FDA's Marty Makary: Everything should be over-the-counter unless it's unsafe or requires monitoring

Key Concepts

• GLP-1s Compounding: Unapproved, mass-produced versions of glucagon-like peptide-1 receptor agonists, often marketed for weight loss.
• 503A & 503B Compounding: FDA regulations governing pharmacy compounding, with 503A for personalized medicine and 503B for larger-scale production.
• mRNA Technology: A novel vaccine technology using messenger RNA to instruct cells to produce antigens, triggering an immune response.
• Over-the-Counter (OTC) Drugs: Medications available for purchase without a prescription.
• Spread Pricing: A practice by Pharmacy Benefit Managers (PBMs) of charging health plans more for drugs than they reimburse pharmacies.
• Pre-IND & IND Applications: Stages in the FDA drug approval process, with Pre-Investigational New Drug (Pre-IND) being an initial consultation and Investigational New Drug (IND) allowing human trials.
• IRB (Institutional Review Board): Committees that review and approve research involving human subjects.

FDA Priorities & Regulatory Updates: A Discussion with Dr. Marty McCary

I. Addressing Mass Compounding of GLP-1s

Dr. McCary emphasized the FDA’s serious concern regarding the mass compounding of GLP-1 receptor agonists (like Ozempic and Wegovy). He highlighted that companies adhering to the FDA approval process – undergoing Phase 1, 2, and 3 trials – are subject to rigorous regulation regarding marketing claims and adverse event reporting. The core issue is that many compounding facilities are not complying with regulations outlined in sections 503A and 503B of the FDA guidelines.

Specifically, the FDA is cracking down on “mass marketing claims” and the importation of Active Pharmaceutical Ingredients (APIs) that haven’t received FDA approval. Dr. McCary stated the FDA is directly communicating with these companies, demanding compliance with regulations. He referenced the HHS referral of “his and hers” compounding clinics to the Department of Justice, noting the FDA issued a warning letter to the company in September regarding their marketing practices, which deviated from FDA guidance.

Dr. McCary expressed hope that this year will see a reduction in unlawful mass compounding, even after the initial shortages have subsided, particularly as more companies source APIs from approved suppliers like Novo Nordisk and Eli Lilly. He believes increased competition, operating within a regulated framework, is beneficial.

II. mRNA Flu Vaccine & FDA Guidance

The discussion shifted to the FDA’s refusal to file Moderna’s mRNA-based influenza vaccine application. Dr. McCary clarified that the traditional seasonal flu shot remains available and has a well-established approval process, backed by 80 years of data and over 40 clinical trials.

The primary concern with Moderna’s application stemmed from the control group used in the trial. The FDA guidance recommends using the standard of care (existing flu vaccine) as a control, not a substandard one. Dr. McCary explained that physicians raised concerns about unnecessarily exposing individuals over 65 to a higher risk of influenza complications by using a substandard control. The FDA reviewed the topline data but communicated to Moderna that they did not follow the agency’s guidance. The company can now submit the full review for further consideration.

Dr. McCary stressed the FDA’s strong guidance process, where scientists provide clear direction on trial design during initial meetings. He acknowledged that occasionally companies deviate from this guidance, which can compromise data integrity, but the FDA evaluates each case individually, considering the strength of the data.

III. Enhancing Predictability in the Review Process

Addressing concerns about predictability in the FDA review process, Dr. McCary highlighted the strength of the initial guidance provided by FDA scientists during pre-trial consultations. He acknowledged instances where companies deviate from this guidance (e.g., early crossover of intervention groups), which can complicate data analysis.

He cited the publication of the FDA’s COVID vaccine framework in the New England Journal of Medicine as an example of proactive communication, outlining a risk-stratified approach and suggesting post-marketing randomized trials. The goal is to provide clarity for markets, patients, drug developers, and investors, fostering a thriving ecosystem.

IV. The Future of mRNA Technology & Vaccine Regulation

Dr. McCary expressed optimism about mRNA technology, stating the FDA will apply the same scientific standards to all drugs, regardless of platform. He emphasized the importance of data: “I am very hopeful and optimistic on mRNA technology in general. I love it. I’d like to see the data.” He cautioned against “hyperenthusiasm” and reiterated the FDA’s commitment to data-driven approvals. He specifically mentioned the potential of mRNA in oncology and expressed a desire to see compelling data in that field.

V. Increasing Access to Medications: OTC Initiatives

Dr. McCary outlined a key FDA goal for the year: increasing the availability of drugs over-the-counter (OTC). Specific medications under evaluation include vaginal estrogen, nausea medications, and naloxone for opioid overdose. He questioned the rationale for requiring prescriptions for these medications in a modern context, advocating for greater trust in individuals to make informed decisions.

He linked OTC availability to lowering drug prices, citing the price transparency associated with shelf pricing compared to the complex pricing structures involving employers, insurance companies, and pharmacy benefit managers (PBMs). He also highlighted the need for Pharmacy Benefit Manager (PBM) reform, specifically addressing “spread pricing” – the practice of PBMs charging health plans significantly more for drugs than they reimburse pharmacies. The Department of Labor recently mandated transparency of spread pricing, a practice Dr. McCary described as “price gouging.”

The FDA aims to streamline the process for companies to switch drugs to OTC status, changing monographs and reducing bureaucratic hurdles. Dr. McCary suggested that most drugs should be available OTC unless they pose a safety risk, require laboratory monitoring, are prone to misuse, or are addictive.

VI. Competition with China in Biotech Innovation

Dr. McCary addressed the growing biotech ecosystem in China, noting that in 2024, China conducted four times the number of Phase 1 clinical trials compared to the United States (2,800+ vs. 800). He acknowledged that this gap has recently begun to close.

He emphasized the need for “giant big ideas” to bring Phase 1 trials back to the US, including reforming hospital contracting and Institutional Review Board (IRB) approval processes, which he described as “clunky” and “non-competitive.” He also highlighted the lengthy Pre-IND to IND application process in the US (520 days) compared to China (just over 200 days, with a goal of 60 days).

Dr. McCary proposed exploring partnerships with health systems and academic medical centers to streamline the Pre-IND process and reduce regulatory burdens on IND applications, suggesting a need to remove redundant questions from the application process. He concluded by emphasizing the importance of collaboration between the FDA and industry to deliver cures and treatments for the American public.

Quote: “If a question has had the same affirmative answer the last 10,000 out of 10,000 times, why are we asking it?” – Dr. Marty McCary.

This discussion highlights the FDA’s proactive approach to addressing emerging challenges in drug regulation, promoting innovation, and ensuring patient safety and access to affordable medications.