11

Critical Path Research: Critical Path Research: Getting New Technology from Getting New Technology from

Bench to BedsideBench to BedsideA Device PerspectiveA Device Perspective

FDA Science BoardFDA Science BoardNovember 5, 2004November 5, 2004

Dan SchultzDan SchultzDirector, CDRHDirector, CDRH

Role of FDARole of FDA

Establish Establish reasonablereasonable

assurance of the safety and assurance of the safety and

effectiveness of medical effectiveness of medical

devices marketed in the U.S.devices marketed in the U.S.

33

HHS/FDA/CDRH

What is a “Device”?What is a “Device”?

44

A Computer You Can SwallowA Computer You Can Swallow

55

A Computer That Helps A Computer That Helps You HearYou Hear

66

Devices that Measure Glucose Devices that Measure Glucose Levels and Deliver Insulin to Levels and Deliver Insulin to

“Communicate”“Communicate”

77

Miniaturized Electrical StimulatorsMiniaturized Electrical Stimulators

Pacemakers

88

Drug-Eluting StentsDrug-Eluting Stents

ComponentsComponents

Stent Platform Stent Platform & Delivery & Delivery SystemSystem

Carrier(s)Carrier(s)

DrugDrug

99

New TechnologyNew Technology

Important TrendsImportant Trends– MiniaturizationMiniaturization– Intelligent DevicesIntelligent Devices– Designed for Consumer UseDesigned for Consumer Use– Minimally invasiveMinimally invasive– Biotechnology RevolutionBiotechnology Revolution

Genomics, ProteomicsGenomics, ProteomicsBiological Medical DevicesBiological Medical Devices

– New MaterialsNew Materials– Combination ProductsCombination Products– Disruptive TechnologiesDisruptive Technologies

That change how we do businessThat change how we do businessThat change how medical devices That change how medical devices deliver valuedeliver value

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CDRH Vision – Total Product Life CycleCDRH Vision – Total Product Life Cycle

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Devices are DifferentDevices are Different

DrugsDrugs– Pure moleculesPure molecules– ToxicologyToxicology– Short half-lifeShort half-life– Long market lifeLong market life– Drug interactionsDrug interactions– Wrong Drug / DoseWrong Drug / Dose– Clinically studiedClinically studied– Good Manufacturing Good Manufacturing

Practices (cGMP)Practices (cGMP)

DevicesDevices– Complex componentsComplex components– BiocompatibilityBiocompatibility– Durable EquipmentDurable Equipment– Rapid product cyclesRapid product cycles– MalfunctionMalfunction– User ErrorUser Error– Bench studiedBench studied– Quality Systems Quality Systems

(ISO 9000)(ISO 9000)

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Critical Path is Different for DevicesCritical Path is Different for Devices

Device RegulationDevice Regulation– Least Burdensome Provision of FDAMALeast Burdensome Provision of FDAMA– Quality Systems and Design ControlsQuality Systems and Design Controls

Device Innovation ProcessDevice Innovation Process– BiocompatibilityBiocompatibility– Iterative ProcessIterative Process– User learning curveUser learning curve– Performance and durabilityPerformance and durability

Device Industry is Represented by Device Industry is Represented by Small ManufacturersSmall Manufacturers

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0

2000

4000

6000

8000

10000

12000

14000

16000

1998 1999 2000 2001 2002 2003 2004

Ophthalmic

Eletromedical

X-Ray

Dental

Surgical

Instruments

Diagnostics

Dun & Bradstreet Medical Device Firm Data

Medical Device Industry GrowthMedical Device Industry GrowthNumber of Manufacturers by YearNumber of Manufacturers by Year

1414

Sales Volume GrowthSales Volume Growth(Billions of Dollars)(Billions of Dollars)

0

50

100

150

200

250

300

350

1998 2000 2003 2004Year

Bil

lio

ns

of

Do

llar

s Ophthalmic

Electromechanical

X-Ray

Dental

Surgical

Instruments

Diagnostics

Note: No Economic Adjustment to Dollar Value

1515

Device Industry Continues to Grow Device Industry Continues to Grow in FY 04in FY 04

Dun and Bradstreet FY 04 data shows the device Dun and Bradstreet FY 04 data shows the device industry grew from 13,579 to 14,937 firms with about industry grew from 13,579 to 14,937 firms with about $320 billion in sales.$320 billion in sales.

Innovation is alive and well!Innovation is alive and well!

20% annual turnover in individual device firms. 20% annual turnover in individual device firms.

FDA-industry interaction is more important than FDA-industry interaction is more important than ever. FDA needs to keep guidances and reviewers ever. FDA needs to keep guidances and reviewers up to date.up to date.

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Innovative Science-based Strategies at Innovative Science-based Strategies at WorkWork

LeveragingLeveraging– Breast Cancer (DMIST): Screening and Digital Breast Cancer (DMIST): Screening and Digital

MammographyMammography– Medical Device Fellowship ProgramMedical Device Fellowship Program

Objective Performance CriteriaObjective Performance Criteria– Heart valvesHeart valves– Hip implantsHip implants

Novel Trial DesignsNovel Trial Designs– Bayesian StatisticsBayesian Statistics– ROC CurvesROC Curves

Guidance DevelopmentGuidance Development

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88

18

106

34

0

20

40

60

80

100

120

140

160

With Guidance Without Guidance

Mfr. Time

FDA Time

Da

ys

*Based on all 510(k)s (1,644) with SE decisions during FY 2002 that were for Class II devices eligible for third party review, excluding special and 3rd party 510(k)s

106

140

(n = 1,021) (n = 623)

Comparison of 510(k) Average Review TimesComparison of 510(k) Average Review Timesfor Devices With and Without Guidancefor Devices With and Without Guidance**

E Rechen, 5/03

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Original PMA Milestones:Original PMA Milestones:2-cycle Scenario2-cycle Scenario

Filing Rev

Scientific Review

Panel Planning

Closeout Review

PMA Received

Panel Go/NoGo

Panel Meeting

Filing Letter

Final Decision

320 days

Major Def.

