Jul 16, 2014

New draft guidance from the US Food and Drug Administration lays out major factors the agency considers when reviewing 510(k) premarket notification applications to make Substantial Equivalence (SE) determinations.

US regulators have issued the new guidance to serve both as a resource for agency reviewers making SE determinations and as a tool for 510(k) applicants to more effectively demonstrate equivalence to predicate devices already on the US market.

The FDA bases its SE determinations on assessments of submitted devices’ benefits and risks in comparison with their predicate devices, according to the new guidance.

First, FDA reviewers assess a 510(k) submission in terms of likely benefits that device would provide compared to its predicate device:

  • Type: How would the device benefit issues including clinical management, patient health and satisfaction, and probability of survival?
  • Magnitude: Would using the device achieve a pre-identified health outcome or threshold?
  • Probability: What percentage of this device’s target patient population would benefit from using the product?
  • Duration: Does the device provide curative or one-time treatment, or must treatments be repeated over time?

Along with the potential benefits of a device under consideration, FDA reviewers also examine risks that device would pose versus its predicate device:

  • Harmful events: What are the severity, types and frequency of harmful events tied to the use of the device?
  • Probability of harmful events: What proportion of the device’s target patient population would be expected to experience a harmful event stemming from use of that device?
  • Probability of patient experiencing a harmful event: Does the device data allow reviewers to predict which patients in a target population may experience harmful events?
  • Duration: How long would a harmful event last? How severe would the effects of the harmful event be?
  • Risks related to diagnostic devices: What are the likelihood and severity of a diagnostic device giving a false positive or false negative result?

FDA reviewers also consider factors when assessing the benefits and risks of 510(k) applicants’ devices. Issues such as characterization of the disease or condition a device is intended to treat, patient risk tolerance, risk mitigation and post-market data on predicate devices all warrant consideration by the agency in order to make SE determinations.

One major factor FDA reviewers must weigh in these decisions is the extent to which 510(k) applicants’ devices make use of innovative technology. In cases where devices undergoing premarket review provide technological improvements that could boost public health, US regulators may be willing to accept greater degrees of uncertainty in terms of benefits and risks compared to predicate devices. Such decisions occur on a case-by-case basis.

Stewart Eisenhart


  • Stewart Eisenhart