The Pipeline for Point-of-Care Viral Load Diagnostics and Development Challenges

Maurine M. MurtaghMSF-UNITAID Co-Hosted Satellite Event

AIDS 2012, XIX International AIDS ConferenceWashington, DC

July 23, 2012

At least one of these, the viral load assay for the Liat platform, may still launch in late 2012.

Additional platforms will follow over the next few years.

New Point-of-Care Options for Viral Load Monitoring are on the Horizon

A number of new Viral Load POC diagnostics are in development.

These will have lower instrument and per-test costs, but will also have lower throughput than lab-based systems.

Technology Pipeline – Viral Load and EID*

2012 2013 2014 2015 2016

Alere Q

NWGHF VL

Lynx EIDSAMBA EID SAMBA VL

Liat

WAVE 80 EOSCAPE

Gene XPert

Micronics

Biohelix

ALL

Cavidi AMP

Lumora

Monitoring HIV Patients on ART – POC Viral Load

Company IQuum Alere WAVE80 DRW

Platform Name Liat™ Analyzer Alere Q WAVE80 EOSCAPE-HIV™ System

SAMBA Analyzer

Type Bench top portable; ~8.3 lbs

Bench top portable; <11 lbs

Bench top portable analyzer with separate processing units

TBD

Output Quantitative or qualitative VL

Quantitative HIV-1 RNA

Quantitative HIV-1 RNA Semi-quantitative for viral load monitoring

Specimen Type 200 µL plasma or 10 - 50 µL fingerstick blood

25 µL fingerstick or 25 µL heel stick

100 µL fingerstick blood 200 µL plasma for viral load

Cost/test TBD TBD <$20 per test TBD

Number of samples/run

~8 - 15 samples per day depending on LOD; TAT 30 - 55 minutes, no batching

Max of ~10 samples per day; TAT 30 – 60 minutes

~50 samples per day with 6-8 processing units and a single analyzer; TAT 50 minutes; random access

4 samples per run; TAT ~90 - 120 minutes depending on the assay

Equipment Cost ($US)

~$25,000, may be lower in LRS

TBD ~$10,000 for one analyzer with 2 processing units

TBD

The Promise of Viral Load Testing at the Point of Care

POC testing has the promise to:

• Reduce the need for large infrastructure investments in diagnostic equipment

• Reduce/eliminate the need for service and maintenance

• Reduce the per test cost of testing

• Yield same day results for prompt clinical decision-making

• Improve patient retention

• Reduce the need for sample transport network

There are a number of Challenges along the Path from Discovery to Development to Delivery of Diagnostic Products

Discovery Proof of Principle Product Development Delivery

Basic Research Platform development and feasibility studies

Prototype development

Clinical Trials

Product Optimization

Pre-market Validation

Scale-up/ Manufacturing

Commercial release and Marketing

The road from discovery to delivery of diagnostic products involves many steps, any one of which can delay product introduction and uptake.

And the process can easily take 5 years or more, even after prototype development, and can cost from $5 million to $50 million or more.

The Obstacles to Product Development

• The early obstacles to product development often include technology issues.

• In addition, funding is frequently a barrier to product development and can slow the process, especially for diagnostic products designed for use in resource-limited settings.

• Once financial and technical hurdles have been overcome and prototype development is achieved, clinical and field trials will be required in-country in order to permit product optimization.

• Manufacturing facilities must be identified to allow for production scale-up.

In-Country Product Introduction

• Once new diagnostics have been developed almost to the point of market introduction, there are still a number of hurdles for diagnostic developers.

• There are complex, non-uniform and costly regulatory frameworks for evaluation and registration of new products at the national level in-country, often requiring producers to submit new diagnostic products to evaluation in every country in which they wish to register their product.

• These pre-market evaluations represent a large financial cost to the developer and are one of the last major hurdles in product development, followed by final scale-up of production and commercial marketing of the product.

Paving the Way: Dialogue with Ministries of Health (MOH)

• The ultimate decision to introduce new diagnostic technologies in-country rests with the MOH. Must have their approval and product must be licensed in-country.

• It is ideal to have trusted, in-country partners to work with the MOH to do the following:

• Introduce new technology to the MOH, describing its features, expected cost, etc.

• Guide development of evaluation protocols – scientifically robust, ethically sound

• Facilitate product evaluations and registration – selection of evaluation sites, troubleshooting

• Guide strategic implementation, including cost-effective scale-up

Paving the Way: Market Evaluations

At the same time, it is important to begin to target major in-country treatment partners that will adopt the test once approved for use in-country – e.g., partners such as ICAP, Harvard, MSF, EGPAF, Johns Hopkins and others, that are on the ground supporting care and treatment programs in Africa with PEPFAR and other international funding.

Paving the Way: Interface with Product Developer

• At the same time, the partner can assist the developer/manufacturer by:

• Providing advice on optimal product design for local needs

• Providing information about the progress of the evaluation and adoption process to help supplier better understand the landscape for market entry and the barriers that need to be tackled

• Making local introductions and facilitate relationships between manufacturer and MOH and decision-makers

• Assisting in defining the role of local distributors and proving oversight on distributor margins

• Developing demand forecasts

• Providing post-market surveillance

This role is best undertaken by a trusted in-country partner that is considered by the MOH to be entirely objective. This has been a particular expertise of the CHAI over the last several years.

Paving the Way: The Funding Partners

• Ultimately, of course, there must be funding for countries to purchase any new diagnostic test in order for there to be effective scale-up and roll-out in-country.

• Funding partners are critical in this process.

• Key players are the Global Fund, PEPFAR, UNITAID and certain NGOs.

• Their funding decisions, in particular the decisions of GF and PEPFAR, are importantly driven by country demand.

• But, advocacy by stakeholders, including activists, is important as well.

Paving the Way: A Call to Stakeholders

• Clear, objective, published tables or summaries/recommendations of existing and new technologies listing the pros and cons and making known good and bad performance, especially if undertaken by the WHO, CDC or an academic institution.

• Technical guidance on how to select and evaluate new technologies, including simplifying the methodology so that evaluations can be done more quickly.

• A strong, coordinated effort by agencies such as the CDC, WHO and other laboratory partners to encourage regional evaluations of new platforms to serve as guides to good quality technology.

• Targeted technical assistance on the adoption of new technology, focusing on selection and strategic implementation/deployment planning, procurement planning and budgeting, setting tender specifications and coordination of partners around a national budget and implementation plan.

• Ongoing in-country capacity building to improve diagnostic systems.

Effective Diagnostic Delivery – it takes a village . . .

• Effectively introducing new diagnostic technologies into resource-limited settings is challenging; it may seem like a mine field.

• An in-depth understanding of the in-country decision-making process and landscape as well as strong local relationships are essential to navigate the country adoption process.

• Many countries will not allow an implementation partner to introduce new technologies without MOH approval – so working with the government is a critical first step.

• Beyond the government, in-country partners, distributors and funders are also critical to the process.

• It is imperative that the manufacturer/developer find a way to effectively work with and coordinate all of these parties.

Acknowledgments

UNITAID

The Bill & Melinda Gates Foundation

Dr. Trevor Francis Peter

Advanced Liquid Logic, Alere, Biohelix, Cavidi, Cepheid, Diagnostics for the Real World, Iquum, Lumora, Micronics, Northwestern Global Health Foundation, and WAVE80

Thank you