un prequalification programme milan smid who prequalification of medicines programme

UN Prequalification Programme UN Prequalification Programme

Milan SmidWHO Prequalification of Medicines Programme

WHO Prequalification Programme, Beijing, P.R. China, DIA, May, 20112

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.


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


Reported Procurement information http://www.theglobalfund.org/en/procurement/pqr/

• Products/Manufacturers distribution

ARV Anti-malarial

anti-TB

Branded: 34%

Branded: 70%

Branded: 22%

Generic: 66%

Generic: 30%

Generic:78%

Over 1, 400 million* US of transactions reported in the PQR system

Sophie Logez, GFATM, March 2011


Quality Criteria

For all productsAuthorization for use in the recipient countries

For ARVs, anti-TB and anti-malarial products

WHO Prequalified or authorized by a Stringent Regulatory Authorities;orRecommended for use by an Expert Review Panel: Only If <2 WHO PQed or SRA authorized products available

GFATM Quality Assurance Policy for Pharmaceuticals (since 2009)

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

+ +



Availability and capacity



HIV / AIDS51 recipient countries

Malaria29 recipient countries

Tuberculosis76 recipient countries

> US$600 mil > US$300 mil- Cross cutting programs: US$109 m for PQ of drugs & diagnostics and transversal programs

> US$200 mil

COUNTRIES RECEIVING COMMODITIES…US$1.1Billion UNITAID funds

Lorenzo Witherspoon, UNITAID, March 2011


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


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


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)


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)


I

Expression of Interest

Compliance

Additional informationand data

Corrective actions

Compliance

Assessment Inspections

Steps in WHO prequalification

Prequalification

Maintenance and monitoring

Product dossierSMF


Invitation for expression of Interest

Dossier and SMF submitted for assessment

Valid for innovators and generics

Two prequalification routes

Medicine assessedby SRA

Medicine notassessed by SRA

WHO assessmentand inspections

organized

Compliance Prequalification

SRA registration )assessment and

compliance check(

Acceptance

Simplified review


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 e-mail to the applicant followed by surface mail


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


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


Outcomes of PQ procedure

Information in public domain: http://www.who.int/prequal/

• 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


www.who.int/prequal/


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

191

2917 8 7

HIV TB Malaria RH Influenza


Prequalified priority essential medicines Prequalified priority essential medicines (September 2010)

0

50

100

150

200

250

HIV/AIDS Tuberculosis Malaria

FDC

Mono-component


1 1 2 2 2 2 5 5 6 7 915

26 26

141

0

20

40

60

80

100

120

140

160

Prequalified medicines according to the country of applicant

China


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


165

198

10357

263

301

568

396

282

4944

805

203

130

73

0

200

400

600

800

1000

1200

1400

2007 2008 2009 2010

Participants in trainings organized or co-organized/supported by PQP

Others

QCL staff

Regulators

Manufacturers


Countries hosting workshops organized or supported by Prequalification Programme in 2006-2010

0

2

4

6

8

10

12

14


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


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.


TAs organized in individual countries (2006-2010)

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Thank you for the attention

[email protected]

un prequalification programme milan smid who prequalification of medicines programme

Documents

prequalification website

recipient countries

mil countries

recipient countries

safety of medicines

mil us

evaluation of quality

quality criteria