Aug 8, 2016

US medical device regulators have issued new recommendations for determining when changes to a registered medical device require filing a new 510(k) application.

The US Food and Drug Administration first published such recommendations in 1997; in its new draft guidance, the agency intends to clarify various points including a particular phrase—“could significantly affect the safety or effectiveness of the device”—that has complicated some manufacturers’ attempts to determine whether changes to their devices do indeed necessitate new 510(k) filings.

Emergo Vice President of Quality Assurance Consulting Richard Vincins says the new draft guidance has taken more industry feedback into account than the last time the FDA attempted to update recommendations for changes to 510(k) devices in 2012 and 2013.

“This time the FDA has published guidance that, after a brief review, seems to have acknowledged and added a few suggestions from industry that were raised previously,”  Vincins  explains. 

“And more interesting is a separate guidance just for changes to software,” he adds. 

(Emergo will provide analysis of the FDA’s new medical software guidance in a separate blog post.)

“Guiding principles” for new 510(k) determinations

The new guidance contains several “guiding principles” that manufacturers should utilize when deciding whether to submit new 510(k)s for changes or modifications to their devices, including:

  • Modifications made with intent to significantly affect safety or effectiveness of a device: Changes made to a device to improve its safety or effectiveness will most probably require a new premarket notification, according to the guidance. But changes not intended to impact a device’s safety or effectiveness should nonetheless be evaluated to determine whether they could have such impacts, which would also require a new 510(k) filing.
  • Making use of risk-based assessments: Regardless of whether a manufacturer intends for modifications to affect a device’s safety and/or effectiveness, that manufacturer should conduct a risk-based assessment to determine what if any new risks are introduced by the device’s modification. Such assessments should enable at least initial decisions as to whether new 510(k)s should be filed, according to the guidance.
  • Unintended consequences: Manufacturers should take steps to see whether modifications to their devices result in any unintended impacts on their devices’ safety or effectiveness. Changes to materials used, for example, may unintentionally impact a device’s performance.
  • Risk management: Manufacturers should utilize risk concepts including those found in the ISO 14971 standard in determining how new modifications to their devices will affect safety and effectiveness. “Because 21 CFR 807.81(a)(3)(i) requires a new 510(k) when a change ‘could significantly affect safety or effectiveness,’ both safety and effectiveness should be considered in evaluating a device’s risk profile,” states the guidance.
  • Choosing appropriate comparative devices: Manufacturers’ risk-based assessments of their changed devices should include comparisons of their changed devices to the most recently FDA-cleared versions of their devices. “Manufacturers may make a number of changes without having to submit a new 510(k), but each time they make a change, the device they should compare it to is their most recently cleared device,” the guidance states.

Key types of changes that may require new 510(k)s

The guidance divides types of device changes that could require new premarket notification into three broad categories: labeling changes; technology, engineering or performance changes; and materials changes.

Regarding labeling changes, the FDA notes that changes made to intended use versus indications for use are a crucial distinction when determining the need for a new 510(k) filing. Examples of indications for use changes on labels that usually do require new 510(k)s are:

  • Reuse of a device previously labeled for single use only
  • Change in a device’s availability from prescription to over the counter
  • Changes that introduce a new therapeutic or diagnostic claim, or that introduce the device to a new patient population

On the other hand, the following examples of label changes would likely not require new premarket notification applications:

  • Changes to a device name or description that are still in line with the product’s current indications for use
  • Changes for clarity or readability that do not affect a device’s cleared indications for use

Technology, engineering and performance changes should prompt several questions and evaluations by manufacturers to decide whether to file new 510(k) applications:

  • Does the change affect a device’s control mechanism, change principle or energy type?
  • Does the change target device sterilization, cleaning or disinfection?
  • Does the change involve packaging or expiration dates?
  • Are there any changes in device dimensions, performance specifications, patient/user interfaces or similar characteristics?

Finally, some types of device materials changes to devices do require new 510(k) filings, and often also result in substantial labeling or specification changes, compounding the need for new premarket notification.

Factors manufacturers should consider when it comes to material changes include:

  • Is the device’s material type or formulation, chemical composition or material processing affected by the change?
  • Will the changed material directly come into contact with body tissues or fluids?
  • Does a risk assessment of the change point to any new or increased biocompatibility issues?

The guidance includes flow charts for all three major types of device changes discussed above.


  • Stewart Eisenhart