On May 12, 2026, FDA Commissioner Marty Makary resigned, and Kyle Diamantas, formerly the agency’s Deputy Commissioner for Food, assumed the role of Acting Commissioner. Three days later, on May 15, Tracy Beth Høeg, M.D., Ph.D. — who had served as acting CDER director since her appointment on December 3, 2025 — was fired. Concurrently, Katherine Szarama transitioned out of the acting CBER director role, replaced by Karim Mikhail. The result: within a single business week, the three highest-ranking positions governing drug and biologics review at FDA turned over simultaneously.
This sequence is operationally significant in ways the public announcements do not address. CDER and CBER are the two centers that own the authority to issue complete response letters, grant accelerated approvals, accept or refuse-to-file NDAs and BLAs, and convene advisory committees. Acting directors carry that authority during transitions — but the legitimacy of interim decisions, the continuity of pre-submission meeting commitments, and the chain of signatory authority for pending actions all depend on clear, documented succession. At the moment of writing, FDA has not published a named acting CDER director to replace Høeg.
What the Succession Gap Actually Means
Under 21 CFR § 5.10, the FDA Commissioner may delegate authority to center directors, and those delegations typically flow through formal designation letters that name the acting official. When an acting director is removed and no successor is publicly designated, sponsors with Type A, B, or C meeting requests in the CDER queue face a practical ambiguity: the official whose name appears on any forthcoming meeting minutes or decision letters may lack a clear, publicly documented delegation chain. That ambiguity rarely invalidates a regulatory action, but it creates grounds for procedural challenge during any subsequent dispute — a risk that is non-trivial for sponsors at the NDA or BLA submission stage.
Høeg’s tenure lasted approximately six months. During that period, CDER managed a substantial active IND portfolio, and the center continued operating against PDUFA VI performance goals. The volume of pending first-cycle reviews did not pause for the leadership change. What changes with acting-director turnover is not the staff reviewer’s work — that continues under division directors — but the center-level decisions that require a director’s signature: major dispute resolutions, clinical holds with novel legal interpretation, and accelerated approval withdrawal proceedings initiated under the 2022 FDORA amendments.
Katherine Szarama’s departure from CBER, and her replacement by Karim Mikhail, carries a parallel concern for sponsors in the cell and gene therapy space, where CBER’s Office of Therapeutic Products has been issuing draft guidances on manufacturing comparability and potency testing at an accelerated pace through early 2026. Mikhail inherits those open comment periods and any pending BLA actions without a publicly documented transition brief — at least none yet available in the Federal Register.
The Pattern Behind the Personnel
Makary’s resignation on May 12 followed a tenure of just over thirteen months — he was confirmed by the Senate on March 25, 2025, and sworn in on April 1, 2025. His departure, combined with the Høeg firing and the Szarama transition, represents a compression of leadership turnover that is structurally unusual even by the standards of administration transitions. For context, Janet Woodcock served as CDER director continuously from October 1, 2007, through April 12, 2021 — a fourteen-year tenure that provided review divisions with stable policy interpretation across multiple administrations.
The current situation differs in kind, not just degree. When a commissioner departs and both major center heads turn over within the same week, the question of policy continuity becomes concrete: which pre-decisional commitments made in Type B meetings under Høeg’s tenure will the next acting CDER director honor? FDA’s own guidance on formal meetings (Formal Meetings Between FDA and Sponsors or Applicants of PDUFA Products, revised 2017) states that meeting minutes are binding on the agency. But the interpretation of those minutes — particularly where the minutes reflect the prior director’s stated flexibility on an endpoint or a manufacturing standard — is an area where new leadership can, and sometimes does, revisit the framing without formally rescinding the commitment.
Acting Commissioner Diamantas, who comes from the food regulatory side of FDA rather than the drug review apparatus, assumed authority on May 12. His prior portfolio did not include PDUFA-governed review centers. That matters because the acting commissioner’s office serves as the final escalation point for major dispute resolutions under 21 CFR § 312.48 and for any accelerated approval withdrawal proceedings that require commissioner-level sign-off. Sponsors with disputes already in the escalation pipeline need to assess whether their procedural clock is still running and who, precisely, has authority to issue a final agency decision.
The Strategic Directive for Sponsors
Sponsors with NDAs or BLAs currently under first-cycle review at CDER should, this quarter, formally document the names of the reviewing division directors and office directors assigned to their application — these are the officials whose authority is least disrupted by center-director turnover. Pre-submission meetings already granted should be confirmed in writing with the assigned project manager, with explicit reference to the meeting minutes date and the specific commitments recorded. Any sponsor whose Type B or Type C meeting produced a written agreement on primary endpoint adequacy, sample size justification, or accelerated approval pathway eligibility should re-confirm that the agreement is reflected in the IND file and request an updated FDA acknowledgment if the original written response predates December 3, 2025 — Høeg’s appointment date.
For CBER-regulated sponsors in the cell and gene therapy space, the same logic applies with added urgency: Mikhail’s assumption of the acting director role means any open comments on draft manufacturing guidances, including potency assay frameworks issued in Q1 2026, should be submitted before comment periods close, since new leadership may elect to finalize guidance on an accelerated or modified timeline.
Investors tracking approval-risk should note that FDA’s PDUFA action dates are legally binding performance targets, not discretionary timelines. Staff-level reviews continue regardless of who holds the acting director title. The risk is concentrated not in approval delays per se, but in the small subset of applications requiring center-director involvement — those involving major efficacy disputes, novel regulatory pathway determinations, or post-market commitment renegotiations under FDORA. Those are the files worth stress-testing against the current succession gap.
The next indicator to monitor: whether FDA publishes a formal announcement naming an acting CDER director in the Federal Register, and whether that announcement includes an explicit delegation-of-authority notice under 21 CFR § 5.10. The absence of such a notice within the next 30 days would extend the ambiguity period into the summer review cycle — a period when several high-profile PDUFA dates are expected to fall.
References
- FiercePharma — “After Makary departure, acting CDER chief Høeg and CBER’s Szarama exit top FDA posts”
- FDA Press Announcement — “FDA Announces Leadership Appointments at Center for Drug Evaluation and Research,” December 3, 2025
- FDA — Martin Makary Commissioner Biography and Departure Record
- HCPLive — “FDA Commissioner Marty Makary Resigns; Kyle Diamantas Steps In as Acting Head,” May 12, 2026
- BioPharma Dive — “Makary Resigns as FDA Commissioner,” May 2026
- FirstWord Pharma — “Katherine Szarama Shifts from Acting CBER Director to New Role Within FDA,” May 2026
- BLA Regulatory — “FDA CDER IND Activity 2024–25”
- Wikipedia — Janet Woodcock, CDER Director tenure October 1, 2007 – April 12, 2021
Moe Alsumidaie, MBA, MSF, is founder and Chief Editor of Vanguard Publications, which publishes Clinical Trial Vanguard, Pharma Vanguard and BullScope, and Head of Research at CliniBiz. He has two decades in clinical trial operations and data science, with earlier roles at Genentech, Abbott Vascular and Stanford University Medical Center, and is a guest lecturer in clinical trial sciences at Rutgers University.
