Is Rank Insubordination at the FDA Real?
The boorish treatment of Congress by the FDA includes dismissing legislation seeking to modernize the ailing agency
By Zaher Nahle, PhD MPA
When announcing his nominee for the commissioner of the Food and Drug Administration (FDA), President Donald Trump was point-blank in stating that the “FDA has lost the trust of Americans, and has lost sight of its primary goal as a regulator.” Trump went on to express great confidence in his choice, asserting that “The agency needs Dr. Marty Makary, a highly respected Johns Hopkins surgical oncologist and health policy expert to course-correct and refocus the agency.”
Many in the public are learning about the inefficiencies at the FDA for the first time from these presidential statements. And the question on everyone’s mind is arguably the following: why has the FDA deviated so much from its chartered course to be inviting such a poignant criticism from the president of the United States?
Makary’s impressive qualifications alongside his long stance as an outspoken reformist assure the public. But what the American people are disconcerted about is the predicament of their premier regulatory health agency, an agency with practically unlimited resources, an educated workforce and an annual budget exceeding $8 billion.
The confirmation hearing of the new Commissioner took place on Capitol Hill on March 6. Clearly, this occurred in a climate of drastic changes in policy across federal agencies, including measures implemented by DOGE. Sharp divisions concerning the best way forward for strengthening scientific and medical research are boiling over. Yet, regardless of one’s political leanings, a firm realization exists on both sides of the aisle that the FDA is in need of structural reforms.
The change in leadership is now an opportunity to transform the agency into the transparent and effective entity the American people desire. Since its inception in 1938, The FDA has been entrusted with the mission of ensuring the safety and efficacy of pharmaceutical drugs as well as the integrity of foods consumed in the U.S. and its territories. The agency is empowered with virtually unchallenged authority and reach.
But from the get-go, the agency also adopted a stock-still, animal-centric paradigm to evaluate, for instance, the toxicity of drugs developed for human use — a paradigm that the FDA has refused to evolve almost a century later. That is despite the emergence of advanced technologies that, across many applications, outperform animal testing in forecasting drug response in humans (e.g., organ-chips; tissue systems). Notably, most new-generation therapies (e.g., cell therapy, immunotherapy) are, by design, human-specific, and testing on animals is a fool’s errand in the first place.
According to the Clinical Development Success Rates report for 2011-2020 from the leading trade organization Biotechnology Innovation Organization (BIO), 92% of drugs fail in human trials, even though they passed preclinical animal tests. Urology drugs had the lowest success rate (only 4% are approved after entering clinical trials), followed by heart drugs (5%), cancer drugs (5%) and neurology drugs (6%). Failed oncology trials alone are estimated to cost $50-$60 billion annually.
The fundamental flaw at the agency is its refractory, dismissive attitude towards outside input or reforms, even those originating from its employer, the U.S. Congress. An example of that is the FDA’s perfunctory conduct towards the FDA Modernization Act 2.0 (FDAMA 2.0), a U.S Law since 2022.
FDAMA 2.0 amended outmoded regulatory statutes at the agency, broadening the options for drug developers to advance clinical investigations. In short, it enables sponsors seeking regulatory clearance for clinical trials to use New Approach Methodologies (NAMs) in lieu of animal data. NAMs, an umbrella term, refers to emerging technologies including Artificial Intelligence (AI), Organoids, Organ-Chip, 3D-bioprinting and other advanced human-relevant cell models (reviewed here).
FDAMA 2.0 amended outmoded regulatory statutes at the agency, broadening the options for drug developers to advance clinical investigations. In short, it enables sponsors seeking regulatory clearance for clinical trials to use New Approach Methodologies (NAMs) in lieu of animal data. NAMs, an umbrella term, refers to emerging technologies including Artificial Intelligence (AI), Organoids, Organ-Chip, 3D-bioprinting and other advanced human-relevant cell models (reviewed here).
Stakeholders expected that the FDA would rush to capitalize on the unprecedented support from lawmakers to modernize its processes, embrace 21st century applications and rid itself gradually of misleading animal testing. Instead, to this day, the published directives at the FDA continue to usurp U.S. laws by instructing drug sponsors — for example under its Drug Development and Review Definitions — to “determine acute toxicity of the [experimental] drug in at least two species of animals.”
