Design the Pre-Sub Plan for the Letter You Hope You Do Not Need

The FDA and the medical device industry reached an agreement in principle on MDUFA VI at MedCon on March 18, the user-fee framework that will govern device submissions from fiscal 2027 through 2032, with the commitment letter now being drafted for Congressional submission by January 15, 2027, per MedTech Dive and RAPS. Inside the agreement is a structural change to how a De Novo submission can land. A new “not grantable” decision option will give an applicant a second pass before the agency issues a formal decline letter, structurally identical to the “not approvable” mechanism that already exists for PMA applicants. Pre-sub fees are being raised, with the fee functioning as a credit toward a future marketing submission, and Breakthrough and STeP-designated devices are exempted. TAP 2.0 is launching, and seven priority expansion areas are codified, including real-world evidence, consensus standards, global alignment, digital infrastructure, digital health, and patient science. For founders who finish hardware companies through an FDA pathway, the operational read is that the structure of a submission has just acquired a new shape, and the pre-submission plan has to be written for that shape rather than for the binary clearance-or-decline outcome that dominated the last five years of De Novo strategy.

If You Are Building a Company in This Environment

The default first-time hardware founder pursuing US clearance treats the pre-submission program as a series of meetings whose purpose is to confirm that the planned submission will land cleanly. The pre-sub strategy is sized to make the De Novo or 510(k) feel as close to pre-approved as possible by the time the package leaves the building. The capital plan is sized to the assumption that the submission lands grant-able on the first pass. The hiring plan is sized to the assumption that commercial launch begins inside the planned clearance window. The trouble with that posture in 2026 is that it never accounted for the real distribution of outcomes the De Novo program produces, which has always included a meaningful share of declined or repositioned submissions that forced the company into a fundraising round it did not plan for. MDUFA VI does not change the underlying distribution, but it does introduce a new mid-path option in the form of the “not grantable” letter. The companies that finish through the new structure will be the ones whose founders treated the “not grantable” outcome as a designed-for state, not as a surprise.

Designing for the letter means writing the pre-submission program so that every meeting produces an artifact the company can use in a second pass. It means structuring the capital plan with a contingency tranche sized to the six to nine months a “not grantable” pass would consume, instead of selling the next round on the assumption that the clearance milestone arrives on the first attempt. It means structuring the leadership team so that the regulatory function and the product function are coordinating against the same architecture document, rather than waiting until after a letter lands to figure out what the response should look like. The founder who finishes a regulated hardware company in this environment is the one who arrives at the agency’s decision point already holding the second-pass plan as a fully formed instrument. The founder who treats the second pass as the failure case is the one whose capital plan runs out before the letter can be answered, regardless of the technical merits of the response.

The same operating logic applies across diagnostics, IVD, combination products, and any other regulated hardware category whose primary review center is CDRH or shares infrastructure with it. The mechanics of the agreement matter because the cost of misreading them is the cost of an unscheduled equity round, which in the current capital environment is more expensive than the cost of any single regulatory submission. Founders Who Finish exists for exactly this kind of decision, where the right answer is to design for an outcome the engineering plan would rather not contemplate, and where the founder is the only person on the team whose job is to make that design choice early enough that the company can survive it.

What MDUFA VI Surfaces as a Case Study

MDUFA VI is useful as a case study because each of its operational changes maps to a different design decision a finished hardware company has to get right. The De Novo “not grantable” letter fixes the binary-outcome problem in the regulatory plan. The pre-sub fee-as-credit structure fixes the meeting-count problem in the pre-submission program. The Breakthrough and STeP exemption from pre-sub fees fixes the front-loading question on designation strategy. TAP 2.0 and the seven priority expansion areas fix the lifecycle question, surfacing real-world evidence and digital infrastructure as formal dialogue channels rather than as activities a company has to invent its own framework for. The FY2028 fee changes and the foreign-domestic establishment split fix the cost-line question, restructuring the basic math of where the company manufactures and how that decision interacts with the capital plan. None of these are surprises. Each of them was negotiated in the field for years before being codified in MDUFA VI. The founders who finish are the ones who read the codification as a binding signal about how the agency is going to behave for the next five years and build the company against that signal, not against the version of the FDA that existed three submission cycles ago.

The Five Questions for an FDA-Gated Hardware Company

The five-question framework in Founders Who Finish applies directly to the MDUFA VI environment. Each question maps to a regulatory-program design decision a founder has to settle before the submission strategy locks in.