Innovation to Commercialization

Challenges and considerations for getting a product to market.

Who is MDxHealth

OncoMethylome Sciences was originally founded in 2003 to discovery and out license technologies surrounding DNA methylation.

As of October 5, 2010, ONCO changed its name to MDxHealth Inc. With new management and new corporate goals: to provide diagnostic, prognostic and predictive assays to service the personalized medicine arena, moving from a discovery license model to a clinical diagnostic model.

MDxHealth is based in Liège, Belgium, and has a subsidiary in Durham, NC. All development activities are centered in Belgium 's ISO 9001 certified laboratory where there are 35 employees.

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How do you sort through development?

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Product Development

Clinical

Quality

Regulatory

Infrastructure

Finance

Some considerations early on

Where does my potential product fit into the market?What is the Intended Use for the product?Will it require regulatory approval?Are there similar products already on the market?Do I have the resources required internally to develop, manufacture, distribute the product or will I need to outsource?How will I finance the business?

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Product Challenges and Hurdles

What are my product challenges– Do I have the right biomarkers?– Do the provide clinical utility?– Do they meet a market need?– Can they work reliably and accurately?– Do they impact a patients life or treatment

decision?

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What are the regulatory considerations?

What potential risk does it pose to the patient?

Does it require FDA approval or can it be launched as a Lab Developed Test (LDT)

If FDA approval is required; is there a predicate device I can use?

If it is a high risk product will it require a Pre- Market Approval (PMA)?

Will it require a clinical trial to prove safety and efficacy?

Will it require compliance with FDA regualtions for manufacturing I.E. Good Manufacturing Practices (GMP)

Do I want or need CE marking for Europe?

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What are my infrastructure considerations?

Do I have the resources and expertise to develop this product on my own or will I need consultants and or contract manufacturers?

If I make the product in house what Quality Systems requirements will I need to address?

Will I be required to obtain licenses or permits from local, state or federal governments?

Does the final product require a Clinical Laboratory Improvements Act (CLIA) certified laboratory?

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What are my clinical considerations?

Do I need to perform a clinical trial?

Can I use retrospective data to substantiate the validity of my product?

Can I use animal studies to perfrom proffo of concept studies?

Will I need human based clinical trials?

How much will it cost?

How long will it take?

If so.. How many patients and how many sites will I need?• Do I need EU and US based patient populations?• Are there other demographic or ethnical

considerations?8

What are my instrument and or reagent considerations?

Is there software required to analyze or interpret the results?

Does the software need to be 21 CFR part 11 compliant

Does the instrument need to be cleared or approved by the FDA?

Do the reagents need to be cleared or approved by the FDA?

Am I required to perform Instrument Qualification (IQ), Operator Qualification (OQ), Process Qualification (PQ)

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What are my product development considerations?

Do I need to maufacture under Design ControlDo I need to meet Federal Quality Systems RequirementsWhat kind of Standard Operating Procedures will I need?Do I have the right team of people to support this development?

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Quality

ClinicalOperation

FinanceTechnical

Input Required

PRODUCT DEVELOPMENT

PLAN

Focus on Regulatory

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Will I require regulatory approval?

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FDA Risk Classification

Determination of the Class of he device helps establish the path to market

Searchable data base available at www.fda.gov

Class I – Common low risk devices– Exempt in most cases unless different intended use

Class II- more complex higher risk– 510(k)– Predictive or Prognostic or risk based assays– May require PMA because there is no predicate ( de novo 510(k))

Class III- most complex highest risk– Support or sustain human life– Diagnose or alter patient care options– PMA required

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Risk Classification

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Clinical Trials based on Risk

For some Class II and most Class III products clinical trials are required.

In the case of some Class II devices restrospective data has been acceptable for review and approval by the FDA

Use of cell lines and biobanked specimens is also acceptable in many Class II products

Determining the correct number of patients or samples to evaluate is essential.

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510 (K) or PMA

510 (K) Pre-Market Notification

PMA Pre-Market Approval

Demonstration of substantial equivalence to a predicate device

Requires demonstration of reasonable safety and effectiveness

As “safe and effective”

as predicate

Class III

Class I, II and some III Class II de Novo products ( no predicate)

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510K review process De Novo

Review 90 days

Respon d30 day

No Issues Review 30 daysIssues 90- 180 days

60 days

30 days

Prep 30-60 days

Prep 60-90 days

360 days

assume no additional clinical trial required

Prep 20 days

Review 60 days

PMA Process

Start 240 days

Pre-IDE prep 30 days

Pre-IDE Review 30 days

Clinical trial requirements ?

PMA Prep 60 days

PMA Review 144- 275

1.75 years with no clinical trial time

Other Considerations once regulatory path is determined

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Quality Subsystems

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Design Control

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Requires Input from all aspects

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Additional Resources

FDA Compliance, Guidelines and Database ,FDA Website www.fda.gov

Medical Device Development A Regulatory Overview by Johnathan S. Kahan

Regulatory Compliance Almanac A Good Guide to Manufacturing, Clinical and Laboratory Practices. By Les Schnoll

The Statistical Evaluation of Medical Tests for Classification and Prediction By Margaret Sullivan Pepe

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QUESTIONS?

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