is intended to remain there for a period of 30 days or more. FDA may, in order to protect public health, determine that devices placed in subjects for shorter periods are also "implants" for purposes of this part.

(e) Institution means a person, other than an individual, who engages in the conduct of research on subjects or in the delivery of medical services to individuals as a primary activity or as an adjunct to providing residential or custodial care to humans. The term includes, for example, a hospital, retirement home, confinement facility, academic establishment, and device manufacturer. The term has the same meaning as "facility" in section 520(g) of the act.

(f) Institutional review board (IRB) means any board, committee, or other group formally designated by an institution to review biomedical research involving subjects and established, operated, and functioning in conformance with part 56. The term has the same meaning as "institutional review committee" in section 520(g) of the act.

(g) Investigational device means a device, including a transitional device, that is the object of an investigation.

(h) Investigation means a clinical investigation or research involving one or more subjects to determine the safety or effectiveness of a device.

(i) Investigator means an individual who actually conducts a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject, or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team.

(j) Monitor, when used as a noun, means 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. Monitor, when used as a verb, means to oversee an investigation.

(k) Noninvasive, when applied to a diagnostic device or procedure, means one that does not by design or intention: (1) Penetrate or pierce the skin or mucous membranes of the body, the oc

ular cavity, or the urethra, or (2) enter the ear beyond the external auditory canal, the nose beyond the nares, the mouth beyond the pharynx, the anal canal beyond the rectum, or the vagina beyond the cervical os. For purposes of this part, blood sampling that involves simple venipuncture is considered noninvasive, and the use of surplus samples of body fluids or tissues that are left over from samples taken for noninvestigational purposes is also

considered noninvasive.

(1) Person includes any individual, partnership, corporation, association, scientific or academic establishment, Government agency or organizational unit of a Government agency, and any other legal entity.

(m) 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.

(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.

(0) 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.

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

(q) Termination means a discontinuance, by sponsor or by withdrawal of IRB or FDA approval, of an investigation before completion.

(r) Transitional device means a device subject to section 520(1) of the act, that is, a device that FDA considered to be a new drug or an antibiotic drug before May 28, 1976.

(s) Unanticipated adverse device effect means any serious adverse effect on health or safety or 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 investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects.

[45 FR 3751, Jan. 18, 1980, as amended at 46 FR 8956, Jan. 27, 1981; 48 FR 15622, Apr. 12, 1983]

§ 812.5 Labeling of investigational devices.

(a) Contents. An investigational device or its immediate package shall bear a label with the following information: the name and place of business of the manufacturer, packer, or distributor (in accordance with §801.1), the quantity of contents, if appropriate, and the following statement: "CAUTION-Investigational device. Limited by Federal (or United States) law to investigational use." The label or other labeling shall describe all relevant contraindications, hazards, adverse effects, interfering substances or devices, warnings, and precautions.

(b) Prohibitions. The labeling of an investigational device shall not bear any statement that is false or misleading in any particular and shall not represent that the device is safe or effective for

the purposes for which it is being investigated.

(c) Animal research. An investigational device shipped solely for research on or with laboratory animals shall bear on its label the following statement: "CAUTION-Device for investigational use in laboratory animals or other tests that do not involve human subjects."

[45 FR 3751, Jan. 18, 1980, as amended at 45 FR 58842, Sept. 5, 1980]

§ 812.7 Prohibition of promotion and other practices.

A sponsor, investigator, or any person acting for or on behalf of a sponsor or investigator shall not:

(a) Promote or test market an investigational device, until after FDA has approved the device for commercial distribution.

(b) Commercialize an investigational device by charging the subjects or investigators for a device a price larger than that necessary to recover costs of manufacture, research, development, and handling.

(c) Unduly prolong an investigation. If data developed by the investigation indicate in the case of a class III device that premarket approval cannot be justified or in the case of a class II device that it will not comply with an applicable performance standard or an amendment to that standard, the sponsor shall promptly terminate the investigation.

(d) Represent that an investigational device is safe or effective for the purposes for which it is being investigated.

§ 812.10 Waivers.

(a) Request. A sponsor may request FDA to waive any requirement of this part. A waiver request, with supporting documentation, may be submitted separately or as part of an application to the address in § 812.19.

(b) FDA action. FDA may by letter grant a waiver of any requirement that FDA finds is not required by the act and is unnecessary to protect the rights, safety, or welfare of human subjects.

(c) Effect of request. Any requirement shall continue to apply unless and until FDA waives it.

§ 812.18 Import and export requirements.

