and for the control of devices under investigation. An investigator also is responsible for ensuring that informed consent is obtained in accordance with Part 50 of this chapter. Additional responsibilities of investigators are described in Subpart G.

[45 FR 3751, Jan. 18, 1980, as amended at 46 FR 8957, Jan. 27, 1981]

§812.110 Specific responsibilities of investigators.

(a) Awaiting approval. An investigator may determine whether potential subjects would be interested in participating in an investigation, but shall not request the written informed consent of any subject to participate, and shall not allow any subject to participate before obtaining IRB and FDA approval.

(b) Compliance. An investigator shall conduct an investigation in accordance with the signed agreement with the sponsor, the investigational plan, this part and other applicable FDA regulations, and any conditions of approval imposed by an IRB or FDA.

(c) Supervising device use. An investigator shall permit an investigational device to be used only with subjects under the investigator's supervision. An investigator shall not supply an investigational device to any person not authorized under this part to receive

it.

(d) Disposing of device. Upon completion or termination of a clinical investigation or the investigator's part of an investigation, or at the sponsor's request, an investigator shall return to the sponsor any remaining supply of the device or otherwise dispose of the device as the sponsor directs.

Subpart F-(Reserved)

Subpart G-Records and Reports §812.140 Records.

(a) Investigator records. A participating investigator shall maintain the following accurate, complete, and current records relating to the investigator's participation in an investigation:

(1) All correspondence with another investigator, an IRB, the sponsor, a monitor, or FDA, including required reports.

(2) Records of receipt, use or disposition of a device that relate to:

(i) The type and quantity of the device, the dates of its receipt, and the batch number or code mark.

(ii) The names of all persons who received, used, or disposed of each device. (iii) Why and how many units of the device have been returned to the sponsor, repaired, or otherwise disposed of. (3) Records of each subject's case history and exposure to the device. Such records shall include:

(i) Documents evidencing informed consent and, for any use of a device by the investigator without informed consent, any written concurrence of a licensed physician and a brief description of the circumstances justifying the failure to obtain informed consent.

(ii) All relevant observations, including records concerning adverse device effects (whether anticipated or unanticipated), information and data on the condition of each subject upon entering, and during the course of, the investigation, including information about relevant previous medical history and the results of all diagnostic tests.

(iii) A record of the exposure of each subject to the investigational device, including the date and time of each use, and any other therapy.

(4) The protocol, with documents showing the dates of and reasons for each deviation from the protocol.

(5) Any other records that FDA requires to be maintained by regulation or by specific requirement for a category of investigations or a particular investigation.

(b) Sponsor records. A sponsor shall maintain the following accurate, complete, and current records relating to an investigation:

(1) All correspondence with another sponsor, a monitor, an investigator, an IRB, or FDA, including required reports.

(2) Records of shipment and disposition. Records of shipment shall include the name and address of the consignee, type and quantity of device, date of shipment, and batch number or code mark. Records of disposition shall describe the batch number or code marks of any devices returned to the sponsor, repaired, or disposed of in other ways

by the investigator or another person, and the reasons for and method of disposal.

(3) Signed investigator agreements.

(4) For each investigation subject to §812.2(b)(1) of a device other than a significant risk device, the records described in paragraph (b)(5) of this section and the following records, consolidated in one location and available for FDA inspection and copying:

(i) The name and intended use of the device and the objectives of the investigation;

(ii) A brief explanation of why the device is not a significant risk device:

(iii) The name and address of each investigator:

(iv) The name and address of each IRB that has reviewed the investigation:

(v) A statement of the extent to which the good manufacturing practice regulation in Part 820 will be followed in manufacturing the device; and

(vi) Any other information required by FDA.

(5) Records concerning adverse device effects (whether anticipated or unanticipated) and complaints and

(6) Any other records that FDA requires to be maintained by regulation or by specific requirement for a category of investigation or a particular investigation.

(c) IRB records. An IRB shall maintain records in accordance with Part 56 of this chapter.

(d) Retention period. An investigator or sponsor shall maintain the records required by this subpart during the investigation and for a period of 2 years after the latter of the following two dates: The date on which the investigation is terminated or completed, or the date that the records are no longer required for purposes of supporting a premarket approval application or a notice of completion of a product development protocol.

(e) Records custody. An investigator or sponsor may withdraw from the responsibility to maintain records for the period required in paragraph (d) of this section and transfer custody of the records to any other person who will accept responsibility for them under this part, including the requirements of § 812.145. Notice of a transfer shall be

given to FDA not later than 10 working days after transfer occurs.

