This SOP describes the requirements for research involving medical devices, including the responsibilities of Principal Investigators (PIs), IRBs, and sponsors.
PIs and IRBs must ensure that research (i.e., clinical investigation) involving medical devices is conducted in accordance with applicable federal regulations. These regulations describe, among other things, requirements for Investigational Device Exemptions (IDEs), use of custom devices and accountability and record retention, and responsibilities of PIs, IRBs, and sponsors when research is conducted with medical devices.
3.1. When human subjects research involves the use of medical devices, FDA regulations
apply. Investigators must provide sufficient information about the device for the
IRB to evaluate its associated risks and benefits, including the FDA approval status
of the product (i.e., approved for marketing or investigational).
3.2. Medical devices can receive FDA approval or clearance for marketing in several
different ways. Examples include pre-market approval, which is given following
clinical trials to determine the safety and efficacy of a new device, and marketing
clearance (510(k) pre-market notification), granted by FDA when a device is determined
to be “substantially equivalent” to a device already on the market. Investigational
devices include medical devices under clinical investigation to test their safety
and efficacy, as well as investigation of certain modifications, or new intended
uses of already marketed devices.
3.3. The FDA requirements for studies involving investigational devices are proportional
to the potential risk level (see “Significant and Non-Significant Risk Device Studies”
below). Studies presenting a significant risk to subjects must be conducted under
an IDE. Non-significant risk studies do not require an IDE but must meet the abbreviated
IDE requirements described in Addendum A. Certain investigational device studies
are exempt from the IDE requirements. For more information about the FDA exemptions
for IDE requirements, see Addendum A.
3.4. When an IDE is required for the proposed use of an investigational device in
research, investigators must submit an application to FDA. An IDE number will be
assigned by FDA upon receipt of the application. Unless earlier notification is
received, studies may be initiated 30 days after FDA’s receipt of the application.
Final IRB approval will not be given until a valid IDE number is provided. For
more information about obtaining an IDE, see 21 CFR 812 Subpart B – Application and Administrative Action and Device Advice: IDE Application.
3.5. An investigator obtaining an IDE for the proposed use of an investigational
device in research becomes a “sponsor-investigator” and additional institutional
resources are available to assist investigators in complying with applicable FDA
regulations (see Additional Responsibilities of Sponsor-Investigators” below).
3.6. FDA regulations allow sponsors to charge for an investigational device. The
charge should not exceed an amount “necessary to recover the costs of manufacture,
research, development, and handling of the investigational device.” Proposed charges
are included in the IDE application. The IRBs should ensure that charges for investigational
devices appear appropriate and equitable and that any additional costs to subjects
are disclosed during the consent process.
3.7. The “off-label” use of a marketed device (i.e., a use other than the indication(s)
approved by FDA) by a physician for treatment purposes does not require an IDE
or IRB approval. When such uses meet the regulatory definitions of research or
clinical investigation, IRB approval is required. An IDE may also be required,
unless the research meets the conditions for an abbreviated IDE (described in Addendum
B) or exemption (described in Addendum A).
3.8. In certain non-emergency situations, an investigational device intended to
treat a serious or immediately life-threatening condition may be used under a Treatment
IDE. Such “treatment use” of an investigational device requires IRB review and
approval. For more information, see 21 CFR 812.36 – Treatment Use of an Investigational Device, Device Advice: IDE Early/Expanded Access, or contact WVU OHRP at irb@mail.wvu.edu.
3.9. The “compassionate use” of an investigational device allows access for a patient
(or small group of patients), who does not meet the requirements for inclusion
in a research protocol for the device, but for whom a physician believes the device
may provide benefit in treating and/or diagnosing the disease or condition. Such
use of an investigational device is considered a protocol “deviation” for which
prior FDA approval and reporting to the IRB is required. For more information,
see FDA guidance Device Advice: IDE Early/Expanded Access and SOP 031: Research
Related Event Reporting.
3.10. Additional requirements apply to the emergency use of an investigational device
or biologic and planned emergency research involving investigational devices subject
to FDA regulations. (See SOP 053: Emergency Use of Investigational Drugs, Biologics,
or Devices and SOP 054: Planned Emergency Research.)
3.11. Although custom devices and humanitarian use devices are not investigational, additional FDA requirements apply to their use, including IRB notification or review as described below (see “Custom Devices” and “Humanitarian Use Devices”).
4.1. To describe proposed uses of medical devices in human subject research, PIs will indicate in their WVU electronic protocol submission that they will be using devices in their proposed research.
4.2. During the pre-review process, WVU OHRP staff are responsible for making an initial determination about the FDA requirements applicable to the device’s use. For investigational devices, one of the following determinations must be made:
4.3. When the research involves a device with an IDE, WVU OHRP staff will verify that the IDE number provided by the PI is valid. Protocol-specific confirmation (e.g., sponsor’s protocol cover sheet, FDA or sponsor correspondence, etc.) will be obtained.