(a) Imports. In addition to complying with other requirements of this part, a person who imports or offers for importation an investigational device subject to this part shall be the agent of the foreign exporter with respect to investigations of the device and shall act as the sponsor of the clinical investigation, or ensure that another person acts as the agent of the foreign exporter and the sponsor of the investigation.

(b) Exports. A person exporting an investigational device subject to this part shall obtain FDA's prior approval, as required by section 801(e) of the act or comply with section 802 of the act.

[45 FR 3751, Jan. 18, 1980, as amended at 62 FR 26229, May 13, 1997]

§ 812.19 Address for IDE correspond

ence.

If you are sending an application, supplemental application, report, request for waiver, request for import or export approval, or other correspondence relating to matters covered by this part, you must address it to the Center for Devices and Radiological Health, Document Mail Center (HFZ401), Food and Drug Administration, 9200 Corporate Blvd., Rockville, MD 20850. You must state on the outside wrapper of each submission what the submission is, for example, an "IDE application," a "supplemental IDE application," or a "correspondence concerning an IDE (or an IDE application)."

[65 FR 17137, Mar. 31, 2000]

Subpart B-Application and Administrative Action

§ 812.20 Application.

(a) Submission. (1) A sponsor shall submit an application to FDA if the sponsor intends to use a significant risk device in an investigation, intends to conduct an investigation that involves an exception from informed consent under $50.24 of this chapter, or if FDA notifies the sponsor that an application is required for an investigation.

(2) A sponsor shall not begin an investigation for which FDA's approval

of an application is required until FDA has approved the application.

(3) A sponsor shall submit three copies of a signed “Application for an Investigational Device Exemption" (IDE application), together with accompanying materials, by registered mail or by hand to the address in §812.19. Subsequent correspondence concerning an application or a supplemental application shall be submitted by registered mail or by hand.

(4)(i) A sponsor shall submit a separate IDE for any clinical investigation involving an exception from informed consent under §50.24 of this chapter. Such a clinical investigation is not permitted to proceed without the prior written authorization of FDA. FDA shall provide a written determination 30 days after FDA receives the IDE or earlier.

(2) A complete report of prior investigations of the device and an accurate summary of those sections of the investigational plan described in §812.25(a) through (e) or, in lieu of the summary, the complete plan. The sponsor shall submit to FDA a complete investigational plan and a complete report of prior investigations of the device if no IRB has reviewed them, if FDA has found an IRB's review inadequate, or if FDA requests them.

(3) A description of the methods, facilities, and controls used for the manufacture, processing, packing, storage, and, where appropriate, installation of the device, in sufficient detail so that a person generally familiar with good manufacturing practices can make a knowledgeable judgment about the quality control used in the manufacture of the device.

(4) An example of the agreements to be entered into by all investigators to comply with investigator obligations under this part, and a list of the names

and addresses of all investigators who have signed the agreement.

(5) A certification that all investigators who will participate in the investigation have signed the agreement, that the list of investigators includes all the investigators participating in the investigation, and that no investigators will be added to the investigation until they have signed the agreement.

(6) A list of the name, address, and chairperson of each IRB that has been or will be asked to review the investigation and a certification of the action concerning the investigation taken by each such IRB.

(7) The name and address of any institution at which a part of the investigation may be conducted that has not been identified in accordance with paragraph (b)(6) of this section.

(8) If the device is to be sold, the amount to be charged and an explanation of why sale does not constitute commercialization of the device.

(9) A claim for categorical exclusion under $25.30 or 25.34 or an environmental assessment under § 25.40.

(10) Copies of all labeling for the device.

(11) Copies of all forms and informational materials to be provided to subjects to obtain informed consent.

(12) Any other relevant information FDA requests for review of the application.

con

(c) Additional information. FDA may request additional information cerning an investigation or revision in the investigational plan. The sponsor may treat such a request as a disapproval of the application for purposes of requesting a hearing under part 16.

(d) Information previously submitted. Information previously submitted to the Center for Devices and Radiological Health in accordance with this chapter ordinarily need not be resubmitted, but may be incorporated by reference.

[45 FR 3751, Jan. 18, 1980, as amended at 46 FR 8956, Jan. 27, 1981; 50 FR 16669, Apr. 26, 1985; 53 FR 11252, Apr. 6, 1988; 61 FR 51530, Oct. 2, 1996; 62 FR 40600, July 29, 1997; 64 FR 10942, Mar. 8, 1999]

§ 812.25 Investigational plan.

