FDA Summary

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FDA Summary

• Amplatzer Septal Occluder
• AGA Medical
• P000039

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FDA Summary

• FDA Review Team
• Device Description
• Nonclinical Evaluation
• Clinical Evaluation
• Panel Questions

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FDA Review Team
ODE - Donna Buckley John Stuhlmuller OSB - Joh
n Dawson OC - Liliane Brown
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Device Description

• Occluder
• Double-disc with connecting waist
• LA disc size gt RA disc size
• 26 sizes based on connecting waist diameter
  (range 4 - 38 mm)
• Sizing Connecting waist diameter is matched to
  the stretched defect diameter

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Device Description

• Delivery Catheter
• 6F to 12F depending on device size
• Occluder is packaged separately
• Manually attached to delivery cable
• Loaded into delivery catheter

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Nonclinical Evaluation

• In vitro Testing
• Biocompatibility Testing
• In vivo (Animal) Testing

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Clinical Evaluation
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Proposed Indications for Use

• Closure of
• Secundum atrial septal defects
• Fenestrations following Fontan procedure

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Clinical Data Sets

• Pivotal Cohort - ASD
• Phase IIB - 459 patients
• Pivotal Cohort - Fenestrated Fontan
• 51 patients enrolled
• Non-pivotal
• Phase I, Phase IIA - ASD
• Continued Access - ASD

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Pivotal Cohorts - ASD

• Device arm
• Non-randomized
• Multicenter
• Surgical control arm
• Non-randomized
• pro- and retrospective patient identification
• prospective 1-year follow-up

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Patient Outcome Assessment

• Composite Clinical Success at 12 months
• Incorporates safety and effectiveness
• Patients attempted without major
  complication, embolization, technical failure,
  or significant shunt
• Secondary safety and effectiveness endpoints

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ASD - Effectiveness

• Insert table

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ASD - Safety

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Pivotal Cohort - Fenestrated Fontan

• Open-label
• Single-arm registry
• No control

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Patient Outcome Assessment

• Effectiveness
• ? 2mm shunt at 12 months
• Safety
• Adverse events

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Fenestrated Fontan - Effectiveness

• Devices implanted in 46 of 48 patients attempted
• ? 2mm shunt in 32 of 32 patients at 12 months

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Fenestrated Fontan - Safety

• Devices implantation attempted in 48 patients
• Complications - 4 patients
• Major - 2 patients
• Minor - 2 patients

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Panel Questions
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Question 1 - ASD Indication
1a. Please discuss whether individual
endpoints, composite endpoints, or a combination
of both should be used to evaluate the safety and
effectiveness of the Amplatzer ASO device?
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Question 1 - ASD Indication

• 1b. The sponsor is seeking approval for device
  sizes from 4 mm to 38 mm. Approximately 89 of
  devices implanted in the pivotal ASD study were
  between 10 mm and 28 mm. Is there sufficient
  data to support approval of the entire range of
  devices (4 mm to 38 mm) or a specific range of
  device sizes?

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Question 1 - ASD Indication

• 1c. Based on the data provided on ASD patients
  and the suggested analysis of the data from
  question 1a., please discuss whether these data
  provide reasonable assurance of safety and
  effectiveness.

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Question 2 - Fontan Indication

• Based on the data provided on Fenestrated Fontan
  patients and the suggested analysis of the data
  from question 1a., please discuss whether these
  data provide reasonable assurance of safety and
  effectiveness.

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Question 3 - Training Program
3a. Please discuss any improvements that
could be made to the training program. 3b.
More than one device was placed in 10 ASD
patients. Please discuss training issues
regarding the placement of multiple devices in
a single patient.
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Question 4 - Product Labeling
4a. Please comment on the INDICATIONS FOR USE
section as to whether it identifies the
appropriate patient populations for treatment
with this device.
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Question 4 - Product Labeling
4b. Please comment on the CONTRAINDICATIONS
section as to whether there are conditions under
which the device should not be used because the
risk of use clearly outweighs any possible
benefit.
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Question 4 - Product Labeling
4c. Please comment on the WARNING/PRECAUTIONS
section as to whether it adequately describes how
the device should be used to maximize benefits
and minimize adverse events.
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Question 4 - Product Labeling
4d. Please comment on the OPERATORS
INSTRUCTIONS as to whether it adequately
describes how the device should be used to
maximize benefits and minimize adverse events.
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Question 4 - Product Labeling

• 4e. Please comment on the remainder of the
  device labeling as to whether it adequately
  describes how the device should be used to
  maximize benefits and minimize adverse events.

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Question 5 - Post Market Evaluation
Based on the clinical data provided in the
PMA, do you believe that additional follow-up
data or post market studies are necessary to
evaluate the chronic effects of the implantation
of the Amplatzer device. If so, how long
should patients be followed and what endpoints
and adverse events should be measured?