All of Us Need to Be Rooting for FDA

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There is very little support among stakeholders and FDA employees for the 2025 version of the FDA.[1] Some of us are discouraged. Some of us are trying hard to find the good in agency proposals and actions.

Regardless of where any of us stand, all of us need to be rooting for FDA to be successful.

Commissioner Makary is operating in a political environment that is arguably more challenging than any FDA commissioner has faced since the agency’s creation in 1906.

Some of the obstacles that Commissioner Makary faces include:

•       An Administration that prefers the “rule of men” and does not respect the “rule of law.”

•     An Administration that does not acknowledge the importance of expertise, notably but not exclusively scientific expertise.

•     An Administration that wants to thwart China’s ambition for global leadership yet is unable or unwilling to see that slashing NIH’s budget by 40%[2] and cutting upwards of 20% of FDA staff is a wholly inappropriate response to that challenge.

•      An Administration that claims it has a commitment to children’s health, food safety, and nutrition, but relies on experts handpicked for their biases and supports cuts to feeding programs and Medicaid without acknowledging any connection between those actions and their stated goals.[3]  

•      An Administration that claims to want to combat chronic disease but has been strangely silent about the most easily implemented action: further reduction in tobacco consumption.

•      An Administration that thinks FDA is a sock-puppet for industry.

Heavy, indeed, is the head that wears the FDA crown.

I appreciate the enthusiasm, intellect, and articulateness that Commissioner Makary brings to the job. I support (up to a point) his plans for shortening review times. I agree with FDA working cooperatively with patients and industry. I hope he has surrounded himself with people who will tell him “no” when the situation warrants a “no.” I really like his commitment to the adoption of AI. The rehiring’s have been a plus, as well as his sensible decision to support user fees negotiations.[4]

Of course, my “being discouraged” and “looking for the good in agency proposals and actions” reflects the many things that I would wish for him to do differently or better. For example, I urged the agency to be more incremental in its roll-out of AI.[5] I am confused by his use of “gold standard science” and “radical transparency.”[6] I am skeptical of his glossy optimism to FDA’s post-RIF capabilities. I would like him to figure out what the FDA cannot do or cannot complete in a specific timeframe…and publicly address statutory, Congressional, and stakeholder concerns.[7] I worry about the decline of outside consultation through advisory committees, and it scares me that the specter of political interference is ever-present.[8]

Why root for FDA and for Commissioner Makary to be successful?

•      Because a stable and functional FDA, regardless of its flaws, will be better for the American public and stakeholders than a chaotic and dysfunctional agency.

•      Because our nation’s public health and commerce are threatened when $3 trillion of goods and services lack meaningful oversight. None of us benefit from a return to “caveat emptor” in the food and drug marketplaces.

•      Because the CDC vaccine debacle, borne at least somewhat from a vacuum of leadership, shows how important it is to have an FDA commissioner who 1/ will defend good science and 2/ resist the triumph of random (and often untrue) anecdotes. Hopefully, Commissioner Makary will commit to defending science in the face of such threats.[9] He certainly understands the bedrock of findings when they are based on statistics and reproducible results.

•      Because the next two to three appropriations cycles and the negotiation of the next user fee agreements will be on Commissioner Makary’s watch. An underfunded regulatory agency will say “no” far more often because it does not have the time, resources, or focus to reach a nuanced “yes.”

Nobody gets a free pass, as reading FDA Matters columns[10] will continue to demonstrate. I may be optimistically projecting more than Dr. Makary can or wants to deliver.

Nonetheless, it is a complex world where the path to a stronger and more effective FDA often contains twists and turns....and “the perfect is often the enemy of the good.”

We need continued dialogue among all stakeholders and the FDA that reflects that the betterment of FDA is a universal goal.

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[1] https://www.linkedin.com/pulse/inside-changing-fda-winners-losers-uncertainty-steve-usdin-15jbe/?trackingId=0rXpBMQ9l6kQ8R3M9Hbkkg%3D%3D

[2] https://www.fdamatters.com/fdamatters/elon-musk-and-the-future-of-government-investment-in-our-nations-future

[3] For example, in 2023, 41.5% of mothers had Medicaid at the time of birth. https://www.marchofdimes.org/peristats/data?reg=99&top=11&stop=154&slev=1&obj=18

[4] https://www.fdamatters.com/fdamatters/finally-some-encouraging-news-from-fda

[5] https://www.fdamatters.com/fdamatters/the-skeptical-enthusiasts-guide-to-ai-at-fda

[6] https://www.fdamatters.com/fdamatters/alice-humpty-dumpty-and-the-new-administration

[7] https://www.fdamatters.com/fdamatters/truth-telling-fda-user-fee-edition

[8] https://www.fdamatters.com/fdamatters/fda-and-politics-an-unhealthy-combination

[9] https://www.nytimes.com/2025/06/05/health/kennedy-stem-cells-experimental-treatments.html

[10] www.fdamatters.com. Readers can subscribe on the website or send a note to sgrossman@fdamatters.com to ask to be added to the subscription list.

“A Dangerous Idea” Revisited

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This article builds upon my May 22 column, entitled A Dangerous Idea: Two Drug Manufacturing Pathways, One Regulated, One Not.[1][2]

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Recently Novo Nordisk dropped out of its arrangement with Hims and Hers because the latter continued to sell compounded GLP-1 weight-loss products that are no longer legal (except in extremely limited situations).

The resulting commentaries and comments on Linked-In have run hot and heavy. Some of the comments are little more than flaming tirades against the pharmaceutical industry, but others reflect thoughtful concerns about access, price, cost, quality, and safety. It is easy to get lost trying to figure out who’s right and for what reasons. 

However, if you step back and look beyond just GLP-1’s, it turns out to be simple: the narrow exceptions that compounders want to expand would cross critical boundaries that FDA needs to preserve.

There is so much that feels special about GLP-1 products that we tend to forget that, from a regulatory perspective, they are just another class of regulated drug products. There cannot be one set of rules for GLP-1’s and another set of rules for other drug products. 

A short history of GLP-1 compounding

Given the anticipation for any new weight loss drug and the sterling results from the GLP-1 obesity clinical trials, it is no mystery why demand for GLP-1 drugs was so large. GLP-1 drugs were quickly the “go to” drugs for weight loss. As a result, the initial manufacturing capacity of Novo Nordisk and Lilly were insufficient, and FDA declared a shortage until the commercially available supply could catch up to demand. 

In March 2025, FDA declared the shortage ended. Compounding was to cease no later than May 22. As we now know, many compounders stopped, but many didn’t.

Those who continue to compound GLP-1’s have shifted their justification from  “shortage compounding” (no longer legal) to “special needs compounding” (the only other exception recognized by law). 

That is problematic because “special needs” is an extremely limited category that requires a specific physician to establish that a specific patient has “special needs” that cannot be met by commercially available products. Special needs compounding was never intended to be  a landing place for shortage compounders to go once a shortage ended. 

“Special needs” might come into play with a Parkinson’s patient who can’t swallow pills or a child who needs special dosing to take a medicine normally intended for adults. 

“Special needs” is not, for example, mass-compounding of GLP-1’s with vitamin B-12 added. Both products are commercially available, there is no clinical rationale, and it is not plausible that that all or most of a company’s GLP-1 patients have the exact same special need. 

Compounding lacks important consumer protections under the FDCA. 

Among other things, the Food, Drug, and Cosmetics Act (FDCA) provides for the regulation of biopharmaceutical products--approval, manufacture, distribution, and labeling. While certainly not perfect, it is a comprehensive set of rules that protect consumers from products that are unsafe or ineffective and that guide appropriate use through labeling. 

Compounding sits outside those FDCA consumer protections. FDA does not approve the compounded product, it does not review whether the compounding is done under Current Good Manufacturing Practices (cGMP), it does not inspect compounding facilities, and there is no requirement for labeling. 

A consumer has no way of knowing if the compounded product is the same as the approved one. Maybe it is just as good, but that is unproven and, in most instances, unknowable.

For that reason, compounding is allowed in only two instances--shortages and special needs--where the additional risk is justified by the circumstances. 

If GLP-1 “special needs” compounding is broadly allowed, then it is precedent for any drug that can be compounded. 

If trivial adjustments to a commercially-available product qualifies as “special needs,” then the shift from regulated manufacturers to unregulated compounders will expand to many additional drug products beyond GLP-1’s. Compounding would then be far beyond what the law was intended to permit, and far from the consumer protections we now enjoy. 

FDA urgently needs to address the permissible scope of special needs compounding or risk the creation of an alternative pharmaceutical market that operates outside the safeguards and consumer protections provided by the Food Drug and Cosmetics Act. 

Beyond consumer protection, an alternative unregulated pharmaceutical market will adversely impact drug development. 

Traditional companies will be less interested in investing in research and development of any product that could be readily compounded by others. Likewise, a generic company will have less incentive to gain FDA approval of their product if the target market is already eroded by compounding. 

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1. For a pharmacist’s perspective—along with illustrations of compounder pitches and commentary on the problems they create: From the FDA to Instagram: How Ozempic Got Hijacked by Compounders by Alec Ginsberg.

2. For an overview of the compound-related marketing practices of telehealth companies: https://sherwood.news/business/the-controversial-rise-of-franken-pills-telehealth-companies-push-to-mix/ 

Alice, Humpty Dumpty, and the New Administration

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As children, we are taught that “sticks and stones will break my bones, but words will never hurt me.” That may have helped children develop resilience against verbal bullying, but it totally discounted the power of words. As adults, we know better. Words matter! 

Notably, words have the ability to control as well as inform. 

“When I use a word,’ Humpty Dumpty said in rather a scornful tone, ‘it means just what I choose it to mean — neither more nor less.’

’The question is,’ said Alice, ‘whether you can make words mean so many different things.’

’The question is,’ said Humpty Dumpty, ‘which is to be master — that’s all.”

― Lewis Carroll, Through the Looking Glass

Each political party uses terms and slogans to advance their causes. In doing so, they often use words that imply a clearer definition and greater certainty than the situation, facts, and proof points justify. 

The new administration is fond of: radical transparency, gold standard science, and ultra-processed foods. But what is meant by these catchphrases may not always be clear.

Radical Transparency. The conclusions and the reasoning behind government decisions should be readily available and easy to understand. They should provide tangible evidence that public opinion was sought, received, and considered. 

At least four federal laws are involved: the Administrative Procedures Act,[1] the Federal Advisory Committee Act[2], the Freedom of Information Act[3], and the National Archives and Records Administration statutes[4]. In the face of these four laws, it is fair to wonder what differentiates “radical transparency” from “transparency?” 

Despite the catchy phrase, the new Administration has shown little interest in transparency as traditionally defined and manifested in existing laws. 

As Dr. Jeremy Faust has observed: visibility—widely-distributed fiat announcement of government policy—is different from transparency about and public inclusion in the government decisionmaking process.[5]

Perhaps “radical visibility” should replace “radical transparency?”

Gold standard science. In my nearly 20 years as an advocate for FDA resources, I made hundreds of references to FDA being “the global gold standard for regulation of food and medical products” because of its reliance on science-based decisionmaking. Recently, FDA Commissioner Marty Makary and CBER Director Vinay Prasad made this their center-piece, describing “the two guiding principles of our philosophy—gold-standard science and common sense.”[6]

In a recent executive order[7], gold standard science was defined, enumerating nine characteristics. 

What seems missing from the administration’s definition of “gold standard science” is an appreciation of the complexity and ambiguity of scientific results. Often, science is (or needs to be) actionable, even if it is not absolute or immutable.

