1. Division of Cardiovascular Devices
Marketing Pathways and Their Different Clinical Goal Lines: PMA, 510(k), and HDE
Donna R. Lochner
Deputy Director
Division of Cardiovascular Devices
Food and Drug Administration Cardiovascular Research and Technologies
February 2010

2. Donna Lochner DISCLOSURES
I have no real or apparent conflicts of interest to report.

3. Overview Regulatory background
risk based classification of medical devices risk-benefit decision making
pre-market regulatory applications
Cardiovascular device examples when/ why is clinical data needed
how much/ what type of clinical data is needed

4. Class I – lowest risk devices
Approval pathway
most exempt from premarket review
Clinical data
n/a

5. Class II – medium risk devices
Approval pathway
Premarket notification (510(k))
Substantial equivalence to a predicate device (clearance)
Clinical data
< 10% contain clinical data

6. Class II – medium risk devices
Substantial Equivalence
device has the same intended use as the predicate device and the device and: has the same technological characteristics as the predicate device, or has different technological characteristics and the information submitted that the device is substantially equivalent to the predicate device contains information, including appropriate clinical or scientific data that demonstrates that the device is as safe and effective as a legally marketed device, and does not raise different questions of safety and effectiveness than the predicate device
FD&C Act Chapter V. SEC. 513 (i)(1)(A)

7. Class II devices/ 510(k) - Need for clinical data
Need for clinical study dictated by:
Degree of difference between proposed device and predicate
Differences in design
New Indications for use
Ability of bench and animal testing to answer questions
Some devices always need clinical data

8. Class II – medium risk devices Example: annuloplasty rings
Clinical data
“Standard” design --- no clinical data
clearance primarily based upon bench, possibly animal testing
Different technological characteristics --- probably will need clinical data
are there different questions of safety or effectiveness? no 510(k)
yes PMA (e.g., mitral repair devices)

9. Class II – medium risk devices Example: annuloplasty rings
Changes in indication --- clinical data likely, if a significant change are there different questions of safety or effectiveness? no 510(k)
yes PMA

10. Class III – highest risk devices
Approval pathway -Premarket approval (PMA) the safety and effectiveness of a device are to be determined—
(A) with respect to the persons for whose use the device is represented or intended,
(B) with respect to the conditions of use prescribed, recommended, or suggested in the labeling of the device, and
(C) weighing any probable benefit to health from the use of the device against any probable risk of injury or illness from such use.
FD&C Act Chapter V. SEC 513(a)(2)

11. Class III – highest risk devices
Clinical data Clinical data required
the effectiveness of a device is to be determined on the basis of well-controlled investigations, including 1 or more clinical investigations where appropriate or valid scientific evidence
FD&C Act Chapter V. SEC 513(a)(3)(A) and (B)

12. Valid scientific evidence is:
evidence from well-controlled investigations,
partially controlled studies,
studies and objective trials without matched controls,
well-documented case histories conducted by qualified experts, and
reports of significant human experience with a marketed device
21 CFR 860.7

13. Class III – highest risk devices
In making a determination of a reasonable assurance of the effectiveness of a device FDA shall consider whether the extent of data that otherwise would be required for approval of the application with respect to effectiveness can be reduced through reliance on postmarket controls.
FD&C Act Chapter V. SEC 513(a)(3)(C)

14. Class III – highest risk devices Example: heart valves
Clinical trial designs
Surgical valves --- single arm study with literature- based controls
Percutaneous valves --- randomized study to optimal medical management or open surgical repair

15. Humanitarian Use Devices
Intended to benefit patients in the treatment or diagnosis of diseases or conditions that affect fewer than 4,000 individuals in the U.S. per year
Approval pathway
Humanitarian Device Exemption (HDE)
exemption from effectiveness requirements

16. Humanitarian Use Devices
Clinical data
Must contain sufficient information for FDA to determine that the device does not pose an unreasonable or significant risk of illness or injury, and that the probable benefit to health outweighs the risk of injury or illness from its use, taking into account the probable risks and benefits of currently available devices and alternative forms of treatment
No comparable devices are available to treat or diagnose the disease or condition
21CFR Subpart H Sec (b)(2) and(3)
SMDA (1990)

17. Humanitarian Use Exemption
Example
Medtronic Melody Transcatheter Pulmonic Valve
The Melody TPV is indicated for use as an adjunct to surgery in the management of pediatric and adult patients with the following clinical conditions:
Existence of a full (circumferential) RVOT conduit that was equal to or greater than 16 mm in diameter when originally implanted and
Dysfunctional RVOT conduits with a clinical indication for intervention, and either:
regurgitation: ≥ moderate regurgitation, or
stenosis: mean RVOT gradient ≥ 35 mm Hg

18. Humanitarian Use Exemption Example: transcatheter valve for dysfunctional RVOT conduits
Clinical data
non-randomized study
99 patients enrolled/ 90 implanted
follow-up 9.2 ± 5.7 months (range 0 to 25.5 months)

19. Conclusions
FDA’s regulatory approval pathways are based upon risk-based classification of devices
Risk/ benefit considerations are key factors for clinical trial design, so that
Choice of primary safety and effectiveness endpoints are as critical as the choice of control in ensuring that a risk/ benefit assessment can be made

20. Contact information
Donna Lochner