5.1. The convened IRBs will review proposed research involving investigational devices considering the criteria for approval as described in SOP 007: IRB Approval Criteria.
Note: Research involving a device for which an IDE (including an abbreviated IDE) is required is not eligible for expedited review.
5.2. When research involves the use of a device, to approve the research the IRBs will also require the following:
6.1. Significant risk (SR) device studies pose the potential for serious risk to the health, safety, and/or welfare of research subjects. Examples include studies involving surgical sutures, cardiac pacemakers, intravascular stents, and orthopedic implants. An IDE is required for SR device studies.
6.2. Non-significant risk (NSR) device studies do not present potential serious risks to subjects. Examples include studies involving most daily-wear contact lenses and lens solutions, ultrasonic dental scalers, and foley catheters. NSR studies do not require an IDE but must follow the abbreviated IDE requirements (see Addendum B).
6.3. Sponsors are responsible for making the initial risk determination for a proposed investigational device research project. The IRB must review the sponsor’s SR or NSR assessment and may modify the determination if the IRB disagrees. If the FDA has made the SR or NSR determination prior to IRB review, the IRB is not required to make this determination (FDA’s determination is final).
Note: FDA makes SR/NSR determinations when an IDE is submitted, or if asked by a sponsor, investigator, or IRB, and will provide documentation of its decision upon request. Upon receipt of an IDE application, sponsors are notified via email of the date that FDA received the original application and the IDE number assigned. An IDE application is considered approved 30 days after it has been received by the FDA, unless the FDA otherwise informs the sponsor via email prior to 30 calendar days from the date of receipt, that the IDE is approved, approved with conditions, or disapproved. In cases of disapproval, a sponsor has the opportunity to respond to the deficiencies and/or to request a regulatory hearing under 21 CFR Part 16.
6.4. The IRB will make the SR or NSR determination for a protocol by convened review. A description of the device, reports of prior studies conducted with the device, proposed investigational plan, risk assessment, and subject selection criteria should be considered. The sponsor’s rationale for its SR or NSR determination (unless already determined by FDA) should also be reviewed. The SR/NSR determination must be documented in the IRB minutes, including a description of the reason(s) for the IRB’s decision.
6.5. The IRB is not required to make a SR/NSR determination for studies involving devices that meet the criteria for exemption from the IDE regulations.
6.6. For examples of SR and NSR devices, see FDA guidance Significant Risk and Nonsignificant Risk Medical Device Studies.
Note: Because the device’s proposed use in a protocol must be reviewed, inclusion
of a device on either list should not be the only consideration used by the IRB
in making the SR/NSR determination.
7.1. Expanded access, sometimes called “compassionate use,” is the use outside of a clinical trial of an investigational medical product (i.e., one that has not been approved by the FDA). Expanded access refers to the use of a medical device when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition rather than to obtain the kind of information about the device that is generally derived from clinical trials. Except for emergency expanded access use, when there is not sufficient time to secure prospective IRB review, an investigator treating a patient with an investigational device under expanded access is responsible for obtaining IRB review and approval before treatment with the investigational device may begin.
7.2. Under FDA’s current regulations, there are three categories of expanded access:
For more information, see FDA guidance Expanded Access for Medical Devices or contact the WVU OHRP at irb@mail.wvu.edu.
8.1. Investigational devices used in WVU research must be appropriately controlled and stored in compliance with IRB and FDA requirements and applicable university policies. Such requirements include processes to ensure that investigational products are manufactured, handled, and stored in compliance with applicable good manufacturing practices; inventory and accountability records are maintained for investigational device receipt, dispensing, and disposition; and investigational devices are used only in accordance with available information regarding their design, physical and chemical composition, performance, safety, biocompatibility, labeling, and the approved protocol.
9.1. Investigators obtaining an IDE to initiate and conduct research must also fulfill
the federal requirements of sponsors. These requirements include (but are not limited
to) additional FDA reporting (e.g., annual progress reports, data monitoring, and
recordkeeping obligations). Additional institutional assistance may be available
when a WVU investigator wishes to obtain an IDE to perform human subjects research.
Sponsor-investigators may be referred to any number of institutional groups who
can assist with IDE requirements related to being a sponsor-investigator.
9.2. In addition to FDA regulations for the protection of human subjects, (21 CFR Parts 50 and 56), additional regulations may apply to sponsor-investigators, depending on the nature of the research. It is the responsibility of the investigator to become familiar with these regulations and requirements if they become a sponsor-investigator for FDA-regulated research. These regulations could include:
9.3. Additional Human Subject Protection training (CITI GCP Course for Clinical Trials Involving Investigational Devices or GCP Course for Clinical Trials with Investigational Drugs or Biologics) for first-time sponsor-investigators will be required prior to protocol approval and activation of the FDA-regulated research.