There is, necessarily, a strong situational relativity when you factor in the difficulty, cost, and timeliness of achieving complete certainty. As a result, sometimes gold standard science has to be “what we knew at the time, exercising best judgment, and having surveyed all relevant evidence.”  

Over time, new data may refine or refute previously held interpretations of previous studies. Mis-directions from the past are not necessarily blameworthy. They may simply reflect how scientific knowledge evolves. 

Ultra-Processed Food. A key plank of the MAHA (Make America Healthy Again) initiative is to build federal and state policies that result in the elimination of ultra-processed foods (UPF) from the American diet. This term was already in use and gaining momentum before the new administration made it a central tenet of government food policy. 

Before UPF becomes a legal standard by which foods are judged to be good/healthy or bad/unhealthy, there needs to be some honesty about how ill-defined the term is.

Is UPF defined by the number of ingredients? By the presence or absence of certain ingredients? By certain processing steps (and which ones)? What, if any, is the level of proof needed to establish a food as “good” or “bad?” 

Something more specific and scientifically-sound is needed...if Congress is to pass a law, FDA and USDA are to promulgate regulations, or government officials are to threaten industry with withdrawal of foods, ingredients, additives, and processes in common usage today. Consumers, too, ought to have the benefit of clarity when government eliminates and/or demonizes certain foods, ingredients, or processes. 

I am not alone in such concerns. Marion Nestle, the doyenne of nutritional food policy, recently offered the following comment about proposed California legislation that would ban UPF’s from the state’s school lunch program:  “I hope it passes, not least because I can’t wait to find out how its authors think the state will go about identifying the specific foods blocked from schools.”[8]

English is enriched every day by new words and new meanings. As the exchange between Humpty Dumpty and Alice illustrates, we are often the initiators of those changes. When that occurs, we should endeavor to be crystal clear about what we mean. 

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1. APA provides for “notice and comment rulemaking,” which solicits public input prior to finalizing regulations. https://en.wikipedia.org/wiki/Administrative_Procedure_Act  

2. FACA sets standards for federal meetings, assuring that the public has advanced notice and, in many instances, opportunity for public comment. https://www.gsa.gov/policy-regulations/policy/federal-advisory-committee-management 

3. FOIA provides a process and rules for public access to government decisional documents. https://www.law.cornell.edu/wex/freedom_of_information_act_(foia) 

4. NARA is a collection of laws/rules about public records retention so that contact with public officials is tracked  https://www.archives.gov/about/laws 

5. https://insidemedicine.substack.com/p/hhs-visibility-transparency-the-legal?r=5p3cr&selection=b8e4fc9f-7268-4cab-a44c-2cf9f664b353&utm_campaign=post-share-selection&utm_medium=web&triedRedirect=true#:~:text=Let%20me%20state%20this%20clearly

6. https://jamanetwork.com/journals/jama/fullarticle/2835314 

7. https://www.whitehouse.gov/presidential-actions/2025/05/restoring-gold-standard-science/ 

8. https://www.foodpolitics.com/2025/06/california-is-considering-banning-ultra-processed-foods-from-schools-really/?lctg=20327868 

Elon Musk and Government Investment in Our Nation’s Future

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Elon Musk thought cutting government programs was about deficit reduction. When the “One Big Beautiful Bill” reconciliation legislation passed the House with a $3 trillion price tag, he realized he had been misled and reacted accordingly. His falling out with the President--charitably compared to two kindergartners squabbling; uncharitably compared to two scorpions trapped in a bottle--was a fascinating part of the last few days. And a distraction from more important issues.

It would be wonderful (although not likely) if their feud morphed into what we really need: 

A deficit-neutral reconciliation bill that does not gut human services programs or abandon government investment in scientific research and innovation. Hint: more revenue and more judiciously-chosen program cuts will be needed. This more balanced approach can (and should) be justified for what it is: an investment in our nation’s future. 

Collective Responsibility and Barriers to Investment 

FDA Matters believes we have a collective responsibility to invest in policies that will drive growth and prosperity in the United States--now and in the future. FDA needs to carry out its mission-driven and statutorily mandated responsibilities because it is just such an investment. It is inexplicable how the proposed 40% cut in NIH funding could be justified as supporting investment from either the governmental or private sectors.

Beyond that, we would point to the need for continued investment in our nation’s deteriorating infrastructure; our system of higher education and research institutions; and programs that assure that everyone has access to food, healthcare, and education, which are a prerequisite for individual success. 

There are two immediate barriers to continuing and expanding government investments in our nation’s future. First, our nation is $36 trillion in debt, and we are adding another $1.9 trillion in FY 25.[1][2] That cannot go unaddressed any longer[3], even if it takes several years to reach the goal of deficit neutrality in annual expenditures.   

Second, DOGE-driven policies and program cuts are not only destroying  government investment, but creating uncertainty for the companies, investors, institutions, and individuals who we want to encourage to invest in our nation’s future. 

A Call for Renewed Government Investment in Our Nation’s Future

For at least three generations, our country has been driven by the worst possible budget cycle. When in power, Democrats tend to expand government programs (increasing expenditures); when in power, Republicans tend to cut taxes (reducing revenue). 

Each approach has popular appeal to certain constituencies. Combined they have left our nation in a precarious position relative to government and private investment: 

• Financing our $36 trillion debt keeps interest rates higher than they otherwise would be--making investments more difficult and more expensive. Ongoing and future deficit spending will eventually reset bond prices and drive interest rates to higher levels. 

• The administration’s FY 26 proposals would shrink our national investment in science, proposing a 40% cut to NIH, a 50% cut to CDC, and a 60% cut to the National Science Foundation. 

• Major research universities are under attack on multiple fronts, including indirect costs, autonomy, and access to foreign scientists and institutions. 

• The environment for private investment has notably deteriorated.[4] There is a low degree of certainty about the rules and programs that will shape the success or failure of investments. Government agencies are no longer reliable partners. The long-standing cooperative relationship between regulated industries and FDA is under fire. The ever-changing tariff situation makes business planning difficult. 

Oscar Wilde famously defined a cynic as "a man who knows the price of everything and the value of nothing". Unless we can reinvigorate our commitment to investing in our nation and its people, cynicism will prevail, and the future is likely to be bleak. 

It doesn’t have to be that way. Choosing between deficit reduction and investment in our nation’s future is a false dichotomy. We can have both if we are prepared to make tough choices and ask everyone to pitch in. We are capable of rising to the occasion, reaching a shared goal of a prosperous future.

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1. https://budget.house.gov/press-release/congressional-budget-office-updates-baseline-deficit-totals-to-third-highest-in-american-history

2. The best  number I can glean from the charts suggests that the House-passed reconciliation bill would reduce this by about $100 to $200 billion in FY 25. Reconciliation changes would add to the deficit in every subsequent year.

3.  Apparently, Elon Musk and I share this view.

4. The House version of the reconciliation bill would restore tax incentives for research and development, business equipment and debt interest through 2029. The Senate is talking about making those permanent.  As proponents assert, these are important pro-growth provisions. However, I consider them “necessary but insufficient.” They reflect no new analysis of what is needed. Notably, they do not offset the impact of budget cuts and disruptive government policies on investment.

The Skeptical Enthusiast’s Guide to “AI at FDA”

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I welcome Commissioner Makary’s embrace of AI[1] and applaud yesterday’s announcement of the next step in agency adoption of AI technology. [2]

I wrote earlier that: “AI can help FDA make better regulatory decisions based on more refined and accurate information…. [although] there are legitimate concerns about relying on AI too quickly and without system refinement and validation.”  

As a result, I characterize myself as a “skeptical enthusiast” on the topic of AI at FDA. Here is why: 

An historical perspective: When the Clinton administration downsized the federal government in the 1990’s,[3] some of the success of that effort was attributable to embracing new technology. The Internet[4] was gaining traction and there was the opportunity to create efficiencies in government around that then-new technology.[5]  

A similar opportunity exists today for AI to play a role in making the US government more efficient. Then, as now, we need to appreciate that we are working with a technology whose capabilities, strengths and weaknesses are formative, not set. 

Fast forward to Current Headlines. HHS Secretary’s “Make America Healthy Again” (MAHA) report was released on May 22, 2025. It contained a number of citations to research that were never undertaken or never published. 

Researchers face frontier justice[6] if they make things up. There need to be consequences for relying on AI output that has not been evaluated for possible computational errors, biased sampling, and invented data, studies, and publications. 

AI is a wonderous tool now and promises to be even better in the future. However, we cannot just dismiss problems because AI is the wave of the future. 

AI 101: Artificial intelligence is the capability of computational systems to perform tasks typically associated with human intelligence, such as learning, reasoning, problem-solving, and decisionmaking.[7] Sometimes AI is faster or has greater bandwidth or possesses more patience than humans; increasingly AI  is capable of producing timely results that involve more inputs and more computations than any human mind could ever handle. 

There are three features that are leading us into broader and more sophisticated uses of AI. These are: 1/high-speed processing that enables AI to take on a broader range of more complex tasks, 2/ expansion of AI engines to include nearly everything ever written (LLM or Large Language Model), and 3/ the transition from predictive AI to generative AI. Predictive AI uses data to predict likely outcomes. Generative AI learns patterns from large datasets and uses that knowledge to generate original, unique outputs.[8] 

The Opportunity and Challenge for AI at FDA. Like most new transformative technologies: the promise of AI is running far ahead of its proven capabilities. 

Nonetheless, FDA has no choice but to move forward. 

It already receives applications for review that incorporate artificial intelligence, be it in patient recruitment, trial design, evaluation of safety and efficacy, or in generating useful post-marketing information.[9] As a result, the agency must have staff that are fully capable of understanding and evaluating what is being proposed. 

Equally interesting is the potential for FDA to incorporate AI into its own processes. FDA already invests in regulatory science,[10] seeing great potential for more efficient, as well as better-informed decisionmaking. AI will accomplish both, with more efficient decisions being very visible, while the better-informed decisionmaking being less visible but profound in its impact. 

FDA’s two greatest strengths are its expertise and the public trust in its decisionmaking. Those are particularly important given the complexity of regulating medical products and the inevitable inexactitude of scientific proof in biomedicine and medtech. 

Before AI can help FDA make better regulatory decisions more rapidly, the agency and its staff need to feel confident that they can trust the output from AI and that there are controls in place to limit misadventure. 

The MAHA report is a reminder that AI is not yet a trustworthy tool for many of its proposed uses--even seemingly simple ones. An error in a policy position paper is a small concern compared to an error in a complicated and important regulatory decision! 

How can FDA use AI effectively while respecting it’s known limitations, including citations to literature that do not exist? 

I asked for some ideas from Shannon Lantzy (shannon@shannonlantzy.com), a regulatory innovation strategist who has led major efforts to assess and improve FDA’s regulatory review performance. She replied: 

Trust in automation is not black and white; it can grow slowly with quality and accuracy checks along the way. Trust in AI needs to grow like trust in a new hire who needs to be trained, monitored, and coached with adequate feedback. 

Yes, GPT hallucinates. Reviewers can check the suggestions of AI review support, just like branch chiefs thoroughly review their brand-new hires’ work. LLMs can be prompted and tailored to reduce hallucination. Use cases can start with humans very much in the loop. It is relatively simple to build an LLM to check another LLM’s work, evaluating the validity of every citation. 

