As the device industry is well aware, one of the greyest areas in device regulation (of which there are many) is determining when changes to a 510(k)-cleared device trigger the need for a new clearance. FDA requires a new 510(k) clearance when a modification to an existing 510(k)-cleared device (or other existing device subject to 510(k) requirements) “could significantly affect the safety or effectiveness of the device.” See 21 C.F.R. § 807.81(a)(3). Manufacturers must evaluate device changes in the first instance to determine whether a new 510(k) is needed or, instead, whether documentation of the change and rationale for not seeking 510(k) clearance is sufficient. This evaluation can be challenging and getting it wrong can mean a manufacturer could run into trouble if FDA later determines that its justification for not seeking clearance is inadequate.
To help in evaluating device changes, manufacturers commonly refer to FDA’s guidance “Deciding When to Submit a 510(k) for a Change to an Existing Device,” which provides FDA’s interpretation of the changes it believes could significantly affect the safety or effectiveness of a device. The guidance includes examples of changes and flowcharts that frequently make their way into formal company procedures. But this guidance has its limitations. Many of the examples FDA provides are obvious cases (at either end of the spectrum) that are unhelpful in evaluating changes that are neither clearly significant or insignificant. Additionally, manufacturers typically need to conduct a risk-based assessment of device changes to determine whether they significantly affect the safety or effectiveness of a specific device. Such assessments are highly individualized and difficult to map onto the few examples provided by FDA in its guidance.
Manufacturers should, therefore, welcome any additional source of examples of device changes to aid in evaluating their own. One potentially underutilized resource for this is FDA Warning Letters (WLs). Industry commonly thinks of WLs as only citing quality system violations. While quality system violations are often cited, we identified more than eighty WLs that appear to cite companies for failing to seek clearance for device changes that FDA believed could significantly affect safety or effectiveness. These letters offer real-world examples of device changes that FDA believed required a new 510(k) or internal documentation that FDA found inadequately evaluated such changes.
For example, in an October 13, 2023 WL to ReNovo, Inc., FDA stated that several of the company’s products required a new 510(k) due to “smaller diameter shafts,” “smaller diameter lumens,” “smaller tip elements,” and/or “longer shafts” than the originally cleared products. Based on FDA’s guidance, dimensional changes only require a new 510(k) if a risk-based assessment identifies new or significantly modified risks resulting from the changes. In the WL, though, FDA faults the company for “not evaluat[ing] how cleaning and re-sterilization of the additional OEM models with different designs could affect the performance specifications and reliability of [the new device models].”
Likewise, in a November 8, 2022 WL to Abbott Point of Care Ltd., FDA found that several changes to an in vitro diagnostic device could affect the safety or effectiveness of the device, including:
- Process change for IgM component that replaced monoclonal antibody product in a live animal with production in cell culture.
- Increase in the amount of caprine and murine IgG and introducing murine IgM in the sample inlet.
- Change in reagent from one that requires reconstitution to one that is already in solution.
- Change in cartridge and gasket diameters to accommodate a new sensor chip.
FDA also found that analytical sensitivity and precision testing provided by Abbott was inadequate to confirm the impact of such changes on the clinical performance of its device. Instead, FDA stated that a direct comparison of the modified and original device was required and key performance data, such as clinical accuracy, should have been documented to support the design changes.
As these two WL examples demonstrate, FDA’s determination that a new 510(k) is required may not be based on the inherent significance of a change and may, instead, be based on the lack of documented data supporting that a change does not significantly affect safety and effectiveness. This underscores the importance of these evaluations and the value of reviewing relevant WLs to identify common gaps in documentation that can lead to FDA requiring a new 510(k).
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Determining whether a device change requires a new 510(k) is a critical aspect of regulatory compliance. While FDA guidance, and the flowcharts and examples it contains, are essential tools, WLs provide an untapped source of real-world insights into FDA’s expectations. By analyzing WLs, manufacturers can better understand the types of changes that require a new 510(k) and avoid common gaps in generating the data and documentation in cases where a new 510(k) is not required. Notably, FDA’s public WL database only goes back to 2020. This can limit the type of information that can be gained from WLs. Thus, when evaluating your next set of device changes and whether a new 510(k) is needed, you may want to consult a third-party database (or an advisor that has access to such a database) to help with this search.
