MDUFA VI Just Reset the De Novo and Pre-Sub Mechanics

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 formal commitment letter now being drafted for Congressional submission by January 15, 2027, per MedTech Dive and RAPS coverage. The operational details that surfaced through the MedCon panel and the subsequent regulatory press matter more to a founder running a De Novo or PMA submission than the fee numbers do. A new PreSTAR template and 30-day walkthrough are coming to the De Novo program, alongside a “not grantable” decision option that gives an applicant a second pass before a decline letter, mirroring the “not approvable” structure that already exists for PMA. Pre-submission 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 as the next version of the Total Product Life Cycle Advisory Program. Seven priority expansion areas are codified in writing for the first time, including real-world evidence, consensus standards, global alignment, digital infrastructure, digital health, and patient science. Most firms will see lower fees in fiscal 2028 as the statutory structure shifts, with submission fees and domestic registration fees coming down and an “America-First” split applied to establishment fees between foreign and domestic manufacturers. None of this is the headline a founder reads on launch day. All of it is the structural ground the company is going to run on for the next five years.

The De Novo “Not Grantable” Letter Is the Single Biggest Founder-Level Change

The De Novo program has historically operated as a binary clearance gate. The agency either granted the request and let the company move into commercial launch, or it declined the request and the company was forced into a Type C meeting cycle, a resubmission, or a pivot to a different pathway entirely. MDUFA VI introduces a third option. A “not grantable” letter will allow the applicant another pass at the submission before the agency issues a formal decline, structurally identical to the “not approvable” letter that already exists for PMA applicants and that has functioned, in practice, as a survival mechanism for companies that would otherwise run out of capital before they could reposition. The PreSTAR template and the new 30-day walkthrough are designed to front-load the conversation, so the company arrives at the substantive review with the agency’s view on the package already understood. For a first-time hard-tech founder whose entire capital plan is sized to the De Novo timeline, the existence of the “not grantable” letter as a real option changes how the pre-submission strategy gets written. The pre-sub program is no longer the place where the company tries to prove it does not need a second pass. It is the place where the company designs the architecture of the second pass in advance, so that if it is needed, the additional six to nine months it buys do not come with a forced equity raise at a punitive mark.

Pre-Sub Fees Become Credits, With Breakthrough and STeP Exempted

The agency is increasing user fees on pre-submissions to promote what RAPS’s coverage described as “strategic and thoughtful utilization,” with the fees functioning as credits toward future marketing submissions. A focused 45-day follow-up timeline applies to certain pre-subs. Breakthrough Device and STeP-designated devices are exempt from the increased pre-sub fees. The structural effect is to penalize the historical pattern of running an inflated number of pre-sub interactions as a free informational fishing expedition, while preserving the program for companies that come in with focused, well-formed questions. For a founder, the operational read is that the pre-sub strategy now has to be designed against a cost-and-credit ledger, not just against a calendar. The Breakthrough and STeP exemption tells you which designation work is worth front-loading. A team that secures Breakthrough designation early not only buys the well-documented review-time and CMS-coverage benefits but also takes the pre-sub fee out of the equation entirely, which is a material cash-flow advantage during the lowest-revenue, highest-burn phase of the company.

TAP 2.0 and the Seven Priority Expansion Areas

The next version of the Total Product Life Cycle Advisory Program is being built into MDUFA VI as TAP 2.0, with FDA committing in writing to seven priority expansion areas the agency and industry have agreed will receive dedicated work over the five-year cycle. Real-world evidence is on the list, which signals that post-market data generation is being formalized as an input to ongoing regulatory decisions rather than treated as a separate research activity. Consensus standards and global alignment are on the list, which matters for any device founder whose commercial plan includes both US clearance and CE mark inside the same product cycle, because the cost of duplicate regulatory programs has been a structural drag on hard-tech companies trying to scale internationally. Digital infrastructure and digital health are on the list, which is the agency acknowledging that the device under review is increasingly inseparable from the software platform it ships inside. Patient science is on the list. The read for a founder is that the agency is publicly committing to working on the questions that have, for years, fallen between the cracks of formal submissions. A company that engages TAP 2.0 with a concrete real-world-evidence plan or a digital-health architecture question has a meaningfully better shot at productive agency dialogue than one that waits for a problem to crystallize inside a 510(k) or De Novo review.

Lower Fees in Fiscal 2028 and the Foreign-Domestic Split

Under the agreement in principle, total user fee funding stays largely flat between MDUFA V and MDUFA VI, but the statutory structure changes so that most firms will see lower submission and domestic registration fees in fiscal 2028, per MedTech Dive. The redistributive move is a split establishment fee, with overseas manufacturers paying a higher rate than domestic ones under what FDA is describing as an “America-First” approach. For a US-based hard-tech founder whose contract manufacturing is domestic, the FY2028 cost line gets easier. For a founder whose finished-device manufacturing is offshore, the same line gets harder, and the operating plan has to account for that. The number is not the issue. The issue is that the cost structure differential will start to show up in pitch deck comparables and in pricing-power assumptions, and any company whose next round will be marked off a comparable that is itself absorbing the new fee structure needs to have that math worked out before the term sheet conversation begins.

The Read-Across to Diagnostics, Combination Products, and Adjacent Regulated Hardware

MDUFA covers medical devices specifically, but the structural shifts inside it shape adjacent categories that share infrastructure with the device center. For a diagnostics founder running an IVD through 510(k) or De Novo, the “not grantable” option and the PreSTAR template are operational realities that need to be incorporated into the regulatory program plan. For a combination-product founder whose primary mode of action sits inside CDRH, the same is true, with the additional consideration that the cross-center review pathway has not been formally rewritten and will continue to require its own coordination plan. For a defense or climate hardware founder whose product has any medical or biological adjacency, like an autonomous medic system or an emergency-response wearable, the TAP 2.0 expansion areas around real-world evidence and digital infrastructure are the door the agency has just opened for early dialogue on a non-traditional product. The pattern is consistent with what RAPS framed as a “historic timeline” on the regulatory side, where the agency and industry are codifying in writing the structural changes that have been negotiated in the field for years. The founders who will read this cleanly are the ones who treat the commitment letter, when it lands publicly in the Federal Register between August and December, as a working document for the company’s regulatory program rather than as a policy update someone else will summarize for them later.