Critics of AI for regulatory work imagine the worst, but they don’t imagine what we already tolerate: drudgery work for experienced and highly skilled reviewers and little scale in review tools despite significant increases in reviewer workloads and medical product complexity. 

Conclusion: Understandably, most of the controversy about AI is focused on the quality of the outputs (useful vs. unvalidated vs. hallucinogenic). We need to move forward to address the  process itself….the difficulty of incorporating fundamental and sophisticated changes into an already complex regulatory decisionmaking system. 

Four things seem most important to me:  

• Acceptance: All parties need to accept that broad application of AI at FDA is appropriate and inevitable. They need to work together to maximize its potential and minimize input and output errors. 

• Transparency: FDA needs to articulate how it uses AI in its work now, what uses are formative, and what uses are aspirational. 

• Validation: If trust in FDA and its decisions is to be maintained, then FDA needs to show how the tools it relies upon, such as AI, have been validated. 

• Control: There needs to be ongoing means by which applications are assessed for bias and error. 

AI changes everything, but not instantly and not without humans assessing the inputs and outputs. 

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1. https://www.fdamatters.com/fdamatters/finally-some-encouraging-news-from-fda 

2. https://www.fda.gov/news-events/press-announcements/fda-launches-agency-wide-ai-tool-optimize-performance-american-people?utm_medium=email&utm_source=govdelivery 

3. https://www.fdamatters.com/fdamatters/what-is-happening-to-federal-workers-at-fda 

4. https://apnews.com/article/trump-musk-doge-clinton-reinventing-government-gore-a95795eb75cacc03734ef0065c1b0a6d.

5. Public access to the Internet and the launch of the Worldwide Web occurred in the early 1990’s. https://en.wikipedia.org/wiki/Internet 

6. Were a researcher to make up a citation or article, colleagues would likely ostracize them; all of their prior research scrutinized; their grants might be cancelled; and their academic affiliations might be suspended. 

7. Once incorporated into common experience, AI is often not perceived as AI per se. AI is already in widespread use in Google Search, Siri, Yelp recommendations, and autonomous vehicles. https://en.wikipedia.org/wiki/Artificial_intelligence

8. That is, a lot of past AI work could, in theory, have been done by a sufficiently large team with a sufficiently large amount of time and infinite patience. For example, how many times does Shakespeare use “thou” in his plays. Generative AI can create outputs that no amount of people or time could accomplish. For example, build an algorithm and demonstrate how a radiologist, in real time,  can compare one X-ray with 100,000 prior ones that are documented in the literature.

9. AI will also play a significant role in food safety regulation, but I have not yet explored the topic.

10. Regulatory Science is the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of some FDA-regulated products. https://www.fda.gov/science-research/focus-areas-regulatory-science-report/focus-areas-regulatory-science-introduction 

Non-Defense Discretionary Spending Threatened By Budget Reconciliation Shortfalls

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“While discretionary spending is not part of the reconciliation process, some policymakers may point to savings from that category as “offsets” for other policies.”[1]

FDA makes significant contributions to public health, public safety, scientific and technological innovation, US investment, and the flow of commerce—producing a positive return-on-investment that far exceeds its budget.[2] Yet, owing largely to our nation’s ongoing and precarious fiscal situation, it gets harder each year to convince the Administration and Congress to provide FDA with robust funding.  

FY 26 (which starts October 1, 2025) may be a year when Congressional appropriators have little or no leeway to “plus-up” funding for  programs and agencies whose appropriations may be targeted for significant cuts (such as FDA and NIH). 

Precarious US Fiscal Situation Worsened Over the Last Two Weeks

Republicans started the budget reconciliation process with the goal of extending tax cuts and enacting other costly Trump priorities…while incorporating enough cuts from mandatory spending so that the total package would be “deficit neutral.” 

Instead, the House bill — re-named “The One Big Beautiful Bill Act” (OBBB) — would increase the national debt by an estimated $3 to $4 trillion over 10 years. 

This has rattled the bond markets. Notably, Moody’s, one of the three major credit rating agencies, has downgraded US debt.[3]

The Squeeze on Non-Defense Discretionary (NDD) Spending

The FY 25 House Budget Resolution (with impacts through FY 34)  drives the current reconciliation process that targets mandatory spending. It also contains assumptions about the amount of discretionary spending in each of the next 10 years — in the aggregate but also by general category. 

As described by the Peter G. Peterson Foundation: 

The tables associated with the House budget resolution include an unlikely assumption that discretionary spending will be reduced by $1.8 trillion between 2025 and 2034 relative to the Congressional Budget Office’s (CBO’s) baseline — all from non-defense programs.[4]

The President’s FY 26 Discretionary Budget Request, released May 2, also targets non-defense discretionary (NDD) spending, albeit some programs will receive increases while others will face deep cuts or elimination.[5] Specifically, NDD spending is reduced by $163 billion or 22.6 percent from the FY 25 enacted level,[6] “while still providing support for our Nation’s veterans, seniors, law enforcement, and other critical priorities for the Federal Government.”

Of specific relevance to FDA: the House and Senate subcommittees handling Agriculture/FDA appropriations would, under the President’s Request, have $5 billion less (-18.3%) to spend in FY 26 compared to the FY 25 enacted levels. 

Spill-over from Reconciliation May Be the Biggest Threat to NDD

As bad as the FY 26 NDD numbers look under the House budget resolution and the FY 26 President’s Budget Request, the greatest threat to NDD funding is the likely failure of reconciliation to achieve deficit reduction. 

Conservative Republican “fiscal hawks” in the House reluctantly voted for OBBB, hoping it comes back from the Senate with deeper cuts and a much smaller increase in the national debt.[7] The Senate bill may be more to their liking (or not), but it is hard to imagine at this point that any reconciliation legislation will meet the original goal of deficit neutrality….or, at least, do so without a larger contribution from discretionary spending.

If reconciliation is not deficit neutral, House and Senate fiscal hawks will be looking for any victories that provide recompense for swallowing the bitter pill of a reconciliation that increases the national debt. They could advocate for a smaller tax cut, argue for increased revenues, or redouble their efforts to cut NDD funding. All three may be needed, but you can be sure that the last option will be on the table.

…. and the Hardest for Appropriators to Overcome. 

NDD funding was always going to be a target for the fiscal hawks. If their votes are needed to pass the final version of the OBBB and that bill increases the deficit (as seems likely), then they will have incredible leverage to force additional NDD cuts to offset the growing deficit. 

There are consequences. Senate Appropriations Chair, Senator Susan Collins, in particular, may find herself in an endgame in which the Appropriations Committees do not have enough discretionary funds for her to patch all the NDD programs she wants to protect (notably, thinking of FDA and NIH). 

Conclusion: Advocates for strong NDD funding (including FDA and NIH) have an important stake in the outcome of reconciliation. The larger the amounts that reconciliation adds to the national debt over the next ten years…the greater the risk that Congressional fiscal hawks will press for additional cuts in NDD funding that are greater than those cuts already anticipated under the House budget resolution and the President’s FY 26 request.

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1.  https://www.pgpf.org/article/the-budget-resolution-contains-optimistic-assumptions-about-discretionary-spending/ 

2.  The same can be said about the larger cluster of FDA, NIH, CDC, and USDA food safety programs.

3.  By itself, the Moody’s downgrade is more a tremor (signal), than  an earthquake. The other two agencies downgraded US debt in 2011 and 2023. Moody’s change in May 2025 is still significant because it is a reaction to growth in the deficit that would occur under OBBB. 

4.  https://www.pgpf.org/article/the-budget-resolution-contains-optimistic-assumptions-about-discretionary-spending/

5.  https://www.whitehouse.gov/wp-content/uploads/2025/05/Fiscal-Year-2026-Discretionary-Budget-Request.pdf 

6.  The budget resolution compares NDD funding cuts to the CBO baseline while the President’s budget compares NDD funding cuts to the FY 25 spending levels. I have not researched whether there is a way to make the numbers comparable.

7.  https://jeffdufour1.substack.com/p/debt-bomb. My thanks to Jeff Dufour and National Journal for making this document available.

A Dangerous Idea: Two Drug Manufacturing Pathways–One Regulated, One Not

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Redefining “Special Medical Needs Compounding” to Permit Mass Production Threatens Consumer Protections

Today, May 22, 2025, is the last day that mass compounded GLP-1 obesity medicines can be sold because FDA has declared the shortage over. Yet, some companies intend to continue selling compounded GLP-1 drugs to a large number of their customers by gratuitously adding other ingredients or making similar modest and unnecessary changes in dosing…then saying it is being compounded for the special medical needs of a specific patient. The hypocrisy is clear: a special medical need is not a mass need. 

What happens next is about consumer protections and manufacturing standards under the Food Drug and Cosmetics Act (FDCA). FDA can enforce the law or allow a race to the bottom that ultimately robs consumers of protections they need and deprives companies of the standards that assure a level playing field and quality products. 

If this were just about a class of products, I would probably not write about it in FDA Matters. However, the stakes are much, much higher than that. 

If a compounder can mass produce any drug they want by claiming special medical needs for individuals --with minimal regulatory requirements and oversight--then we have enabled an alternative pathway for the manufacturing and sale of both prescription and generic drug products. Manufacturers would be regulated. Mass production compounders would not. That doesn’t sound good for consumers or innovators…and it really isn’t[1] (see important footnote). 

The Current System Works and It Protects Consumers 

There are over 20,000 pharmaceutical drug products that are FDA-approved in the US[2]. Most pharmacies will carry several thousand of those, depending on store volume. What a pharmacy does not already have in stock, it can usually fill within 2 or 3 days from a central warehouse.

This is a system that works, fulfilling essentially all patient needs in the US through more than 60,000 pharmacies nationwide. FDA-approved drugs dispensed through pharmacies are FDA-evaluated and approved, and have uniform quality and formulation. They are standardized and manufactured by companies that follow FDA guidance on Current Good Manufacturing Procedures (cGMP) in facilities subject to FDA inspection. They are proven to be safe and effective. 

Compounding Addresses Shortages and the Special Medical Needs of a Specific Patient

By its nature, compounding by-passes the entirety of this process and the comprehensive consumer protections built into the Food Drug and Cosmetics Act (FDCA). Not only is the compounded product unregulated, but it can be given to patients without even so much as FDA-approved labeling. For good reason, compounding of commercially available drug products is only permitted under certain well-defined and limited circumstances. 

In addition to shortage situations, compounding is permitted to address the special medical needs of a specific patient. 

Such compounding is triggered by a specific doctor determining that a specific patient’s special medical needs require a compounded product, dosage, or method of delivery that will make a “significant difference” for the patient compared to an available commercial product. A wide variety of circumstances might be involved; examples might be a child who cannot tolerate a bad tasting oral medicine or a person with a swallowing disorder who needs a different dosage form than what is being marketed. 

Special Medical Needs of a Specific Patient Is Inconsistent with Mass Compounding

I am told there is no clinical evidence supporting delivery of GLP-1’s other than the current approved FDA labeling. For example, why mix vitamin B3 or B12 into the GLP-1 compounded product other than to be able to claim it is different? Or why allow oral, sublingual, or patch methods of delivery--except on an individual basis--since no such product has yet been considered or approved by FDA? If and when FDA approves any of those routes of administrations, there will be a commercial-available product that should preclude mass compounding (while leaving the special medical needs exemption in place for legitimate individual patients). 

There may be some limited cases where modifying GLP-1’s makes sense, but only if it truly addresses a specific patient’s special medical needs and not as a stratagem to support mass production. 

