DHHS / FDA / CDRH 1 FDA Summary CardioSEAL® Septal Occlusion System with Qwik Load NMT Medical P000049

DHHS / FDA / CDRH 2 FDA Summary FDA Review Team Device Description HDE Approval Nonclinical Evaluation Clinical Evaluation Panel Questions

DHHS / FDA / CDRH 3 FDA Review Team ODE- Donna Buckley John E. Stuhlmuller OSB- Lakshmi Vishnuvajjala OC- Liliane Brown

DHHS / FDA / CDRH 4 Device Description Occluder Double umbrella design Size range: mm Device size : Stretched defect diameter ratio is : 1

DHHS / FDA / CDRH 5 Device Description Delivery Catheter Size: 10F Qwik Load device Used to collapse and load occluder into the delivery catheter

DHHS / FDA / CDRH 6 Humanitarian Device Exemption Similar to PMA application Exempt from effectiveness requirements Humanitarian Use Device Device that is intended to benefit patients in the treatment and diagnosis of diseases or conditions that affect fewer than 4,000 individuals in the United States.

DHHS / FDA / CDRH 7 Humanitarian Device Exemption CardioSEAL® device approved under H in September 1999 Same intended use as PMA

DHHS / FDA / CDRH 8 Nonclinical Evaluation In Vitro Testing Biocompatibility Testing In Vivo (Animal) Testing

DHHS / FDA / CDRH 9 Clinical Evaluation

DHHS / FDA / CDRH 10 Clinical Data Sets Pivotal Cohort - VSD Non-pivotal Clamshell I F/U - VSD High-Risk Registry - non-VSD Clamshell I F/U - non-VSD Acquired VSD - s/p MI

DHHS / FDA / CDRH 11 Pivotal Cohort - VSD Patient subset of High-Risk Registry Open-label, single arm No control group Meets criteria for “Compassionate Use” Primarily single-center study

DHHS / FDA / CDRH 12 Pivotal Cohort - VSD 74 patients Devices placed in 57 of 58 patients attempted Multiple procedures - 6 patients Multiple devices - 26 patients

DHHS / FDA / CDRH 13 Patient Outcome Assessment Effectiveness Clinical Status Scale (CSS) Safety Adverse Events

DHHS / FDA / CDRH 14 Patient Outcome Assessment Clinical Status Scale Developed at Boston Children’s Hospital 8 nominal variables each using an ordinal scale Change of 1 on ordinal scale is clinically meaningful change

DHHS / FDA / CDRH 15 VSD - Effectiveness Effectiveness determined at 6-month F/U 44 of 57 implanted patients Anatomical Scale - 14 patients L to R Shunt - 22 patients Different scales - 8 patients Pre - Anatomical & Post - L to R Shunt

DHHS / FDA / CDRH 16 VSD - Effectiveness Pre-procedure and 6-month follow-up 44 of 57 implanted patients Median change of 2 categories 84% of procedures successful at 6 months

DHHS / FDA / CDRH 17 VSD - Safety Assessment at 1, 6, 12, and 24 months Characterization of adverse events Device related arm fractures Implantation related Catheterization related

DHHS / FDA / CDRH 18 VSD - Safety Adverse events in 57 of 58 patients Total of 222 events Device - 32 Implantation - 35 Catheterization - 85 Arm fractures in 34 of 107 devices

DHHS / FDA / CDRH 19 Panel Questions

DHHS / FDA / CDRH 20 Question 1- Safety and Effectiveness 1a. Based on the information provided, please discuss the description “complex VSD” as the defining indication for use of the CardioSEAL® for VSD closure.

DHHS / FDA / CDRH 21 Question 1- Safety and Effectiveness 1b. In the absence of a control group, please discuss how to evaluate the safety and effectiveness of the CardioSEAL® device.

DHHS / FDA / CDRH 22 Question 2 - Safety and Effectiveness 2. Does the use of the Clinical Status Scale allow for a clinically meaningful assessment of effectiveness for the device?

DHHS / FDA / CDRH 23 Question 3 - Safety and Effectiveness 3. Based on the data provided and your comments regarding questions 1 and 2, please discuss whether these data provide reasonable assurance of safety and effectiveness.

DHHS / FDA / CDRH 24 Question 4 - Training Program 4a. Please discuss any improvements that could be made to the training program. 4b. Please discuss training issues regarding the placement of multiple devices in a single patient.

DHHS / FDA / CDRH 25 Question 5 - Product Labeling 5a.Please comment on the INDICATIONS FOR USE section as to whether it identifies the appropriate patient populations for treatment with this device.

DHHS / FDA / CDRH 26 Question 5 - Product Labeling 5b.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.

DHHS / FDA / CDRH 27 Question 5 - Product Labeling 5c.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.

DHHS / FDA / CDRH 28 Question 5 - Product Labeling 5d. Please comment on the OPERATOR’S INSTRUCTIONS as to whether it adequately describes how the device should be used to maximize benefits and minimize adverse events.

DHHS / FDA / CDRH 29 Question 5 - Product Labeling 5e. Please comment on the remainder of the device labeling as to whether it adequately describe how the device should be used to maximize benefits and minimize adverse events.

DHHS / FDA / CDRH 30 Question 6 - Post-Market Evaluation 6. Do you believe that additional follow-up data or post market studies are necessary to evaluate the chronic effects of the implantation of the CardioSEAL® device? If so, how long should patients be followed and what endpoints and adverse events should be measured?