# **SOP 20**

**RESEARCH INVOLVING INVESTIGATIONAL DEVICES**

## 1.0 PURPOSE AND SCOPE

1.0 To establish a policy for the use of investigational devices at the
Ralph H. Johnson VA Medical Center.

**[2.0 POLICY]{.underline}**

2.1 The Department of Veterans Affairs clinical investigations of
medical devices are subject to Federal regulations and unless exempted
under certain specified conditions, are required to comply with
Investigational Device Exemption (IDE) regulations as outlined in
21CFR812. VA investigators are expected to fulfill all of the
responsibilities delineated in the FDA regulations. Investigational
devices in use at this institution must be stored, secured, and
dispensed in accordance with specific device requirements and as
outlined in the research project. Principal Investigators are
responsible for the appropriate storage, security, dispensing, and use
of investigational devices. Investigational devices may only be used at
the Ralph H. Johnson VA Medical Center after the research project and
associated documentation have been approved by the Institutional Review
Board (IRB) and the Research & Development Committee (R&D), excluding
exceptions for the emergency use of an unapproved medical device as
outlined in this policy.

**[3.0 DEFINITIONS:]{.underline}**

3.1 An **Investigational Device** as defined by the FDA is a device that
is the object of an investigation \[21CFR812.3(g)\]. Investigational
devices include transitional devices (21CFR812.3(r)) that are objects of
investigations. According to VHA Handbook 1200.5, July 15, 2003, (3.j.),
an investigational device may be an approved device that is being
studied for an unapproved use or efficacy.

3.2 An **Unapproved Device** is defined as a device that is used for a
purpose or condition for which the device requires, but does not have,
an approved application for pre-market approval under section 515 of the
Federal Food, Drug, and Cosmetic (FD&C) Act \[21 U.S.C. 360 (e)\]. An
unapproved device may be used in human subjects only if approved for
clinical testing under an approved application for an Investigational
Device Exemption (IDE) under section 520 (g) if the Act \[21 U.S.C.
360(j)(g)\] and 21CFR part 812. Medical devices that have not received
marketing clearance under section 510(k) of the FD&C Act are also
considered unapproved devices.

3.3 A **Non-significant Risk Device** is one that does not present
significant risk to the human subjects.

3.4 A **Significant Risk Device** is one that presents a potential for
serious risk to the health, safety or welfare of the human subjects.
\[21CFD812.3(m)\] Such a device is:

> \(1\) Intended for use as an implant;
>
> \(2\) Used in supporting or sustaining human life;
>
> \(3\) Intended for a use that is of substantial importance in
> diagnosing, curing, mitigating or treating disease, or otherwise
> preventing impairment of human health; or
>
> \(4\) One that otherwise presents a potential for serious risk to the
> health, safety, or welfare of subjects.

**[4.0 RESPONSIBILITIES:]{.underline}**

4.1 The Associate Chief of Staff for Research & Development is
responsible for developing and managing policies and procedures related
to the use of investigational devices at the RHJVAMC.

4.2 The Research and Development Committee is responsible for the
initial and continuing review of the scientific quality and
appropriateness of and approving or disapproving the research projects
involving investigational devices with human subjects.

4.3 The Institutional Review Board is responsible for approving or
disapproving research projects involving investigational devices in
accordance with the procedures outlined in 5b below.

4.4 Principal Investigators are responsible for:

> \(1\) Submitting the scientific protocol and all required
> documentation, including the informed consent form and the
> Investigational Device Information Sheet D to the IRB and R&D
> Committee review prior to beginning the study.
>
> \(2\) Submitting continuing review documentation and all adverse
> events to the IRB and R&D in a timely manner.
>
> \(3\) Using the investigational device only after notification of IRB
> and R&D approval and informed consent is obtained.
>
> \(4\) Adhering to the Investigational Device Exemption regulations at
> 21CFR812. Research projects involving non-significant risk devices
> must adhere to the abbreviated requirements at 21CFR812.2 (d).
>
> \(5\) Providing secure storage for all investigational devices
> according to their storage requirements.
>
> \(6\) Ensuring proper dispensing and utilization of the
> investigational devices as defined in the research project proposal.

**[5.0 PROCEDURES:]{.underline}**

5.1 A research project proposal must be submitted to and approved by
both the IRB and R&D prior to use of the investigational device. An IDE
must be obtained from the sponsor for significant risk devices prior to
project review.