You don’t hear much about this type of compounding because it is limited to a specific patient’s special medical needs relative to commercially-available product. Pertinently, special medical needs compounded products cannot be produced beforehand or in quantity--the exemption is justified by its application to an individual patient’s needs[3].  

However, you will start hearing a lot about this type of compounding if FDA allows “special medical needs” and “significant difference” and “mass compounding” to be defined by compounders. Then the race will be on to find other lucrative drugs that can be retrofitted into the GLP-1 compounding model[4][5].,

Conclusions 

It would seem self-evident that an exemption permitting compounding for the special medical needs of an individual patient is incompatible with mass compounding. Special medical needs compounding was never intended to be a place for shortage-driven mass compounding to move after the shortage has concluded. 

It is like trying to pull an elephant through a mousehole. If you make the hole big enough to accommodate the elephant, it is no longer a mousehole. 

FDA urgently needs to address the permissible scope of special needs compounding or risk the creation of an alternative pharmaceutical market that operates outside the safeguards and consumer protections provided by the Food Drug and Cosmetics Act. 

In addition to the risk of FDA losing its ability to protect consumers by setting and enforcing manufacturing standards for drug products, there is a significant market competition risk. Paraphrasing Gresham’s Law that bad money always drives out good money[6]: 

If there are two forms of pharmaceutical products in circulation, both of which are accepted by regulatory authorities as validly marketed, then the more valuable product (the one that is FDA-approved) will gradually disappear from the market.

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[1] Note: there are two very important issues not addressed here: whether the compounded products work as well and are as safe as the manufactured ones, and ownership of the intellectual property. 

[2] FDA Facts at a Glance. November 2020. https://www.fda.gov/media/143704/download

[3] The risk-benefit of going outside the proven and approved labeling is acceptable for a single person with genuine special medical needs that cannot be met by a commercially-available product.

[4] As previously noted, this analysis does not address whether the compounded products are as safe and effective as the manufactured one. FDA must have some inkling that they are not: In May 2025, FDA disclosed plans for an extensive survey of compounding pharmacies, in part because “FDA continues to find concerning quality and safety problems during inspections of outsourcing facilities.” https://public-inspection.federalregister.gov/2025-07557.pdf 

[5] As previously noted, this analysis does not address intellectual property rights, which are a significant issue all by itself.

[6] Application of Gresham’s Law is not always intuitive. If enough readers would like a further explanation, I will do a follow-up column. https://en.wikipedia.org/wiki/Gresham%27s_law.

Finally, Some Encouraging News from FDA

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The most important questions facing FDA and the stakeholder community are: 

After the lay-offs, RIFs, and voluntary departures, does the FDA have enough staff and expertise to fulfill the agency’s responsibilities?

If there are tasks and obligations that will not be met--or not met in a specified timeframe--will the agency address statutory, Congressional, and stakeholder concerns? 

It will take a while for Commissioner Makary to have answers. When he does, I hope he will address them forthrightly and not increase the many uncertainties about the agency’s future and priorities. 

Meantime, FDA Matters is monitoring the situation and can report some encouraging signs of progress. 

Rehiring. We are starting to hear more reports about RIF’ed and laid off employees being asked to return to their old jobs. I have no idea whether this is a few or a lot of people. It is not ideal (actually quite cruel) to have fired a large number of people and only then start reviewing their remit to figure out who should have been retained rather than fired.

That said, callbacks are occurring and that is an encouraging sign for the agency. Among other things, it looks like the commissioner is upholding his promise to Congress that he would review all of the downsizing that occurred before he was confirmed. 

User fees. Along with other commentators, I have had serious concerns about the future of user fees. That’s understandable given Trump/Kennedy/Makary projecting their views along the lines of “FDA is a sock puppet for industry.” 

There are now some encouraging signs we can point to. Regulatory Focus reported[1] on Deputy Commissioner Grace Graham’s speech to FDLI last week in which she discussed some early thinking about restructuring user fees. Also, July dates have been announced for the first PDUFA and GDUFA  public hearings. 

Asked by a reporter to comment on concerns about Graham’s thinking. I replied “1/ you can’t get to the end unless there is a beginning and we weren’t certain there would be a beginning,  2/ no matter the starting position of FDA, it is a long negotiation and there is no reason at this point to believe that the end-product won’t be satisfactory to all parties, and 3/ the PDUFA agreements have evolved over 30 years and it is appropriate that a new administration is looking at how to improve the program.” I added: “All that said: this one is likely to be testier and more public than past negotiations….but the administration engaging the process is all good news.” 

More Insights from the Commissioner About His Plans and Priorities. Commissioner Makary seems to have picked up the pace on talking publicly about his views. As we have all seen, he is smart and articulate. 

He has some interesting ideas, which he delivers in an “I can get it done” breeziness that is refreshing. While we disagree about the likely impact of the RIF’s, he seems to understand the FDA cannot be run without a substantial and expert staff. 

Whether you like what he says or not, having him out in public advocating for the agency is encouraging. 

Staff Travel and Meetings. It’s not unusual for incoming administrations to limit employee participation in stakeholder meetings and  tamp down or even freeze travel until new officials are in place. For a while it looked like the Trump administration might try to maximize the time during which things were halted. 

I am hearing enough reports to believe things are going in the right direction. 

Implementation of AI. AI is the future, especially for an agency like FDA that often receives reports that are thousands of pages long and relies on databases that might contain millions of data points. In particular, AI can help FDA make better regulatory decisions based on more refined and accurate information. 

Commissioner Makary’s embrace of AI is encouraging news. There are legitimate concerns about relying on AI too quickly and without system refinement and validation. Details are scarce at the moment, so I am inclined to believe that the actual uptake will be appropriately spaced over time and not rushed.

Finally, there is some encouraging news from FDA. I am pleased to share it.

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1.  https://www.raps.org/news-and-articles/news-articles/2025/5/fda-deputy-commissioner-hints-at-potential-changes?utm_campaign=regulatory_focus&utm_medium=email&_hsenc=p2ANqtz-_rvGbKXqqfzLXRI-d3eFQauxxlA8mWMNMs_7z5LGbDSTAy7GqADQny6Z8sg6TPlJ6S2He5SoKuLXOWBbkfsd1njgOcFQ&_hsmi=362270950&utm_content=362270950&utm_source=hs_email 

If You Are Not Confused, Then You Are Not Paying Attention: FDA Edition

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“Flooding the zone” has worked as a strategy for the Trump Administration, at least so far. We are all so busy reacting to the newest proposals that we don’t have time to address the previous week’s initiatives from the Administration.

While I can’t seem to get ahead, I usually have a good sense of what is coming next or, at least, the range of possibilities. That’s an important aspect of both my FDA Matters writing and my client work.

However, it has been unusually difficult this year because of another strategy being used by this Administration: pervasive norm-breaking. Norms limit the number of plausible scenarios even in complex situations. Without norms, our predictions have to account for a nearly endless stream of improbable possibilities that cannot be eliminated.

In contrast, FDA’s strength should be in its predictability, the opposite of norm-breaking. The agency reliably sets and enforces standards (norms) for $3 trillion worth of goods and services.

Because of norm-breaking scenarios, my FDA crystal ball has never been more opaque. Here are some of the items with the most impact and the least clarity:

Will the Secretary Try to Control FDA? Secretary Kennedy’s predecessors were chosen for a combination of their management experiences, and political and policy chops.[1] Kennedy has none of that, plus he has no known interest in how his predecessors ran the department.

So, it is unclear whether he will adhere to past norms about when--and how much--the Secretary of HHS intervenes in FDA’s decisions and operations. Here is my interpretation of those norms:  

• Budget: okay for HHS to intervene;

• Regulatory policy: okay for HHS to intervene on a case-by-case basis on major items;

• Product decisions: not okay for HHS  to intervene, but there is some history of HHS involvement in reproductive health products;  and

• scientific and medical evaluations and information: not okay for HHS to intervene.

Nothing prevents the Secretary from breaking those norms and making himself the final clearance for all FDA actions, including product decisions.[2] How can we predict or create scenarios for future FDA actions if intervention by the Secretary--ad hoc, selective, total, or permanent--is an ever-present variable?

Will the Commissioner Defend FDA’s Independent, Science-Based Evaluations? I feel certain that Commissioner Makary intends to stand up for FDA with regard to scientific and medical evaluations and information. He didn’t take the Commissioner’s job so that others above him--who do not have appropriate education or training--could substitute their medical and scientific judgment for his own and that of FDA staff.

However, with an unpredictable and self-certain HHS Secretary who is interested in public health, food, nutrition, and vaccines, a continuing stream of large and small disagreements seems inevitable. Some may be uncomfortable or worse for Dr. Makary. We could see this as soon as next week when the MAHA report comes out…or it could come at any time down the line.

How these conflicts are resolved is all-important to predicting  future FDA actions. Yet, the situation is opaque, at least in part because norm-breaking opens up so many possibilities.  

How Much Can FDA Do With Reduced Staff? While far, far from perfect, FDA mostly fulfills its responsibilities and completes its tasks in credible fashion, and in a reasonably timely manner. That is the norm we are all used to.

Because of the 20-25% staff loss, I have urged FDA and the Commissioner to engage in some truth-telling about what the agency can still do and in what timeframe.[3]  I am doubtful that things are fine. I assume there will be an increasing number of missed deadlines.

Much of FDA’s future over the next couple of years depends on whether there is a staff shortage and how existing staff are deployed. What is the new norm for FDA in this regard?  We do not know and may not know for months. The situation is opaque and makes scenario-building and prediction nearly impossible.

FDA will survive whatever comes next…and the next thing after that. However, our ability to see the agency’s direction and predict its future depends on the resolution of several unknowns. The potential for norm-breaking by the Administration multiplies the scenarios and makes each situation opaque.

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1. https://www.fdamatters.com/fdamatters/is-rfk-jr-better-suited-to-be-an-advisor-than-an-executive

2. From an earlier FDA Matters column: FDA statutory authority is assigned to the Secretary, who has delegated it to the Commissioner, who I believe has delegated certain decisions to the center directors. All of these delegations can be withdrawn, in whole or part, at any time.  https://www.fdamatters.com/fdamatters/fda-and-politics-an-unhealthy-combination.

3. https://www.fdamatters.com/fdamatters/truth-telling-fda-user-fee-edition 

Picking Apart the Destructive Claim That Industry Controls FDA

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I am tired of the continued defamation of FDA as an agency controlled by industry. 

That is not to say that FDA is perfect or that there have never been FDA-industry interactions that looked (and maybe were) bad. However, as a generalization….no, FDA is not controlled by industry. 

Such allegations are usually based on ignorance or a genuine misunderstanding of how FDA works. Sometimes it is hard to tell, as with recent statements that advisory committees: decide drug approvals (not true)[1], are dominated by industry (not true), and are cleansed in some meaningful way by eliminating the single, non-voting industry member of the committee (not true)[2]. 

While untrue…allegations of industry-control have consequences. They weaken public acceptance of FDA’s  independent, science-based decisions. They endanger the upcoming user fee reauthorization negotiations. They demoralize staff—a significant proportion of whom want lengthy public service and public health careers at FDA and are not looking for industry jobs. 

The Resolving Door: An Every Day, Everywhere Phenomena

One of the most often cited examples of industry influence is the so-called “FDA revolving door.”  One of my readers even wrote me a note last week, wondering “Isn’t it interesting  how many ex-FDA officials wind up in prominent roles within the industry they were charged to provide oversight.”  

