The need for clinical data to support substantial equivalency with medical devices can be challenging for the industry to determine, given it has historically only been required in a small number of 510(k) submissions.
In cases where robust non-clinical safety and performance data are not sufficient to demonstrate substantial equivalency or when stipulated by special controls or regulation, FDA’s review of clinical data during the 510(k) submission process is necessary to establish that the intended use of the new device and the predicate device are the same and that any differences in technological characteristics do not raise questions about safety and effectiveness.
Newly published draft guidance outlines criteria for selecting appropriate clinical data, considerations for different types of devices, and requirements for study design, data analysis, and reportingi. This guidance aims to ensure that clinical data submitted with 510(k) applications are reliable, relevant, and support the safety and effectiveness of medical devices.
The draft guidance document outlines four common examples where clinical data may also be required for the 510(k) submission:
- Scenario #1 – Differences in the indications for use
- Scenario #2 – Differences in the technological characteristics
- Scenario #3 – Substantial equivalence cannot be determined by non-clinical testing
- Scenario #4 – Newly identified or increased risk for the predicate device
It is noted that there may be circumstances in which these scenarios arise, yet clinical data may not be needed, depending on the specific situation.
Scenario #1 – Differences in the indications for use:
When there are differences between the indications for use of the new device and the predicate, the FDA evaluates whether the new device’s indications for use fall under the predicate device’s intended use. To do so, the FDA reviews the new device’s labeling and indication for use statement in the 510(k) and potentially other clinical and/or scientific information submitted with the 510(k). Factors that may dictate the need for clinical data to be included in the 510(k) submission, where the indications for use differ between the new device and the predicate device, include:
- Patient population differences
- Disease differences
- Anatomical site, structure, or pathology differences
- General to specific considerations
- Expansion of the new device’s currently cleared indications for use
- Different or unknown benefit-risk profile for the proposed indications for use
Scenario #2 – Differences in the technological characteristics:
Clinical data may be required to establish that a new device performs equivalent to the predicate device despite the differences in the technological characteristics – and that do not raise different questions of safety and effectiveness. Factors that may dictate the need for clinical data to be included in the 510(k) submission, where there are differences in the technological characteristics of the new device and the predicate device, include:
- Significant change in device design
- Significant change in other device features
- Significant change in materials
- Significant change in energy source
Scenario #3 – SE cannot be determined by non-clinical testing:
Clinical data may be required to establish that a new device performs equivalent to the predicate device where non-clinical testing (e.g., analytical testing, bench testing, and/or animal testing) is not sufficient to establish substantial equivalence. Factors that may dictate the need for clinical data to be included in the 510(k) submission, where non-clinical testing may not be suitable for a device, include:
- There are anatomical and/or pathophysiological species-specific questions that rely on clinical evidence
- The model may not be predictive of clinical outcomes
- The available model(s) may not be appropriate due to the model having particular limitations that do not allow for an adequate assessment
- There is no model (e.g., analytical, bench, animal) available
Scenario #4 – Newly identified or increased risk for the predicate device:
Where possible, the FDA recommends that devices should not be used as predicate devices if they have new or increased risk. This is especially so where a predicate device exists that does not have these new or increased risks. However, if an alternative predicate is not available without the new or increased risk, then additional clinical data may be required to determine the substantial equivalence to the predicate device even if there are no identified differences between the devices in terms of technological characteristics that raise different questions of safety and effectiveness.
About the author: John Lockwood is Senior Director, US Head of Medical Devices and IVDs, Cencora PharmaLex. John has over 25 years of experience in quality, regulatory, operations, and development roles in the life sciences industry
