The Material Difference: FDA Warning Letters Reinforce 510(k) Expectations for Material Changes

Two recently published FDA warning letters caught our attention as they cite manufacturers for failing to submit a 510(k) for changes to device materials.

FDA’s guidance Deciding When to Submit a 510(k) for a Change to an Existing Device provides recommendations for evaluating changes to devices to determine when a new 510(k) should be submitted.  For a change to a device’s patient-contacting materials, the guidance frames the significance analysis around whether a risk assessment identifies any new or increased biocompatibility concerns.  If so, the change is generally considered significant and a new 510(k) should be submitted.  Discussion related to this question states that an example of a new concern would be “a material change that requires a new type of biocompatibility test, such as an implantation test, that was not required for the original device” or “where a new chemical component added to a material requires a genotoxicity analysis of the component (because, for instance, the particular component is noted in the literature as potentially genotoxic), but the original device already required a genotoxicity analysis.”

In practice, many changes in device materials stem from supply chain changes or are implemented to make minor improvements to the product line.  They are often minor variations in formulation that do not require a different type of biocompatibility test, and device manufacturers may be tempted to conclude that the biocompatibility risk is the same as that of the original device, even if they elect to repeat one or more biocompatibility tests that were also required for the original device.

In the two recent warning letters, it is these types of changes that FDA has identified as violative.

In a warning letter to Pro-Optics, LLC, the company was cited for failing to submit a new 510(k) related to changes in the polymers and colorants used in its contact lens cases, which FDA found represented “a significant material deviation” from the cleared version of the device.  FDA specifically called out the addition of new colors, noting that they introduce “unreviewed biocompatibility risks” and are “significant changes to the chemical compositions of the devices that could significantly affect their safety or effectiveness.”

In a warning letter to Next Medical Products Company, LLC, FDA found that a change in the preservative in an ultrasound gel was significant, noting that it “could affect the device’s biocompatibility, stability, sterility and shelf life.”  FDA further notes that the new preservative “represents a change in the chemical profile…and therefore the biocompatibility must be re-evaluated” to ensure the new preservative “maintains the same preservative effectiveness, stability, sterility and shelf-life claims as previously cleared. The repeat biocompatibility testing, preservative effectiveness, shelf life, and stability should be reviewed in a new 510(k) by the Agency. The firm must demonstrate that the number of organisms in the subject ultrasound gel is limited throughout its shelf life.”

Taken together, these warning letters are a reminder that even seemingly modest material changes—new colorants, a different preservative, or a reformulated component sourced from a new supplier—can cross the threshold for a new 510(k).  Manufacturers evaluating such changes should document their risk analysis carefully against the factors in FDA’s change guidance, resist the temptation to equate repeat testing with equivalent risk, and, where any doubt remains about whether a change could significantly affect safety or effectiveness, consider a new 510(k) submission or engage with FDA before implementing the change.