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DRAFT

CIRCULATORY SUPPORTDEVICES PANELThursday, June 23, 2005

Abiomed, Inc.

Abiocor® Implantable Replacement Heart

HDE H040006

DRAFT

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FDA Review Summary

Abiomed, Inc.

Abiocor® Implantable Replacement Heart

Eric Chen M.S.

FDA/CDRH/ODE/DCD

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Overview of Presentation

• What is an HDE?• History of Feasibility Study• Pre-clinical Evaluation• Clinical Evaluation• Panel Questions

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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.

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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)

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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)

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AbioCor Implantable Components

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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.

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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

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Candidate Selection Process

• Two stage process– Screening

• Determine severity of heart failure (AbioScore)• Potential fit of the AbioCor (AbioFit)

– Implant consent

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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)

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Preclinical EvaluationDetermined To Be Satisfactory

• Alarms• Battery Performance• Biocompatibility• Electrical Safety and EMC• Manufacturing• Software• Sterilization, packaging, shelf life, shipping

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Preclinical EvaluationConcerns Remain

• Reliability– Internal components

• Membrane wearout

• Bearing failure

– Device end of life indicator

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ReliabilityBench 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

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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

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Engineering Summary

• Replacement requires major surgery• Device end of life behavior seen during

bench testing• 2 device malfunctions

– 1 membrane wearout– 1 bearing wearout

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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.