To which I replied: next jobs are built on current jobs. In both the public and private sectors, employers hire well-qualified people based largely on their career experiences.  

There is nothing nefarious—or even out of the ordinary—that people leaving FDA wind up working in regulated industries. That’s where the bulk of the opportunities will be for them. It’s also where people with their credentials—with or without FDA experience--are most likely to be valued. 

There may be a lot of ways a pharmacologist (or a food chemist, or a biostatistician) can make a living, but a significant percentage of those opportunities will be in industry. Does a PhD chemist have to become a car salesperson because otherwise he or she would be perceived as taking advantage of their education, training, and experience to work in or adjacent to FDA regulated industry? 

A Self-Fulfilling Prophecy of Alleged Industry Influence

The DOGE initiative was responsible for the RIF of 3,500 FDA employees. Incentives and lay-offs were used to drive an unknown number of others to leave FDA. 

The bulk of these people had made their careers at FDA or were planning to do so. They were not looking for industry jobs but are being forced to do so now. 

DOGE has created a self-fulfilling prophecy of FDA employees going to work for industry. By Fall, I envision stories that will feed the defamation of FDA: “John Smith, formerly FDA division director for X, now works at [insert name of company with interests in developing X-type products].”

Why shouldn’t they hire him: no one else will have a better understanding of what FDA will require for approval of their product. The company will still have to prove the product is safe and effective and can be supplied at scale to the market using current good manufacturing practices and after an inspection.

FDA Is Not So Easy to Influence

The supposed revolving door is not the only argument you hear. Each and every medical and food decision that appears to favor industry seems to be fair game for the accusation that influence was involved. 

Let me repeat my caveat here: I am not saying that FDA is perfect or that there have never been FDA-industry interactions that looked (and maybe were) bad. However, as a generalization….no, FDA is not controlled by industry. 

At least on the medical products review side, FDA decisionmaking has three characteristics: it is bottom-up; it is multi-disciplinary; and no one has authority to make non-routine final decisions except the center directors.

As a result, lots of FDA staff have the opportunity to have their say about recommended actions as they make their way up the chain. Plus, if there is continued contention, there is often an internal review that includes senior staff not previously involved. In addition, the decisionmaking process often includes a public advisory committee meeting, with independent experts. 

No one can make a decision at FDA that hasn’t been scrutinized by at least a few people and, in most cases, by many people. There is no secret or unilateral decision making[3]. There is really not much opportunity to influence FDA (no less control it) that dozens of people would not know about. 

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1. FDA cannot delegate drug approvals to a non-governmental entity or person, even if it wanted to.

2. Applying Chesterton’s Fence to Industry Representatives on FDA Advisory Committees. Third item at: https://www.fdamatters.com/fdamatters/how-many-people-still-work-for-fda-amp-other-fda-thoughts 

3. There are a few well-publicized examples of center directors overruling senior staff on efficacy issues (not safety), but the issues involved were well-aired publicly both before and after the decision was made. https://www.fiercebiotech.com/biotech/fdas-marks-i-contradict-fda-reviewers-trepidation 

New CBER Leadership: The FDA Matters Analysis

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The headline, “Dr. Prasad to succeed Peter Marks as CBER director,” spread like wildfire Tuesday night after Endpoints News broke the story. 

Reactions ranged from “Omigod, he’ll destroy the industry and the hopes of patients” to “no big deal, staff do the product reviews regardless of who runs the Center.” Experience tells me his tenure is likely to be a little bit of “omigod” and a little bit of hands-off deference to reviewers….but mostly his time at CBER will be measured by how well he led the center during a time of great promise for products within its jurisdiction. 

My three observations (below) were written before two further stories broke last night, recounting the results of Dr. Prasad’s incredibly positive first meeting with FDA staff. The stories are at Inside Medicine and STAT News. They more than vindicate my belief that Dr. Prasad’s prior and more recent statements should not pre-judge what he will do as the CBER director. 

Observation 1: When outsiders become insiders, they take on responsibilities that did not burden their prior opinions. 

It is easy to have an opinion when someone else will be making the decisions and bearing the consequences. It is quite a different matter when you have the power to decide, and your decision will directly affect the course of many people’s lives. 

It is not so much that Dr. Prasad will change his mind, but rather personal responsibility and public accountability change your perspective. He may come to the same conclusion as when he was a commentator, but often he will see things differently. 

I said this of Dr. Makary—and it is the universal experience of becoming a government official--nobody knows for certain how they will respond to a given situation until they actually have to make the decision that affects people’s lives. 

Observation 2: Advocates would be well-advised to continue focusing on their medical and policy positions and not project a straight-line from Dr. Prasad’s past comments to his future actions.

I received a frantic note from a friend and former colleague asking how to block the appointment because Dr. Prasad was going to kill off research and investment in targeted cancer therapies. I could have gotten similar notes with any of a half-dozen other topics in the subject line.

I responded that there was no way (to my knowledge) to block the appointment. I added that while CBER will be different under Dr. Prasad, it doesn’t mean that all the decisions will be different from his predecessors. Some will be genuinely different, but some might be the same, perhaps with small tweaks and new names.

In light of this, I would advise advocates to focus on tightening the case for the policy they want. Show that the science is good and the unmet need serious and worthy of attention. 

Rebutting past statements by Dr. Prasad just feels off by tying him to the past. Advocates should stick with positive positions that are deeply documented and convincingly presented. 

Observation 3: Drs. Makary and Prasad appear to be aligned on vaccines (cautious support but also skeptical), but do not initially appear to be aligned on cell and gene therapy and orphan drugs. 

Along with Dr. Makary, Dr. Prasad was part of a group of physicians who were loudly critical of much of the US public health response to COVID-19. There is a presumption (but no evidence yet) that the two are aligned on vaccines. The bigger question is likely to be how the two of them will handle Secretary Kennedy’s far more critical view of vaccines. 

On orphan drugs (including cell and gene therapies), there is an initial misalignment that I do not expect to last. Dr. Makary has advocated for a new pathway for drugs for ultra-rare diseases (based on plausible mechanism)[1] and has acknowledged the difficulties of trials with small populations. Dr. Prasad has generally emphasized stronger trials that are designed to produce more definitive information. 

Based on my own sense of the situation—reinforced by the Inside Medicine and STAT News articles on his first remarks to FDA staff—I see an easy transition for him to be more supportive of orphan drugs without backing down overall on seeking greater clinical trial rigor. 

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1.  https://friendsofcancerresearch.org/news/biocentury-makary-new-ultrarare-path-will-provide-approval-based-on-plausible-mechanism/

Truth-Telling: FDA User Fee Edition

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After 50 years in Washington, I have no expectation of being told the truth by government officials—elected or appointed. I like to think I have seen it all—shading the truth, burying the truth, plausibly deniable truth, and sometimes things entirely made up and called the truth[1]. 

I try not to be fooled. I imagine that my audience is also world-weary in this regard. 

Despite my low expectations, I have never abandoned the hope that someone will come along and prove that you can tell the truth and not lose your job. 

Which brings me to my point: I really want to believe in the truthfulness of what Commissioner Makary says. He is smart and earnest, although his hard job has become even more difficult between the time he said “yes” and the time he was sworn in (FDA and Politics: An Unhealthy Combination).  More importantly, it is hard to be trusting of him when his boss and his boss’ boss are on such notoriously poor terms with truth-telling. 

In an April 2 column (Random Arbitrary RIF’s Drive the Initial Makary Agenda), I laid out some next steps for the new Commissioner. As far as I can tell, he is following them (because they are logical, not because I suggested them). I wrote: 

Thus, the single most pressing priority for Commissioner Makary is figuring out what FDA can still do….Equally important, he will have to figure out what the FDA cannot do or cannot complete in a specific timeframe…and address statutory, Congressional, and stakeholder concerns. 

There is a lot to unpack there, but today I want to focus on medical products user fees. 

Based on the leaked OMB budget memo[2], there is a commitment to finish the current five-year user fee cycle[3], even if the next round is uncertain[4]. 

In exchange for user fees, FDA has agreed to targets for the amount of time needed to complete certain reviews. The metric is the time, not the people, but it is obvious that FDA cannot be on time if it lacks enough fully staffed review teams to do the work. 

There have been a few times in the past when FDA has known, in advance, that it would not make a significant number of user fee due dates. I am fairly sure there was a blip after the 2018-2019 government shutdown. I have a vaguer recollection of a prior blip---maybe associated with the late passage of the 2017 user fee reauthorization bill. [After publication, two readers pointed me to January 2008 when CDER warned that—due to the increased workload from implementing FDAAA requirements and short-staffing—that reviewers were free to miss deadlines for a while. Eventually, the on-time completion rate leveled-up]

Each of those had a discernable reason outside FDA’s control. FDA was able to acknowledge delays and speak generally about when the agency would be back on schedule. 

Once Commissioner Makary knows better what he can and cannot do (maybe around June 2 when the RIF’s take effect?), he needs to forthrightly address the shorter term. It is not pocket change: medical products companies have a $5 billion financial commitment to FDA for activities in FY 26 and FY27[5]. 

They know they don’t get approvals for that money, but they have been promised a timely process. If FDA cannot deliver, then it makes sense to re-set the goals so as to make the next two years as certain, timely, and productive as possible. 

As hard as it might be for Dr. Makary to do so, that discussion starts with FDA being truthful about the situation.

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1. “Making things up” type of truths has gained a rather large foothold in DC over the last decade. Once its main adherent is gone, I like to think we will return to “barely true” as the historical floor for political and governmental discussions. 

2. Discussed here: https://www.fdamatters.com/fdamatters/leaked-fy-26-fda-budget-document-explained 

3. The document explicitly says the proposed budget authority (BA) appropriations will be sufficient to meet the maintenance of effort provisions in law that trigger FDA’s ability to collect user fees. 

4. https://www.fdamatters.com/fdamatters/the-possible-demise-of-user-fees-existential-threats-require-outside-the-box-thinking 

5. I want to emphasize that this pays for a robust process, not for any particular outcome. I feel strongly that this is legitimate and look forward to further offering my views on this when the renewal cycle gets started.

The American People in the Hands of an Indifferent Government

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Several decades ago, when I was a Senate staffer, I observed that I could spend the entire Gross Domestic Product on the good ideas that people brought to us. I soon learned that lawmaking requires a substantial amount of restraint and a lot of prioritizing. Those are hard virtues to develop and very hard to keep when you face voters every few years. 

Annual Budget Deficit Is Not Sustainable. Our country has been driven by the worst possible budget cycle: when in power, Democrats vote to expand government programs (increasing expenditures); when in power, Republicans cut taxes (reducing revenue)[1]. Not surprisingly then, we annually spend $1.5 trillion to $2 trillion more than the revenue that comes in and we have accumulated a national debt of more than $35 trillion[2]. Unless we can get the annual deficit under better control, we could face a $17 trillion increase in the national debt over the next decade. 

There are only three ways to reduce the deficit: cut discretionary program spending; cut entitlement and mandatory program spending; and/or raise revenue (mainly taxes)[3]. None of these options are popular. 

The Trump Approach Is Unambiguous; Indifferent to Goals Other Than Cost-Cutting. The Trump approach is rapid and massive program cuts sufficient to pay for continuation of 2017 tax cuts and to make, at best, a token contribution to deficit reduction[4]. Adding any substantial revenue increase is unthinkable. Any obstacle to tax cuts and programs cuts must be moved aside, regardless of the consequences. 

This is philosophically comfortable for the Trump Administration because they are fundamentally anti-government. I discussed this is an earlier column, Three Historical Forces Clashing Over the Future of American Government. 

