FDA’s Draft Guidance on The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications 510(k)

• By: Staff Editor
• Date: March 02, 2012

On December 27, 2011, the FDA released new draft guidance on 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications. The guidance aims to explain the decision-making process of FDA for determining substantial equivalence and provides additional details about the regulations, strategies, and norms upon which the FDA’s review of the 510(k) application is based. The guidance also provides information about new policies regarding Special 510(k) and Abbreviated 510(k) submissions to FDA.

• More limitations on the ability to use multiple predicates
• More chances of the new device being categorized as ‘Not Substantially Equivalent (NSE)’  as a result of differences in indications for use when compared with the predicate device
• More restrictions on the use of the Special 510(k) application, especially when animal and performance data are submitted to support the new device.
• Modified standards, when a new intended use constitutes changes in indications for use

• A premarket notification (also referred to as 510k) should be submitted by the manufacturers in order to introduce a device into commercial distribution or in case an existing device has undergone a considerable change in its safety, efficacy, manufacturing process, intended use etc.
• This application should be submitted at least 90 days before delivering the device for commercial distribution, so that FDA can conclude whether or not the device meets the requirements for market clearance.
• This applies to all devices except those exempt under the FD&C Act (Food, Drug and Cosmetic Act).
• Manufacturers should provide information in tabular form about the technical characteristics of the new device as well as the predicate device.
• If the Agency has set special controls applicable to a particular device, then the 510(k) application should sufficiently address such issues.

• Manufacturers should compare their new device to a predicate device in order to support its Substantial Equivalence and the best preferred way to demonstrate this is through submission of the 510 (k) application or premarket notification to the FDA for review and further clearance.
• A 510(k) summary's description of device's attributes should include a list of all device components included in the submission such as  model numbers, device characteristics etc and the summary should indicate the level of evidence required to support a Substantial Equivalence (SE) determination.
• FDA points out that a finding of Substantial Equivalence indicates that the new device's indications for use fall within the intended use of the legally marketed device. All new indications for use should be properly evaluated to determine whether they reflect a new intended use.
• FDA stipulates that intended use, technological characteristics of the new device and the legally marketed device should be the same and the new device is safe and effective as its predicate.
• The Agency adopts a flexible approach to determine “Substantial Equivalence (SE)” keeping in view evolving technology, thus maintaining predictability and consistency in its review and clearance.
• The Agency will review all information in the new device's proposed labeling, its indications for use in order to evaluate its intended use.
• The Agency will request clinical data (animal data) when it considers that:
  • Other forms of performance data is inadequate to confirm Substantial Equivalence
  • Technological differences between the new and legally marketed device do not   support an immediate ‘Not Substantially Equivalent’ determination due to various questions of safety and effectiveness
  • Few issues cannot be addressed properly using non-clinical methods.

• A new device found to be ‘Not Substantially Equivalent (NSE)’ to a predicate device will result it in being classified as a Class III device and will require an approval or granting of relevant petition before marketing. The new device need not be identical to the predicate device but should be substantially equivalent to the predicate device.
• If the manufacturer does not provide the requested information or a sufficient justification regarding the safety and effectiveness of the new device, then the Agency will categorize the new device as’ NSE’ even if it has not affirmed that the new device has a different intended use or different technological characteristics.

• If the manufacturer fails to respond to the Agency’s requests, the submission will be subsequently withdrawn within the assigned timeline and the manufacturer will have to submit a new 510(k) with required information that addresses the outstanding deficiencies.
• Manufacturers should submit a new 510(k), if they wish to delete a contradiction as labeling changes increase the scope of the indications for use
• A new 510(k) application should be submitted when changes are implemented in:
  • Fundamental scientific technology used  or
  • Device specifications as they affect the safety, performance or effectiveness of the device.

• The FDA may change a Special 510(k) or an Abbreviated 510(k) into a normal 510(k) if it finds that the submission does not meet the requirements of the specific program.
• Manufacturers should include a risk analysis chart (containing nine specified elements) with their Special 510(k) submissions to document their device modifications.

 Additional Resources

Read the FDA Draft Guidance The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)]