FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular...

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FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of In Vitro Diagnostics

Transcript of FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular...

Page 1: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

FDA Overview of Molecular Diagnostics and the Critical Path Initiative

Steven Gutman, MD, MBADirector, Office of In Vitro

Diagnostics

Page 2: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Medical Device Amendments of 1976

General controlsRegistration and listingGood manufacturing practicesPost market reporting

Page 3: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Premarket Review

510(k)sPMAAdministrative differencesCommon scientific base

Page 4: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Analytical Performance

AccuracyPrecisionAnalytical specificityAnalytical sensitivity

Page 5: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Clinical Performance

Signals can be turned in to clinical actionDiagnostic sensitivityDiagnostic specificityPredictive value or positive or negative results

Page 6: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Labeling -- 809.10(b)

Intended usePerformance characteristicsLimitations

Page 7: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Life Cycle

Analytical performanceFeasibility *Clinical performance FDA approval – market access---------------------Real world use

Page 8: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

The Real World of Regulation

FDA CMS (CLIA)CMS and others (third party pay)

Page 9: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of
Page 10: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of
Page 11: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Critical Path Initiative

Biomarkers appear in two contextsDiagnosisDrug discoveryConcept of personalized medicine grounded in genomic map but not bounded by this

Page 12: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Critical Path Initiative

InfrastructureOpportunities listPilot programs

Page 13: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Bad News

Cutting edge new technology --multiplex, bioinformatics, nanotechnologyPaucity of material or method standardsBiological and clinical nuancesFinancial uncertainties

Page 14: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Bad News

Scientific limitations are clear Spectrum biasVerification biasImpact of missing data pointsDiscrepancy

Page 15: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Good News

Regulatory trail is well litLiteratureStandardsGuidances

Page 16: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Principle Road Maps

STARD InitiativeReMARK Initiative

Page 17: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Growing Literature on Co-Development

Simon and Wang, 2006Pennello and Vishnuvajjala, 2005Sargent et al, 2005Pustzai and Hess, 2004

Page 18: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Growing FDA Guidance

Voluntary Genomic Data Submissions guidanceConcept paper on co-developmentStatistical guidance on IVD labelingGuidance on pharmacogenetic and heritable genetic testsBayesian statistics

Page 19: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Good News

Broad menu of regulatory toolsMandate to be least burdensomeNew scientific resources -- MDUFMANew regulatory programs -- FDA data template, critical path

Page 20: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Flexible Regulatory Tools

Pre-IDEExpedited reviewsReal time reviewsDe novo classification

Page 21: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Review Successes

Cystic Fibrosis test – 109 daysAvian flu – 14 daysUGT1A1 – 9 days

Page 22: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Co-Development

If predictive diagnostic determines drug choiceSafety and effectiveness of drug becomes hostage to diagnosticNeed to understand system as a whole

Page 23: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Predictive Marker

Identify patients by biomarker status; randomize therapy across all patientsIdentify patients by biomarker status; randomize therapy in subsetsRandomize by treatment; look back at biomarkers

Page 24: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Predictive Marker

H (non-response)

G (response)

F (non-response)

E(response)

Placebo

D (non-response)

C(response)

B (non-response)

A (response)

Therapy

Neg testNeg testPositive test

Positive test

Page 25: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Predictive Marker

F (non-response)

E(response)

Placebo

B (non-response)

A (response)

Therapy

Positive test

Positive test

Page 26: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

FDA Mission

Promote public healthProtect public healthTension in objectives

Page 27: FDA Overview of Molecular Diagnostics and the Critical Path … · FDA Overview of Molecular Diagnostics and the Critical Path Initiative Steven Gutman, MD, MBA Director, Office of

Good Science


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