This is also stylistically comfortable, as well. President Trump’s favorite part of The Apprentice was saying: “you’re fired.” It’s music to his ears.

The Price Is Steep and Will Fall Hardest on Programs that Help People. Within our FDA stakeholder community, I keep being asked: where is the sense in cutting staff who ensure food and medical product safety? Why would they risk losing global leadership in medical products innovation by cutting both NIH and FDA? Why would they drive a major program initiative (food chemicals) and then lay off staff that are experts in that area? 

Every day, I also look beyond FDA and see things like deliveries to food banks halted; CDC staff working on lead poisoning in children laid off; deep cuts to fundamental life sciences research; and the planned end of Head Start[5]. 

The sad truth, as I explained in Random Arbitrary RIF’s Drive the Initial Makary Agenda, is “you do not downsize the DOGE way if your only goal is a smaller, more efficient federal workforce that serves the American public and its needs.” 

While difficult to fully grasp, the current administration is indifferent to the human plight. There is no interest in making government work for the good of the people or to promote innovation and investment or much of anything else that might get in the way of cost cutting and downsizing the federal government. 

The Solution is in Congress, If there is to be a Solution at All

We are about to start the part of the budget and appropriations cycle where Congress will get to have its say. In the next few weeks, the FY 25 reconciliation process will begin. A FY 25 rescission bill is likely to be received from OMB[6], and we will have a skinny and then a regular FY 26 president’s budget request. 

A substantial number of Republican Members of Congress disagree with at least some part of what is going on in the Executive Branch. Whether they will speak up and vote their beliefs remains to be seen. 

An immediate hot spot will be Medicaid. The program is far more popular, particularly in red states, than Republicans had realized before the threat of enormous cuts. Plus, there are wide swaths of government programs that have been bipartisan until this year. Are there Republican Members who are prepared to vote for halving NIH or disrupting FDA? 

Finally—and perhaps significantly—President Trump has received terrible polling numbers on his first one hundred days—the lowest for any President at this juncture in the last 80 years (here). The White House is in angry denial, but there is no indication that the Administration will act differently in order to raise his polling numbers. However, some Republican Members of Congress might be influenced by this seeming weakening of Trump support. 

Please let Congress know that you support carefully planned, targeted reductions in government programs[7]….but not wanton disregard for the programs that matter most to the American people, and which provide excellent value.

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1. I am aware of one exception. President Clinton managed to reduce the deficit AND expand government programs. His government downsizing initiative, which was largely bloodless, played a part, but so did a booming economy,  widespread integration of the internet into government and other workplaces, and a “peace bonus” from the end of the Cold War.

2. Anticipating an objection: I am not necessarily against some level of deficit spending. It is often necessary (war, pandemic, countercyclical support for an economy in recession, investment in future growth and innovation). However, piling up another $17 trillion in debt over the next decade is foolhardy. Even getting the annual shortfall down to $500 billion would be an enormous accomplishment. 

3. Elsewhere in my writings I have referred to this as “the iron triangle of deficit reduction.” 

4. There is a relationship between the two. If the 2017 tax cuts are continued but not offset by budget cuts, then the deficit will explode. 

5. https://apnews.com/article/head-start-trump-funding-budget-cuts-education-204077e046329eb22c71445d57ba002b 

6. The predominant Constitutional view is that the President is obligated to spend money that has been appropriated. If he wants to do otherwise, he must send Congress a rescission bill specifying current year cuts being proposed. Congress has to adopt the bill for the monies to be withdrawn. 

7. The successful Reinventing Government initiative in the 1990’s resulted in significant downsizing. I describe that earlier effort at https://www.fdamatters.com/fdamatters/what-is-happening-to-federal-workers-at-fda and https://www.fdamatters.com/fdamatters/three-historical-forces-clashing-over-the-future-of-american-government

How Many People Still Work for FDA & Other FDA Thoughts

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FDA’s responsibilities have not changed since January 20th. However, its capacity to carry out its duties has been meaningfully reduced by the Administration’s downsizing. We should all be able to agree on that. 

It has not been clear how many people still work for FDA after the RIF and voluntary departures. How many employees are left to get the work done? That seems especially important to know[1]. 

Yet, in the absence of an announcement or the release of budget documents, we have been left in the dark.

I have been working with the assumption that there are 19,500 full-time equivalent employees[2], which is based on extrapolating from older budget documents and reflects the flat taxpayer funding and modest user fee increases in FY 24 and FY 25. My number should be reduced by the RIF announced by Secretary Kennedy (3,500) and the lay-offs and voluntary separations (reported to be 900-1000 but I have no confirmation). 

That projects to roughly 15,000 remaining employees and is a 20% to 25% downsizing of the FDA workforce. Also, we can reasonably assume there are unfilled vacancies that occurred between July 1 and December 31, 2024. It is unclear if they are included in the 4,500 or are additional to it. 

In contrast to my rough calculation of a 20% to 25% downsizing, one news organization is calling it a 15% downsizing of FDA. They did not include voluntary separations because that number has never been announced. Anecdotally, we know there are a lot of voluntary separations, but excluding them makes sense if we do not know whether it is 100 or 1000. 

Further, that news organization was working from the Office of Personnel Management’s official FedScope database, which shows the FDA workforce in September 2024 as just under 21,000 (here).  That is an official source, presumptively more accurate than mine. However, I cannot reconcile the OPM numbers with any data I have in my files[3]. Using their methodology, FDA might have as many as 17,500 FTE employees remaining. 

How many employees are left to do the work is profoundly important. Yet, we have a discrepancy of 2,500 FTE employees between two good-faith estimates!

I am not sure my numbers are right. In fact, I hope that they are way too low. 

I am not critical of the other analysis. It is a less speculative than mine and based on better documentation of January 1 staffing levels. However, it probably does not account for other sources of departures and may overstate the baseline headcount. 

If somebody has better numbers, please let me know. 

False Choices: Priorities Do Not Need to Compete

Based on his recent interview, Dr. Makary believes that the microbiome[4] is the key to many  chronic conditions. Coming from a family with a long history of gastrointestinal diseases, this seems plausible, even intriguing.

However, “plausible and intriguing” is a reason to put more resources into a particular area of  research……not a reason to put less into other areas that have already proven their value (e.g., cell and gene therapy). 

Why would we choose one or the other, rather than pursue both? 

The same could be said about two of Secretary Kennedy’s priorities. Why does an autism focus need to be framed in a way that diminishes other areas of research on childhood diseases? Why emphasize chronic disease as if infectious diseases no longer have the power to rapidly reshape human destiny. 

To be clear, I favor more attention and investment in the microbiome, autism, and chronic diseases. In the process we should not lessen our efforts on cell and gene therapy, other childhood illnesses, and infectious diseases. We need to be able to find the resources to give proper attention to all of these priorities. 

Applying Chesterton’s Fence to Industry Representatives on FDA Advisory Committees

I was quoted in BioSpace, this week, observing that:

Industry representatives on advisory panels do not vote; do not have a professional or monetary interest in the outcome; and have little ability to sway the outcome. Yet, they do provide a useful perspective that other panelists often value. Nonetheless, the appearance is jarring, and it is understandable that questions are being raised. 

Missing from my quote and most of the public discussion has been a description of the benefits of including industry reps. Once companies deliver their presentations and answer questions, they must remain silent.

If the committee discussion misstates the company’s data or position, often the industry representative is the one who clarifies the company’s point and gets the advisory committee’s discussion back on track.

I do not see the tide turning in favor of keeping the industry representatives. However, I wish that someone had applied Chesterton’s Fence[5] first: do not take down a fence until you understand why someone put it up.

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1. I have written several times about the other part of the problem: since RIF’s were random and arbitrary, is there any reason to think the remaining workforce has the needed distribution of expertise to match the agency’s responsibilities. https://www.fdamatters.com/fdamatters/rx-for-fda-an-agenda-for-the-commissioner 

2. Full-time equivalent (FTE) is a way to standardize headcounts within a workforce. Two half-time employees equals one FTE. 

3. I wonder if the dramatically higher OPM number counts total employees rather than FTE’s. Or maybe there are one thousand never-to-be-filled slots in the total that are now permanent vacancies. 

4. https://www.niehs.nih.gov/health/topics/science/microbiome#:~:text=The%20microbiome%20is%20the%20collection,our%20bodies%20and%20inside%20us 

5.  https://www.fdamatters.com/fdamatters/chestertons-fence-the-meaning-of-deregulation-other-thoughts-about-fda 

FDA and Politics: An Unhealthy Combination

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Dr. Makary is a physician, healthcare quality and outcomes researcher, and self-styled iconoclast. When he accepted the Commissioner position in November 2024[1], I am sure he believed that Trump 2.0 would be a hospitable place to harness those personal attributes in the cause of a more effective, consumer and patient-focused FDA. 

I am certain, as well, that at that time he would have wholeheartedly affirmed my mantra: FDA will  be okay as long as it is committed to incorporating good policy, good medicine, good public health practices, and good science into all agency decisions. 

A Lot Has Changed Since Dr. Makary Said “Yes” to Being Commissioner

From the perspective of last Fall, I doubt he anticipated that this Administration would devote itself so vigorously and globally to  “norm-breaking.”  Or that it would relentlessly pursue its positions with a highly politicized and deeply personal fervor. 

Likewise, he could not have foreseen in the Fall of 2024 that the value of public and private investment in life sciences and health would be so dramatically devalued in March and April of 2025[2] or that his staff would be cut by more than 20% via random and arbitrary RIF’s[3]. He could not have foreseen that “radical transparency” would include frequent suspension of the “notice and comment” provisions of the Administrative Procedures Act, which are the bedrock of our government’s commitment to be inclusive of all views. 

When Dr. Makary said yes in November 2024, I doubt he intended to fill the agency with political appointees or to politicize agency decisions or to abandon good science. 

A Tradition of Keeping FDA Out of Politics

Traditionally—and this is a deeply imprinted cultural norm—the Commissioner stays out of product decisions. And so does the Secretary[4]. Such decisions are made by the center directors, who, to my knowledge, have never been political appointees. Even the center directors have tried their best (not always successfully) to keep the focus on what the review team decides, often with input from an advisory committee. 

Product approvals should be based on science, not politics. FDA’s process, while not always perfect, is intended to reinforce that. 

So far, no line has yet been crossed in 2025[5]. The three appointments announced this week are known quantities with strong ties to the agency[6]. 

Nonetheless, pressures are building. The leadership ranks have  thinned considerably, and more appointments are coming. Also, presumably, a backlog of decisions has been growing since January. 

As far as I can tell, there are no legal barriers to politicization. Specifically, FDA statutory authority is assigned to the Secretary, who has delegated it to the Commissioner, who I believe has delegated certain decisions to the center directors. All of these delegations can be withdrawn, in whole or part, at any time. 

All of which is to say: the integrity of FDA and of FDA decisionmaking are at risk. It is up to Dr. Makary to either be the bulwark against politicization….or to defer to his boss and the prevailing ethos of the new Administration. 

I am sure that some readers are saying: Steven, why are you putting this in writing? Do not give the new Administration any ideas. To which I can only respond: nothing in this column is a surprise to the Administration, HHS, or FDA. 

The issue is whether–despite deeply rooted tradition and good common sense--Dr. Makary and his bosses want to politicize the agency. It is not whether they have the authority or means to do so. 

Along with the rest of the stakeholder community, I have a preferred outcome and await evidence of which course of action they pursue.

