QUALITY REPRODUCTIVE HEALTH

SUPPLIES

Dr Hans V. HogerzeilDirector

Essential Medicines & Pharmaceutical Policies

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Part 1: Overview of the WHO / UN Prequalification Programme

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Prequalification objectives

Produce list of prequalified products (for priority therapeutic areas), and of manufacturing sites, that meet international norms and standards for quality, efficacy and safety

Produce list of PQed medicine control laboratories that meet international norms and standards for quality, efficacy and safety

Ensure re-evaluation and maintenance of the list of PQed medicines, including assessment of variations and changes

Help national drug regulatory authorities build capacity in assessment, inspection and control

Develop local capacity in manufacturing production and clinical studies by offering customized technical assistance

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Recent developments

In addition to PQ of 241 medicines and 14 QCLs to date:

concept of medicines quality better and more widely understood by countries, partner agencies and manufacturers

increased access to quality-assured priority medicines products; more supplier security, more price competition

more rapid development of some quality products through provision of standards, technical assistance and training

faster regulatory approval of some products e.g. by making info about PQed products and evaluation/ inspection outcomes publicly available

monitoring and evaluation of the quality of medicines circulating on the market: large difference between PQ-ed and non-PQed

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Products prequalified

PQed 2010 to date:

-3 HIV/AIDS -2 TB

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Products prequalified, by therapeutic category

0

20

40

60

80

100

120

140

160

180

200

HIV/AIDS

TuberculosisMalaria

Reproductive health

Influenza

7

Number of inspections 2005–2009

0

10

20

30

40

50

60

2005 2006 2007 2008 2009

FPP

API

CRO

QCL

total

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Number of dossiers assessed 2007–2009

0

5

10

15

20

25

30

HIV

Mal

aria

TB

RH

HIV

Mal

aria

TB

RH

HIV

Mal

aria

TB

RH IN

HIV

Mal

aria

TB

RH IN

HIV

Mal

aria

TB

RH IN DI

HIV

Mal

aria

TB

RH IN DI

H1 2007 H2 2007 H1 2008 H2 2008 H1 2009 H2 2009

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Training & capacity building 2007–2010

165

198

103

57

263

301

568

396

282

4944

233

904

0

100

200

300

400

500

600

700

800

2007 2008 2009 2010 I-III

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

Others

QCL staff

Regulators

Manufacturers

165

198

103

57

263

301

568

396

282

4944

233

904

0

100

200

300

400

500

600

700

800

2007 2008 2009 2010 I-III

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

Others

QCL staff

Regulators

Manufacturers

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Technical assistance to manufacturers, CROs and QCLs

by year 2006–2010 and WHO region

1

3

2

3

2

1

2

2

0

2

4

6

8

10

12

14

2006 2007 2008 2009 2010(IV)

REG

GPCL

GCP

GMP

7

7

2

2

2

1

8

1

14

1

2

0

2

4

6

8

10

12

14

16

18

AFRO AMRO EMRO EURO SEARO WPRO

REG

GCP

GPLC

GMP

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Quality control laboratories:Prequalified or interested in becoming prequalified

Prequalified QCLsin:

Algeria Canada France India Kenya Morocco Singapore South Africa Ukraine Vietnam

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New directions

Survey of manufacturers of prequalified products: use the results to improve PQP services

Targeted outreach to potential new manufacturer applicants

Focus on improving quality of active pharmaceutical ingredients

Joint dossier assessments (between countries)

Assess value to manufacturers of WHO prequalification

Assess benefits to partners of WHO prequalification

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Challenges

Increasing number of variations

Reducing timelines to prequalification

Funding for PQ of RH products ends on 31 May 2010

Procurement practices by agencies do not always follow and support WHO/UN prequalification

Lack of harmonized regulatory standards in countries; national authorities don't effectively use PQP's information for registration

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Part 2: PQP's experience of prequalifying reproductive health products

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Invitations to manufacturers of RH products to submit

expression of interest for product evaluation (EOIs)

1st Invitation - October 2006Oral and injectable hormonal contraceptives

2nd Invitation - December 2007Prevention and treatment of post-partum haemorrhage and ecclampsia

3rd Invitation - May 2008Extended to injectable hormonal contraceptives and oxytocics, implant

4th Invitation - July 2009Extended to oral, injectable and implantable hormonal contraceptives

5th Invitation - May 2010Deletion of lynestrenol, better specification for oxytocin and mifepristone

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37 RH product dossiers submitted to PQP to date

0

2

4

6

8

10

12

14

16

Not accepted Cancelled Pending Approved

17

RH medicines submitted, by country

0

2

4

6

8

10

12

Argentina Chile China Denmark Germany Hungary India Indonesia USA

Non-accepted Cancelled Pending Approved

18

Submissions by R&D and 'generic' companies

0

5

10

15

20

25

30

R&D Multisource

Non-accepted CancelledPending Approved

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Reasons for rejections and cancellations

Multisource

• Data in dossier do not demonstrate product quality - API or FPP data

• Bioequivalence is not demonstrated

• GMP standard is not acceptable (premises, QA)

Common denominator: lack of experience, lack of technical skills and

lack of co-operation

R&D companies

• Product is not invited for prequalification

• Product is not identical as approved by stringent authority

• Product assessment is not documented by stringent authority

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Workshops focused on therapeutic groups 2006–10

1

5

15

3

HIV/AIDS medicines Antimalarials

TB medicines RH products

Pediatric formulations

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Benefits for manufacturers of participating in prequalification

Potential for increased financial profit by meeting requirement of procurers and sponsors participation in global market and international tenders

Enhanced reputation

Access to technical support – opportunity to save resources and to increase competitiveness

Facilitation of national registration in recipient countries and in "regulated" markets

PQP levies no charges for services

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Manufacturers' reasons for not participating in PQP

The need to make human and financial investments

A lack of technical and regulatory skills

Not yet ready to participate globally

Differences between PQP and national regulatory requirements

Varying requirements and standards of procurers

Risk of losing traditional markets once defined as sub-standard

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How can we promote prequalification and quality among RH manufacturers?

Increases understanding of RH quality issues among procurers and international donors

Procurement agencies stop buying poor-quality RH products: develop joint QA policy, harmonize requirements make manufacturers aware of joint QA policy

publicly set target date for implementation of QA policy (i.e. deadline for suppliers to meet new QA requirements)

PQP analyses barriers to investing in improving quality and defines incentives for encouraging such investment

PQP secures donor funding for providing enhanced support to RH manufacturers aimed at prequalification

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Recommended actions for improving quality procurement

• Invest sufficient financial and human resources into quality assurance– Quality assurance costs 2 - 2.5% of procurement value– Procurement organizations are legally liable for the quality of the products

• Develop and publish an agency quality assurance policy– Define and confirm agency's long-term commitment and plan of action– Serves to inform consumers / recipients– Good example: the quality policy of the Global Fund (2009)

• Promote and use the WHO/UN Prequalification Programme– Inform and set deadline to manufacturers

• Make specific arrangements for the (temporary and exceptional) procurement of items neither prequalified or approved by SRA

– WHO Expert Panel Review for risk-based advice on alternative suppliers

• Offer specific quality procurement training to key staff

• Hold meeting with WHO to discuss draft plan, define concrete steps