FDA to Restrict Future COVID-19 Vaccine Recommendations to Older Adults, High-Risk Groups

The FDA has announced a shift in how the agency will evaluate COVID-19 vaccines, with future recommendations set to prioritize adults aged 65 years and older and those with 1 or more risk factors that put them at risk for severe COVID-19 while requesting additional randomized controlled trial data for healthy persons between the ages of 6 months and 64 years. The change in regulatory framework was announced by FDA Commissioner Martin A. Makary, MD, MPH, and Vinay Prasad, MD, MPH, director of the Center for Biologics Evaluation and Research, in an editorial published in New England Journal of Medicine.^1,2

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“The FDA will approve vaccines for high-risk persons and, at the same time, demand robust, gold-standard data on persons at low risk,” Makary and Prasad explained in the editorial. “These clinical trials will inform future directions for the FDA, but more important, they will provide information that is desperately craved by health care providers and the American people.”¹

Focusing on Older Adults, Those at Highest Risk

Since COVID-19 vaccines were first developed and proliferated throughout the United States in late 2020 and early 2021 under emergency use authorizations, they have been recommended by the FDA, CDC, and public health officials to eventually include everyone aged 6 months and older. As protection from the vaccine wanes over time, manufacturers developed booster doses of the vaccine to bolster protection months after a first dose is received. Additionally, due to the tendency of SARS-CoV-2 to mutate over time and change its viral composition, updated vaccines that included new circulating strains—like Delta and Omicron—have begun to be produced and authorized by the FDA yearly.^3-6

Now, under new leadership following the confirmation of Robert F. Kennedy Jr. as secretary of Health and Human Services, the FDA has signaled its intention to adapt the COVID-19 vaccination regulatory framework. In their editorial, Makary and Prasad wrote that they anticipated being able to make “favorable benefit-risk findings” regarding the ability of COVID-19 vaccines to generate antibody titers in people for adults over 65 years and all persons over 6 months with 1 or more risk factors for serious disease. But for healthy individuals with no risk factors for serious disease, the FDA officials “anticipate the need for randomized, controlled trial data evaluating clinical outcomes” before a biologics license application (BLA) is granted to a COVID-19 vaccine targeting this population.¹

New Requirements for COVID-19 Vaccines in Healthy Populations

“Insofar as possible, when approving a COVID-19 vaccine for high-risk groups, the FDA will encourage manufacturers to conduct randomized, controlled trials in the population of healthy adults as part of their postmarketing commitment,” Makary and Prasad wrote. This intention was seen with the FDA’s recent approval of Novavax’s Nuvaxoid, a protein-based COVID-19 vaccine indicated only for patients aged 65 and older and high-risk individuals aged 12 to 64 years. In accordance with the new policy, the FDA requested a phase 4 prospective, randomized, placebo-controlled trial in patients aged 50 through 64 years without high-risk conditions for severe COVID-19.⁷

Makary and Prasad described the FDA’s preferred study design for these new trials. Manufacturers should focus on the 50-to-64-year-old age group for future trials, with a primary end point of symptomatic COVID-19 and special attention to rates of severe COVID-19, hospitalization, and death. Critically, the officials advocated for the inclusion of Americans who have had COVID-19 in the past year while calling for a minimum 6-month follow-up period “to ensure that early booster gains persist.” At this point, it remains unknown whether vaccine manufacturers, such as Pfizer and Moderna, can conduct such trials in a timely manner as to ensure the vaccines are available for the 2025-2026 respiratory season.¹

With the FDA significantly altering its regulatory framework for COVID-19 vaccines, pharmacists are a critical resource for patients with questions. Many younger patients may be concerned about how future guidance may impact their options for protection against COVID-19, while older adults could express confusion and hesitation given the fluctuating state of current guidelines. Pharmacists should ensure they are up to date on the evolving landscape of COVID-19 vaccine recommendations and prepare their teams for a focus on older adults and those with comorbidities this upcoming respiratory season. At the same time, they must make sure that younger patients are not left behind in their care and know their options if they have severe COVID-19, including a litany of antiviral medications now available.¹

REFERENCES

1. Prasad V and Makary MA. An evidence-based approach to COVID-19 vaccination. N Engl J Med. Published May 20, 2025. Accessed May 21, 2025. doi:10.1056/NEJMsb2506929

2. Stein R. A stricter FDA policy for COVID vaccines could limit future access. NPR. Published May 20, 2025. Accessed May 21, 2025. https://www.npr.org/sections/shots-health-news/2025/05/20/nx-s1-5405013/fda-covid-vaccine-limits

3. Antrim A. FDA authorizes updated COVID-19 boosters from Moderna, Pfizer-BioNTech. Pharmacy Times. Published August 31, 2022. Accessed May 21, 2025. https://www.pharmacytimes.com/view/fda-authorizes-updated-covid-19-boosters-from-moderna-pfizer-biontech

4. Halpern L. Updated COVID-19 vaccines approved by FDA to defend against circulating variants. Pharmacy Times^®. Published August 22, 2024. Accessed May 21, 2025. https://www.pharmacytimes.com/view/fda-authorizes-updated-covid-19-boosters-from-moderna-pfizer-biontech

5. CDC. Staying up to date with COVID-19 vaccines. Updated January 7, 2025. Accessed May 21, 2025. https://www.cdc.gov/covid/vaccines/stay-up-to-date.html#cdc_vaccine_recommendations_section_2-recommended-covid-19-vaccines

6. Cleveland Clinic. COVID Vaccine – Overview. Last Updated October 23, 2023. Accessed May 21, 2025. https://my.clevelandclinic.org/health/procedures/covid-vaccine

7. Halpern L. FDA approves Novavax COVID-19 vaccine for patients 65 years and older, those with underlying conditions. Pharmacy Times. Published May 19, 2025. Accessed May 21, 2025. https://www.pharmacytimes.com/view/fda-approves-novavax-covid-19-vaccine-for-patients-65-years-and-older-those-with-underlying-conditions