In a nutshell: Hold the duties of sponsors and investigators in a medical device study
Use it when: You are running a medical device study and want the monitoring, records and reports it owes in one place.
(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.
(5) Sufficient accurate financial disclosure information to allow the sponsor to submit a complete and accurate certification or disclosure statement as required under part 54 of this chapter. The sponsor shall obtain a commitment from the clinical investigator to promptly update this information if any relevant changes occur during the course of the investigation and for 1 year following completion of the study. This information shall not be submitted in an investigational device exemption application, but shall be submitted in any marketing application involving the device.
(d) Selecting monitors. A sponsor shall select monitors qualified by training and experience to monitor the investigational study in accordance with this part and other applicable FDA regulations.
(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.
(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) Financial disclosure. A clinical investigator shall disclose to the sponsor sufficient accurate financial information to allow the applicant to submit complete and accurate certification or disclosure statements required under part 54 of this chapter. The investigator shall promptly update this information if any relevant changes occur during the course of the investigation and for 1 year following completion of the study.
(e) 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.
(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. Case histories include the case report forms and supporting data including, for example, signed and dated consent forms and medical records including, for example, progress notes of the physician, the individual's hospital chart(s), and the nurses' notes. 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. The case history for each individual shall document that informed consent was obtained prior to participation in the study.
(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.
(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 including the financial disclosure information required to be collected under § 812.43(c)(5) in accordance with part 54 of this chapter.
(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
(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, a notice of completion of a product development protocol, a humanitarian device exemption application, a premarket notification submission, or a request for De Novo classification.
(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.
(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 investigation 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.
(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, a sponsor shall also submit progress reports to FDA. A sponsor of a treatment IDE shall submit semi-annual progress reports to all reviewing IRB's and FDA in accordance with § 812.36(f) and annual reports in accordance with this section.
If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.
If the sponsor identifies a study as NSR, the sponsor must provide the reviewing IRB an explanation of its determination (21 CFR 812.2(b)(1)(ii)) and should provide any other information that may help the IRB in evaluating the risk of the study.
If FDA has determined that the study is NSR, the sponsor should so inform the IRB.
The sponsor must advise its clinical investigators about the SR status and obtain their agreement to comply with the applicable regulations governing such studies (i.e., 21 CFR Parts, 50, 56, 812)
If the IRB disagrees with the sponsor’s NSR assessment and decides the study is SR, the IRB must tell the clinical investigator, and where appropriate, the sponsor.
You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance.
Unless FDA has already made a risk determination for the study, the IRB must review the sponsor's SR or NSR determination for every investigational medical device study reviewed and modify the determination if the IRB disagrees with the sponsor.
SR device studies must follow all the IDE regulations at 21 CFR 812.
SR device studies must have an IDE application approved by FDA before they may proceed.
NSR device studies must follow the abbreviated requirements at 21 CFR 812.2(b).
The sponsor must submit an IDE application to FDA and obtain the agency’s approval of the study.
IRBs should have standard operating procedures that explain how the IRB makes SR and NSR determinations and that the decision should be documented.
IRBs should make the SR or NSR determination about a study by reviewing relevant information at a convened meeting.
To facilitate the IRB’s review of the study, an IRB may ask the sponsor for proof (i.e., a copy of FDA’s approval or conditional approval letter) that an SR study has an FDA-approved IDE application.
The IRB should document its SR/NSR determination in the IRB meeting minutes.
(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.
(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.
(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.
(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 the sponsor first learns of the IRB's determination.
(10) Other. A sponsor shall, upon request by a reviewing IRB or FDA, provide accurate, complete, and current information about any aspect of the investigation.
However, the IRB must still review the study in accordance with the IRB regulations before the investigation may begin.