1. BME-IDEA Workshop, September 28, 2005
Fostering Innovation on the Critical Path to Medical Device Development
BME-IDEA Workshop, September 28, 2005
Donna-Bea Tillman, Ph.D
Director, Office of Device Evaluation
Center for Devices and Radiological Health

2. FDA Mission: Historical Basis
Protect the public from unsafe products
I’d like to start my talk by looking back at the historical roots of FDA, which trace back to a public health protection problem.
107 people, mostly children, died when sulfanilamide, the first “wonder drug” was formulated into an elixr containing the toxin ethylene oxide. Exisiting laws did not require the drugs manufacturer to test the formulation for safety before it was sold.
Congress corrected this weakness in the law the next year when it passed the Federal Food, Drug, and Cosmetic Act. This law, for the first time, required companies to prove the safety of new drugs before putting them on the market.

3. Over the next hundred years, Congress continued to give FDA new responsibilities , including the requirement that drugs and medical devices be proven effective as well as safe before they can be sold.
This is the only painting in the series wherein Perez caricatures a recognizable, well-known doctor-former U.S. Surgeon General, C. Everett Koop. Dr. Koop receives this honor because Jose Perez has been so impressed by Koop's leadership in national and global public health. God bless our unheralded public-health doctors.

4. FDA Mission Today Promote Protect
Today, FDA’s mission has broadened beyond public health protection to also include public health promotion – ensuring the availability of new products that promote the health of the American people.
When most people think of FDA, they think of our public health protection role:
-Historical roots of FDA
-Methods well understood
-Good business – basis of public confidence in medical products
However, many of FDA’s most difficult challenges lay in the public health promotion arena.

5. The world today… Technological changes occur at lightning speed
Medical devices are more complex than ever
The Internet is the new “snake oil” salesman
The American public is demanding great control over healthcare decisions
The global marketplace means global regulation

6. Technology trends Miniaturization Smart devices Minimally invasive
Biotechnology revolution
Combination Products
Home use
Special Populations
New technology is smaller, uses computer intelligence, and allows less invasive procedures. New materials, sometimes tissue derived and combined with pharmaceuticals create new combination products with features of both a drug and a device.
Some of these innovations are referred to as “disruptive technologies” because they change the way we do business and they change how medical devices deliver value.
Consider if a hand held ultrasound could be added to the stethoscope as a tool for your doctor. No longer would your doctor thump your back, or poke at your liver, or listen to your neck. Your doctor could easily see if you have gall stones, carotid artery narrowing, a bicuspid aortic valve, a pleural effusion, ascities, a renal cyst, or fibroid uterus. All this in about the same time as a normal exam, and only requiring a referral to the radiologist for more detailed or specialized images.

7. Disruptive Technologies
That change the nature of medical devices
That change how medical care is delivered
That change health outcomes, hopefully for the better
…that change how the industry and FDA do business.

8. Challenges to Innovation
Basic biomedical science investment & progress has surpassed medical product development investment and progress

9. Challenges to Innovation
We are using the evaluation tools and infrastructure of the last century…
to develop this century’s advances.

10. Challenges to Innovation
This has resulted in a bottleneck at the “critical path” for delivering new products to patients

11. Critical Path Research
Leverages basic science knowledge
Leverages cumulative research experiences
Does not compromise
safety and effectiveness
evaluations

12. Critical Path for Medical Devices
Market
Application
Approval
Basic
Research
Prototype
Design or
Discovery
Preclinical
Development
Clinical
Development
FDA Filing/
Approval &
Launch
Preparation
Critical Path
The journey from medical product candidate to full-scale production and marketing

13. Why is FDA interested?
Because of the significant benefit of bringing innovative products to the public faster
Because of our unique perspective on product development -- we see success, failure and missed opportunities
Because it will help us to develop guidance and standards that foster innovation and improve chances of success

14. What does FDA want to accomplish?
Work together with industry, academia and patient care advocates to
modernize, develop and disseminate solutions (tools) to address scientific hurdles impacting industry-wide product development.

15. What are the Critical Path tools?
The methods and techniques used for:
Assessment of Safety – how to predict if a potential product will be harmful?
Proof of Efficacy - how to determine if a potential product will have medical benefit?
Industrialization – how to manufacture a product at commercial scale with consistent quality?

