Page 61 - Biomedical Engineering and Design Handbook Volume 2, Applications

40 MEDICAL DEVICE DESIGN

Sec. 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 inves-
tigation was terminated under paragraph (b)(2) of this section, FDA approval.
Id. §§ 812.40-46.

Part 812 also delineates the duties of the investigator:

Sec. 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, 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.
Sec. 812.100 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) 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 state-
ments 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 comple-
tion 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.
Id. §§ 812.100 and 812.110.

The process under which research is conducted on humans under Part 812 is called an Investigational
Device Exemption (IDE). It is called an exemption because it allows a device to be transported in
commerce for testing without being approved. Without this exemption, the device would be adulter-
ated (a violation of the FDCA). The exemption is granted on a limited basis to allow testing of the
device to gather evidence for FDA submissions.
There are three paths through Part 812 for conducting research: (1) exempt studies; (2) abbreviated
IDE (nonsignificant risk) studies; and (3) IDE studies.