Marty Makary just passed his second anniversary as FDA Commissioner, and he is using the moment to make demands of Congress. Some of those demands are reasonable. Some are overdue. A few are alarming. All of them will, sooner or later, walk into a Florida exam room.
If physicians want any say in how this rewrite of American drug regulation actually plays out, the time to engage is now — before the legislative cement dries.
The News, in Plain Terms
Two years into the job, Makary is asking Congress for three big things, and pushing several more administratively from inside the agency.
A new approval pathway for individualized therapies. On February 23, the FDA issued draft guidance on what it is calling the Plausible Mechanism Pathway — a framework that would allow approval of bespoke gene-editing and other ultra-personalized treatments based on a credible biological rationale and data from a handful of patients, rather than the traditional two adequate and well-controlled trials. The draft launched with HHS leadership, Makary, and members of Congress on stage together at a Rare Disease Week event. That kind of joint rollout is rare; it was a signal that the administration wants this codified faster than draft guidance usually moves.
A permanent rare disease priority review voucher program. The FDA’s FY2027 budget request asks Congress to permanently authorize rare disease vouchers (the program that lets sponsors who develop a treatment for a rare pediatric condition earn a transferable voucher for expedited review of a future drug). The current authority has been allowed to lapse and revive on a short leash for years. Makary wants it nailed down.
Lower PDUFA user fees, in exchange for reform. During the July 2025 PDUFA reauthorization kickoff, Makary openly told industry he would like to see lower user fees so that “small companies, individual investors, and people in academics” can afford to play. PDUFA expires in September 2027, and the negotiations now underway will set the FDA’s funding base — and its independence — for the next five years.
Alongside the formal asks, Makary has already moved on his own: a Commissioner’s National Priority Voucher program tying expedited review to national health priorities, an explicit willingness to approve standard drugs on a single pivotal trial in many circumstances, and a steady stream of guidance documents intended to shrink time-to-market.
In the same window, the FDA’s chief of biologics, Vinay Prasad, was pushed out in late March amid an internal fight over how aggressively to deregulate. Senator Bill Cassidy, who chairs the Senate HELP Committee, released a white paper titled Patients and Families First: Building the FDA of the Future that more or less lays out Congress’s terms for any deal. None of this is happening in a vacuum.
Why This Matters for Florida Physicians
Florida is not a bystander in any of this. We are the third-largest state, the second-oldest by median age, and one of the largest medical-tourism markets in the country. We have University of Florida, Mayo Clinic Jacksonville, Nicklaus Children’s, Moffitt, Cleveland Clinic Florida, and the Max Planck Florida Institute all running serious rare disease and translational programs. Whatever pathway the FDA settles on for individualized therapies, Florida is going to be one of the first places where it gets used in actual practice.
Three things are about to change for the physician at the bedside.
First, the meaning of “FDA approved” is going to shift, and our patients won’t necessarily know it. A drug approved through the Plausible Mechanism Pathway based on n-of-6 data is not the same product, epistemically, as a drug approved on two large randomized trials. Both will carry the same label. The clinical conversation — how confident am I that this works, and how confident am I that it won’t hurt you? — is going to require us to read the basis-of-approval section more carefully than we ever have. The number of physicians who currently do that is, charitably, small.
Second, payer and pharmacy benefit decisions are going to lag the science. Florida Medicaid, the state’s commercial plans, and the major PBMs are going to take time to write coverage policies for the new flood of accelerated and individualized approvals. Expect prior authorization denials to spike. Expect appeals. Expect patients with rare neurological, oncologic, and metabolic conditions to land in our offices asking why the drug their geneticist promised them is not actually available. We will be the ones explaining the gap between an approval pathway in Washington and a covered benefit in Tallahassee.
Third, post-market surveillance is going to stop being optional. If the FDA is going to approve more drugs on less evidence, the only thing standing between the patient and an unrecognized harm is what happens after the drug reaches the pharmacy. That means MedWatch reports, registry participation, REMS compliance, and the kind of documentation discipline that most of us treat as a regulatory annoyance. Under the Makary framework, that documentation is the safety net. There isn’t another one.
What’s Right About This — and What Should Worry Us
Let me be direct about both sides, because physicians are not served by reflexive opposition any more than by reflexive cheerleading.
The case for what Makary is doing is real. The traditional two-trial, large-N pathway was never going to deliver therapies for ultra-rare conditions where you cannot enroll a thousand patients because there are not a thousand patients. The kids with Charcot-Marie-Tooth subtypes, the families with Batten disease, the patients with single-gene metabolic disorders we can now diagnose with a $300 panel — they have no good options under the old system. Lowering PDUFA user fees to reopen the door for academic and small-developer applications is also a defensible move, especially if it cuts the FDA’s financial dependence on a handful of large sponsors.
The case for caution is also real. A single pivotal trial means a single chance to detect a signal. A “plausible mechanism” approval for an n-of-six therapy means we are accepting a much higher prior probability of being wrong, and trusting post-market surveillance systems that have historically been underfunded and inconsistent. When a Commissioner’s Voucher links approval to “national priorities,” physicians have a legitimate question about who decides what those priorities are, and what happens to a worthy drug that does not fit the political moment. The Prasad ouster suggests that the internal disagreements at FDA right now are not gentle.
