# Presentation: 850833

## DRAFT

- Abiomed, H040006

- June 23, 2005

## CIRCULATORY SUPPORTDEVICES PANELThursday, June 23, 2005

- Abiomed, Inc.
- Abiocor® Implantable Replacement Heart
- HDE H040006

- DRAFT

## FDA Review Summary

- Abiomed, Inc.
- Abiocor® Implantable Replacement Heart
- Eric Chen M.S.
- FDA/CDRH/ODE/DCD

- Abiomed, H040006

- June 23, 2005

## Overview of Presentation

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

- Abiomed, H040006

- June 23, 2005

## 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.

- Abiomed, H040006

- June 23, 2005

## 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)

- Abiomed, H040006

- June 23, 2005

## 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)

- Abiomed, H040006

- June 23, 2005

## AbioCor Implantable Components

- Abiomed, H040006

- June 23, 2005

## Slide 9

- Abiomed, H040006

- June 23, 2005

## 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.

- Abiomed, H040006

- June 23, 2005

## 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

- Abiomed, H040006

- June 23, 2005

**Notes:**
First of its kind so we setup an incremental gate for study continuation.  Would prevent excess risk to additional patients if none of the first 5 patients survived beyond 30 days post implant or if at least one patient out of a group of five didn’t survive to 60 days without significant complications.

## Candidate Selection Process

- Two stage process
- Screening
- Determine severity of heart failure (AbioScore)
- Potential fit of the AbioCor (AbioFit)
- Implant consent

- Abiomed, H040006

- June 23, 2005

## 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)

- Abiomed, H040006

- June 23, 2005

**Notes:**
* Change factors considered; match w/regs HUD = Humanitarian Use Device
OOPD = Office of Orphan Product Development
Important distinction between HDE and PMA is that in an HDE a controlled clinical study is not required, but we do need information on all the clinical experience with the device, both good and bad: case reports, literature, etc.

## Preclinical EvaluationDetermined To Be Satisfactory

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

- Abiomed, H040006

- June 23, 2005

## Preclinical EvaluationConcerns Remain

- Reliability
- Internal components
- Membrane wearout
- Bearing failure
- Device end of life indicator

- Abiomed, H040006

- June 23, 2005

## 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

- Abiomed, H040006

- June 23, 2005

## 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

- Abiomed, H040006

- June 23, 2005

## Engineering Summary

- Replacement requires major surgery
- Device end of life behavior seen during bench testing
- 2 device malfunctions
- 1 membrane wearout
- 1 bearing wearout

- Abiomed, H040006

- June 23, 2005

## 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.

- Abiomed, H040006

- June 23, 2005