FDA Questions Safety of Giving Multiple Vaccines at Once

The U.S. Food and Drug Administration (FDA) is re-evaluating the long-standing federal vaccine use policy that allows multiple vaccines to be given during the same visit—particularly COVID-19, influenza and RSV shots. In a memo last month, Vinay Prasad, MD, MPH, director of the FDA’s Center for Biologics Evaluation and Research (CBER), wrote that the agency “cannot affirm” the safety or effectiveness of administering coronavirus, influenza, and other respiratory virus vaccines simultaneously.^{1 2}

Dr. Prasad added that new clinical trials will be required before pharmaceutical companies can continue to claim that co-administration of vaccines and the RSV monoclonal antibody is safe and effective. Prasad cautioned:

At the same time, the potential downside is that multiple vaccines administered together may interfere with efficacy—one or more vaccines may not be as effective—or there may be new or higher rates of safety signals that would not have occurred with sequential vaccination.

Andrew Nixon, a spokesperson for the U.S. Department of Health and Human Services (DHHS), confirmed that the FDA will soon release a new framework outlining these vaccine use changes.^{1 2}

This marks the latest in a series of major policy shifts under Secretary of Health and Human Services Robert F. Kennedy, Jr. Since taking office, Secretary Kennedy has announced plans to restructure both the DHHS and improve operation of the federal Vaccine Injury Compensation Program (VICP). He has replaced members of the CDC’s Advisory Committee on Immunization Practices (ACIP); canceled or halted funding to mRNA vaccine development projects; suspended U.S. funding for Gavi, the Vaccine Alliance; reinstated a federal vaccine safety task force; and enacted sweeping vaccine policy shifts, including removing thimerosal (a mercury-containing preservative) from influenza vaccines, and enabled FDA and CDC officials to roll back recommendations for COVID shots to be given to pregnant women and healthy children.^{3 4}

Pfizer Counters FDA, Doubles Down on Support for Combination Vaccines

The FDA’s re-evaluation was a setback for Pfizer, which had been negotiating with the agency for approval of its updated mRNA coronavirus booster shots—millions of which have already been manufactured and may now be at risk for remaining unsold and unused, according to anonymous sources who spoke to The Washington Post. In a letter to physicians, Pfizer suggested that, although the FDA had not cleared the language, its COVID shot could still be administered simultaneously with other shots, also adding that certain batches contain “unapproved prescribing information inside the cartons.”¹

Evidence of Other Combination Vaccines Causing Adverse Events

Critics of the FDA’s shift argue that the existing practice of simultaneous co-administration of vaccines is safe, pointing to studies showing that receiving the influenza and coronavirus shots at the same time does not pose significant risks. However, a CDC study showed that people who received flu and coronavirus shots at the same time were “slightly more likely to have reactions including fatigue, headache, and muscle ache than people who got only a COVID-19  shot, but those reactions were mostly mild and went away quickly.”^{1 5}

The FDA’s new scrutiny of co-administering COVID, influenza, and RSV shots raises questions about whether similar attention will eventually be directed at all products that are labeled vaccines, which are typically given together, such as diphtheria, tetanus, and pertussis (DTaP), polio, Haemophilus influenzae type b (Hib), pneumococcal, measles-mumps-rubella (MMR), and varicella.

While different vaccines recommended for children have long been administered simultaneously with each other, research has documented instances where adverse events were more frequent with co-administration. For example, a 2010 study found that febrile seizures occurred at higher rates when children received the combined measles-mumps-rubella-varicella (MMRV) vaccine compared with administering separate MMR and varicella shots. A 2014 study reported that infants given influenza and pneumococcal conjugate vaccines (PCV13) at the same visit had an increased risk of fever compared to those who received the shots on separate days. Similar findings have been noted with the meningococcal B (4CMenB) vaccine administered simultaneously with other infant vaccines, where higher rates of fever and systemic reactions were observed.^{6 7 8}

Co-Administration of Vaccines Has Not Been Proven to Be Risk-Free

Public health professionals often emphasize that co-administration of vaccines has been practiced for decades and is considered safe based on pre-licensure clinical trial data and post-marketing surveillance. Yet much of that evidence comes from studies that did not use true inert placebos as a control for determining the safety and effectiveness of new vaccine products. Historically, clinical trials of new childhood vaccines have compared experimental products not with saline or another inactive substance, but with a “bioactive placebo,” such as another licensed vaccine or a vaccine ingredient like an adjuvant. These active comparators carry their own risks, making it difficult to definitively establish whether co-administration is truly risk-free.⁹

The DHHS has announced plans to change this proof of safety standard and require true placebo-controlled studies for future vaccines. With the previous design, at best, it shows that co-administration does not appear worse than what is already in use, which is not the same as proving the practice itself is risk-free.⁹

On Apr. 30, 2025, the DHHS announced that all newly developed vaccines will now be required to undergo placebo-controlled clinical trials before being licensed by the FDA. “Under Secretary Kennedy’s leadership, all new vaccines will undergo safety testing in placebo-controlled trials prior to licensure—a radical departure from past practices,” department officials said in a prepared statement. “The COVID vaccines, including new ones by Pfizer and Moderna, are new and must have more gold standard science to ensure safety and efficacy for the public.”⁹

Prasad pointed out in his memo that past company claims about giving vaccines together were “made on the basis of small randomized studies showing non-inferior antibody titers.” But, he wrote, antibody levels do not always translate into real-world protection, and such small studies are “inherently incapable of adequately documenting safety signals.” The studies, he says, are “simply too small to identify potential increases in adverse events, which Americans may wish to know.”²

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