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US FDA Updates Guidance on Identifying and Responding to Deficiencies

The US FDA has revised its guidance document to update the considerations on identifying and responding to deficiencies in premarket submissions.

US FDA formally proposes aligning Quality System Regulations with ISO 13485

December 2, 2022

The US Food and Drug Administration has revised the guidance document Developing and Responding to Deficiencies in Accordance with the Least Burdensome Provisions to update the considerations on identifying and responding to deficiencies in premarket submissions. The document supersedes the one of the same title issued on November 2, 2000.

The revised document further clarifies the content and format of a deficiency letter and includes a new list of examples of deficiencies and applicant responses.

Guidance on requesting additional information for market registration

The FDA has finalized the guidance document​ to help agency staff develop requests for additional information needed to make a decision on a medical device marketing application. Requests for additional information for medical device marketing applications are known as deficiencies. The guidance also recommends the most efficient formats for agency and industry to send or reply to such deficiencies.

FDA staff often identify the need for added information in order to make a premarket approval (PMA) determination of reasonable assurance of safety and effectiveness (RASE), a humanitarian device exemption (HDE) determination of substantial equivalence (SE), or a classification determination for a De Novo request.

Least burdensome information request pathways

The Least Burdensome Provisions of the Food and Drug Administration Modernization Act (FDAMA) were added to the FD&C Act in 1997. The Least Burdensome Provisions were amended by the Food and Drug Administration Safety and Innovation Act (FDASIA) and the 21st Century Cures Act.

The provisions state that:

  • Substantially equivalent – When the Secretary requests information to demonstrate that devices with differing technological characteristics are substantially equivalent, only that information necessary to making substantial equivalence determinations and the least burdensome means of demonstrating substantial equivalence will be requested.
  • Clinical data – When the Secretary requests clinical data, including one or more well-controlled investigations for demonstrating a reasonable assurance of device effectiveness, it will only be requested after consultation with the applicant to determine the least burdensome means of evaluating device effectiveness.
  • PMA applications – When requesting additional information for a PMA application, the Secretary shall consider the least burdensome appropriate means necessary to demonstrate a reasonable assurance of device safety and effectiveness.
  • Post-market information – The Secretary shall consider the role of post-market information in determining the least burdensome means of demonstrating a reasonable assurance of device safety and effectiveness.
  • Minimum required information – The Secretary shall request the minimum required information to support a determination of substantial equivalence or a reasonable assurance of safety and effectiveness.
  • Premarket approvals – The least burdensome provisions do not change the standards for premarket approval or substantial equivalence.

Deficiency letters will undergo supervisory review to ensure the deficiencies cited are relevant to marketing authorization decisions (e.g., 510(k) clearance, PMA approval, and De Novo classification).

Deficiency letters in marketing applications

When writing deficiency letters, FDA staff should follow certain guiding principles.

Deficiency guidelines are:

  1. Information unrelated to the marketing authorization decision should not be included.
  2. Alternative approaches to deficiency letters to resolve regulatory issues should be tried to optimize the time, effort and resources needed for industry to develop a response.
  3. Deficiency letters should request the minimum/least burdensome amount of information necessary to adequately address the identified issue.
  4. The total information needed to evaluate the device’s benefit-risk profile, as well as uncertainty in making benefit-risk determinations for PMAs and De Novos should be considered.
  5. Major deficiencies should only be included if their resolution is needed to reach a final decision.
  6. If the agency is including minor deficiencies, the agency should identify these requests separately from major issues, and whenever possible, attempt to resolve minor questions interactively. The agency should not issue a letter for only minor deficiencies.
  7. FDA may include additional suggestions or requests not related to a favorable marketing authorization decision but these do not require a response.

Applicants should provide complete responses to all deficiencies within the timeframe indicated in the agency’s deficiency letter.

Emergo by UL will continue to post updates to FDA guidance as they become available.