Plan FDA engagement before you commit to validation

Manufacturers often begin thinking about an FDA Pre-Submission when they believe their 510(k) is nearly ready. By then, the development team may have completed studies, committed substantial resources, and built its submission around assumptions that have never been discussed with FDA.

Zaliance has encountered the same question hundreds of times: “When does a submission need a Pre-Sub?”

Zaliance’s practical position is that early FDA engagement should be considered in nearly every development program, particularly a manufacturer’s first submission. The decision belongs in feasibility planning, when feedback can still shape the evidence strategy and the schedule.

A Pre-Submission is not universally required. Its value lies in resolving consequential uncertainty before that uncertainty becomes expensive.

Understand what a Pre-Submission provides

A Pre-Submission provides FDA feedback on specific questions about a proposed development or submission approach. It is not a preliminary review of the completed 510(k), and it does not establish that the submission will be acceptable.

FDA’s Q-Submission guidance distinguishes this feedback from pre-review of a marketing submission or its study results. Certain focused questions involving preliminary findings may be appropriate, but the process does not provide a general verdict that a completed evidence package “looks good.” [1]

That distinction matters when preparing the questions. A manufacturer might seek feedback on whether its proposed validation protocol, sampling approach, and performance criteria would adequately address a particular aspect of the intended use. The response informs that proposed approach. It does not establish that every necessary study has been identified or that the eventual results will support clearance.

A useful question connects three things: the evidence the manufacturer proposes to generate, the rationale supporting that proposal, and the specific uncertainty FDA is being asked to address.

Include FDA engagement in feasibility planning

Regulatory affairs needs an ongoing role in development planning. Identifying a likely submission pathway is an early task; determining how the product will generate adequate evidence continues throughout development.

During feasibility, the team should identify the assumptions most likely to affect its validation strategy:

• What performance must the device demonstrate, and how will minimum acceptable performance be justified?
• Which populations, configurations, operating conditions, and use environments must the evaluation represent?
• What sampling approach will support the conclusions the manufacturer intends to draw?
• How will verification and validation collectively support the intended use and product claims?
• Which use-related risks and critical tasks need to be addressed through human factors validation?

These questions help define the FDA engagement plan. They do not mean every protocol must be complete during feasibility. They mean the team should know which questions require feedback, when the supporting proposal will be ready, and which development commitments depend on the answer.

Once design inputs and validation plans incorporate an unsupported assumption, a change to that assumption can affect requirements, risk analyses, protocols, sample selection, and work already performed.

Give performance validation and human factors their own attention

For devices incorporating machine learning, Zaliance treats early discussion of the performance-evaluation strategy as an essential planning step. Dataset composition, independence of evaluation data, reference methods, subgroup coverage, and acceptance criteria can materially affect what a study demonstrates. Those decisions deserve attention before the team commits to definitive validation.

Human factors planning warrants similar consideration when critical tasks are involved. Zaliance recommends seeking feedback on the proposed validation approach before conducting the study, with questions addressing the intended users, use environments, critical tasks, and how the study will evaluate them.

These are development recommendations grounded in the consequences of getting the evidence strategy wrong. A protocol can be executed exactly as written and still fail to address the question the submission needs to answer.

Plan a sequence of interactions

A first submission may require more than one Pre-Submission. Performance validation, clinical evidence, and human factors can mature at different points in development. Their questions may also depend on one another.

FDA identifies challenges with reviewing related Q-Submissions simultaneously when feedback on one could influence another. Its guidance supports prioritizing topics and using subsequent interactions as the program develops. [2]

The schedule should reflect those dependencies. Questions about population or intended use may need resolution before the team finalizes sampling and acceptance criteria. Human factors questions may require a sufficiently developed interface and use-related risk analysis.

Submitting several requests together does not necessarily compress the work if their underlying assumptions remain unsettled.

Account for the feedback cycle

FDA’s guidance provides for written feedback within 70 calendar days of the review-clock start, with meetings typically around days 70–75. Preparation, follow-up, and implementation of resulting changes add project time beyond that interval. [3]

Development rarely has the luxury of waiting without consequence. The plan should identify work that can proceed while feedback is pending and commitments that should wait.

For example, engineering characterization and protocol development may continue while a question about definitive validation remains open. Beginning the definitive study before that question is resolved creates a different exposure: the team may have to repeat work if the feedback changes its approach.

The purpose of early planning is to make those decisions explicit.

A late Pre-Submission can still help—but at a cost

In one Zaliance engagement, a manufacturer had already prepared its 510(k) when it sought assistance with a Pre-Submission. The team believed FDA could review the completed results and provide reassurance that the submission was ready.

Zaliance clarified the purpose of the process. The manufacturer understood that it could proceed directly with its 510(k), but chose to seek feedback on the validation protocols and sampling rationale before filing.

The questions were intentionally framed around whether those approaches would provide appropriate evidence for the planned submission.

FDA’s feedback exposed weaknesses in the sampling rationale. Addressing these flaws delayed the initial submission by nine months. An additional three months of interactive FDA review followed before final clearance—ultimately pushing the commercial launch a full year past the manufacturer’s original target.

The late interaction was valuable. It identified a problem that needed attention. The missed opportunity was to obtain that feedback while the validation strategy was still being developed.

Make feedback part of the development plan

The most useful time to consider a Pre-Submission is while the team can still act on the answer without undoing substantial work.

For each planned interaction, identify the question, supporting proposal, decision owner, expected timing, and development activities that depend on the response. After receiving feedback, carry its conditions into the affected requirements, protocols, and evidence plans.

A well-planned Pre-Submission helps a manufacturer understand what its evidence needs to address. Its greatest value comes when that understanding arrives early enough to guide the work.

References

[1] FDA. Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program. Final guidance, May 29, 2025. Section II.A: Pre-Submissions; Section III.B(4)(a): questions and feedback.

[2] FDA. Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program. Final guidance, May 29, 2025. Section III: Q-Submission Program, printed p. 11 (PDF p. 14).

[3] FDA. Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program. Final guidance, May 29, 2025. Table 1 and Section III.B(4)(a): review process and timelines.