The investigational plan shall include, in the following order:

(a) Purpose. The name and intended use of the device and the objectives and duration of the investigation.

(b) Protocol. A written protocol describing the methodology to be used and an analysis of the protocol demonstrating that the investigation is scientifically sound.

(c) Risk analysis. A description and analysis of all increased risks to which subjects will be exposed by the investigation; the manner in which these risks will be minimized; a justification for the investigation; and a description of the patient population, including the number, age, sex, and condition.

(d) Description of device. A description of each important component, ingredient, property, and principle of operation of the device and of each anticipated change in the device during the course of the investigation.

(e) Monitoring procedures. The sponsor's written procedures for monitoring the investigation and the name and address of any monitor.

(f) Labeling. Copies of all labeling for the device.

(g) Consent materials. Copies of all forms and informational materials to be provided to subjects to obtain informed consent.

(h) IRB information. A list of the names, locations, and chairpersons of all IRB's that have been or will be asked to review the investigation, and a certification of any action taken by any of those IRB's with respect to the investigation.

(i) Other institutions. The name and address of each institution at which a part of the investigation may be conducted that has not been identified in paragraph (h) of this section.

(j) Additional records and reports. A description of records and reports that will be maintained on the investigation in addition to those prescribed in subpart G.

§ 812.27 Report of prior investigations. (a) General. The report of prior investigations shall include reports of all prior clinical, animal, and laboratory

testing of the device and shall be comprehensive and adequate to justify the proposed investigation.

(b) Specific contents. The report also shall include:

(1) A bibliography of all publications, whether adverse or supportive, that are relevant to an evaluation of the safety or effectiveness of the device, copies of all published and unpublished adverse information, and, if requested by an IRB or FDA, copies of other significant publications.

(2) A summary of all other unpublished information (whether adverse or supportive) in the possession of, or reasonably obtainable by, the sponsor that is relevant to an evaluation of the safety or effectiveness of the device.

(3) If information on nonclinical laboratory studies is provided, a statement that all such studies have been conducted in compliance with applicable requirements in the good laboratory practice regulations in part 58, or if any such study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance. Failure or inability to comply with this requirement does not justify failure to provide information on a relevant nonclinical test study.

[45 FR 3751, Jan. 18, 1980, as amended at 50 FR 7518, Feb. 22, 1985]

§ 812.30 FDA action on applications.

(a) Approval or disapproval. FDA will notify the sponsor in writing of the date it receives an application. FDA may approve an investigation as proposed, approve it with modifications, or disapprove it. An investigation may not begin until:

(1) Thirty days after FDA receives the application at the address in § 812.19 for the investigation of a device other than a banned device, unless FDA notifies the sponsor that the investigation may not begin; or

(2) FDA approves, by order, an IDE for the investigation.

(b) Grounds for disapproval or withdrawal. FDA may disapprove or withdraw approval of an application if FDA finds that:

(1) There has been a failure to comply with any requirement of this part or the act, any other applicable regula

tion or statute, or any condition of approval imposed by an IRB or FDA.

(2) The application or a report contains an untrue statement of a material fact, or omits material information required by this part.

(3) The sponsor fails to respond to a request for additional information within the time prescribed by FDA.

(4) There is reason to believe that the risks to the subjects are not outweighed by the anticipated benefits to the subjects and the importance of the knowledge to be gained, or informed consent is inadquate, or the investigation is scientifically unsound, or there is reason to believe that the device as used is ineffective.

(5) It is otherwise unreasonable to begin or to continue the investigation owing to the way in which the device is used or the inadequacy of:

(i) The report of prior investigations or the investigational plan;

(ii) The methods, facilities, and controls used for the manufacturing, processing, packaging, storage, and, where appropriate, installation of the device;

or

(iii) Monitoring and review of the investigation.

(c) Notice of disapproval or withdrawal. If FDA disapproves an application or proposes to withdraw approval of an application, FDA will notify the sponsor in writing.

(1) A disapproval order will contain a complete statement of the reasons for disapproval and a statement that the sponsor has an opportunity to request a hearing under part 16.

(2) A notice of a proposed withdrawal of approval will contain a complete statement of the reasons for withdrawal and a statement that the sponsor has an opportunity to request a hearing under part 16. FDA will provide the opportunity for hearing before withdrawal of approval, unless FDA determines in the notice that continuation of testing under the exemption will result in an unreasonble risk to the public health and orders withdrawal of approval before any hearing.

[45 FR 3751, Jan. 18. 1980, as amended at 45 FR 58842, Sept. 5, 1980]