that the investigator is not eligible to conduct clinical investigations subject to requirements for prior submission to the Food and Drug Administration and that the results of any clinical investigations conducted by the investigator may not be considered by the Food and Drug Administration in support of any application for an exemption or premarket approval application. The notice shall further state that it is given because of the professional relations between the investigator and the person notified and that the Food and Drug Administration is not advising or recommending that any action be taken by the person notified.

(2) A determination that an investigator has been disqualified and the administrative record regarding such determination are disclosable to the public under Part 20 of this chapter.

(3) Whenever the Commissioner has reason to believe that an investigator may be subject to disqualification, he may, in his discretion, so notify the sponsor of any ongoing clinical investigation in which that investigator is participating simultaneously with or subsequent to proposing disqualification of the investigator under paragraph (c) of this section, unless there are overriding safety considerations that warrant earlier notification of the sponsor.

(i) Alternative or additional actions to disqualification. Disqualification of an investigator under this subpart is independent of, and neither in lieu of nor a precondition to, other proceedings or actions authorized by the act. The Food and Drug Administration may, at any time, institute any appropriate judicial proceedings (civil or criminal) and any other appropriate regulatory action in addition to or in lieu of (and prior to, simultaneously with, or subsequent to) disqualification. The Food and Drug Administration may also refer pertinent matters to another Federal, State, or local law enforcement or regulatory agency for such action as that agency deems appropriate.

(j) Suspension or termination of an investigator by a sponsor. The sponsor of an investigational study may at any time remove an investigator from fur

ther participation in the study, whether or not the Food and Drug Administration has begun any action to disqualify the investigator. The sponsor need not use either the grounds or the procedures for disqualification set forth in this subpart. If a sponsor removes an investigator from a study, the sponsor shall notify the Food and Drug Administration in writing of the reasons for such removal as soon as possible, but in no event later than 5 days after such removal.

(k) Reinstatement of a disqualified investigator. An investigator who has been disqualified may be reinstated as eligible to conduct clincial investigations subject to requirements for prior submission to the Food and Drug Administration, or as acceptable to be the source of clinical investigations to be submitted to the Food and Drug Administration, if the Commissioner determines, upon an evaluation of a written submission from the investigator, that the investigator can adequately assure that he will conduct such studies in compliance with the requirements set forth in this part. A disqualified investigator who wishes to be so reinstated shall present in writing to the Commissioner reasons why he believes he should be reinstated; the investigator shall also submit a detailed description of the corrective actions he has taken or intends to take to assure that the acts or omissions that led to disqualification will not recur. The Commissioner may condition reinstatement upon the submission of an acceptable protocol for a specific clinical investigation providing for additional corrective actions and/ or the submission of special undertakings by a sponsor, an institution, an institutional review committee, or another investigator to review in detail the investigator's compliance with the requirements of this part and/or the investigator's being found in compliance with the applicable regulations upon an inspection. If an investigator is reinstated, the Commissioner shall so notify the investigator and all organizations and all persons who were notified under paragraph (h) of this section of the disqualification of the investigator. A determination that an investigator has been reinstated in dis

closable to the public under Part 20 of this chapter.

[42 FR 58889, Nov. 11, 1977, as amended at 53 FR 11253, Apr. 6, 1988]

Subpart F-[Reserved]

Subpart G-Inspections, Reports, and Records

§ 813.150 Inspections.

(a) Any sponsor, institutional review committee, or investigator shall permit an authorized employee of the Food and Drug Administration, at reasonable times and in a reasonable manner, to inspect and copy any records concerning the investigational study that are required to be kept by this part.

(b) Any sponsor or investigator who has authority to grant access to the facility shall also permit authorized FDA employees, at reasonable times and in a reasonable manner, to inspect any facilities where the intraocular lens is manufactured, processed, held, used, or implanted.

(c) Any investigator shall permit an authorized employee of the Food and Drug Administration to copy records that identify the names of human subjects, upon notice that the Food and Drug Administration has reason to believe that the consent of human subjects was not obtained, that reports submitted by the investigator to the sponsor or to the institutional review committee do not represent actual cases or actual results obtains, or that such reports or other required records appear to be otherwise false or misleading.

[42 FR 58889, Nov. 11, 1977; 43 FR 1940, Jan. 13, 1978]

§ 813.153 Reports.

(a) Recall reports. Any sponsor shall notify the Food and Drug Administration of any request that investigators return, or otherwise dispose of, any supplies of the intraocular lens, or examine any patients that previously received a lens.

