Critical Path Research: Getting New Technology from Bench to Bedside A Device. Perspective FDA Science Board November 5, 2004

1. Critical Path Research: Getting New Technology from Bench to Bedside A Device Perspective FDA Science Board November 5, 2004

Dan Schultz
Director, CDRH
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2. Role of FDA

Establish reasonable
assurance of the safety and
effectiveness of medical
devices marketed in the U.S.

3. What is a “Device”?

HHS/FDA/CDRH
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4. A Computer You Can Swallow

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5. A Computer That Helps You Hear

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6. Devices that Measure Glucose Levels and Deliver Insulin to “Communicate”

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7. Miniaturized Electrical Stimulators

Pacemakers
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8. Drug-Eluting Stents

Components
Stent Platform
& Delivery
System
Carrier(s)
Drug
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9. New Technology

Important Trends
–
–
–
–
–
Miniaturization
Intelligent Devices
Designed for Consumer Use
Minimally invasive
Biotechnology Revolution
Genomics, Proteomics
Biological Medical Devices
– New Materials
– Combination Products
– Disruptive Technologies
That change how we do business
That change how medical devices
deliver value
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10. CDRH Vision – Total Product Life Cycle

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11. Devices are Different

Drugs
–
–
–
–
–
–
–
–
Pure molecules
Toxicology
Short half-life
Long market life
Drug interactions
Wrong Drug / Dose
Clinically studied
Good Manufacturing
Practices (cGMP)
Devices
–
–
–
–
–
–
–
–
Complex components
Biocompatibility
Durable Equipment
Rapid product cycles
Malfunction
User Error
Bench studied
Quality Systems
(ISO 9000)
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12. Critical Path is Different for Devices

Device Regulation
– Least Burdensome Provision of FDAMA
– Quality Systems and Design Controls
Device Innovation Process
–
–
–
–
Biocompatibility
Iterative Process
User learning curve
Performance and durability
Device Industry is Represented by
Small Manufacturers
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13. Medical Device Industry Growth Number of Manufacturers by Year

16000
14000
12000
Ophthalmic
Eletromedical
X-Ray
Dental
Surgical
Instruments
Diagnostics
10000
8000
6000
4000
2000
0
1998
1999
2000
2001
2002
2003
Dun & Bradstreet Medical Device Firm Data
2004
13

14. Sales Volume Growth (Billions of Dollars)

350
Billions of Dollars
300
Ophthalmic
250
Electromechanical
200
X-Ray
Dental
150
Surgical
Instruments
100
Diagnostics
50
0
1998
2000
2003
2004
Year
Note: No Economic Adjustment to Dollar Value
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15. Device Industry Continues to Grow in FY 04

Dun and Bradstreet FY 04 data shows the device
industry grew from 13,579 to 14,937 firms with about
$320 billion in sales.
Innovation is alive and well!
20% annual turnover in individual device firms.
FDA-industry interaction is more important than
ever. FDA needs to keep guidances and reviewers
up to date.
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16. Innovative Science-based Strategies at Work

Leveraging
– Breast Cancer (DMIST): Screening and Digital
Mammography
– Medical Device Fellowship Program
Objective Performance Criteria
– Heart valves
– Hip implants
Novel Trial Designs
– Bayesian Statistics
– ROC Curves
Guidance Development
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17.

Comparison of 510(k) Average Review Times
for Devices With and Without Guidance*
140
160
140
106
120
Days
100
34
18
Mfr. Time
FDA Time
80
60
40
88
106
20
0
With Guidance
(n = 1,021)
Without Guidance
(n = 623)
*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
E Rechen, 5/03
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18. Original PMA Milestones: 2-cycle Scenario

320 days
PMA Received
Filing Rev
Clock Stops
Filing Letter
Scientific Review
Consults
Complete
Scientific Review
Major
Def.
Letter
Panel Go/NoGo
Interactive
Review
Status Letter
Panel Planning
Panel Meeting
Closeout Review
Final Decision
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19. Original PMA Milestones: 1-cycle Scenario

180 days
PMA Received
Filing Review
Filing Letter
Scientific Review
Interactive Review
Panel
Consults Status
Go/No Go Complete Letter
Panel Planning
Panel Meeting
Closeout Review
Final Decision
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20. The rest of the story…

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21.

Boston Scientific Stent
Recall Grows to 96K Units
Boston Scientific Expands Recall
of Troubled Stent
FDA won't expand recall of stents
Drug-coated stents may face
additional FDA scrutiny
FDA Is Reviewing
Reports of Trouble With
Taxus Stent
Boston Scientific's Older Stents
Draw
Scrutiny of FDA
FDA Temperature
up over Cordis
FDA Advises Physicians of Adverse Events
Associated with Cordis Cypher Coronary Stents
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22. Goal: Prioritize Actions on GMP Risks Correlating to Patient Risks

Patient
Quality (Patient)
Factors
Processes
Inspection Risk
GMP
RISK
RISK
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23. Postmarket Questions of Interest

Long Term Safety
Performance in Community Practice
Change in User Setting
Rare/Unexpected Events
Rates of Anticipated Adverse Events
Human Factors Issues – Use Error
Off-Label Use
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24. Achieving Pre/Postmarket Balance

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25. Why Balance Works

Speeds Product to Market by Moving Some
Premarket Requirements to Postmarket
Offers Added Assurance to FDA and
Advisory Panel
Free Up ODE Staff for Premarket Review
Generates Data for Next Generation
Generates Data for Enhanced Labeling
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26. Postmarket Studies - Present

Ill-Conceived
Not Initiated
Not Completed
Not Tracked
Not Enforced
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27. Postmarket Studies - Future

Better Designs
Standardized Reporting System
Better Tracking
Make Status of Studies Public
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28. Life Sciences Laboratory

Awards
2004, GSA Construction
Excellence, Projects Over
$25 Million
2004, Washington Building
Council, Craftsmanship
Award (Mechanical / HVACSheet Metal, Mechanical /
Plumbing, Mechanical /
HVAC-Piping)
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29. Critical Path Projects Being Developed

Establishing a pedigreed and credentialed blood
panel that could be used for assessing the
sensitivity/specificity of new hepatitis assays
Developing computer models of human physiology
that allow testing and soft failure of peripheral
vascular stents before animal and human studies are
ever considered
Developing a clear regulatory path with consensus
from the Obstetrics community for intrapartum fetal
diagnostic devices
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30. Critical Path Projects Being Developed

Establishing agreed pathways for the
statistical validation of surrogate markers
Working with Medical Specialty
Organizations to develop practice guidelines
for appropriate monitoring of permanently
implanted devices
Obtaining consensus on the extent of
neurotoxicity testing for neural tissue
contacting materials
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31. Summary

Steady progress towards meeting review
performance goals and TPLC strategic goals
Success is achievable but highly resource-intensive
CDRH continues to seek innovative methods and
partnerships for evaluating new technology based
on sound science in a least burdensome manner
Critical path will further our existing efforts to
achieve the right regulatory balance and ensure the
safety and effectiveness of medical devices
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32. CDRH Vision – Total Product Life Cycle

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