What Happens When the Rules Change Mid-Game
A pharmaceutical company spent years and over a billion dollars developing a new flu vaccine, consulted extensively with federal regulators about how to test it, got the green light, ran the trial — and then watched the agency refuse even to look at the results. That is not a regulatory disagreement. That is a breakdown in the basic compact between government and the companies it oversees.
Sarah Longwell, Tim Miller, and Bill Kristol open with a detail that should unsettle anyone who expects public health agencies to operate predictably: Moderna publicly announced the bad news itself, a move so unusual for a drugmaker that it signals how far outside normal bounds this decision falls.
"This is not the type of development you would normally expect a pharmaceutical company to broadcast."
The company's mRNA flu vaccine — leveraging the same messenger RNA technology that produced COVID vaccines at unprecedented speed — had cleared every hurdle the Food and Drug Administration set for it. Regulators told Moderna the trial design was "acceptable." The company enrolled more than 40,000 participants across eleven countries. It submitted the application in good faith. Then came the "refuse to file" letter: not a rejection of the vaccine, but a refusal to even consider it.
The authors quote Michael Osterholm, director of the University of Minnesota's Center for Infectious Disease Research and Policy, who frames the institutional damage plainly:
"Even if a product didn't work, ultimately — even if it wasn't shown to be effective — there was at least a well-defined process to get to that endpoint. What you saw this past week was the FDA completely turning that process on its head."
The Decision Came From Above
Career FDA staff — the scientists who worked most closely with Moderna — apparently believed the review should proceed. The refusal originated with Vinay Prasad, a physician-researcher appointed to lead the vaccines division by Robert F. Kennedy Jr., who now oversees the Department of Health and Human Services. A division director overruling career staff on a decision of this scale is, by historical standards, extraordinary.
"For FDA to change a decision at this late stage, the rules should be similar to instant replay in football — you need new evidence and a compelling explanation to overturn the call on the field. I don't see how that's the case here."
That assessment comes from Joshua Sharfstein, a former FDA deputy director known as an industry critic — which makes his criticism of the agency's conduct all the more telling.
The administration's defense — that Moderna "refused to follow very clear FDA guidance" by not testing against a higher-dose senior vaccine — contradicts the agency's own 2024 statement that the trial design was acceptable. And the logic of the demand itself is flawed: a new vaccine does not need to outperform every existing alternative to merit approval. Multiple options in the market matter. They protect against supply shocks — a real concern when avian flu is decimating poultry flocks that provide the eggs used to manufacture traditional flu shots. They offer alternatives for patients with allergies. They create competition that improves quality over time.
"Moderna appears to have been set up — like they were given a set of expectations, and now the rug has been pulled out from under them."
The Ripple Effect
The flu vaccine market is one thing. The chilling effect on future research is something else entirely.
Seasonal influenza kills tens of thousands — possibly over 100,000 — Americans each year. An mRNA flu vaccine could be designed later in the season, closer to actual virus circulation, improving strain matching. It avoids the egg-based mutation problem. The advantages are real. But if companies cannot trust that regulators will honor their own guidance, the billion-dollar investments required for vaccine development become gambles rather than calculations.
"Developing something that is an effective treatment for a disease is a long-term process and a long-term investment. And so companies — if they don't have certainty about what kinds of expectations FDA is going to have, or what FDA's views on the science are — that long-term investment in innovation is difficult to do."
That uncertainty is already producing visible damage. Moderna has paused research into mRNA treatments for other conditions. The authors note that early studies suggest messenger RNA vaccines could prove effective against certain cancers — an area of enormous therapeutic promise now shadowed by regulatory unpredictability.
Adam Lauring, an infectious disease physician at the University of Michigan, captures the scope of the risk:
"If this is going to happen — and if it's going to happen again and again — it can really cast a pall over the field, and the ability to develop new approaches and new technologies to be delivered to people with not just infections, but a variety of diseases."
There is also the pandemic-preparedness angle. mRNA vaccines can be manufactured at scale within weeks of identifying a pathogen. If a novel flu strain began transmitting between humans, that speed would be invaluable. But building that capacity requires sustained investment, and investment requires trust in the regulatory process.
"It's kind of naïve to think that there's never been any sort of political interference with the FDA decisions over many years, but there's never been anything like this."
Counterpoints
Critics might note that the FDA's core mandate is protecting public safety, not encouraging industry investment — and that requiring comparison against the best existing senior vaccine, rather than a standard-dose alternative, is a scientifically defensible position for a population with weakened immune systems. The authors also do not engage with whether the original FDA guidance may have been insufficiently specific, leaving room for legitimate reinterpretation as the data matured. And there is the broader question of whether regulators should weigh the opportunity cost of approving a marginally-different vaccine when resources — clinical trial participants, manufacturing capacity, public attention — are finite.
None of those arguments, however, explain why the refusal came from a political appointee over the objections of career staff, or why the FDA could not have approved the vaccine for adults aged 50 to 65 while deferring the over-65 question pending further study. That option existed. It was not taken.
"The idea that approval of a vaccine might depend — even a little bit — on whether the manufacturer says 'pretty please' speaks volumes about what role scientific judgment is now playing in the approval process."
Bottom Line
A regulatory agency that changes its standards after the fact — and refuses to explain why — does not just lose one company's trust. It damages the incentive structure for every firm considering whether to invest years and hundreds of millions of dollars into the next vaccine, the next treatment, the next pandemic defense. The cost of this decision will be measured not in dollars but in the therapies that never get developed because the rules of the game proved unreliable.