Overview of Non-Exempt, Abbreviated Requirements Medical Device Clinical Studies

August 15, 2016 - Lael Pickett; and Liz Scheurer, Principal Clinical Research Scientist, Neurocritical Care

The white paper “Overview of U.S. Medical Device Clinical Trials” provided a brief overview of US clinical studies regulations, types of clinical studies and how to determine if an Investigational Device Exemption (IDE) is required (Figure 1). This paper will focus on Non-Exempt clinical studies that do not present a significant risk to study subjects and must comply with “abbreviated” FDA regulatory requirements. Non-Exempt/Non-Significant risk (NSR) studies do not require an IDE application be filed with the US Food and Drug Administration (FDA) prior to initiating the study.

figure 1 us fda clinical study regulations by study type

FDA regulations in 21 CFR § 812.2(b) define what is an “abbreviated requirements” clinical study:

  • An investigation of a device, other than a significant risk device, if the device is not banned (e.g. prosthetic hair fibers) and the sponsor complies with the following requirements:
    • Labels the device as “CAUTION – Investigational device. Limited by Federal (U.S.) law to investigational use.”
    • Obtains Institutional Review Board (IRB) approval of the study after the IRB has confirmed that device is not a significant risk device.
    • Ensures that each study investigator obtains informed consent from each subject, unless informed consent requirements have been waived by the IRB.
    • Monitors the clinical sites to ensure compliance with the study protocol and investigates any unanticipated adverse devices effects.
    • Maintains required records and submits required reports.
    • Ensures that investigators maintain required records and submits required reports.
    • Prohibits device promotion as well as other specified practices.

The key to determining whether a study of an investigational device is subject to “abbreviated requirements” is whether or not the device meets the definition of a “significant risk device.”

A significant risk device is defined in 21 CFR § 812.3(m) as an investigational device that:

  1. Is intended as an implant and presents a potential for serious risk to the health, safety or welfare of a subject. Note: “implant” is defined in 21 CFR § 812.3(d) as a device that is placed into a surgically or naturally formed cavity of the human body for a period of 30 days or more. FDA may determine that devices placed in subjects for shorter time periods meet the definition of implant.
  2. Is purported or represented to be for use in supporting or sustaining human life and presents a potential for serious risk to the health, safety or welfare of a subject. Note: life support or life sustaining devices are described in 21 CFR § 860.3(e) as devices that are essential to, or that yield information that is essential to, the restoration or continuation of a bodily function important to the continuation of human life.
  3. Is used for substantial importance in diagnosing, curing, mitigating or treating disease, or otherwise presenting impairment of human health and presents a potential for serious risk to the health, safety or welfare of a subject.
  4. Otherwise presents a potential for serious risk to the health, safety or welfare of a subject.

Interestingly FDA does not define “serious risk” in its 21 CFR Part 812 Investigational Device Regulations, even though it is critical to determining whether or not a device meets the definition of significant risk device. However a definition of risk to health is described in 21 CFR § 806.2(k) as “a reasonable probability that use of, or exposure to, the product will cause serious adverse health consequences or death; or that use of, or exposure to, the product may cause temporary or medically reversible adverse health consequences, or an outcome where the probability of serious adverse health consequences is remote.” FDA has published an information sheet “Guidance For IRBs, Clinical Investigators, and Sponsors – Significant Risk and Non-Significant Risk Medical Device Studies,” that provides examples of Non Exempt, non-significant risk studies that could be subject to abbreviated study requirements. Examples include: conventional gastroenterology and urology endoscopes/accessories, conventional implantable vascular access devices (ports) and externally worn monitors for insulin reactions. See the FDA information sheet for additional examples. If there are questions as to whether a study is Non Exempt and subject to abbreviated study requirements, a Sponsor may consult FDA in accordance with its “Procedures for Handling Inquiries Regarding the Need for an Investigational Device Exemptions Application for Research Involving Medical Devices – October 26, 2001 (#D01-01).”

While abbreviated requirement clinical studies carry a lower risk profile and do not require an IDE, there are regulatory requirements that this apply to ensure that patient welfare and safety is protected.

FDA’s regulatory provisions for Non-Exempt Non-Significant Risk studies are meant to facilitate continued medical research that does not put subjects at serious risk.

At Minnetronix, our extensive development experience, commitment to patient safety, and flexible manufacturing environment provide ideal partnership opportunities for limited clinical builds. We equip our customers with Minnetronix developed product design and/or manufacturing information to ensure successful clinical study applications.