Transcript WHO Prequalification of Medicines Programme 18 November 2008 Raul Kiivet, MD, PhD Manager, Prequalification of Medicines Programme Quality Assurance and Safety: Medicines (QSM) Department of Essential.

WHO Prequalification of Medicines
Programme
18 November 2008
Raul Kiivet, MD, PhD
Manager, Prequalification of Medicines Programme
Quality Assurance and Safety: Medicines (QSM)
Department of Essential Medicines and Pharmaceutical Policies (EMP)
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Web site updated constantly – www.who.int/prequal
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Prequalification of Medicines Programme
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The UN Prequalification Programme is ensuring that medicines procured with
international funds are of assessed and inspected quality, efficacy and safety.
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The Prequalification Programme is an action plan for expanding access to
priority essential medicines in the following four areas:
- HIV/AIDS
- Tuberculosis
- Malaria
- Reproductive Health
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A UN Prequalification Program of Quality Control Laboratories exists to
facilitate the quality control of the prequalified products.
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Prequalification of Medicinal Products: Objectives
- Propose a list of prequalified products and manufacturers meeting
international norms and standards of which the quality, efficacy and safety
has been assessed, inspected and controlled
- Ensure that international norms and standards are applied at all the
steps of the Prequalification Programme.
- Make sure re-evaluation and maintenance of the list are performed and
that variations and changes are correctly controlled.
- Help the national drug regulatory authorities to build up capacity in
assessment, inspection and control meeting international norms and
standards.
- Develop the local possibilities of production and clinical studies by
offering customized technical assistance.
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Prequalification of Priority Essential Medicines
Organisation (1)
Assessment of the product dossier i.e. quality specifications,
pharmaceutical development, stability, bioequivalence…
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Copenhagen assessment week
- 15 to 20 assessors during one week at least every two months
- Every dossier is assessed by at least two assessors including one senior
assessor for the second assessment
- An assessment report is issued
- Letter summarizing the findings and asking for clarification and
additional data if necessary; sent first by e-mail to the applicant followed
by surface mail
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Handling of variations of already prequalified products
- Done in house and during Copenhagen-week
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Prequalification of Priority Essential Medicines
Organisation (2)
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Inspections of manufacturers of Finished Products (FP)
Active Pharmaceutical Ingredient (API) and also Contract
Research Organizations (CRO, which carry out
bioequivalence studies)
Team of inspectors
- WHO representative (qualified GMP inspector)
- Inspector from well-established inspectorate
- National inspectors invited to be part of the team but have no
decision making power (different GMP standards, potential
conflict of interest)
- Inspector of developing countries as observer, for capacity building
purpose.
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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August 2008 - 6th Invitation to
manufacturers of anti-malarial medicines
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1. Artemisinin-based fixed dose oral combination formulations
Artemether + Lumefantrine, tablet 20 mg + 120 mg; tablet 40 mg + 240 mg
tablet 60 mg + 360 mg; tablet 80 mg + 480 mg
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2. Artemisinin-based fixed dose combination or co-blistered oral
formulations
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Artesunate + Amodiaquine, tablet 25 mg + 76.5 mg; tablet 50 mg + 153 mg
tablet 100 mg + 306 mg
Artesunate + Mefloquine, tablet 25 mg + 250 mg; tablet 50 mg + 250 mg
tablet 100 mg + 250 mg
Artesunate + Sulfadoxine + Pyrimethamine, tablet 25 mg + 500 mg + 25 mg
tablet 50 mg + 500 mg + 25 mg; tablet 100 mg + 500 mg + 25 mg
3. Artemisinin-based fixed dose combination or co-blistered oral
paediatric formulations, preferably dispersible
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Assessment & Inspections
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Key numbers for 2007
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21 products prequalified (28 in 2008*),
90 dossiers submitted (66 in 2008*)
463 assessment reports (487 in 2008*)
46 inspections (43 in 2008*)
* (8 months)
For each prequalified product in 2007 there were:
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5-15 assessment reports
3-7 inspections
it took 2 years in average to be prequalified
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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List of WHO Prequalified Medicinal Products
Currently prequalifed (15 November 2008):
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162 for treatment of HIV/AIDS and related diseases
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18 for treatment of tuberculosis (10 prequalified in 2007-08)
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13 for treatment of malaria (8 prequalified in 2007-08)
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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New submissions to prequalification
2005
2006
2007
HIV
67
42
25
39
TB
17
9
17
13
Malaria
3
5
7
11
Repr Health
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Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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2008 * (8 months)
Currently under evaluation in
WHO Prequalification Programme
As of 1 November 2008:
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120 products for treatment of HIV/AIDS and related
diseases
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48 products for treatment of tuberculosis
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23 products for treatment of malaria
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11 reproductive health products
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Transparency – dossier status information on the web
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Anti-malaria medicines under evaluation
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Inspections - statistics in 2007 vs 2006
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A total of 45 (2006 – 42) inspections were carried out in 2007:
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26 (17) inspections of the manufacturing sites of
finished product manufacturers
6 (10) inspections of the manufacturing sites of active
pharmaceutical ingredients (APIs)
13 (15) inspections of contract research organizations
(CROs)
In 2006 two inspectors in house, four in 2008
