A new guidance document just published by the US Food and Drug Administration (FDA) is intended to present a "least burdensome regulatory approach" for sponsors of class III in vitro diagnostic devices to obtain approval from regulators.
In the US, medical devices are regulated according to their potential risk. Class I medical devices are those with the least risk, and are generally given minimal regulatory oversight and may often bypass regulators entirely. Class II medical devices, meanwhile, are those with the potential to cause some harm, but which are generally known to be safe and effective because similar devices, known as predicates, have already been brought to market.
Class III medical devices, however, are considerably more resource- intensive from a regulatory perspective. The devices, which are defined as those that are life-sustaining or life-supporting, have the potential to kill or seriously maim an individual if problems occur. And while there are ample examples of those sorts of devices-pacemakers, heart valves and other implants among them-one sub-categorization of medical devices is rarely included in the category: In vitro diagnostics.
That's because IVDs are almost never in physical contact with a patient, vastly reducing the ways in which the product could conceivably harm someone. But those devices can be classified as a "high risk" device by default under FDA's understanding that if it doesn't know enough about the device to definitely classify it as Class I/II, it will by default be a Class III device.
Migration from Old to New
That understanding generally leaves most IVDs out of Class III, but FDA's new guidance document, Assay Migration Studies for In Vitro Diagnostic Devices, notes that there are situations where such a classification would otherwise have been required.
FDA explains that some IVD's cleared through the 510(k) premarket notification system transition to new systems after clearance, presenting "specific concerns, either because of the nature of the analyte and indications, or because of the specific technology used (e.g., nucleic acid amplification tests)."
At issue for regulators is whether up-classifying them as Class III medical devices is necessary or appropriate, and whether a less burdensome approach might achieve the same results for patient safety and at lesser costs.
The answer, according to the guidance document, is yes-such an approach would accomplish just that.
"The FDA believes that the assay migration study paradigm discussed in this guidance provides a least burdensome scientific and regulatory pathway for manufacturers to transfer a previously approved or licensed assay with full clinical data from an old system to a new system (not approved, licensed, or cleared)," FDA explained. "The paradigm is suitable in cases when sufficient knowledge can be derived from the documentation of design controls, risk analyses, and prior performance studies on an old system."
Such studies are particularly appropriate when an assay or IVD uses an output that generates a numeric result or is otherwise expressed as a signal to cutoff (S/CO) ratio. Other types of outputs may indicate that a device is not well-suited for the approach FDA outlines in its guidance, it said. All sponsors are advised to discuss their proposed migration studies with FDA prior to initiation of testing, FDA added.
FDA's guidance goes on to establish a five-part framework for determining whether a device is appropriate for a device migration study:
- The intended use and indications should remain unchanged relative to the existing system.
- Reagent and assay parameters (e.g., cutoff) should be unchanged, although "very minor differences" are allowed if they pertain to the process and can be validated.
- Some high-precision assay technologies may not be suitable for the migration studies.
- Assay and system technologies should remain unchanged, though minor changes may be acceptable on a case-by-case basis.
- Assay performance should remain unchanged.
FDA's guidance goes on to note submission requirements, which include a side-by-side comparison of the old and new devices, as well are summaries of data validating the new device's operations.
The full guidance, which includes an extensive explanation of the testing requirements for migration studies, may be found here.
FDA: Assay Migration Studies for In Vitro Diagnostic Devices
Federal Register Notice