WHO Prequalification of Diagnostic and Laboratory Technologies Business Plan September 26, 2005.

WHO Prequalification of Diagnostic and Laboratory

Technologies

Business Plan

September 26, 2005

Outline

• Context

• Methodology

• Findings

• Path Forward

Need for diagnostic prequalification project is urgent

• Testing needed for diagnosis, clinical staging & monitoring – Large volume of testing is required to meet treatment targets– Capacity has to cater for a wide distribution of patients and clinical sites

• To meet testing demand new technology is needed that is cost effective and appropriate for resource poor settings

– Testing now more expensive than drug pricing in some regions of the world– To fully expand program technology needs to be simple, cost-effective robust

and provide reliable, accurate results

• Promising, low-cost technology beginning to be developed but needs independent validation

– Could allow price reductions of up to 70% in low volume labs– Potentially more appropriate for rural settings (small, robust, allows for %

read)– Not yet validated by independent group and anecdotal reports of quality

problems

• Large scale procurement planned over the next two years and purchasers left with few good options

Substantially expanded testing capacity is required in order to meet treatment targets

100,000

ARV treatment

target

# people HIV+ not

eligible for treatment

300,000

# HIV diagnostic

tests required

2,400,000 Illustrative

400,000

# HIV+ people

# HIV- people tested

2,000,000

Number of HIV Diagnostic Tests Needed in Country with Treatment Target of 100,000

Courtesy of Dr. Trevor Peter

300

5,600

CD4 testing volumes per month expand rapidly as scale-up progresses

Courtesy of Dr. Trevor Peter

2,800

300

VL testing volumes per month expand rapidly as scale-up progresses

Cost effective technologies are required to ensure sustainability of programs

44.4%

23.3%

10.2%6.3%

6.3% 3.6%3.5% 2.5% 100%

Treatment Budget – Country XILLUSTRATIVE

In Country X, lab costs constitute 23.3% of total

treatment budget

South Africa

Figures presume scale-up of 53,000 people on ARVs by end 2005 and ~800,000 people on ARVs by end 2010 in South Africa

The cost implications for high volume countries are dramatic

Appropriate technology is beginning to be developed but needs independent evaluation

• New technology that is cost-effective and appropriate for resource poor settings is beginning to be developed

– Point of Care technology for CD4 & VL– Platforms that allow for multiplexed assays– Combination rapid tests (e.g. HIV/Hep B, HIV/Hep C)– Test kits with longer shelf life and lower refrigeration requirements

• Proliferation of small manufactures including a number of manufacturers in poorly regulated markets

• Few National Regulatory Authorities (NRA’s) that can adequately monitor market

– NRAs is resource poor settings lack capacity– Stringent regulatory authorities limited in scope

Non-representative samplesTechnology not validated in appropriate settingsLack of interest in products aimed at resource poor settings (e.g. infant diagnostics)

• Seventeen years of experience managing evaluation program for test kits

• Existing relationships with WHO collaborating centers around the world

• Network of regulators and other experts

• Relationship with National Laboratories in resource poor settings

The WHO’s EHT team is uniquely positioned to take on this responsibility

Outline

• Context

• Methodology

• Findings

• Path Forward

WHO/CHAI team conducted an assessment to determine resource req. for expanded program

• Consulted leading experts to determine process improvements required

• Interviewed industry leaders and implementing partners to develop demand projections

• Reviewed WHO supplier database to collect historical data on success rates through various stages of the program, average time to approval and average annual demand

• Reviewed contracts with collaborating centers and vendor invoices to collect cost information

• Mapped current evaluation process

• Developed demand and resource model• Developed business plan including work plan and milestones

Overview of process

2006 2007 2008

CD4 5 3 5

VL Technologies 5 3 3

HIV Rapid & Elisa 23* 22 22

Hep B & Hep C 0 17 17

Demand was estimated based on interviews with industry and implementing partners

Demand Estimates for 2006 & 2007* Note: The EHT team will put its evaluation process for rapid tests on hold until mid-2006 while it is implementing certain process changes. At that time it will resume dossier review. It will begin conducting GMP inspections in approx. ten of the companies (most currently on the bulk procurement list)

Assumptions

CD4

VL

HIV Diagnostics

• 2006: Products currently available on market • 2007: Point of care technology in pipe-line• 2008: Platforms that allow for multiplex assays, dipstick technology

• 2006: DBS protocol with market leaders & infant diagnosis• 2007: New technology in pipeline• 2008: New technology in pipeline

• Combination rapid tests (e.g. HIV/ Hep B)• Tests with improved performance• Major manufacturing changes

• Antigen/ antibody tests• New companies

Ind. Report

Lab Eval.