\(1\) Submit all of the required documentation to the IRB and R&D for
review.

> \(2\) Store the investigational device in a locked and secured area as
> outlined in the research protocol.
>
> \(3\) Dispense and use of the investigational device is limited to
> appropriate personnel as outlined in the research protocol.
>
> \(5\) Obtain and document informed consent for each individual prior
> to using the investigational device.
>
> \(6\) Maintain the appropriate research records and tracking of the
> investigational device per 21 CFR812.140.
>
> \(7\) Report the protocol modifications to the IRB immediately.

**5.2 IRB and R&D Review of Medical Devices**

> \(1\) The IRB and/or R&D Committee must determine whether an
> investigational device is either of Significant Risk (SR) or
> Non-Significant Risk (NSR).
>
> \(a\) The determination of level of risk of the device is based on the
> proposed use of the device and not on the device alone.
>
> \(b\) The designation of NSR for a device is independent of the
> designation of a study as minimal risk.
>
> \(c\) The IRB and/or the R&D Committee makes its decision of
> significant or non-significant risk level of the device based on the
> review and evaluation of the following:
>
> i\. the risk evaluation provided by the sponsor or
> sponsor-investigator;
>
> ii\. investigator's brochure, if applicable;
>
> iii\. federal regulations;
>
> iv\. the MUSC IRB Device Information Sheet D
>
> v\. any additional correspondence regarding the device that may be
> from the FDA, sponsor, and/or investigator;
>
> \(d\) The IRB and/or R&D may determine a device to be SR even if the
> sponsor considers the device to be NSR. If the sponsor indicates that
> the device is NSR, but the IRB or R&D determines it to be SR, then the
> sponsor must obtain an Investigational Device Exemption from the FDA.
>
> \(e\) Because NSR studies do not require an IDE, a clinical
> investigation involving an investigational device classified by the
> sponsor as NSR may be submitted to an IRB for review without an IDE.
> The sponsor should provide the IRB and or R&D with a risk assessment
> and the rationale used in making its NSR risk determination.
>
> \(f\) If the sponsor or FDA has determined a device to be SR, the IRB
> must also consider the device to be SR during the IRB review.
>
> \(g\) The rationale for the IRB's and/or R&D Committee NSR/SR
> determination must be documented in the IRB/R&D minutes.
>
> \(2\) The IRB and/or R&D Committee must initially review the
> risk/benefit ratio of all non-significant and significant risk devices
> compared to alternative devices and procedures.

\(3\) Expedited Review

> \(a\) Research projects involving significant risk devices do not
> qualify for expedited review during the initial review.
>
> \(b\) Research projects involving significant risk devices may be
> considered for expedited review during the continuing review, if the
> IRB determines it to be consistent with the research categories
> published in the Federal Register, Vol. 63, No.216, 11/09/1998:
> Expedited review of significant risk device studies is allowed at
> continuing review under certain specified
>
> conditions.
>
> \(4\) The IRB must determine the frequency of review for research
> projects involving investigational devices.
>
> \(5\) The IRB and/or R&D Committee must review the risk/benefit ratio
> of the device compared to alternative devices and procedures and
> approve or disapprove on a continual basis, research projects
> involving investigational devices.
>
> \(6\) The IRB and/or R&D Committee may only approve significant risk
> device studies only after an IDE approval is obtained by the sponsor.
> In instances where the sponsor has appropriately obtained a 510(k) or
> Humanitarian Use Device designation, the IRB and/or R&D Committee may
> only approve these studies once these approvals have been obtained and
> verified with the IRB and/or R&D Committee.
>
> \(7\) The IRB and/or R&D Committee will notify the investigator and/or
> sponsor of the review decisions, actions and any needed modifications
> regarding the research project.
>
> \(a\) If a device study is submitted as SR and the IRB and/or R&D
> Committee verifies that IDE approval has been obtained by the sponsor,
> the IRB and/or R&D Committee does not have to notify the sponsor or
> investigator of the SR determination.
>
> \(b\) If the IRB and/or R&D Committee determines the investigational
> device to be significant risk and the sponsor has not obtained IDE
> approval from the FDA, the IRB and/or R&D Committee will notify the
> sponsor and investigator of its determination in writing.
>
> \(8\) The IRB and/or R&D Committee must maintain records for reviewed
> research project in accordance with the IRB Standard Operating
> Procedures, which is in accordance with 21CFR56.

M. Rita I. Young

Associate Chief of Staff for Research