You should submit comments and suggestions regarding this draft document within 90 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit e lectronic comments to Identify a ll comments with the docket number listed in the notice of availability that publishes in the Federal Register.

For questions regarding this document, contact (CDRH) Owen Faris, 301-796-6356 or or (CBER) Office of Communication, Outreach and Development at 1-800-835-4709 or 301-827-1800.


U.S. Department of Health and Human Services

Food and Drug Administration

Center for Devices and Radiological Health

Center for Biologics Evaluation and Research


FDA recognizes the public health benefit of permitting well-designed clinical investigations of medical devices to proceed in a timely and efficient manner while ensuring proper subject protections. When determining whether to approve an IDE application, FDA considers many factors, as discussed in this document. Where appropriate, FDA seeks to offer flexibility in how outstanding issues can be addressed (i.e., approval with conditions, staged approval, and future considerations) to allow clinical investigations to commence without unnecessary delay, while ensuring that human subjects are adequately protected.

1 21 CFR 812.3(m): A significant risk device means an investigational device that:

(1) Is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject;

(2) Is purported or represented to be for a use in supporting or sustaining human life and presents a potential for serious risk to the health, safety, or welfare of a subject;

(3) Is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease, or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject; or

(4) Otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.

2 This guidance does not offer specific information related to the design of a clinical investigation, nor does this guidance discuss the specific content that should be provided in an IDE application. For additional information on those topics, please refer to FDA’s regulations (21 CFR 812.20 and 812.25) and to FDA’s Guidance on IDE Policies and Procedures.

3 21 CFR 812.30.

4 FDA has traditionally referred to IDE approvals that have conditions as “Conditional Approvals.” FDA believes that the term “Approval with Conditions” is more appropriate because the term conveys that the IDE has been approved and may begin without awaiting further FDA review.

5 21 CFR 812.3(n): Sponsor means a person who initiates, but who does not actually conduct, the investigation, that is, the investigational device is administered, dispensed, or used under the immediate direction of another individual. A person other than an individual that uses one or more of its own employees to conduct an investigation that it has initiated is a sponsor, not a sponsor-investigator, and the employees are investigators.

6 21CFR 812.3(o): Sponsor-investigator means an individual who both initiates and actually conducts, alone or with others, an investigation, that is, under whose immediate direction the investigational device is administered, dispensed, or used. The term does not include any person other than an individual. The obligations of a sponsor-investigator under this part include those of an investigator and those of a sponsor.

The remainder of this document uses the term “sponsor” for both sponsor and sponsor-investigator.

7 The term “approval” in this document and in FDA’s communications means approval without conditions.

8 The remainder of this document references 45 days as the specified timeframe.

9 Once an IDE is approved or approved with conditions, subsequent submissions to FDA related to the IDE are designated as “IDE supplements.”

10 The remainder of this section will use the term “staged approval” to refer to staged approval and staged approval with conditions.

11 Pivotal studies are discussed in more detail in the FDA draft guidance titled, “Design Considerations for Pivotal Clinical Investigations for Medical Devices

12 Feasibility studies are developmental studies that are not intended to provide the primary clinical evidence to support a marketing application. A draft guidance document entitled “ Investigational Device Exemptions (IDE) for Early Feasibility Medical Device Clinical Studies, Including First in Human (FIH) Studies,” discusses the types of feasibility studies.

13 If the available information strongly indicate that the study will be underpowered and unlikely to produce valid scientific evidence, this concern may instead result in disapproval or approval with conditions.

14 If an IDE has not yet received approval or approval with conditions, subsequent submissions to FDA related to the IDE are designated as “IDE amendments.” There is no required timeframe within which a response to an IDE disapproval must be submitted.

15 21 CFR 860.7 (c)(2): Valid scientific evidence is evidence from well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with a marketed device, from which it can fairly and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use. The evidence required may vary according to the characteristics of the device, its conditions of use, the existence and adequacy of warnings and other restrictions, and the extent of experience with its use. Isolated case reports, random experience, reports lacking sufficient details to permit scientific evaluation, and unsubstantiated opinions are not regarded as valid scientific evidence to show safety or effectiveness. Such information may be considered, however, in identifying a device the safety and effectiveness of which is questionable.

16 Additional information is provided in the guidance entitled “The Least Burdensome Provisions of the FDA Modernization Act of 1997: Concept and Principles

17 The guidance document entitled “Changes or Modifications During the Conduct of a Clinical Investigation,” discusses the types of changes that require FDA approval and those that qualify for notification.

18 The guidance entitled “Guidance on IDE Policies and Procedures,” discusses Compassionate and Emergency Use.