The Resignation
On May 12, 2026, around 5pm Eastern, Endpoints News reported that FDA Commissioner Marty Makary was preparing to resign. The job had been in limbo for several days. The announcement followed the same afternoon. By May 13, the post-hoc pieces had been written: Drew Armstrong at Endpoints wrote that Makary never had a chance, caught between MAHA, RFK Jr., and the Trump administration.
The political analysis is not the part of this story that matters to a regulatory writing team. The part that matters is: the agency now has another senior leadership vacancy, on top of the ongoing CBER director search we wrote about last week. Every sponsor with an active submission, a planned briefing-book commitment, or a pending Type B / Type C meeting needs to read the next 90 days differently than they planned to.
What Changes During an Interim
Three things change predictably when an FDA Commissioner seat opens up.
New guidance pauses. Draft guidance documents that were in the pipeline stay in draft. Final guidance documents that were close to publication often slip a quarter or two. The agency is unusually careful during transitions about pushing out new substantive positions, because they can be reversed by the next confirmed leader. For sponsors that were waiting on a guidance update to clarify a regulatory question, the planning assumption needs to flip: existing guidance is the operative reference for at least the next two quarters.
Decisions on novel matters get more careful. Decisions that require precedent-setting interpretation — particularly for first-in-class modalities or for pilot programs that depend on commissioner-level discretion — slow down. Career staff continue to make routine decisions on routine matters. Novel matters tend to wait for clearer political authority.
Pilot programs and commissioner-discretion mechanisms come under review. The Commissioner's National Priority Voucher pilot is the clearest example here. We just landed the seventh CNPV approval on May 8, and a public hearing on the pilot is scheduled for June 4. Whether that hearing proceeds as planned, and whether the pilot continues in its current form, depends on decisions the next leadership will have to make. Sponsors with active CNPV considerations need to plan for both continuation and discontinuation as live scenarios.
What does not change is the day-to-day review work. Reviewers continue to review. Filing reviews proceed on schedule. Information Requests still get sent. The submission you put in last quarter is still being read at the same pace it would have been.
The 90-Day Re-Plan
Sponsors with active submissions should do five concrete things in the next two weeks.
Pull the current Gantt and identify every dependency on a forthcoming guidance, FDA decision, or pilot program. Each of these is now a higher-risk node than it was three weeks ago. Document the alternative path that does not depend on the forthcoming item.
Update Type B / Type C meeting briefing documents to lean harder on existing guidance and precedent. In interim periods, the reviewer's ability to escalate ambiguous questions is constrained. Briefing documents that anticipate and address the questions in writing, with explicit reference to current guidance, do disproportionate work.
Front-load engagement on novel-matter submissions. If your submission requires a precedent-setting interpretation, request the meeting now rather than later. The career staff handling the meeting are stable. The escalation path is what's uncertain.
Calibrate timelines on commissioner-discretion pathways. CNPV considerations, accelerated approval consultations, breakthrough therapy designations — anything where commissioner-level authority enters the chain — needs a two-track plan: one that assumes the program continues, one that assumes it is paused.
Identify the next two informational triggers that will sharpen the picture. In 2026, those are: the next confirmed Commissioner's name and the June 4 CNPV public hearing outcome. Plan for both decisions to happen on a 60-90 day window from now.
What Stays Operative
Existing FDA guidance is the operative reference for the entire next 6-12 months at minimum. Guidance documents do not get withdrawn during transitions, with rare exceptions. Existing pilot program approvals stand. Existing meeting decisions stand. Existing review timelines hold.
The discipline this requires is to treat the existing guidance corpus as the foundation of submission strategy, not as a transient state to be replaced. Teams that built their submission narratives against "the new guidance we expect next quarter" need to rewrite those narratives against the guidance that already exists.
This is unfashionable advice in fast-moving organisations. The temptation in transitional periods is to wait for the new picture to emerge. The teams that come out of these windows in the strongest shape are the ones that operate on what is currently published, file on schedule, and adjust when the new picture actually arrives.
The Larger Pattern
The CBER director search has been open for months. The Commissioner seat is now also vacant. Other senior FDA roles — including the search narrowing for a CBER leader — are likely to be on hold pending broader political decisions about agency leadership.
Sponsors who treat 2026 as a year in which agency leadership is a constant will be repeatedly surprised. Sponsors who treat 2026 as a year in which leadership is in transition, and who plan their submission strategies accordingly, will run cleaner cycles.
The work itself does not change. The plan around the work has to.