5 Key Regulatory Shifts From Makary's Era at the FDA

The FDA has undergone a series of major policy shifts under Marty Makary, MD, MPH, who recently resigned from his position as FDA commissioner.¹ These shifts reflect an agenda centered on accelerating drug development, modernizing review systems, and recalibrating evidentiary standards.

Here are 5 key developments defining his regulatory landscape:

1. Ended the 2-Trial Standard for Drug Approvals

In a landmark shift announced in February 2026, Makary and FDA deputy Vinay Prasad, MD, MPH, declared the agency would move away from the long-standing 2-trial standard for drug approvals, making a single pivotal trial the new default for most therapies.² The change marks one of the FDA’s biggest regulatory shifts in decades, replacing guidance that, since 1998, had generally been interpreted as requiring 2 clinical studies to establish safety and efficacy.

Makary and Prasad argued that advances in biologic understanding, trial design, and statistical methods have reduced the need for duplicative studies.

“Going forward, the FDA’s default position is that 1 adequate and well-controlled study, combined with confirmatory evidence, will serve as the basis of marketing authorization of novel products,” they wrote.

The FDA also noted that roughly 60% of first-in-class drugs approved in the past 5 years were already cleared based on a single study, particularly in oncology and rare diseases.

2. Pushed to Accelerate Biosimilar Competition

The FDA issued draft guidance removing the routine requirement for comparative efficacy studies in biosimilar development and stated that all biosimilars should be considered interchangeable.³ The agency said advances in analytical science can often provide more sensitive and reliable evidence of similarity than traditional clinical trials.

Under the updated framework, developers may rely more heavily on comparative analytical assessments, pharmacokinetic similarity studies, and immunogenicity data to demonstrate biosimilarity, reducing the need for large, resource-intensive efficacy trials. The FDA said this shift could significantly lower development costs, often estimated at $100 million to $300 million, and shorten timelines that typically span 6 to 9 years.

Makary framed the guidance as part of a broader effort to cut regulatory barriers, increase competition, and lower biologic drug prices, though stakeholders note that market and manufacturing challenges may still limit the pace of uptake.

3. Commissioner’s Priority Voucher Program Accelerated Reviews

In June 2025, the FDA launched the Commissioner’s National Priority Voucher (CNPV) pilot program to dramatically shorten review timelines for select drug and biologic applications.⁴ The CNPV initiative aims to reduce review periods from more than 6 months to as little as 1 to 2 months for products addressing priorities such as public health emergencies, breakthrough therapies, unmet medical needs, supply chain resilience, and affordability.

The program uses a multidisciplinary “tumor board-style” review process and offers enhanced communication and rolling review to participating companies. Despite the accelerated timeline, the FDA stated that products in the program must still meet the agency’s existing standards for safety, effectiveness, and regulatory approval.

4. Integrated AI into FDA Drug Review

In October 2025, the FDA launched a generative artificial intelligence (AI) system called Elsa to improve efficiency across scientific review, inspection, and regulatory workflows.⁵ Built within a secure GovCloud environment, the tool is designed to support FDA staff by summarizing documents, assisting with clinical protocol reviews, and streamlining scientific evaluations.

Elsa is already being used to accelerate tasks such as adverse event summarization, label comparisons, and prioritization of inspection targets. The system is powered by a large language model and is intended to help employees read, write, and synthesize large volumes of regulatory information more quickly.

Makary, alongside FDA leadership, said the tool represents an early step in integrating AI across agency operations, with plans to expand its use in data processing and other regulatory functions while maintaining strict data security.

5. Revised COVID-19 Vaccine Recommendations for Lower-Risk Groups

In May 2025, Makary and Prasad outlined a shift away from broad COVID-19 booster recommendations toward a more risk-based approach in a New England Journal of Medicine policy framework.⁶

Under the new framework, boosters would be supported primarily for adults over 65 and individuals 6 months and older with risk factors for severe disease, using immunogenicity data as the basis for authorization. For healthy individuals ages 6 months to 64 years, the FDA said it would require randomized controlled trial evidence on clinical outcomes before granting broader approval.

The policy reflects uncertainty about the benefit of repeated boosters in low-risk populations and declining uptake of annual COVID-19 vaccines while maintaining broader access for those at highest risk.

References

1. Mattina C. Makary to resign as FDA commissioner. AJMC®. Last updated May 12, 2026. Accessed May 13, 2026. https://www.ajmc.com/view/makary-to-resign-as-fda-commissioner
2. Bonavitacola J. FDA will require only 1 study to approve new drugs, speeding up the process. AJMC. February 19, 2026. Accessed May 13, 2026. https://www.ajmc.com/view/fda-will-require-only-1-study-to-approve-new-drugs-speeding-up-process
3. Jeremias S. FDA guidance to remove one of the largest barriers to biosimilar development. AJMC. October 29, 2025. Accessed May 13, 2026. https://www.ajmc.com/view/fda-guidance-to-remove-one-of-the-largest-barriers-to-biosimilar-development
4. Commissioner's National Priority Voucher (CNPV) pilot program. FDA. Current as of April 28, 2026. Accessed May 13, 2026. https://www.fda.gov/industry/commissioners-national-priority-voucher-cnpv-pilot-program
5. McNulty R. FDA launches agency-wide AI tool to aid in scientific review. AJMC. June 3, 2025. Accessed May 13, 2026. https://www.ajmc.com/view/fda-launches-agency-wide-ai-tool-to-aid-in-scientific-review
6. Prasad V, Makary MA. An evidence-based approach to COVID-19 vaccination. N Engl J Med. 2025;392(24):2484-2486. doi:10.1056/NEJMsb2506929