In Vitro Diagnostic (IVD) devices used in clinical trials are classified according to the risk that is involved based on the potential outcomes and impact if the test does not perform properly. The risk class (Class I, II, or III) determines the review pathway for regulatory assessment. If the device is classified as Class I or II, and if it is non-exempt, a premarket notification (510(k)) will be required for marketing. A 510(k) is a premarket submission made to the FDA to demonstrate that the device is at least as safe and effective as a legally marketed device (21 CFR 807.92(a)(3)) that is not subject to a Premarket Approval (PMA).
As stated in the FDA guidance document issued on July 28th, 2014, “The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]”, the new device is classified into the same class and subject to the same requirements as the predicate device. The risk assessment and device classification is based on the intended use as defined by the manufacturer or Sponsor. Aspects considered in the intended use include:
- What is detected (e.g., analyte)
- Function (screening, monitoring, diagnosis)
- Specific disorder or condition that it is intended to detect
- Testing population
- The testing is noninvasive.
- The testing does not require an invasive sampling procedure that represents significant risk.
- The testing does not by design or intention introduce energy into a subject.
- The testing is not used as a diagnostic procedure without confirmation of the diagnosis by another medically established diagnostic product or procedure.
- The product is labeled “For Investigational Use Only. The performance characteristics of this product have not been established”.
In order for a test to be considered noninvasive, the following must apply as stated in 21 CFR 812.3(k):
- The test or procedure does not penetrate or pierce the skin or mucous membranes of the body, the ocular cavity, or the urethra.
- The test or procedure does not enter the ear beyond the external auditory canal, the nose beyond the nares, the mouth beyond the pharynx, the anal canal beyond the rectum, or the vagina beyond the cervical os.
- Blood sampling that involves simple venipuncture and the use of surplus samples of body fluids or tissues that are leftover samples from routine purposes are considered noninvasive.
If the study device does not meet the above criteria, and is therefore considered to be non-exempt, the level of risk associated with the device needs to be determined, as discussed in the FDA draft guidance document issued on December 18th, 2017, “Investigational IVDs Used in Clinical Investigations of Therapeutic Products”. The FDA may consider certain non-exempt IVDs to be non-significant risk (NSR).
If an investigational IVD is considered NSR, the Sponsor does not need to submit an Investigational Device Exemption (IDE) application and obtain FDA approval before starting the trial. For Significant Risk (SR) device studies the Sponsor will need an approved IDE application before the start of the trial and must follow all IDE regulations in 21 CFR 812. If the device does not meet any of the criteria below, it is considered NSR. If the device meets any of the criteria below, it is considered a SR device according to 21 CFR 812.3(m):
- The device is an implant and presents a potential for serious risk to the health, safety or welfare of a subject.
- The device is 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.
- The device is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety or welfare of a subject.
- The device otherwise presents a potential for serious risk to the health, safety, or welfare of a subject.
Sponsors and manufacturers can look up the classification of a device, as well as whether any exemptions exist, by using the FDA’s classification database. This database contains medical device names, the associated product codes, and the category of a device.
Ensuring that the classification of an IVD is accurate is an important step in making sure that the device is safe and effective. What steps do you take in ensuring that the risk determination for your product is accurate? What are some possible outcomes that could result from having the product risk incorrectly assessed?Chemistry via photopin (license)