16. Devices are not drugs!

17. Drugs Yesterday
Drugs Today
Drugs Tomorrow

18. Devices
HHS/FDA/CDRH

19. Devices are Different: Development
Complex components
Designed
Drugs
Pure molecules
Discovered
How do devices differ from drugs? What are the challenges that must be met to assure that such products are safe and effective?
Drugs are chemically synthesize pure molecules while devices complex products assembled out of many components.
Drug toxicology establishes the pharmacologic problems that occur from metabolites or in special situations such as pediatrics or pregnancy, while we examine devices from an engineering perspective, looking at issues ranging from mechanical integrity, to electrical safety and biocompatibility.

20. Devices are Different: Life-cycle
Short product life-cycle
Durable equipment
Drugs
Long market life
Short half-life
How do devices differ from drugs? What are the challenges that must be met to assure that such products are safe and effective?
Drugs have long market lives, protected by patents which can be extended by FDA approval, while Devices have rapid product cycles with continuous incremental improvement.
Drugs have short half lives while devices are durable equipment, often still in use long after manufacturing has ceased.

21. Devices are Different: Adverse Events
Drugs
Drug interactions
Wrong drug/wrong dose
Devices
Malfunction
User error
How do devices differ from drugs? What are the challenges that must be met to assure that such products are safe and effective?
With drugs we worry about drug interactions, name confusion, dosage errors, while with devices we worry about mechanical failure and malfunction and problems with user errors.

22. Devices are Different: Regulatory Requirements
Drugs
Clinical trial
Clinical endpoints
Devices
Risk-based
Surrogate endpoints
How do devices differ from drugs? What are the challenges that must be met to assure that such products are safe and effective?
Drugs are almost always studied clinically while over 90% of devices are studied at the bench for performance characteristics. Clinical trials for drugs almost always involved clinical endpoints. Devices frequently have well-understood mechanisms of actions, so surrogate endpoints are frequently used.

23. Risk-Based Classification of Medical Devices
Class I: simple, low risk devices
General controls
Most exempt from premarket submission
8% class III, 46% class I, 46% class II-substantial equivalence to a legally marketed device-decision usually based on descriptive information, sometimes bench or animal, rarely clinical data.
Determination of risk based on technology and intended use. These two aspects must be assessed in concert.

24. Risk-Based Classification of Medical Devices
Class II: more complex, higher risk
Special controls
Premarket Notification [510(k)]
Substantial equivalence
10-15% require clinical data
Performance testing
8% class III, 46% class I, 46% class II-substantial equivalence to a legally marketed device-decision usually based on descriptive information, sometimes bench or animal, rarely clinical data.
Determination of risk based on technology and intended use. These two aspects must be assessed in concert.

25. Risk-Based Classification of Medical Devices
Class III: most complex, highest risk
Data “soup to nuts”
Premarket Application [PMA]
Establish safety and effectiveness
Bench - Animal - Human
May include post-approval study requirements
8% class III, 46% class I, 46% class II-substantial equivalence to a legally marketed device-decision usually based on descriptive information, sometimes bench or animal, rarely clinical data.
Determination of risk based on technology and intended use. These two aspects must be assessed in concert.

26. 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

27. Some Critical Path Tools…
Biomarkers
Bayesian statistics
Animal models biomarkers
Clinical trials design
Computer simulations
Quality assessment protocols
Post-market reporting
Suggestions???

28. Medical Device Critical Path Projects of Interest
Validation of biomarkers
Blood panel to assess sensitivity and specificity
Peripheral vascular stents
Computer models of human physiology to test and predict failure (before animal and human studies)
Intrapartum fetal diagnostic devices
Clear “Regulatory Path” -- with consensus from the Obstetrics community)

29. Medical Device Critical Path Projects of Interest
Permanently implanted devices
Practice guidelines for appropriate monitoring -- with medical specialty organizations
Neural tissue contacting materials
Extent of neurotoxicity testing

30. Are you interested? Web Address
Open Docket
Docket # 2004N-0181
CDRH webpage (under news and events) provides links to the critical path white paper and docket

31. Questions? One does what one is; one becomes what one does.
Robert von Musil