1. Novel Devices Focus—The Path Forward for New DES, DEB, and Biodegradable Stents: FDA View
Hina M. Pinto, MSE
Scientific Reviewer
Interventional Cardiology Devices Branch
Division of Cardiovascular Devices
Office of Device Evaluation
CDRH/FDA
CRT 2010
Washington, D.C.
February 23, 2010

2. Hina M. Pinto DISCLOSURES
I have no real or apparent conflicts of interest to report.

3. Overview New Drug Eluting Stents (DES) Drug Eluting Balloons (DEB)
DES Guidance document
Different considerations
Drug Eluting Balloons (DEB)
Pre-clinical bench testing
Animal testing
Clinical considerations
Biodegradable Stents
Challenges
Testing
Conclusions

4. New Drug Eluting Stents
DES Guidance currently in draft at:
Many of the current recommendations would apply to new DES.
Certain modifications and additional testing may be recommended for novel devices based on indication and design.

5. New Drug Eluting Stents
Different considerations for novel devices
Dedicated Bifurcation DES
Modified bench testing
Accelerated durability testing
Particulates testing
Appropriate animal study model
Identify appropriate trial design (e.g., control)
Different materials (e.g., Nitinol)
Surface characterization
Nickel leaching
Fracture due to overlapping of dissimilar materials
New Coatings (e.g., antibody coated stents, biologics)
Textured Coatings

6. Drug Eluting Balloons Some of the challenges are the same as DES
Local drug delivery and associated toxicities
Effects on healing as observed in the animal studies
Pre-clinical Testing
Characterization of finished, sterilized product to be studied essential
Coating/drug loading characteristics for different balloon sizes
Particulates and Coating Integrity
Concern about particulate generation on deployment
Simulated use testing condition recommended
Identification of Particulates
Additional to support other indications (e.g., ISR, small vessels)
Animal Studies to assess Safety
Safety/healing related to drug toxicity
Safety margin overdose

7. Drug Eluting Balloons Animal Studies to assess Effectiveness
Neointimal proliferation
Proof of principle vs. PTCA or stent control
Clinical Data
Potential use of multiple balloons
Higher dose to patient
Although drug is rapidly delivered acutely, the drug can remain in the tissue longer and could result in delayed healing.
Therefore, we have recommended 180-day animal studies to understand the time course for healing
Animal studies: 3-5d, 30d, 90d, 180d follow-up
Recommend 9-month clinical data to understand whether effectiveness is maintained over time.

8. Biodegradable Stents—Challenges
Apply also to durable stent platforms with biodegradable coatings
Answers to these questions will guide the testing paradigm:
What is the expected degradation profile?
What are the degradation products?
What are the expected advantages of this degradable stent?
How does the proposed stent design balance the need for mechanical integrity following deployment with the ability to degrade over time?

9. Biodegradable Stents—Testing
Challenges in Characterization
Degradation profile
Mechanism
Characterization of intermediate breakdown products
Characterization of polymer
Bench Testing Considerations
Mechanical properties (e.g., radial stiffness, radial strength)
Particulates testing challenges when stent and/or polymer degrade
Coating integrity
Accelerated durability testing
Need to conduct mechanical tests at multiple time points (in a physiologically relevant environment) to fully characterize the impact of degradation on mechanical integrity.

10. Biodegradable Stents—Testing
Animal Studies
Measurement time points may need to be modified to better capture critical safety parameters
Safety and Effectiveness evaluation
Assessment of downstream myocardial pathology critical
Evaluate embolization due to bulk degradation
Biologic effects of degradation products

11. Biodegradable Stents—Testing
Clinical Study
Duration of patient follow-up reflects degradation profile
To adequately capture outcomes before, during, and after stent degradation
Follow-up imaging to confirm degradation (IVUS, OCT)
Evaluate visibility on fluoroscopy
Assess frequency of geographic miss
Ability to accurately deploy overlapping stents in bailout situations
Assess DAPT use and optimal duration

12. Conclusions
Lessons learned from DES and draft guidance can provide a starting point for evaluation of novel DES, DEB, and biodegradable DES.
FDA takes into consideration specific features of each to recommend appropriate modifications to key elements of nonclinical and clinical testing.
FDA has multiple mechanisms for interactions – formal and informal.
We encourage interactions early and often to identify appropriate clinical and pre-clinical considerations.

13. Thank You! Hina M. Pinto Interventional Cardiology Devices Branch
Ashley Boam
Chief, Interventional Cardiology Devices Branch
Combination products