1. High Risk Investigative Devices
Procedure for Submitting Applications
to Regulatory Authorities

2. High Risk Investigative Devices
Procedure for Submitting Applications
to Regulatory Authorities

3. Objectives
1. Understand the process for submitting the IDE
application for high risk devices.
2. Describe the roles of sponsor and IRB in the device
application process.
3. Understand the process for premarket approval

4. Significant Risk Device (GCP)
presents the potential for serious risk to the health,
safety or welfare of a human subject
-and 1 of these:
i. Intended as an implant and presents a potential for serious
risk.
ii. Purported or represented to be for use to support/sustain
human life.
iii. Is of substantial importance in diagnosing, mitigating,
curing or treating disease or preventing the impairment of
human health.
iv. Otherwise presents the potential for serious risk.

5. Who Determines Risk?
i. Sponsor submits assessment to IRB.
ii. IRB can call upon FDA for assistance and has power to
override sponsor's decision.
iii. Upon submission, FDA has final authority for risk
assessment.

6. Application Submission to FDA
i. Sponsor submitting application must indicate
whether informed consent exceptions may occur.
(21CFR 50.24)
Other Inclusions to Application
i. Report of prior investigations
ii. Summary of investigation plan
iii. Description of manufacturing process to ensure
GMP compliance

7. Other Inclusions to Application
iv. Regarding Investigators.
-samples of agreements
-investigator list with contact information
-written certification that agreements are signed
v. Regarding Investigational Review Boards
-Contact information for each chairperson
-Certified description of actions taken by each IRB

8. Other Inclusions to Application
vi. Contact Information for each trial center.
vii. If device is sold, description of price.
-include a defense for non-commercialization
viii. Statement of exclusion for need of environmental
assessment/impact or other waiver (CFR 21 25.40)
ix. Copies of labeling.
x. Copies of informed consent documents

9. Summary of Key Points
Responsibility for completion of the IDE application
rests with the sponsor.
Initial review of each application and approval of any
amendments initially rests with the IRB.
Upon review, the FDA can request additional
information or suggest changes to the investigational
plan or application if warranted.

10. Premarket Approval of High Risk Devices

11. Application for Premarket Approval (CFR 814)
Inclusions:
i. Indications for use.
ii. Device name, description as to use and performance
characteristics.
iii. Alternative procedures for device use.
iv. Description of foreign and US marketing history.

12. Application for Premarket Approval (CFR 814)
Inclusions:
v. Summary of clinical and non-clinical studies
with conclusions.
vi. Description of risks, benefits and adverse events.
vii. Device description to include
-image
-functional components and relation to control or mitigation
of disease
-method of operation
-summary of GMP procedures for device manufacture

13. Application for Premarket Approval (CFR 814)
Inclusions:
viii. Confirmation that the device meets safety
standards.
(i.e. radiation, toxicology with supportive animal studies)
ix. Clinical investigations and findings
x. Statements of investigation compliance with IRB
regulations

14. Application for Premarket Approval (CFR 814)
Inclusions:
xi. Confirmation that investigations were completed in
accordance with FDA regulations.
xii. Bibliography of published reports not included in
dossier.
xiii. Any other data pertinent to the safe and effective
use of device

15. Application for Premarket Approval (CFR 814)
Inclusions:
xiv. Information obtainable and requested by the FDA.
xv. Device sample.
xvi. Proposed labeling.
xvii. Financial disclosures.
Xviii. Studies and Information for use in pediatric
populations

16. Updating PMA Applications
Applications are amended by the MAH with updated
safety information within 3 months of initial
submission.
Post marketing supplements submitted to the FDA
include changes to product design, manufacturing,
labeling, packaging.