(b) Adverse reaction reports. If during the study a seriously adverse reaction occurs that may reasonably be regarded as lens related and that

was not previously expected in nature, severity, or degree of incidence in the investigational plan (including any incidence of hypopyon, intraocular infection, or acute corneal decompensation), the following actions shall be effected:

(1) The investigator shall investigate the reaction and submit an accurate and adequate report of the investigation to the sponsor and to the committee as soon as possible but in no event later than 5 days after learning of the reaction;

(2) The sponsor shall evaluate any adverse reaction report submitted by the investigator any reports received from other sources and within 5 days after learning of the adverse reaction, shall report the adverse reaction and the results of is evaluation to the Food and Drug Administration, any committee(s) monitoring the study, or part of the study, in which the reac tion occurred (if the investigator(s) has not already reported the reaction to the committee(s)), and all other investigators and sponsors participating in the study. In the case of hypopyon, except where the Food and Drug Administration directs otherwise, a sponsor need only report the adverse reaction and results of his evaluation to other investigators and committees particpating in the study where the incidence of the reaction exceeds that which was previously anticipated in materials provided to investigators.

(c) Progress reports. (1) Any investigator shall submit accurate progress reports to the investigational review committee and sponsor (or his monitor) at appropriate intervals but in no event at intervals exceeding 1 year.

(2) The sponsor shall make accurate and adequate progress reports to the Food and Drug Administration at appropriate intervals not exceeding 1 year. Such reports shall include any significant findings of the study and any necessary amendments or corrections to previous reports or to the application to keep them accurate.

(d) Suspension/termination reports. (1) Any investigator shall report to the sponsor any suspension or termination of the investigational study by a committee within 5 days.

(2) Any institutional review committee shall immediately report any suspension or termination of a study it is reviewing and monitoring under this part to the Food and Drug Administration.

(e) Final reports. (1) Within 3 months after the completion or discontinuance of or withdrawal of the exemption for the investigational study (or the investigator's portion of the study), any investigator shall notify the committee and sponsor and make an accurate and adequate final report to the sponsor, and the final report shall include all reports not previously submitted to the sponsor but required by paragraphs (b), (c), or (d) of this section.

(2) Within 30 days after the completion or discontinuance of a study or the suspension or termination of a study by a committee, the sponsor shall notify the Food and Drug Administration of the action.

(3) Within 6 months after the study is completed, discontinued, suspended, or terminated or the exemption is withdrawn, the sponsor shall make a final report to the Food and Drug Adminstration.

8813.155 Records.

(a) The sponsor, any investigator, and any committee shall maintain adequate and accurate records concerning the investigational study, including copies of all correspondence, among themselves and with the Food and Drug Administration regarding the study.

(b) (1) The sponsor and any investigator shall maintain adequate and accurate records showing the shipment, receipt, or other disposition of all supplies of all lenses shipped or received. (2) The sponsor either shall provide to each investigator an identification card that is to be provided to each subject after implantation or shall provide each subject with such a card. The card shall include the following information on each lens: Lens name, manufacturer's name and address, model number, style and serial, batch, lot, or other identification number for each lens. The sponsor and each investigator shall maintain the following records: identification by name of the

investigator who received each unit of the lens and who adminstered the device; the idenfification by code of the subject who received it; and identification of each unit otherwise disposed of (including identification of the person who disposed of it, the person, if any, who received it, and the purpose or reason for its disposal, e.g., because of contamination or return to the sponsor).

(c) An institutional review committee shall prepare and maintain adequate documentation of its activities regarding each investigational study, including records of information submitted to the committee by sponsors or investigators, information compiled on committee members pursuant to § 813.62, minutes of committee meetings on issues involved in the study and their resolution, committee decisions on the study, and dated reports of successive monitoring as it is performed.

(d) Contents of investigator records. An investigator shall maintain an adequate and accurate case report on each subject, which shall include the following:

(1) All relevant observations, information, and data on the condition of the subject at the time the subject enters into the study, including information regarding any relevant previous medical history and the results of all diagnostic tests performed to determine that the subject is appropriate for entry into the study.

(2) All documentation regarding the consent of the human subjects, as required by Part 50 of this chapter.

(3) All relevant observations and data on the condition of the subject throughout the duration of his participation in the study.

(e) The sponsor shall retain a copy of any application, report, or correspondence that he submits to the Food and Drug Administration under this part.

(f) A sponsor, investigator, and institutional review committee shall maintain records required under this part for whichever of the following periods is shortest:

(1) A period of 2 years after the date on which the Food and Drug Administration approves the marketing of the

lens for the purposes that were the subject of the study.

