IDE Overview

An investigational device exemption (IDE) allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval (PMA) application or a Premarket Notification [510(k)] submission to FDA. Clinical studies are most often conducted to support a PMA. Only a small percentage of 510(k)’s require clinical data to support the application. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices. All clinical evaluations of investigational devices, unless exempt, must have an approved IDE before the study is initiated.

Clinical evaluation of devices that have not been cleared for marketing requires:

• an IDE approved by an institutional review board (IRB). If the study involves a significant risk device, the IDE must also be approved by FDA;
• informed consent from all patients;
• labeling for investigational use only
• monitoring of the study and;
• required records and reports.

An approved IDE permits a device to be shipped lawfully for the purpose of conducting investigations of the device without complying with other requirements of the Food, Drug, and Cosmetic Act (Act) that would apply to devices in commercial distribution. Sponsors need not submit a PMA or Premarket Notification 510(k), register their establishment, or list the device while the device is under investigation. Sponsors of IDE's are also exempt from the Quality System (QS) Regulation except for the requirements for design control.

Good Clinical Practices (GCP) refers to the regulations and requirements that must be complied with while conducting a clinical study. These regulations that apply to the manufacturers, sponsors, clinical investigators, institutional review boards, and the medical device. The primary regulations that govern the conduct of clinical studies are included in the Code of Federal Regulations, Title 21 (21 CFR):

• 21 CFR 812, Investigational Device Exemptions, covers the procedures for the conduct of clinical studies with medical devices including application, responsibilities of sponsors and investigators, labeling, records, and reports.
• 21 CFR 50, Protection of Human Subjects, provides the requirements and general elements of informed consent;
• 21 CFR 56, Institutional Review Boards, covers the procedures and responsibilities for institutional review boards (IRBs) that approve clinical investigations protocols;
• 21 CFR 54, Financial Disclosure by Clinical Investigators, covers the disclosure of financial compensation to clinical investigators which is part of FDA’s assessment of the reliability of the clinical data.
• 21 CFR 820 Subpart C, Design Controls of the Quality System Regulation, provides the requirement for procedures to control the design of the device in order to ensure that the specified design requirements are met.

Each of these regulations is discussed in detail throughout this section.

Definitions and Acronyms

Some of the pertinent definitions used in the IDE regulation are as follows.

Application Integrity Policy (AIP)

Application Integrity Policy (AIP) is FDA's policy for the integrity of data or information submitted in an application. If it is suspected that an applicant has submitted false or misleading information, the data are thoroughly investigated. Submitting false or misleading information may result in FDA refusal to review submissions until certain requirements are met.

Implant is a device that is placed into a surgically or naturally formed cavity of the human body and is intended to remain there for a period of 30 days or more. In order to protect public health, FDA may determine that devices placed in subjects for shorter periods are also implants.

Institutional Review Board (IRB) is a board, committee, or other group formally designated by an institution to review, to approve the initiation of, and to conduct periodic review of biomedical research involving human subjects. The primary purpose of such review is to assure the protection of the rights, safety, and welfare of human subjects. The IRB should be established, operated, and function in conformance with 21 CFR 56. The term has the same meaning as "institutional review committee" in section 520(g) of the FD&C Act.

Investigation is a clinical investigation or research involving one or more subjects to determine the safety and/or effectiveness of a device.

Investigational device is a device, including a transitional device, that is the object of an investigation.

IDE refers to the regulations under 21 CFR 812. An approved IDE means that the IRB (and FDA for significant risk devices) has approved the sponsor’s study application and all the requirements under 21 CFR 812 are met.

Investigator is an individual who actually conducts a clinical investigation, i.e., under whose immediate direction the investigational device is administered, dispensed to, or used involving a subject. In the event of an investigation being conducted by a team of individuals, "investigator" refers to the responsible leader of that team.

When used as a noun, monitor is an individual designated by a sponsor or contract research organization to oversee the progress of an investigation. The monitor may be an employee of a sponsor, or a consultant to the sponsor, or an employee of or consultant to a contract research organization. When used as a verb "monitor" means to oversee an investigation.

A premarket approval means any premarket approval application for a Class III medical device, including all information submitted with or incorporated by reference therein. (21 CFR 814.3)

510(k) refers to the type of submission to FDA described under 21 CFR 807 Subpart E in which the applicant must establish that their device is substantially equivalent to a legally marketed device. This type of submission is used for most Class II devices and some Class I devices.

Significant risk device is 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 for use in supporting or sustaining human life and represents 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 a subject.

Sponsor is a person or other entity that initiates but does not actually conduct the investigation. An entity other than an individual (e.g., a corporation or an agency) which uses one or more of its own employees to conduct an investigation that it has initiated is considered to be a sponsor, not a sponsor-investigator, and the employees are considered to be investigators. The sponsor of an IDE must be located in the United States (see 21 CFR 812.18).

Sponsor-investigator is an individual who both initiates and actually conducts, alone or with others, a clinical investigation, i.e., under whose immediate direction the investigational device is administered, dispensed, or used. The term does not, for example, include a corporation or agency. The obligations of a sponsor-investigator include those of an investigator and those of a sponsor.

Subject is a human who participates in an investigation, either as an individual on whom or on whose specimen an investigational device is used or who participates as a control. A subject may be in normal health or may have a medical condition or disease.

Transitional device is a device subject to section 520(l) of the FD&C Act and which FDA previously regulated as a new drug or an antibiotic drug before May 28, 1976.

Unanticipated adverse device effect is any serious adverse effect on health or safety, any life-threatening problem or death caused by, or associated with a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the application; or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

Last updated date7/8/2003