[45 FR 3751, Jan. 18, 1980, as amended at 45 FR 58843, Sept. 5, 1980; 46 FR 8957, Jan. 27, 1981]

§812.145 Inspections.

(a) Entry and inspection. A sponsor or an investigator who has authority to grant access shall permit authorized FDA employees, at reasonable times and in a reasonable manner, to enter and inspect any establishment where devices are held (including any establishment where devices are manufactured, processed, packed, installed, used, or implanted or where records of results from use of devices are kept).

(b) Records inspection. A sponsor, IRB, or investigator, or any other person acting on behalf of such a person with respect to an investigation, shall permit authorized FDA employees, at reasonable times and in a reasonable manner, to inspect and copy all records relating to an investigation.

(c) Records identifying subjects. An investigator shall permit authorized FDA employees to inspect and copy records that identify subjects, upon notice that FDA has reason to suspect that adequate informed consent was not obtained, or that reports required to be submitted by the investigator to the sponsor or IRB have not been submitted or are incomplete, inaccurate, false, or misleading.

§ 812.150 Reports.

(a) Investigator reports. An investigator shall prepare and submit the following complete, accurate, and timely reports:

(1) Unanticipated adverse device effects. An investigator shall submit to the sponsor and to the reviewing IRB a report of any unanticipated adverse device effect occurring during an investigation as soon as possible, but in no event later than 10 working days after the investigator first learns of the effect.

(2) Withdrawal of IRB approval. An investigator shall report to the sponsor, within 5 working days, a withdrawal of approval by the reviewing IRB of the investigator's part of an investigation. (3) Progress. An investigator shall submit progress reports on the inves

tigation to the sponsor, the monitor, and the reviewing IRB at regular intervals, but in no event less often than yearly.

(4) Deviations from the investigational plan. An investigator shall notify the sponsor and the reviewing IRB (see §56.108(a) (3) and (4)) of any deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency. Such notice shall be given as soon as possible, but in no event later than 5 working days after the emergency occurred. Except in such an emergency, prior approval by the sponsor is required for changes in or deviations from a plan, and if these changes or deviations may affect the scientific soundness of the plan or the rights, safety, or welfare of human subjects, FDA and IRB in accordance with §812.35(a) also is required.

(5) Informed consent. If an investigator uses a device without obtaining informed consent, the investigator shall report such use to the sponsor and the reviewing IRB within 5 working days after the use occurs.

(6) Final report. An investigator shall, within 3 months after termination or completion of the investigation or the investigator's part of the investigation, submit a final report to the sponsor and the reviewing IRB.

(7) Other. An investigator shall, upon request by a reviewing IRB or FDA, provide accurate, complete, and current information about any aspect of the investigation.

(b) Sponsor reports. A sponsor shall prepare and submit the following complete, accurate, and timely reports:

(1) Unanticipated adverse device effects. A sponsor who conducts an evaluation of an unanticipated adverse device effect under §812.46(b) shall report the results of such evaluation to FDA and to all reviewing IRB's and participating investigators within 10 working days after the sponsor first receives notice of the effect. Thereafter the sponsor shall submit such additional reports concerning the effect as FDA requests.

(2) Withdrawal of IRB approval. A sponsor shall notify FDA and all reviewing IRB's and participating investigators of any withdrawal of approval of an investigation or a part of an investigation by a reviewing IRB within

5 working days after receipt of the withdrawal of approval.

(3) Withdrawal of FDA approval. A sponsor shall notify all reviewing IRB's and participating investigators of any withdrawal of FDA approval of the investigation, and shall do so within 5 working days after receipt of notice of the withdrawal of approval.

(4) Current investigator list. A sponsor shall submit to FDA, at 6-month intervals, a current list of the names and addresses of all investigators participating in the investigation. The sponsor shall submit the first such list 6 months after FDA approval.

(5) Progress reports. At regular intervals, and at least yearly, a sponsor shall submit progress reports to all reviewing IRB's. In the case of a significant risk device, the sponsor shall also submit progress reports to FDA.

(6) Recall and device disposition. A sponsor shall notify FDA and all reviewing IRB's of any request that an investigator return, repair, or otherwise dispose of any units of a device. Such notice shall occur within 30 working days after the request is made and shall state why the request was made.

