How to Respond to an FDA Deficiency Letter for Medical Devices

In the submission of medical devices, the key to a favorable marketing authorization decision is sufficient evidence. When applications lack that evidence, the FDA can identify where that evidence, or the explanation behind it, falls short through a Deficiency Letter. During substantive review, deficiency letters typically cite a gap between what evidence the applicant has presented and what evidence the FDA needs. Some gaps can be addressed with clarification and context, but many cannot be closed without new testing to meet the evidentiary burden. This article addresses the medical device deficiency letter as part of the broader review sequence for a 510(k), De Novo request, or PMA, and gives the applicant a practical, step-by-step approach for building a response.

The Deficiency Letter in the FDA Review Sequence

FDA device reviews move through a defined sequence of stages, each with its own point at which the agency can determine that something necessary is missing. For a 510(k) or De Novo request, that sequence runs from acceptance review, to substantive review, to a final decision. A PMA follows a comparable sequence but includes both acceptance and filing reviews before substantive review begins.

What to Expect in a Deficiency

FDA guidance directs reviewers to build each deficiency around a specific set of elements, and reading a deficiency with that structure in mind is usually more productive than jumping straight to the request at the end. In general, a deficiency should include:

1. The Issue: what specifically FDA found to be missing, unclear, or inadequately supported in the submission.
2. Basis for Deficiency: why the information already provided does not resolve the question, and what effect the gap has on the marketing authorization decision.
3. Information Requested: the specific data, analysis, or explanation FDA needs to move forward, along with any alternative approaches FDA considers acceptable.
4. Response Window: the date by which a complete response is due.

An applicant must read the basis of the deficiency as the correspondence details it and formulate further action and response from the specific questions asked. 

The Least Burdensome Principle and its Implications For FDA Interaction

Deficiency requests for device submissions are governed by the FDA’s “least burdensome” principle. “Least burdensome” is defined as the minimum amount of information necessary to resolve a specific regulatory question, through the most efficient approach available, at the appropriate point in review. This means that the FDA should, in addressing deficiencies with an applicant, refrain from asking for extraneous information irrelevant to the applicant device, while maintaining the stringent evidentiary bar for clearance or approval.

Deficiencies generally fall into major and minor deficiency categories; the distinction between these dictates how an applicant should prioritize response. According to the FDA's guidance, Developing and Responding to Deficiencies in Accordance with the Least Burdensome Provisions, they are defined as follows:

• Major deficiencies are those based on least burdensome principles that, if not resolved, will preclude a favorable marketing authorization decision. 
• Minor deficiencies can be resolved in a straightforward manner, but still need to be addressed to meet regulatory requirements. They should be resolved, if possible, through interactive review. 

Thus, the applicant should note that a deficiency letter is not an invitation to resubmit the application, and it is not a signal to hand over every document the company has on the topic. The strongest response is well-organized and answers the specific regulatory question(s) the FDA asks. 

Building the Response

For each deficiency, the applicant is generally choosing among the same three paths specified by FDA guidance:

1. Provide the specific information or data requested;
2. Explain why the identified issue does not, in fact, affect the marketing authorization decision; or
3. Present alternative information, along with an explanation of why that information adequately addresses the concern.

It is important to identify what the deficiency requires in response quickly, because the timelines on necessary actions may differ. For example, resolving a deficiency through providing context for data or device specification may be as simple as document review and submission. However, more common with major deficiencies, additional testing may be required, which means significantly more time and incur cost. 

Clarity and targeted information provision are key when building a response. Restate or clearly reference each deficiency in your answer. Answer only what was asked. Breadth of information is not equivalent to a stronger response. Review the package as one submission to ensure descriptions, specifications, software versions, and conclusions match everywhere they appear. A technically correct answer can still raise a new question if it conflicts with something stated elsewhere in the response.