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1.  https://hub.jhu.edu/2024/12/01/marty-makary-fda-appointment/

2. For example, if one were to believe (I do not) that life sciences should be advanced solely in the  private sector and not publicly-stimulated through NIH, then you still need to support FDA. Without an expert and credible FDA with predictable standards and well-understood process, there will not be much private investment in the life sciences. 

3.  https://www.fdamatters.com/fdamatters/random-arbitrary-rifs-drive-the-initial-makary-agenda

4. In the rare instances this has been challenged, it has always been around reproductive issues and products. To the best of my knowledge, it has always been resolved without impacting issues or products beyond reproductive ones. 

5.  With the possible exception of one review of a vaccine that is past its PDUFA due date. This is a serious concern, but not sufficient by itself to decide that FDA has been politicized.

6.  https://www.statnews.com/2025/04/22/fda-marty-makary-new-leaders-deputy-commissioner/

Leaked FY 26 FDA Budget Document Explained

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There is a document widely-circulated this morning that purports to be the OMB passback to HHS of the draft proposed FY 26 HHS President’s budget request. It includes proposed numbers for FDA funding for the coming fiscal year. 

It is still subject to negotiation and therefore may change between now and the release of the President’s request. Note that it is not the FY 25 recissions package—anticipated in the next week or two—that would, if enacted, reduce current-year FY 25 funding and make the proposed FY 26 cuts look smaller. 

The table (below) compares the FY 26 leaked proposal with the FY23 numbers for the budget authority (BA) portion of FDA funding. This is the non-user fee portion that comes from taxpayer funding[1]. 

In the aggregate, FDA BA funding in FY 24 and FY 25 (current year) are slightly lower than FY 23. Individual line items varied more, so the comparison with FY 23 should be viewed as illustrative of the general magnitude of proposed changes over a three-year period. They are not definitive, relative to the FY 24 and FY 25 appropriations. In particular, Human Drugs BA spending decreased in FY 24, so that the one-year decrease (compared to FY 25) is not as great as it looks by reference to the three-year decrease. 

Based on the text and the table, the following conclusions can be drawn: 

• I have focused only on the BA appropriations level because user fee funding levels are derived by formula rather than calling for any policy judgment by either the Administration or Congress[2]. 

• There is a statement in the HHS text that these proposed appropriations numbers are sufficient to meet maintenance of effort funding requirements (i.e., permitting user fees to be collected). I have no way to confirm this, but OMB/HHS/FDA have accurate numbers for the necessary amounts. It is, therefore, reasonable to assume their statement is accurate. 

• I have called into question the long-term prospects for user fees (here). However, proposing sufficient appropriated funding to meet the maintenance of effort requirements in FY 26 suggests that the intent is to at least complete the existing five-year cycle. The real risk in the long-term is to reauthorization in 2027, as reflected by the expressed opposition of Trump/Kennedy to industry funding of some FDA activities. 

• The overall cut from FY 23 funding levels would be in the vicinity of 17%. I will have more to say about this in my follow-up next week.

• The food budget cut is accompanied by reference to moving all routine facilities inspections to the states. The viability of this approach would turn, among other things, on 1/ whether the state contracts would include enough additional dollars to offset increased state costs; 2/ which states have the infrastructure to go it alone; 3/ how much money will be left in FDA for national coordination and enforcement plus reinspections.  

• There is no funding proposed for buildings and facilities and no monies appear to be allotted for pay increases based on time in grade. (Cost-of-living increases are explicitly rejected). Any such costs will need to be absorbed by FDA within the proposed budget levels. 

• I have referenced in earlier columns that FDA spends about $2 billion in BA funding on medical products programs. This number is derived from a “major functions analysis” that appears in budget documents in most years. It includes funds that are in every line item—not just CDER, CBER, and CDRH. As a result, the OMB passback numbers do not tell us how much overall medical product spending from BA funds will be cut. 

• The HHS reorganization document circulated  at the same time….is interesting but does not appear to affect FDA or its proposed funding. 

If subscribers to “FDA Matters: The Grossman FDA Report” (subscribe on the website at www.fdamatters.com) have additional questions, please send them to me. I will try to answer them via a column early next week.

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1. Note that FDA took all budget documents off their website in late January, making it nearly impossible to do any comparative budget analysis. However, I have the FY 23 enacted numbers, which are accurate, and I am using as the baseline. I have seen analysis that uses the FY 24 baseline, which I believe is also accurate. Using FY 23 vs. FY 24 should not make any fundamental change in my conclusions. 

2. Note that total medical product user fees are derived by excluding tobacco user fees, indefinite user fees, and a smattering of food user fees. The total does appear to increase in FY 26 but only modestly and presumably in line with the amounts called for in the five-year user fee agreements. 

Rx for FDA: An Agenda for the Commissioner

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While FDA’s responsibilities have not changed, its capacity to perform its duties has been significantly reduced. After subtracting approximately 4,500 employees[1] from the agency’s 19,000 employee workforce, it cannot possibly sustain its heavy workload. 

Outrage is justified. With little more than a wave of a hand, tens of thousands of hours of valuable expertise have been lost. The next challenge will be FDA’s struggle to retain its current appropriated funding levels once rescissions are sent to Congress[2] and House budget cutters dig into other spending vehicles. Last, but hardly least, the $2.6 billion that FDA derives from medical product user fees is under attack by the Secretary of HHS. 

A greatly diminished FDA threatens potentially devastating consequences for our nation’s public health and commerce. 

Nonetheless, we should all root for FDA’s success. Any other position risks making the situation even worse. 

Here are some elements for an FDA action plan that tries to maximize results despite the agency’s diminished capacity. 

Continue to incorporate good policy, good medicine, and good science into agency decisions. We know that this is what Dr. Makary intends. However, he did not necessarily sign on for random arbitrary RIF’s and such a substantially diminished staff. Nonetheless, it falls to him to make the best of the situation and to re-create the most effective FDA he can. 

First, the Commissioner needs to take careful inventory of the education, skills, and experience of remaining staff, focusing upon rebuilding the multidisciplinary review and inspection teams. Leadership of the agency matters, but it is those teams that get the work done. 

Second, inventory in hand, Dr. Makary needs to figure out what FDA can still do, given a workforce that is at least 20 to 25% smaller. Equally important, he will have to figure out what the FDA cannot do (or cannot complete in a specific timeframe)....and address statutory, Congressional, and stakeholder concerns.

Third, the Commissioner must re-start the engine of production. FDA employees are incredibly talented and amazingly committed—but no one could have maintained full productivity from the February 14 lay-offs through the April 1 RIF’s and through the recent tone-deaf visit by the HHS Secretary. It will take time for teams to re-form, and work-arounds figured out. Then it will take additional time for productivity to begin to approach former levels. 

We did see some progress with last week’s announcement of FDA’s plans to phase out the animal testing requirement for monoclonal antibodies and other drugs (announcement and Americans for Medical Progress and my comments). 

Despite the cries of victory from animal rights groups, the underlying policy is an evolutionary one—roadmaps, pilot projects, and incentives for greater use of animal alternatives where scientifically feasible. It is the result of decades of work by FDA, NIH, and the drug development community. 

A few quick solid accomplishments like the animal testing announcement will not make the pain and disappointment go away. But it could get us started on a new narrative that takes the agency from disruption back to production.

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1. The RIF announced by Secretary Kennedy (3,500) and the lay-offs and voluntary separations (reported to be 900-1000 but I have no confirmation). Secretary Kennedy has said that up to 20% of the RIF’ed employees were mistakes who  would be rehired, but there is no evidence of follow-through on that. Also, we can reasonably assume there are also unfilled vacancies that occurred between July 1 and December 31, 2024. We do not know if they are included in the 4,500 or are additional to it.

2.  After Easter recess we are told.

Chesterton’s Fence: The Meaning of Deregulation & Other Thoughts About FDA

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Earlier this week, I posted an “FDA-Related Thought of the Day.” According to LinkedIn, it has generated an astounding 29,796 impressions (and counting!). That’s a lot more interest than it garnered when I first posted it a month ago (here). Here is what I said (slightly edited): 

Understaffed regulatory agencies (i.e., FDA) will tend to say “no” more often because they do not have the staff, time, or focus needed to reach “a nuanced yes.” 

Think of the breakthroughs at FDA; think about how much extra time and experienced and well-trained staff were required. 

The LinkedIn posting drew a brilliant question (thank you Christy):  “Would that still be the case [less capacity for a nuanced “yes”] if an administration has a goal of cutting regulatory burden while also taking savings from cutting staff?”

Here is how I replied (again, slightly edited): 

In most cases, the opposite of regulation is not "no regulation" or “deregulation”....it is "less burdensome regulation." You want food to be safe--you can decide some current steps are unnecessary, but history tells us that going to "no regulation" does not deliver a safe food supply. Caveat emptor is rightfully associated with a notoriously unsafe food supply and “anything goes” patent medicines.

Deciding that three checkpoint steps assures safety just as well as five checkpoint steps is important in lessening regulation. However, if it really is "as good," then most of the savings will be on the industry side (two fewer checkpoints), not at FDA where they still need to assure the outcome, such as “a safe food supply.”

"Chesterton's Fence" is metaphor for why you cut regulations carefully: Do not tear down a fence until you know why it was put up to begin with.

That leads to two other points:
1/ you do not cut employees today on the promise of cutting regulatory burden sometime in the future.
2/ government is not a business. But no business would do a large RIF without a plan in place to assure the downsized entity can function. In the DOGE-led downsizing, there is no plan--the RIFs were random and arbitrary.

“Deregulation” and “eliminating regulations” are universally extolled and make great campaign slogans. However, they are just that: slogans. 

Rather, “less burdensome regulation” or “lessen the regulatory burden” seem like appropriate goals to me. That allows us to encourage re-evaluation and change in the regulatory environment…while minimizing bad outcomes and not carrying forward the biased assumption that less regulation is always better. 

Yesterday, the Administration ordered government-wide wholesale repeal of regulations. To facilitate this, they suspended the requirement for “notice and comment rulemaking” under the Administrative Procedures Act. “Notice and comment rulemaking” is the bedrock of government transparency. 

Politico was not impressed. https://www.politico.com/news/2025/04/10/federal-agencies-public-notice-comment-trump-administration-00284499. Nor am I. It reinforces my view that “eliminating regulations” is most-often a slogan rather than a mindful exercise. 

Response to Possible/Proposed Massive Reorganization of FDA. The Center for Science in the Public Interest (President Peter Lurie/Director of Regulatory Affairs Sarah Sorscher) posted an insightful critique of the reorganization proposal being circulated by the administration (here). 

I reposted it on LinkedIn and added the following thoughts: 

“A massive reorganization of FDA—changing functions, philosophy, and process--will endanger consumers and patients, create chaos for industry, and dramatically reduce FDA productivity for months. Therefore, it follows: even if the proposed reorganization of FDA is brilliant (and we can certainly disagree about that), the unknown long-term benefits of such change (5 years?) is unlikely to exceed the extremely high and far more certain short-time costs (2-3 years). Count me as a fan of well-planned incremental changes.” 

In turn, the article by the Center for Science in the Public Interest and my comment were reposted by former Commissioner Califf, who observed: 

“Hard to tell what is really being planned vs what is being "floated". Transparency would be helpful.”

Response to FDA Commissioner Makary’s Decision to Permit Some Reviewers to Work from Home. Mathew Perrone of Associated Press (AP) reported the story here. 