This is exactly the kind of policy moment where the loudest voices in the room are sponsors, patient advocacy groups (often funded by sponsors), and members of Congress with constituents who are dying. The voice that is usually missing is the one that has to actually prescribe the drug, monitor the patient, and absorb the risk if something goes wrong. That is us.
What Florida Physicians Should Do Now
- Read the Plausible Mechanism Framework draft guidance and submit comments. The comment window is the only formal channel where individual physicians can put dissent or support on the record. The Federal Register listing for the draft guidance is open. Even a one-page comment from a practicing Florida specialist carries weight in a docket that is otherwise dominated by industry submissions.
- Contact your county medical society and the FMA. The Florida Medical Association needs to be at the table on PDUFA reauthorization with a clear position on what physicians want in exchange for any user fee reduction — better post-market surveillance funding, mandatory long-term outcome registries for accelerated approvals, real authority to require label updates when post-market data goes the wrong way. Push them. They will respond to physician pressure.
- Brief your office staff on the coming prior authorization wave. When the first Plausible Mechanism approvals hit the market, your prior auth team is going to be overwhelmed. Decide now how you will document medical necessity for therapies whose underlying evidence is a mechanistic argument and a small case series. Build the appeal templates before you need them.
- Talk to your state legislators about Florida Medicaid coverage policy. The Agency for Health Care Administration sets coverage rules for Medicaid recipients in Florida. Once accelerated approvals start arriving, AHCA will be making decisions about whether the state pays for them. Physicians who treat Medicaid patients should make sure those decisions are informed by clinical reality, not just budget pressure.
- Engage with your senators on PDUFA reauthorization. Senator Rick Scott sits in a position to be heard on FDA reform. Senator Ashley Moody is new to the job and looking for issues where physician input matters. Both are reachable. The question to put to them is simple: if user fees are reduced, where does the lost revenue come from, and how will safety monitoring be protected?
- Pay attention to the Commissioner’s Voucher program in real time. Track which drugs receive a CNPV, and ask why. If the criteria for “national priority” begin to look more political than clinical, organized medicine should be the first profession to say so out loud.
The Bigger Picture
Drug regulation is one of the few places in American medicine where the rules are written far enough away from the bedside that physicians have stopped showing up for the fight. The result is that the rules end up being written by people who do not have to face the patient on the other side of them. Makary’s reform agenda is not, by itself, the problem. The problem is what happens when an entire reform agenda gets negotiated between an administration that wants speed, an industry that wants profit, and a Congress that wants stories of cures — with the doctors who will actually prescribe, monitor, and explain these drugs not in the room.
We can be in the room. The Federal Register comment system is free. The FMA exists for this reason. Senators answer constituent mail from physicians at a higher rate than they do from almost anyone else. The Plausible Mechanism Pathway, the Commissioner’s Voucher, and the next PDUFA are going to be written one way or another. The only question is whether organized medicine helps write them, or whether we wait until they arrive in our exam rooms and then complain.
I would rather we write them.
Frequently Asked Questions
What is the FDA’s new Plausible Mechanism Pathway?
The Plausible Mechanism Pathway is a draft framework released by the FDA on February 23, 2026 that would allow approval of individualized and ultra-rare disease therapies — particularly bespoke gene-editing treatments — based on a credible biological mechanism and data from a small number of patients, rather than the traditional standard of two adequate and well-controlled clinical trials. It is intended for conditions where conventional trial designs are not feasible.
How will FDA reform affect Florida physicians and their patients?
Florida physicians should expect more accelerated and individualized approvals reaching the market over the next 18 to 24 months, a corresponding lag in payer coverage decisions from Florida Medicaid and commercial plans, and a heavier burden on post-market surveillance. Prior authorization denials and appeals for newly approved rare disease therapies are likely to increase significantly.
What is the Commissioner’s National Priority Voucher program?
The Commissioner’s National Priority Voucher (CNPV) is a Makary-era program that grants expedited FDA review to drugs and biologics deemed aligned with U.S. national health priorities. Critics have raised concerns about how those priorities are defined and whether the program risks politicizing approval decisions. Florida physicians should monitor which products receive a CNPV and ask whether the criteria are clinically defensible.
Why does PDUFA reauthorization matter for Florida doctors?
The Prescription Drug User Fee Act (PDUFA) is the law that funds most of FDA’s drug review activities through fees paid by pharmaceutical sponsors. It must be reauthorized by Congress before September 2027. Commissioner Makary has signaled he wants user fees reduced. The terms of that deal will determine how independent FDA is from industry and how well it can fund post-market safety monitoring — which is exactly the system Florida physicians will rely on as more drugs are approved on smaller datasets.
How can a Florida physician submit comments to the FDA on the new pathway?
Draft FDA guidance documents are published in the Federal Register and accept public comment through regulations.gov. Physicians can search for the Plausible Mechanism Framework docket and submit a written comment under their professional credentials. Even brief, well-reasoned submissions from practicing clinicians are read and counted as part of the official record.