(2) A period of 5 years after the date on which the results of the study are submitted to the Food and Drug Administration in support of the marketing of the lens for the purpose that was the subject of the study.

(3) In other situations, e.g., where the investigational study does not result in the submission of an application for marketing the device for the purposes that were the subject of the study, a period of 2 years after the date on which the investigational study (not merely an investigator's portion of a study) is terminated, completed or discontinued, or the exemption is withdrawn.

(g) A Sponsor, investigator, or committee may withdraw from the responsibility for maintaining records for the period of time required in paragraph (f) of this section by transferring custody to any other person who will accept responsibility for the records. Notice of such transfer shall be given to the Food and Drug Administration.

(h) The Food and Drug Administration may require a sponsor to submit any records concerning the investigational study, including any records required to be kept under this part.

[42 FR 58899, Nov. 11, 1977; 43 FR 1940, Jan. 13, 1978, as amended at 47 FR 46080, Oct. 15, 1982]

Subpart H-Investigational Studies That Do Not Involve Human Subjects

§ 813.160 Conditions of exemption.

(a) Where an investigational device is intended for use in humans, a shipment of the device that is intended solely for tests in animals used only for laboratory research purposes, or for in vitro or mechanical tests or similar tests that do not involve use of human subjects, shall be exempt from any of the otherwise applicable provisions of the act listed in § 813.1(b) if:

(1) The labeling of the device complies with the requirements of § 813.5 (a) and (b) and bears the following additional statement:

CAUTION-DEVICE FOR INVESTIGATIONAL USE ONLY IN LABORATORY ANIMALS OR OTHER TESTS THAT DO NOT INVOLVE HUMAN SUBJECTS

(2) The person who ships the device under this subpart uses due diligence to assure that the consignee is regularly engaged in conducting tests in animals used only for laboratory research, or similar for in vitro or other mechanical tests or tests that do not involve use of human subjects and that the shipment of the investigational device will actually be used only in such tests.

(3) The person who ships the device under this subpart maintains adequate records showing the name and address of the consignee to whom the device is shipped, date, quantity, and batch or code mark of each shipment for a period of 2 years after such shipment and, upon the request of a properly authorized employee of the Department at reasonable times, make such records available for inspection and copying or submits such records to the Food and Drug Administration.

(b) This subpart does not apply to any use of an investigational device that involves use of human subjects.

[42 FR 58889, Nov. 11, 1977, as amended at 53 FR 11253, Apr. 6, 1988]

§ 813.170 Termination of exemption.

(a) The commissioner shall terminate an exemption under this subpart if he makes either of the following findings:

(1) The person shipping an investigational device under this subpart has failed to comply with any of the conditions for the exemption under this subpart.

(2) Any of the grounds for withdrawal of an investigational device exemption under § 813.35 apply.

(b) The Commissioner shall notify the sponsor of the termination of an exemption under this subpart with a full statement of the reasons for such termination and shall afford an opportunity for a regulatory hearing under Part 16 of this chapter. The person whose exemption is terminated shall recall or otherwise assure the destruction of any unused devices.

(1) Was not on the market (introduced or delivered for introduction into commerce for commercial distribution) before May 28, 1976, and is not substantially equivalent to a device on the market before May 28, 1976, or to a device first marketed on, or after that date, which has been classified into class I or class II; or

(2) Is required to have an approved premarket approval application (PMA) or a declared completed product development protocol under a regulation issued under section 515(b) of the act;

or

(3) Was regulated by FDA as a new drug or antibiotic drug before May 28, 1976, and therefore is governed by section 520(1) of the act.

(d) This part amends the conditions to approval for any PMA approved before the effective date of this part. Any condition to approval for an approved PMA that is inconsistent with this part is revoked. Any condition to approval for an approved PMA that is consistent with this part remains in effect.

§ 814.2 Purpose.

The purpose of this part is to establish an efficient and thorough device review process

(a) To facilitate the approval of PMA's for devices that have been shown to be safe and effective and that otherwise meet the statutory criteria for approval; and

(b) To ensure the disapproval of PMA's for devices that have not been shown to be safe and effective or that do not otherwise meet the statutory criteria for approval. This part shall be construed in light of these objectives.

§ 814.3 Definitions.

For the purposes of this part:

(a) Act means the Federal Food, Drug, and Cosmetic Act (sections 201902, 52 Stat. 1040 et seq., as amended (21 U.S.C. 321-392)).

(b) FDA means the Food and Drug Administration.

(c) IDE means an approved or considered approved investigational device exemption under section 520(g) of the act and Parts 812 and 813.