The Food and Drug Administration’s (FDA) Center for Devices and Radiological Health (CDRH) issued a draft guidance to clarify when changes to an existing device will require the submission of a new 510(k) premarket notification.1 The issuance of the draft guidance fulfills one of the 25 action items outlined in CDRH’s January 2011 510(k) and Science Report Recommendations, part of the agency’s ongoing review of the device premarket review process. When finalized, this guidance document will supersede the agency’s 1997 guidance, Deciding When to Submit a 510(k) for a Change to an Existing Device. While the draft guidance is not legally binding, it represents the FDA’s current thinking on the subject.  

The purpose of the draft guidance is to aid manufacturers in distinguishing changes that require submission of a new 510(k) from changes that may simply be documented in accordance with device Quality System Regulations (QSRs).2 Among other changes, the revised guidance omits the flowcharts and clarifying definitions found in the 1997 guidance document. Instead, the draft guidance presents a series of questions, representing various types of device modifications, and provides numerous example responses. The revised format is likely a deliberate effort by the agency to force manufacturers to consider the full text of the guidance in deciding whether to submit a new 510(k), instead of relying on the simplified flowchart. The guidance focuses on manufacturing, labeling, technology or performance specifications, and materials changes.  

The FDA regulations require the submission of a new 510(k) whenever a device will be “significantly changed or modified in design, components, method of manufacture, or intended use.”3 The regulation further states that the following situations constitute “significant changes” that require premarket notification:

  1. A change or modification in the device that could significantly affect the safety or effectiveness of the device, e.g., a significant change or modification in design, material, chemical composition, energy source or manufacturing process.
  2. A major change or modification in the intended use of the device.4

As with the 1997 guidance, this revised draft guidance is intended to clarify the meaning of “significant changes.” The draft guidance emphasizes the distinction between a change that does and a change that could affect a device’s safety or effectiveness, noting that 510(k) submissions are also required for the latter, which encompasses a greater number of potential changes. The potential effect of the new guidance is significant, as the circumstances that will not require a new 510(k) appear to be limited. The FDA notes that, “device changes intended as improvements to a device’s safety or effectiveness could significantly affect” the product’s safety or effectiveness and, therefore, require a new 510(k). Before providing specific examples, the draft guidance outlines the following seven underlying “basic principles” to guide manufacturers in deciding whether to submit a premarket notification:

  1. 510(k) notifications are required before initially marketing a new device (i.e., one that is not a modified version of the manufacturer’s already-cleared device).
  2. Changes to 510(k)-exempt devices do not require premarket notification if the particular change falls within specified limits, as stated in the applicable regulations.
  3. In determining whether a modification is significant, manufacturers should compare the modified device to the most recently FDA-cleared version of the device, not to a more recent version of the device that was modified by changes not requiring submission of a 510(k).
  4. For each individual change to the device, manufacturers should consider the questions presented in the draft guidance (i.e., each scenario summarized in the table below) to determine whether a new 510(k) is required.
  5. Even if individual changes do not require a new 510(k), premarket notification could be required if, collectively, the changes could significantly affect the device’s safety or effectiveness.
  6. Manufacturers must comply with the QSRs to document, validate or, where appropriate, verify specification changes prior to implementation, unless the device is exempt from QSRs.
  7. Manufacturers should establish standard operating procedures for evaluating whether changes trigger the 510(k) requirement. If only one of multiple proposed changes triggers the premarket notification requirement, all proposed changes should be described in the notification (including changes implemented without notification since the device’s last 510(k) clearance). If a manufacturer determines that the device modification could not significantly affect safety or effectiveness and decides not to submit a new 510(k), the conclusion should be scientifically justified, and the rationale should be documented in accordance with the QSRs.  

The draft guidance attempts to classify device modifications into three categories:

  1. Changes likely to require a new 510(k).
  2. Changes generally unlikely to require a 510(k).
  3. Changes in a gray area where manufacturers should consult the appropriate review division to determine whether a 510(k) should be submitted.

The agency notes that the draft guidance does not address issues unique to specific devices or combination products. In particular, the FDA plans to release device-specific guidance to address nanotechnology. In the interim, the draft guidance urges manufacturers to consult with the agency regarding nanotechnologyrelated changes to devices. Manufacturers should continue to consult existing device-specific guidance, as appropriate.

The following table summarizes various types of modifications and notes additional considerations for manufacturers in determining whether a 510(k) notification is required.5 As previously noted, one of the “basic principles” advises manufacturers to consider whether any of the following situations apply to each proposed change. For example, proposed changes to a device’s length, thickness and material should be considered three individual changes.

Click here to see table