Letter

Scientific Review

Clock Stops

Status Letter

Interactive Review

Consults Complete

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Original PMA Milestones:Original PMA Milestones:1-cycle Scenario1-cycle Scenario

Filing Review

Scientific Review

Panel Planning

Closeout Review

PMA Received

Panel Go/No Go

Panel Meeting

Filing Letter

Final Decision

180 days

StatusLetter

Consults Complete

Interactive Review

2020

The rest of the story…The rest of the story…

2121

Boston Scientific Stent Recall Grows to 96K Units

FDA Is Reviewing Reports of Trouble With

Taxus Stent Boston Scientific's Older Stents

Draw Scrutiny of FDA

Boston Scientific Expands Recall of Troubled Stent

FDA won't expand recall of stents

FDA Temperature up over Cordis

Drug-coated stents may face additional FDA scrutiny

FDA Advises Physicians of Adverse Events Associated with Cordis Cypher Coronary Stents

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Goal: Prioritize Actions on GMP Risks Correlating to Patient Risks

RISK

Pro

ces

ses

In

spe

ctio

n R

isk

RISK

Qu

alit

y (

Pat

ien

t)

Fa

cto

rs

GMP Patient

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Postmarket Questions of InterestPostmarket Questions of Interest

Long Term SafetyLong Term Safety

Performance in Community PracticePerformance in Community Practice

Change in User SettingChange in User Setting

Rare/Unexpected EventsRare/Unexpected Events

Rates of Anticipated Adverse EventsRates of Anticipated Adverse Events

Human Factors Issues – Use ErrorHuman Factors Issues – Use Error

Off-Label UseOff-Label Use

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Achieving Pre/Postmarket BalanceAchieving Pre/Postmarket Balance

2525

Why Balance WorksWhy Balance Works

Speeds Product to Market by Moving Some Speeds Product to Market by Moving Some Premarket Requirements to PostmarketPremarket Requirements to Postmarket

Offers Added Assurance to FDA and Offers Added Assurance to FDA and Advisory Panel Advisory Panel

Free Up ODE Staff for Premarket Review Free Up ODE Staff for Premarket Review

Generates Data for Next GenerationGenerates Data for Next Generation

Generates Data for Enhanced LabelingGenerates Data for Enhanced Labeling

2626

Postmarket Studies - PresentPostmarket Studies - Present

Ill-ConceivedIll-Conceived

Not InitiatedNot Initiated

Not CompletedNot Completed

Not TrackedNot Tracked

Not Enforced Not Enforced

2727

Postmarket Studies - FuturePostmarket Studies - Future

Better Designs Better Designs

Standardized Reporting SystemStandardized Reporting System

Better TrackingBetter Tracking

Make Status of Studies PublicMake Status of Studies Public

2828

Life Sciences LaboratoryLife Sciences Laboratory

Awards2004, GSA Construction Excellence, Projects Over $25 Million

2004, Washington Building Council, Craftsmanship Award (Mechanical / HVAC-Sheet Metal, Mechanical / Plumbing, Mechanical / HVAC-Piping)

2929

Critical Path Projects Being DevelopedCritical Path Projects Being Developed

Establishing a pedigreed and credentialed blood Establishing a pedigreed and credentialed blood panel that could be used for assessing the panel that could be used for assessing the sensitivity/specificity of new hepatitis assayssensitivity/specificity of new hepatitis assays

Developing computer models of human physiology Developing computer models of human physiology that allow testing and soft failure of peripheral that allow testing and soft failure of peripheral vascular stents before animal and human studies are vascular stents before animal and human studies are ever consideredever considered

Developing a clear regulatory path with consensus Developing a clear regulatory path with consensus from the Obstetrics community for intrapartum fetal from the Obstetrics community for intrapartum fetal diagnostic devicesdiagnostic devices

3030

Critical Path Projects Being DevelopedCritical Path Projects Being Developed

Establishing agreed pathways for the Establishing agreed pathways for the statistical validation of surrogate markersstatistical validation of surrogate markers

Working with Medical Specialty Working with Medical Specialty Organizations to develop practice guidelines Organizations to develop practice guidelines for appropriate monitoring of permanently for appropriate monitoring of permanently implanted devices implanted devices

Obtaining consensus on the extent of Obtaining consensus on the extent of neurotoxicity testing for neural tissue neurotoxicity testing for neural tissue contacting materialscontacting materials

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SummarySummary

Steady progress towards meeting review Steady progress towards meeting review performance goals and TPLC strategic goals performance goals and TPLC strategic goals

Success is achievable but highly resource-intensiveSuccess is achievable but highly resource-intensive

CDRH continues to seek innovative methods and CDRH continues to seek innovative methods and partnerships for evaluating new technology based partnerships for evaluating new technology based on sound science in a least burdensome manner on sound science in a least burdensome manner

Critical path will further our existing efforts to Critical path will further our existing efforts to achieve the right regulatory balance and ensure the achieve the right regulatory balance and ensure the safety and effectiveness of medical devicessafety and effectiveness of medical devices

3232

CDRH Vision – Total Product Life CycleCDRH Vision – Total Product Life Cycle