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

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

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

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

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

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)

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

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)

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

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)

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)

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

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)

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

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

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. 814.104(b)(2) and(3) SMDA (1990)

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

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)

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

Contact information Donna Lochner donna.lochner@fda.hhs.gov 301-796-6309