9.4. For more information describing the FDA requirements for sponsor-investigators when research is initiated and conducted with investigational devices, see FDA’s Investigational New Drug Application (21 CFR 312) Subpart D – Responsibilities of Investigators and Sponsors. Additional guidance describing the international standards for good clinical practices in human subjects research (ICH/GCP) is available at ICH E6(R2): Good Clinical Practice Industry Guidance.
Leftover specimens are frequently used in feasibility studies and studies to characterize the performance of new in vitro diagnostic devices. Routine clinical care testing can provide information about the laboratory characteristics of the specimen that allow investigators to quickly ascertain whether the specimen will meet the research protocol inclusion criteria. The remnants of these specimens therefore become valuable to the research at a point when they are of no value to the patient and are ready to be discarded. It is possible, in certain circumstances, for IVD devices to be conducted using leftover specimens obtained without informed consent while protecting the human subjects who are the sources of such specimens. FDA can exercise enforcement discretion as to the informed consent requirements if the following are true:
11.1. An approved humanitarian device exemption (HDE), containing sufficient information for FDA to determine that the probable benefits outweigh the risks of a device’s use, is required for marketing a humanitarian use device. Note: Results from scientifically valid clinical investigations demonstrating efficacy are not required for HDEs. For a list of approved HDEs, see Approved HDE Summaries of Safety and Possible Benefit.
11.2. Humanitarian use devices (HUDs) are marketed products; therefore, their use
does not constitute research when used according to the approved labeling. However,
IRB approval is required before the HUD is initially used at an institution. FDA
regulations require that initial IRB review and approval of the HUD occur at a
convened meeting. Continuing review must be performed at least annually but may
be conducted by expedited review procedures.
11.3. IRB review of HUDs should consider the criteria for approval (as applicable)
described by regulations and WVU OHRP Policy (SOP 019: Full Board Review). The
following materials should be reviewed:
Patient information packets are available for most HUDs and contain a description
of the potential risks and benefits of the HUD and any procedures associated with
its use. The HDE approval order, product labeling, and patient information packet
for a HUD can be obtained from the FDA website; see Approved HDE Summaries of Safety and Possible Benefit.
11.4 Informed consent should be obtained orally or in writing before HUD use. Minimally,
the consent process should contain a discussion of the potential risks and benefits
of the HUD, description of the procedures associated with its use, and a statement
that the device is a “humanitarian use device” that has not undergone clinical
testing for effectiveness. Use of the HUD should not be referred to as “research”
or a “clinical investigation.” The IRBs will approve the consent process, its content,
and any associated documents (i.e., consent form, information packet, etc.) that
will be distributed to recipients of the HUD. HIPAA research authorization is not
required unless the HUD is used as part of a research protocol.
11.5 FDA regulations require the institution and/or device manufacturer to report
to FDA, and the IRB, deaths or serious injuries that may have been caused by a
HUD or malfunctions that would, “be likely to cause or contribute to a death or
serious injury if the malfunction were to recur.”
11.6 Investigational use of a HUD (i.e., for broader or different indication than
approved by FDA) requires an approved IDE in addition to IRB approval when the
HUD is a significant risk device. For more information on HUDs, including investigational
and emergency uses, see FDA Guidance on HDE Program.
12.1. FDA regulations do not require IRB review and approval for custom device use. However, to ensure adequate patient protections, the requirements for the emergency use of devices, including prior notification, informed consent, and five-day reporting, should be followed when custom devices are used. For more information on these requirements, see SOP 053: Emergency Use of Investigational Drugs, Biologics, or Devices.
WVU Policies:
SOP 007: IRB Review Criteria
SOP 019: Full Board Review
SOP 031: Research Related Event Reporting
SOP 053: Emergency Use of Investigational Drugs, Biologics, or Devices
SOP 054: Planned Emergency Research
Federal Regulations:
21 CFR 50
21 CFR 56
21 CFR 812
21 CFR 814
AAHRPP:
Standard I-7
No IDE is required if the research meets one of the exemption categories in [812.2(c) Exempted Investigations] that apply to human subjects research. All criteria in each category must be true in order to meet the exemption category. IRB review and informed consent are still required.
No IDE is required if the research meets one of the exemption categories in [812.2(c) Exempted Investigations] that apply to human subjects research. All criteria in each category must be true in order to meet the exemption category. IRB review and informed consent are still required.
Please note: The following categories of investigations are considered to have approved applications for IDEs, unless FDA has notified a sponsor under 812.20(a) that approval of an IDE application is required. If a device risk level is considered Non-Significant Risk (NSR), it is subject to IDE Abbreviated Requirements. In this case, the IRB acts as a surrogate to FDA. For significant risk (SR) devices, formal IDE submission to FDA is still required.