The team has developed a business plan to ensure that it can meet projected demand

Activity

Time Required

# Days Required

Direct Cost

• Initial contact w/ company

• Background research conducted

• Process explained

LOADossier Review

Formal Request

Initial Contact

Evaluation ProcessPlan to add GMP Inspections

1 -3 months (dossiers never close)

1-3 days/ suppliers

• Materials reviewed by technical officer

• Missing materials gathered

1 -7 months

0.5 -7 days/ suppliers

• Short-list of suppliers reviewed by full team

• Prioritization for lab eval. developed

3-5 months

0.5-1 days/ suppliers

• Letter of Agreement sent to companies

• Companies pay fee

0.5-1 month

0.5-1 days/ suppliers

• Tests evaluated by WHO Collaborating Center (performance & ease of use)

1-2 month

1-3 days/ suppliers

2-3 month

• Data collected • Company sent

draft report• Report

published

Outline

• Context

• Methodology

• Findings

• Path Forward

EHT needs to enhance its evaluation protocols and formalize its review process

A. Enhance current evaluation protocols and formalize review process

B. Implement procedural changes to reduce cost of process and improve time to approval

C. Improve communication to internal and external stakeholders

EHT needs to enhance its evaluation protocols and formalize its review process

1. Increase stringency of dossier requirements to bring in-line with Global Harmonization Task Force

2. Implement GMP inspections of manufacturing sites

3. Implement feasibility studies at clinical sites, where appropriate

4. Seek oversight from WHO Expert committee

$0

$10

$20

$30

$40

$50

$60

$70

There are inefficiencies built into the current evaluation process that have added cost..

Cost/ Evaluation (USD Thousands)

High Low Avg. Avg. (inc.

failures)

Avg. w/o failures

Quality of Dossier Quality of Product

• Quality of Dossier• Only 10% of dossiers

submitted include all of the documentation required

• The EHT team spends up to $30k/company helping them organize their dossier submissions

• Quality of Product• For every product approved

nearly $20k is spent evaluating sub-standard products

Ind. Report

Lab Eval.

LOADossier Review

Formal Request

Initial Contact

Evaluation ProcessPlan to add GMP Inspections

Initial Contact

Formal Request

Dossier Review

LOA Lab Eval. Ind. Report

Total

WHO 1 0.6 1.5 0.5 0.5

Supplier 1.3 1.5 0.5 0.5 0.75 1

Collab.

Center

1.5 1 1

Toltal 2.3 2.1 3.5 1 1.75 2.5 13.18

… and caused delays in the review process

Avg. Time Through Process

It currently can take between 8 and 24 from the time a supplier submits a request to the time that they are fully evaluated

Outline

• Context

• Methodology

• Findings

• Path Forward

Procedural changes can be made that will help speed review process and save money

Adjust WHO HR Policy

Clarify Guidelines

Strengthen Contracts

Recommended Change

1. Publish document that clarifies evaluation requirements

2. Hold annual meetings with industry to review process

1. Include requirements for 2 week turn around time with WHO collaborating centers

1. Create fixed term positions within team to ensure consistency

2. Add capacity to team

Problem • First few steps of process are time consuming and costly Close dossier after period of time (3 months)

• Up to a two month lag time between dossier approval and lab evaluation b/c of scheduling problems at Laboratory

• Suppliers left in queue for up to one year b/c of inadequate staffing

• Program coordinator spends time getting new staff up learning curve

Recommended Procedural Improvements

Procedural changes can be made that will help speed review process and save money

Strengthen Coordination b/w

WHO teams

Close Dossiers Improve Communications

Recommended Change

1. Once guidelines are clear can close dossiers after period of time (3 months)

1. Create formal prequalification list

2. Conduct regular survey of stakeholders to ensure communications reaching users

1. Revive diagnostics working group

Problem • Team spends substantial amount of time following up with companies that never make it through the process

• Evaluation reports published two times/year which can lead to a delay in time to market

• Not all Member States aware of Bulk Procurement Scheme

• Validation of diagnostic products for HIV, TB, Malaria and STIs all managed in different WHO groups

Recommended Procedural Improvements

Baseline 2006 2007

Total Cost (USD MM) $1.2 $2.3 $2.1

Staffing (# FTEs) 2.5 6 6

Project will need additional resources to add new products and to enhance review process

Summary of Resources Required

Staffing Plan

• 1 Coordinating Technical Officer – oversee process• 1 Non-technical Officer (budgeting & planning, contract negotiation, external and

internal communications)• 3 Technical Officers - manage product evaluation, review dossiers; write

evaluation reports, write guidelines• 1 Administrative Assistant• 2 External Consultants to support CD4 evaluation process & 2 consultants to

support VL process- Train field sites, assist in protocol development• GMP Inspectors -6 in 2006,

A number of challenges that will need to be managed to ensure success of program

Key Challenges Plan

• Inspector/ Consultant availability

• Coordination between groups at WHO

• Sustainability

• Management Support

• Utilize network to develop a pool of inspectors & develop inspection schedule

• Develop back-up plan including use of private consultants

• Revive diagnostic working group & include group in protocol development and ongoing planning

• Build capacity at regional and national level

• Ensure annual prioritization of products in pipeline

• Include focus on fundraising in TOR for non-technical officer

• Ensure management support so that decisions are made quickly & appropriate resources made available

• Secure approval to hire technical officer to manage CD4 process• Draft new evaluation protocols• Recruit assessors & consultants• Recruit 2 additional technical officers and 1 non-technical officer

Next Steps

Immediate Next Steps