Needless to say, such problematic guidance is causing regulatory confusion in the scientific and biotechnology communities, which remain unable to reconcile the conflict between the disparate FDA directives and the U.S. law on this critical issue. FDA failure to act has also precipitated a lack of confidence in the workings of federal institutions, including the U.S. Congress, whose legislations are being boorishly ignored by the agency.
Rendering a U.S. Law obsolete through intransigency is nothing short of rank insubordination at the FDA. The resistance to implementing FDAMA 2.0 by the agency is at least one reason for the incoming Commissioner to shake up the working of the FDA and set the agency on the path of accountability.
In 2023, a bipartisan group of Senators, led by Rand Paul, R-Ky., and Cory Booker, D-N.J., sent a letter to the FDA demanding an explanation for the stultification and an implementation timeline of the enacted law. But no progress materialized.
Not to be deterred, a forward-thinking group of senators guided the U.S. Senate to unanimously pass on December 12, 2024, the FDAMA 3.0, demanding that the FDA execute the indivisible implementation of FDAMA 2.0 within a defined timeframe. This bipartisan legislation was re-introduced in February 2025 (S.355) in the current 119th Congress by Senators Cory Booker (D-N.J.), Eric Schmitt (R-Mo.), Rand Paul (R-Ky.), Angus King (I-Maine), Sheldon Whitehouse (D-R.I.), John Kennedy (R-La.), Richard Blumenthal (D-Conn.), Ben Ray Luján (D-N.M.), and Roger Marshall (R-Kan.).
The need for decisive action from FDA leadership is underscored by the following statements from key Senate republicans and democrats upon the reintroduction of the FDA Modernization Act 3.0:
- “The FDA Modernization Act 3.0 builds on the critical reforms we achieved with FDA Modernization Act 2.0, ensuring that modern, humane, and scientifically advanced testing methods can finally replace outdated animal testing. For too long, bureaucratic inertia has delayed the implementation of these changes, which are vital to saving lives, reducing costs, and bringing life-saving treatments to patients more efficiently. This legislation sends a clear message: Americans deserve a regulatory system that embraces innovation, not one stuck in the past,” said Dr. Rand Paul.
- “It’s been over two years since Congress ended the statutory mandate that investigational new drugs (INDs) undergo mandatory animal testing before human clinical trials,” said Senator Booker. “We cannot allow the FDA to continue to delay on implementing this critical law. If passed, this bipartisan legislation will require the FDA to finally update its regulations and will pave the way for more scientifically reliable and humane methods of drug development.
- “The FDA Modernization Act 3.0 is aimed to do exactly what this bipartisan legislation is named to accomplish — modernize the FDA and remove overbearing animal testing mandates and regulations on new drugs. I am thankful for the support of my colleagues in helping to ensure passage, and I look forward to President Trump signing this legislation into law,” said Senator Schmitt.
- “The Biden administration had two years to implement the FDA Modernization Act 2.0, but it didn’t act. Congress should send this bill to Pres. Trump’s desk to help protect animals from mandatory testing at the FDA,” said Senator Kennedy.
- “Modern technology has led to innovative medical solutions — it’s time we take advantage of them and move on from outdated, unnecessary animal testing. With the FDA Modernization 3.0 Act, we protect animals from often inhumane testing and update our drug testing protocols, paving the way for more accurate and reliable health care treatments,” said Senator Blumenthal.
- “Congress has continued to press the FDA to modernize its research and shift away from testing on animals to more humane models that would expedite our drug development. However, there is more work to be done. I am proud to be a part of this bipartisan legislation to advocate for the FDA to abide by the directives Congress has passed into law,” said Senator Marshall.
Generally, the public is unaware, and to a certain degree, not particularly interested in the operational details of drug development. The American people expect their health agencies, funded mostly by taxpayers, to be diligent and remain on top of advanced technologies to advance the public good. Today, the cost of developing a single new drug is a stupefying $2 billion with an average development time of 10-15 years from target identification in the laboratory to market release, not factoring in withdrawals or recalls.
