1. June 23, 2005Abiomed, H0400060 DRAFT

2. CIRCULATORY SUPPORT DEVICES PANEL Thursday, June 23, 2005 Abiomed, Inc. Abiocor® Implantable Replacement Heart HDE H040006 DRAFT

3. June 23, 2005Abiomed, H0400062 FDA Review Summary Abiomed, Inc. Abiocor® Implantable Replacement Heart Eric Chen M.S. FDA/CDRH/ODE/DCD

4. June 23, 2005Abiomed, H0400063 Overview of Presentation What is an HDE? History of Feasibility Study Pre-clinical Evaluation Clinical Evaluation Panel Questions

5. June 23, 2005Abiomed, H0400064 FDA Review Team M. Berman, Ph.D. E. Chen, M.S. V. Covington D. Fleischer K. Foy, M.S. E. Harvey, Ph.D. D. Headlee M. Mendelson I. Piña, M.D. J. Rinaldi, M.S. W. Scott, Ph.D. J. Swain, M.D.

6. June 23, 2005Abiomed, H0400065 What is an Humanitarian Device Exemption? An HDE application is similar in both form and content to a premarket approval (PMA) application, but exempt from the effectiveness requirements of a PMA. An approved HDE authorizes marketing of a Humanitarian Use Device (HUD). (Humanitarian Device Exemption Regulation: Questions and Answers Final Guidance for Industry http://www.fda.gov/cdrh/ode/guidance/1381.pdf)

7. June 23, 2005Abiomed, H0400066 What is an Humanitarian Use Device? A device that is intended to benefit patients in the treatment and diagnosis of diseases or conditions that affect or is manifested in fewer than 4,000 individuals in the United States per year. (Federal Food, Drug, and Cosmetic Act, http://www.access.gpo.gov/uscode/title21/chapter9_.html)

8. June 23, 2005Abiomed, H0400067 AbioCor Implantable Components

9. June 23, 2005Abiomed, H0400068

10. June 23, 2005Abiomed, H0400069 Proposed Indication for Use The AbioCor is indicated for use in severe end stage heart disease patients who: are less than 75 years old, are not transplant candidates at the time of assessment, require multiple inotropic support, are in biventricular failure not treatable by LVAD destination therapy, and are not weanable from biventricular support if on such support and not awaiting transplantation.

11. June 23, 2005Abiomed, H04000610 U.S. Feasibility Study IDE G000329 –Single arm prospective feasibility trial to determine safety of the AbioCor –Sample size of 14 patients –6 investigational sites –No prospective statistical plan or control group –Incremental gate for study continuation If none of first 5 patients survived 30 days - stoppage At least 1 out of 5 patients – survived 60 days –Slow enrollment

12. June 23, 2005Abiomed, H04000611 Candidate Selection Process Two stage process –Screening Determine severity of heart failure (AbioScore) Potential fit of the AbioCor (AbioFit) –Implant consent

13. June 23, 2005Abiomed, H04000612 HDE Regulation (21 CFR 814 Subpart H) REASONABLE assurance of safety and probable benefit Factors considered (21 CFR 814.104b) –Patient population –No other comparable device available (other than another HDE device or device approved under IDE) –Probable benefit vs. probable injury Clinical experience (21 CFR 814.104b)

14. June 23, 2005Abiomed, H04000613 Preclinical Evaluation Determined To Be Satisfactory Alarms Battery Performance Biocompatibility Electrical Safety and EMC Manufacturing Software Sterilization, packaging, shelf life, shipping

15. June 23, 2005Abiomed, H04000614 Preclinical Evaluation Concerns Remain Reliability –Internal components Membrane wearout Bearing failure –Device end of life indicator

16. June 23, 2005Abiomed, H04000615 Reliability Bench Testing 25 units on test Mock circulation loop –Implanted components in 37ºC buffered saline –Failure times between 8.2 to 40.5 months –Average runtime – 18.8 months –Reliability greater than 80% at 80% confidence level for one-year operation 3 failure modes –Hydraulic membrane wearout –Bearing failure –Fluid ingress

17. June 23, 2005Abiomed, H04000616 Clinical Failures Patient #2 –Membrane wearout at 17 months (expected) –Patient refused to have AbioCor replaced –Propose to tighten tolerance on energy converter –Continue to monitor membrane wearout Patient #13 –Bearing failure at 5 months (unexpected) –Position of AbioCor different than pre-placement CT scans –Corrective actions have been accepted by FDA

18. June 23, 2005Abiomed, H04000617 Engineering Summary Replacement requires major surgery Device end of life behavior seen during bench testing 2 device malfunctions –1 membrane wearout –1 bearing wearout

19. June 23, 2005Abiomed, H04000618 Summary Results of the pre-clinical testing in conjunction with the outcome of the reliability results from the clinical trial suggest that the device performs according to specifications.