each submission shall state what the submission is, for example an "IDE application," a “supplemental IDE application," or "correspondence concerning an IDE (or an IDE application).” [45 FR 3751, Jan. 18, 1980, as amended at 53 FR 11252, Apr. 6, 1988; 55 FR 11169, Mar. 27, 1990] Subpart B-Application and $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 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. (b) Contents. An IDE application shall include, in the following order: (1) The name and address of the spon sor. (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 $25.24 or an environmental assessment under § 25.31. (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] §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 com prehensive 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] $812.35 Supplemental applications. (a) Changes in investigational plan. A sponsor shall: (1) Submit to FDA a supplemental application if the sponsor or an investigator proposes a change in the investigational plan that may affect its scientific soundness or the rights, safety, or welfare of subjects, and (2) obtain FDA approval under §812.30(a) of any such change, and IRB approval when the change involves the rights, safety, or welfare of subjects (see §§ 56.110 and 56.111), before implementation. These requirements do not apply in the case of a deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency, which deviation shall be reported to FDA within 5 working days after the sponsor learns of it (see §812.150(a)(4)). (b) IRB approval for new facilities. A sponsor shall submit to FDA a certification of any IRB approval of an investigation or a part of an investigation not included in the IDE application. If the investigation is otherwise unchanged, the supplemental application shall consist of an updating of the information required by §812.20(b) and (c) and a description of any modifications in the investigational plan required by the IRB as a condition of approval. A certification of IRB approval need not be included in the initial submission of the supplemental application, and such certification is not a precondition for agency consideration of the application. Nevertheless, a sponsor may not begin a part of an investigation at a facility until the IRB has approved the investigation, FDA has received the certification of IRB approval, and FDA, under § 812.30(a), has approved the supplemental application relating to that part of the investigation (see § 56.103(a)). [50 FR 25909, June 24, 1985; 50 FR 28932, July 17, 1985] IDE; or a notice of completion of a product development protocol for the device has become effective. (b) Availability of summaries or data. (1) FDA will make publicly available, upon request, a detailed summary of information concerning the safety and effectiveness of the device that was the basis for an order approving, disapproving, or withdrawing approval of an application for an IDE for a banned device. The summary shall include information on any adverse effect on health caused by the device. (2) If a device is a banned device or if the existence of an IDE has been publicly disclosed or acknowledged, data or information contained in the file is not available for public disclosure before approval of an application for premarket approval or the effective date of a notice of completion of a product development protocol except as provided in this section. FDA may, in its discretion, disclose a summary of selected portions of the safety and effectiveness data, that is, clinical, animal, or laboratory studies and tests of the device, for public consideration of a specific pending issue. (3) If the existence of an IDE file has not been publicly disclosed or acknowledged, no data or information in the file are available for public disclosure except as provided in paragraphs (b)(1) and (c) of this section. (c) Reports of adverse effects. Upon request or on its own initiative, FDA shall disclose to an individual on whom an investigational device has been used a copy of a report of adverse device effects relating to that use. (d) Other rules. Except as otherwise provided in this section, the availability for public disclosure of data and information in an IDE file shall be handled in accordance with §814.9. [45 FR 3751, Jan. 18, 1980, as amended at 53 FR 11253, Apr. 6, 1988] ensuring proper monitoring of the investigation, ensuring that IRB review and approval are obtained, submitting an IDE application to FDA, and ensuring that any reviewing IRB and FDA are promptly informed of significant new information about an investigation. Additional responsibilities of sponsors are described in Subparts B and G. §812.42 FDA and IRB approval. A sponsor shall not begin an investigation or part of an investigation until an IRB and FDA have both approved the application or supplemental application relating to the investigation or part of an investigation. [46 FR 8957, Jan. 27, 1981] § 812.43 Selecting investigators monitors. (a) Selecting investigators. A sponsor shall select investigators qualified by training and experience to investigate the device. (b) Control of device. A sponsor shall ship investigational devices only to qualified investigators participating in the investigation. (c) Obtaining agreements. A sponsor shall obtain from each participating investigator a signed agreement that includes: (1) The investigator's curriculum vitae. (2) Where applicable, a statement of the investigator's relevant experience, including the dates, location, extent, and type of experience. (3) If the investigator was involved in an investigation or other research that was terminated, an explanation of the circumstances that led to termination. (4) A statement of the investigator's commitment to: (i) Conduct the investigation in accordance with the agreement, the investigational plan, this part and other applicable FDA regulations, and conditions of approval imposed by the reviewing IRB or FDA; (ii) Supervise all testing of the device involving human subjects; and (iii) Ensure that the requirements for obtaining informed consent are met. (d) Selecting monitors. A sponsor shall select monitors qualified by training and experience to monitor the inves tigational study in accordance with this part and other applicable FDA regulations. § 812.45 Informing investigators. A sponsor shall supply all investigators participating in the investigation with copies of the investigational plan and the report of prior investigations of the device. $812.46 Monitoring investigations. (a) Securing compliance. A sponsor who discovers that an investigator is not complying with the signed agreement, the investigational plan, the requirements of this part or other applicable FDA regulations, or any conditions of approval imposed by the reviewing IRB or FDA shall promptly either secure compliance, or discontinue shipments of the device to the investigator and terminate the investigator's participation in the investigation. A sponsor shall also require such an investigator to dispose of or return the device, unless this action would jeopardize the rights, safety, or welfare of a subject. (b) Unanticipated adverse device effects. (1) A sponsor shall immediately conduct an evaluation of any unanticipated adverse device effect. (2) A sponsor who determines that an unanticipated adverse device effect presents an unreasonable risk to subjects shall terminate all investigations or parts of investigations presenting that risk as soon as possible. Termination shall occur not later than 5 working days after the sponsor makes this determination and not later than 15 working days after the sponsor first received notice of the effect. (c) Resumption of terminated studies. If the device is a significant risk device, a sponsor may not resume a terminated investigation without IRB and FDA approval. If the device is not a significant risk device, a sponsor may not resume a terminated investigation without IRB approval and, if the investigation was terminated under paragraph (b)(2) of this section, FDA approval. Subpart D-IRB Review and Approval §812.60 IRB composition, duties, and functions. An IRB reviewing and approving investigations under this part shall comply with the requirements of Part 56 in all respects, including its composition, duties, and functions. [46 FR 8957, Jan. 27, 1981] §812.62 IRB approval. (a) An IRB shall review and have authority to approve, require modifications in (to secure approval), or disapprove all investigations covered by this part. (b) If no IRB exists or if FDA finds that an IRB's review is inadequate, a sponsor may submit an application to FDA. [46 FR 8957, Jan. 27, 1981] If an IRB determines that an investigation, presented for approval under §812.2(b)(1)(ii), involves a significant risk device, it shall so notify the investigator and, where appropriate, the sponsor. A sponsor may not begin the investigation except as provided in § 812.30(a). [46 FR 8957, Jan. 27, 1981] Subpart E-Responsibilities of § 812.100 General responsibilities of investigators. An investigator is responsible for ensuring that an investigation is conducted according to the signed agreement, the investigational plan and applicable FDA regulations, for protecting the rights, safety, and welfare of subjects under the investigator's care, |