Most animal disease models have little resemblance to the human diseases they were created to study. Nonetheless, financial interests, fierce industry competition and poor government oversight perpetuated the myth of animal models in biomedical research (reviewed here). Federal agencies like the FDA, operating in the first place from an animal-centric “gold standard” since 1938, were easily co-opted to go along even further, requesting to this day “acute toxicity of the drug in at least two species of animals,” for clearance of any experimental drug at the preclinical stages.
Unfortunately, the obsessive reliance on animal testing at the FDA translates into irrecuperable delays in the development of medicines, missed opportunities due to misguided regulatory principles and exorbitant costs ultimately passed onto consumers. In actuality, one-third of new drugs on the market had safety problems after FDA approval.
Perhaps no one has been more acutely aware of the glaring deficiencies at the FDA than the rare disease community where 95% of the 7000-plus rare diseases that affect 25-30 million Americans have not a single FDA approved drug. In this regard, a much-needed reform known as the Promising Pathways Act (PPA) — a bill that provides for expedited, provisional approval of drugs for serious or life-threatening diseases or conditions — has been stalled in Congress because of strong opposition from the FDA and its surrogates.
In summarizing the challenge, Senator Mike Braun (R-Ind.) explains that “Americans with life-threatening and terminal diseases like ALS [Amyotrophic lateral sclerosis, formerly known as Lou Gehrig’s Disease] don’t have time to waste on a bureaucratic journey through red tape, only to be denied access.” Braun, here explaining the Bill, is a co-sponsor of the bipartisan legislation, and the then ranking member of the Senate Special Committee on Aging whose committee hosted on September 26, 2023 a hearing on PPA.
Issues needing attention at the FDA are not limited to debacles with drug development and the regulatory process. Some, especially parents of young children, got a glimpse of the poor strategic planning at the agency albeit from a different angle: the FDA failing to heed warnings about the shortage of infant formula, which caused, a couple of years ago, anxiety and distress to a large segment of the U.S. population. This failure in preparedness triggered congressional hearings, including hearings by the House Committee on Oversight and Accountability. Other pressing challenges relate to FDA’s reliance on user fees from big Pharma to partly fund its operation.
A troubling practice that the commissioner must put an end to is the revolving door between the FDA and the pharmaceutical industry that the agency is supposed to regulate. The new secretary of the U.S. Department of Health and Human Services (HHS), Robert F. Kennedy Jr., who oversees the FDA, assured his staff that he would “shut the revolving door to reestablish public trust” in the department. The recent hiring of Dr. Patrizia Cavazzoni to a key position at pharmaceutical giant Pfizer, only weeks after stepping down from one of the most influential positions at the FDA, was seen as a jarring illustration of the revolving door tradition.
In conclusion, the incoming FDA Commissioner Dr. Marty Makary has his work cut out for him. But the Commissioner also has a once in a lifetime opportunity to make history by bringing relief to millions of Americans, reducing futile animal testing in the regulatory process and streamlining a prescription drug marketplace, which in 2023, was valued at $1,225.78 billion.
The Commissioner will be served to implement a clear, accountable and transparent system of checks and balances built around the intentional use of innovative technologies in drug discovery and food safety, away from the deadweights of animal testing. Ostensibly, this could start by terminating rank insubordination at the FDA through the speedy implementation of FDAMA 2.0 and the commencement of its woefully overdue rulemaking at the modernized agency.
Zaher Nahle, PhD, MPA, is an accomplished scientist and consultant. He served as chief executive officer, vice president for research and chief scientific officer at U.S. medical foundations. Earlier in his career, he led award-winning research teams and was on the faculty of major universities, including Cornell and Vanderbilt. Zaher has a Master’s degree in Public Administration (MPA) from Harvard University, where he was a Mason fellow, and a PhD in Physiology and Biophysics from Stony Brook University/Cold Spring Harbor Laboratory (joint programs). He is the Senior Scientific Advisor for the Center For a Humane Economy and Animal Wellness Action. Zaher is also the founder of IVYCTORY Solutions, a research services and business advisory firm specializing in the technology and biomedical discovery markets. He is a Dean’s Scholar at The Johns Hopkins Carey Business School.