(7) Final report. In the case of a significant risk device, the sponsor shall notify FDA within 30 working days of the completion or termination of the investigation and shall submit a final report to FDA and all reviewing the IRB's and participating investigators within 6 months after completion or termination. In the case of a device that is not a significant risk device, the sponsor shall submit a final report to all reviewing IRB's within 6 months after termination or completion.

(8) Informed consent. A sponsor shall submit to FDA a copy of any report by an investigator under paragraph (a)(5) of this section of use of a device without obtaining informed consent, within 5 working days of receipt of notice of such use.

(9) Significant risk device determinations. If an IRB determines that a device is a significant risk device, and the sponsor had proposed that the IRB consider the device not to be a significant risk device, the sponsor shall submit to FDA a report of the IRB's determination within 5 working days after

Subpart H-Investigational Studies That Do Not Involve Human Subjects

813.160 Condtions of exemption. 813.170 Termination of exemption.

AUTHORITY: Secs. 301, 501, 502, 520, 701, 704, 801 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 331, 351, 352, 360j, 371, 374, 381). SOURCE: 42 FR 58889, Nov. 11, 1977, unless otherwise noted.

Subpart A-General Provisions §813.1 Scope.

(a) General. This part provides that intraocular lenses may be exempted from any of the requirements of the act enumerated in paragraph (b) of this section that would otherwise be applicable to the device, to permit investigational studies of the device by experts who are qualified by scientific training and experience to investigate the safety and effectiveness of the lenses. This part implements sections 520(g) and 520(1) of the act with respect to intraocular lenses.

(b) Effect of exemption. (1) In general, intraocular lenses are exempted from provisions of the following sections of the act and regulations thereunder when an application for exemption applicable to the lenses is in effect under this part: Misbranding under section 502, registration and premarket notification under section 510, performance standards under section 514, premarket approval under section 515, records and reports under section 519, restricted devices under section 520(e), good manufacturing practices under section 520(f), and color additives under section 721.

(2) Intraocular lenses shall not be extempted from a provision of the act listed in paragraph (b)(1) of this section where the Commissioner indicates that the lens is not exempt from such a provision in an order of disapproval, approval, or approval with modifications under § 813.30.

[42 FR 58889, Nov. 11, 1977, as amended at 59 FR 14366, Mar. 28, 1994]

§813.2 Applicability.

This part applies to all implantations of intraocular lenses in humans unless a premarket approval application has been approved for these lenses under section 515 of the act.

§813.3 Definitions.

(a) Intraocular lens means a lens intended to replace surgically the natural lens of the human eye. An intraocular lens is, for purposes of this part, synonymous with "investigational device," lens, or lenses.

(b) Investigational device means a device that is used in an investigational study involving human subjects, where the study is for the purpose of determining if the device is safe or effective.

(c) Investigational plan means a plan or protocol for using an investigational device in an investigational study. See §813.25 for requirements applicable to an investigational plan.

(e) Investigator means an individual who actually conducts an investigational study, i.e., under whose immediate direction the investigational device is administered or dispensed to, or used involving, a subject.

(f) Monitor, when used as a noun, means an individual selected by a sponsor or contract research organization to oversee the progress of an investigational study. The monitor may be a full-time employee of a sponsor or contract research organization or a consultant to the sponsor or contract research organization. (Monitor, when used as a verb, means the act of reviewing the progress of an investigational study.)

(g) Sponsor means a person who initiates an investigational study, but who does not actually conduct the study (i.e., the investigational device is administered or dispensed to, or used involving, a subject under the immediate direction of another individual). A person other than an individual, e.g., corporation or government agency, that uses one or more of its own employees to conduct an investigational study that it has initiated is considered to be a sponsor (not a sponsor-investigator), and the employees are considered to be investigators.

(h) Sponsor-investigator means an individual who both initiates and actually conducts, alone or with others, an investigational study (i.e., under whose immediate direction the investigational device is administered or dis-1 pensed to, or used involving, a subject). * The term does not include any person other than an individual. Any sponsorinvestigator shall carry out the responsibilities under this part of a sponsor and of an investigator.

(i) Institution means a person (other than an individual) who engages in the conduct of research on human subjects or in the delivery of medical services to human subjects as a primary activity or as an adjunct to providing residential or custodial care to human beings. The term includes a hospital, retirement home, prison, university, or device manufacturer. Facility as used in section 520(g) of the act is deemed to by synonymous with the term institution for purposes of this part.

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