The story quotes me about first steps for Dr. Makary and how “work at home” fits in: 

"Dr. Makary needs to rebuild teams and restart the engine of productivity lost to weeks of job insecurity, uncertainty and shortages of team members,” said Steven Grossman, a former HHS official. “Turning commuting time back into work time is a great first step in achieving both.” 

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The Possible Demise of User Fees: Existential Threats Require Outside-the-Box Thinking

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Last Thursday, Alec Gaffney of AgencyIQ declared “…the future of FDA’s user fee programs is in extreme jeopardy” (here). Alec has a well-deserved reputation as one of the best FDA analysts. Alec talks; people listen. 

For the most part, I agree with him and have been building up to this conclusion since January (see addendum “Rising Concerns About User Fees”). 

There is an urgent need to counter the widespread assumption that user fees will be renewed because the alternatives are unthinkable. True, Congress is not going to provide the extra $2.6 billion in taxpayer funding. But we now have leaders who seem ready, perhaps eager, to let the user fee programs lapse. 

The existential threat is real. Fresh, outside-the-box thinking is essential if we are to prevent a potential disaster.

Today’s column is about my reasons for coming to the same conclusion as Alec (albeit with some differences in perspective). An upcoming column will look at various scenarios for the endgame.

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The case for renewing medical product user fees[1] rests on the belief that FDA needs a robust, credible, and expert staff to: 1/ assure safe and effective medical products, 2/ maintain its “gold standard” reputation as a global regulatory agency, and 3/ be an engine of medical product innovation[2]. 

President Trump and Secretary Kennedy see FDA in an entirely different light. Among other things, they point to user fees, the revolving door, and an emphasis on products that treat rather than cure chronic diseases….and conclude that the agency is overstaffed, corrupt, and controlled by the biopharmaceutical, medtech, and food industries[3]. 

So far, there is no evidence that President Trump and Secretary Kennedy:

• see the benefit to the US of having an FDA that is robustly staffed with credible experts.

• appreciate that FDA’s food and medical product responsibilities require complex, multidisciplinary teams whose members are not interchangeable with each other[4].

• care whether cuts to FDA and NIH will hurt patients, undercut FDA’s standing as the global regulatory “gold standard,” and  jeopardize the development and review of innovative biopharmaceutical and medtech products in the United States.

• would make an exception to a government-wide RIF and severe budget cuts in order to preserve an agency they think is in the hands of industry and making decisions that they see as antithetical to the public interest. 

In short, we are going to be trying to change the minds of people who are indifferent to what most of us value. We may see a disaster coming, but they do not. This is the challenge ahead as stakeholders and Congress work toward reauthorization of medical product user fees. 

These are not just rhetorical points. Secretary Kennedy has acted (or failed to act) with disregard for FDA’s ability to do its job as it has historically been defined and funded. 

• With RIF’s (3500 employees) and voluntary departures (variously estimated at 900-1000 employees), FDA will have lost upwards of a quarter of its workforce 1/ suddenly, with no time for transition, 2/ with no analysis or plan to guide the RIF process, and 3/ protecting only reviewers and inspectors from the RIF without regard for the fact that it is “review teams” and “inspection teams” that are required 

• Medical product user fees account for slightly more than 40% of the agency’s total budget[5] and account for well more than half of monies spent on medical product programs[6]. Altogether, FDA spends approximately $4.6 billion on medical products-- $2.6 billion from user fees and $2 billion from appropriated (taxpayer) funding. Any reduction in the FDA workforce and funding requires consideration of the status of medical product user fees, especially of the underlying “letter of agreement” workplans. 

• User fee agreements contain 1/ targets for funding additional employees[7],  so that FDA’s capacity to perform work in a specific timeframe is enhanced and 2/ maintenance of effort provisions designed to ensure that user fees supplement rather than supplant budget authority (BA) appropriation (taxpayer funding)[8]. Both provisions are problematic after the lay-offs and RIF’s, and with the President’s plan to submit a proposal to Congress to rescind FY 2025 appropriated funds.

For lack of what President Trump and Secretary Kennedy view as “extra staff,” the agency is going to start missing product review dates and fail to complete other user fee tasks in a timely manner. For lack of appropriated dollars, FDA may fail to maintain the share of their activities that must be paid by taxpayers in order to be able to collect user fees[9]. 

Medical product user fees should have been a major part of the conversations thus far. The deafening silence on this issue does not bode well for the user fee reauthorization cycle that starts this coming summer.

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1.  They are renewed in five-year cycles and might be likened to a cooperative agreement between FDA and the involved industry. There is another $700 million in tobacco user fees. That program is permanent, not cyclical, and is an imposition on an unwilling industry. This article concerns medical product user fees and is not applicable to the tobacco program. 

2.  All of those goals are also true for food and nutrition. However, user fees are not part of funding those programs. 

3.  Politico’s April 3, 2025 interview with Secretary Kennedy’s primary surrogate, Calley Means: https://www.politico.com/video/2025/04/03/inside-rfk-jr-s-maha-agenda-with-calley-means-playbook-deep-dive-1561174

4.  Discussed further at: https://www.fdamatters.com/fdamatters/what-is-happening-to-federal-workers-at-fda. NB: it may be possible to have fewer teams, but in many (if not most) cases, you cannot have fewer team members.

5.  Higher percentages are often shown that reflect mixing medical and tobacco user fees, which are in no way alike. 

6.  Roughly, FDA’s $6.8 billion budget is divided: BA for medical products programs $2 billion; BA for food programs $1.5 billion; UF for medical products programs $2.6 billion; and UF for tobacco $700 million.

7.  Expressed as FTE’s—that is full-time equivalents to reflect the common situation in which an employee is funding partly from user fee funds and partly from BA appropriated funds. https://www.fdamatters.com/fdamatters/special-edition-fda-rifs-and-user-fees-explained 

8.  Maintenance of effort—and its consequences—are well-explained by Alec Gaffney, here. 

9.  Resolution of the MOE issue is necessary but not sufficient for the continuation of the user fee programs. I believe that there are likely to be both bookkeeping and legislative solutions for the MOE triggers issue that can be negotiated if the continuation of user fees is otherwise accepted by all necessary parties. 

Rising Concerns About User Fees Addendum to: “The Possible Demise of User Fees: Existential Threats Demand…”

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January 24, 2025 column in FDA Matters: https://www.fdamatters.com/fdamatters/keep-calm-and-carry-on-lessons-from-trump-10 

Eight years ago, just before President Trump was sworn in for the first time, I expressed my belief in FDA’s ability to survive change. I wrote: 

“Despite the stridency of the rhetoric and the substantial uncertainty about 2017, Republicans and Democrats have, for decades, mutually supported an FDA that is well-functioning and fulfills its incredibly important public health mission.”  

It is reasonable to have doubts whether this remains true in 2025. 

February 14, 2025 column in FDA Matters: https://www.fdamatters.com/fdamatters/short-takes-and-updatesfebruary-14-2025 

1. When Will Congress Engage on the Future of FDA User Fees?

Either the agency is captured by industry (Secretary Kennedy), or it is a hindrance to industry (Vivek Ramaswamy). I understand how it could be neither…but not how it can be both.

The lack of clarity is of concern to nervous corporate executives and many FDA employees. I have pointed out that PDUFA VII and MDUFA V and GDUFA III do not expire until September 30, 2027, with initial discussions only just starting this summer. There is time for this discussion after the new Administration has been in office for a while and taken care of more pressing issues. 

I am starting to feel a bit nervous about this answer. So far, the new Administration has shown little patience for waiting on anything. If they feel strongly, they seem to want to engage immediately….contractual agreements and statutes not necessarily representing barriers. 

This is not a prediction, just a lessening of my certainty that user fees are off the table until later. 

February 18, 2025 column in FDA Matters: https://www.fdamatters.com/fdamatters/if-being-mission-critical-is-not-important-enough-what-is 

Government-wide, protecting the more valuable functions of the government (agencies, service  and people) formed no apparent part of the employee reductions[1]. 

It may be crazy to do a RIF at FDA when laid-off employees are mission-critical to medical advances and food safety and play a key role in national and global commerce…. 

*** 

In assessing the current situation, I am left with an obvious question that appears to have no immediate answer: if being mission-critical is not valuable enough to save an employee, service, or program, what is?

February 23, 2025 column in FDA Matters: https://www.fdamatters.com/fdamatters/special-edition-fda-rifs-and-user-fees-explained 

Footnote 3: To assure that user fees did not supplant BA (appropriated) funding, the user fee laws contain “maintenance of effort” provisions for how much BA money must be appropriated before user fees can  be collected. The triggers vary for each program. These “maintenance of effort” provisions are not likely to be triggered by lay-offs but become an issue later if Congress tries to shrink the FDA’s BA budget beyond a certain point. We will address this in a future column if it becomes relevant. 

[April 4, 2025, observation: assuming a reasonable amount of bookkeeping flex on BA vs. UF staff, the RIF’s as such do not trigger the crisis. Rather, the triggers become an issues when/if Congress lowers FDA’s BA appropriations, which is likely to be part of an upcoming recission package to be sent to Congress]

March 7, 2025 column in FDA Matters: https://www.fdamatters.com/fdamatters/short-takes-and-updates-march-7-2025 

4. User Fees Still Likely to Continue, But Not a Sure-Thing

The process of negotiating the next set of medical product user fees would normally start with some public hearings in the Summer or Fall of this year. That allows enough time to have user fee legislation before Congress by January 2027. 

In my Short Takes column of February 14 (here), I suggested that the new Administration might want to begin sooner and have a broader conversation about the purpose and value of user fee programs. 

This week, AgencyIQ (in a members-only analysis of recent EO’s and prior RFK, Jr.’s statements) concluded that “user fee programs could undergo major reforms, or even be terminated, during the next reauthorization cycle – all over concerns about undue “industry influence.”

 March 27, 2025 story in Roll Call: https://rollcall.com/2025/03/27/targeting-fda-user-fees-would-leave-agency-gutted-experts-say/. 

Steven Grossman, a regulatory consultant at HPS Group and author of the FDA Matters newsletter, said in an email to CQ Roll Call that his concerns about the future of the user fee program have grown since the Trump administration took over. 

“The risk of dramatically different medical product user fee programs — or none at all — has gone from blue (general risk) to at least yellow (significant risk),” he wrote. “If somebody suggested orange (high risk), I would not say they are exaggerating.”

Writing in a Feb. 14 blog post, Grossman said the process for negotiating the next set of user fee programs would typically start with hearings beginning in the summer or fall, allowing time for the legislation to be drafted by January 2027. 

“My hope is that it warns stakeholders not to take renewal for granted,” he said in an email. 

April 2, 2025 column in FDA Matters: https://www.fdamatters.com/fdamatters/random-arbitrary-rifs-drive-the-initial-makary-agenda

When you stop trying to rationalize what is going on, you get to the simple but startling truth: random, arbitrary RIF’s are intended to: 

1/ destroy government credibility and expertise, 

2/ demoralize remaining staff, 

3/ make it near-impossible to recruit experts in the future; and 

4/ reduce staffing levels to where competent program performance will be challenging if not impossible. 

It feels like such a big leap to such a radical conclusion—that the mind wants to deny the possibility. 

However, you do not downsize the DOGE way if your only goal is a smaller, more efficient federal workforce that serves the American public and its needs[1].

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1.  It was done successfully in the 1990’s with a minimum amount of disruption and only modest RIF’s that were implemented at the end of the process. See my analysis of the “Reinventing Government” initiative.