
Assessment
Inspections
Additional information
and data
Corrective
actions
Compliance
Compliance
Prequalification
Maintenance and monitoring
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011
WHO Expert Committee on Specifications, Oct 2010

13. Two prequalification routes
Invitation for
expression of Interest
Medicine not
assessed by SRA
Medicine assessed
by SRA
Dossier and SMF
submitted for assessment
Valid for innovators and generics
SRA registration
(assessment and
compliance check)
WHO assessment
and inspections
organized
Simplified review
Prequalification
Compliance
Acceptance
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011
WHO Expert Committee on Specifications, Oct 2010

14. Evaluation 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 to the applicant followed by surface mail
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

15. Inspections Team of inspectors for each inspection
WHO 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 etc
Inspections are product oriented
APIs and Bioequivalence studies inspected based on risk assessment
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

16. Standards
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, Beijing, P.R. China, DIA, May, 2011

17. Outcomes of PQ procedure
Information in public domain:
Lists of PQ medicinal products
WHOPAR (SPC, PIL, labelling)
WHOPIR (both FPP and API)
Notices of Concern and Suspensions
Information on progress of assessment procedure and inspections
Supportive documents: WHO guidelines, description of PQ procedure, training materials
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

18.
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

19. Products already prequalified (XII/2010)
Prequalified generics and innovators as of December 31st 2010: 252 products (assessed and inspected by PQ)
Total listed as of December 31st 2010 (including those listed based on USFDA/EMA/HCnda approvals): 350 products
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

20. Prequalified priority essential medicines (September 2010)
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

21. Prequalified medicines according to the country of applicant
China
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

22. Contribution 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, Beijing, P.R. China, DIA, May, 2011

23. WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

24. WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

25. Technical Assistance Provision of expert consultants to
Manufacturers
Quality control laboratories
Regulators
Assistance focuses on
GMP, GCP or GLP compliance
Dossier development
Assistance is separated from the assessment / inspections and may be followed by specific trainings
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

26. Conditions for provision of technical assistance
Manufacturers:
Participation in the prequalification programme,
Found to be capable and willing to improve
Location in a developing country
Products:
Inclusion in the list of expression of interest
High value for Public Health purpose
Poor representation on the Prequalification list.
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

27. TAs organized in individual countries (2006-2010)
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011

28. Thank you for the attention
WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 2011