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Transparency – Inspection outcomes on the web
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Problems
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Antimalarials and antituberculosis products – old problems
but few new solutions
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No new innovator products
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Generic products with no innovator
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…or problem "new" products
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GMP (both for finished dosage form and API)
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Quality part of the dossier – specifications, stability data etc
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Safety and efficacy – poor clinical and safety data, poor quality information
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Training activities in 2008
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In total 13 training courses of 3 to 5 days: ten courses organized and 3
co-organized
In Belgium, Brazil, China, India, Iran, Jordan, Morocco, Nicaragua,
Pakistan, Tanzania
More than 500 participants - staff of regulatory authorities and
pharmaceutical manufacturers
Topics:
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Development of diossiers for submission
Asssessment of Interchangeable medicines
Pharmaceutical Development of Paediatric Formulations
GMP, Quality and Bioequivalence of malaria ATC products
GMP, Quality and Bioequivalence of Reproductive Health products
Pharmaceutical Development of Paediatric Formulations
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Prequalification of Quality Control Laboratories
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So far mainly for AFRO region, now wider scope
6 QC Labs prequalified
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13 QC Labs audited, corrective measures proposed
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RIIP, South Africa – 07/2005
LNCPP, Algeria – 10/2005
Adcock, South Africa – 01/2008
National QCL, Kenya – 07/2008
National QCL, Marocco – 07/2008
Vimta Labs, India – 07/2008
Cameroon, Mali, Madagascar, Niger, Senegal
Ghana, Etiopia, Kenya NQCL, Kenya MEDS, Uganda, Tanzania
8 QC Labs expressed interest, but not send LIF yet
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Benin, Burkina Faso, Cote d'Ivoire, Guinea
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Technical Assistance - Policy
Criteria for the products in relation to which technical assistance is considered:
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Inclusion in the list of expression of interest
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High value for Public Health purposes
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Poor representation on the Prequalification list
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Manufacture has applied for PQ (exemptions can be made upon justified
requests for technical assistance from regional offices) danger
Criteria for the experts:
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Excellent qualifications and long standing experience in the area where
expertise is required
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Absence of conflict of interest
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Total intellectual independence from the prequalification programme, no
participation in inspections or assessments.
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Technical Assistance - Examples 2007
Manufacture of oral solid
dosage forms anti TB
Ukraine
Technical Assistance on stability
studies
06-09 February 2007
Manufacturer of sterile anti
malarial API
China
TA on manufacture of a sterile
API under aseptic conditions
05-10 March 2007
Manufacture of oral solid
dosage forms anti malarial
Cambodia
TA on packaging of co-blisters
26 March – 02 April 2007
Manufacture of oral solid
dosage forms ARV
Zimbabwe
TA on GMP compliance
01-05 May 07
Manufacturer of anti TB API
India
TA on manufacturing process
validation and GMP
20-26 May 2007
Manufacture of oral solid
dosage forms anti malarial
Manufacture of oral solid
dosage forms ARV.
Manufacture of oral solid
dosage forms ARV
Cambodia
TA on packaging of co-blisters
17-29 July 2007
Bangladesh
TA on GMP and engineering
23–29 August 2007
Zimbabwe
TA on GMP compliance
04-09 November 2007
Manufacturer of anti TB API
India
Manufacturer of sterile anti
malarial API
China
TA on manufacturing process
validation and GMP
TA on manufacture of a sterile
API under aseptic conditions
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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17-21 December 2007
17-22 December 2007
Revision of PQ procedure in 2008
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Reasons for revision
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5 years experience from implementation
discrepancies between rules and practices
unclear responsibilities of parties
Aims of revision
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increase transparency of PQ activities
publish more details of prequalified products
harmonize terminology and clarify procedures
better define responsibilities
confidentiality agreement with applicants
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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New PQ procedure for APIs in 2009
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until now the qualification of API source and manufacturer is the
responsibility of finished product manufacturer => API manufacturer
seldom inspected and API dossier commonly not evaluated
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API source considered "confidential" information
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Oct 2008 WHO Expert Committee on Specifications for
Pharmaceutical Preparations will discuss
 Procedure for API Master File in Prequalification Programme
 PQ procedure for active pharmaceutical ingredients (APIs) – new
"regulatory" approach
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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Summary remarks
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The purpose of the prequalification programme is to list good quality, safe and
effective medicinal products in the interest of public health in resource-limited
countries.
The products should be submitted with technical data proving the quality of API
and finished product together with necessary data on safety and efficacy
Manufacturing sites of API s and finished products should operate according to
GMP principles in order to deliver consistent quality products
Technical assistance for promising manufacturers/products can be made
available to achieve the goal and speed up the prequalification process.
Close cooperation with international procurement and financial institutions
 quality as prerequisite for procurement decision
 instruments to support quality production
Encourage manufacturers to invest into quality, and to apply for
independent evaluation
Main aim of PQ – to increase choice and access to quality products
Department of Medicines Policy and Standards,
Health
Technology and Pharmaceuticals
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