Off-Label Vaccine Use Persistent, Increased Awareness Needed

An increase in off-label vaccine use has persisted and is varied across several countries since the COVID-19 pandemic, according to a study published in Vaccine.¹

Amid the limited number of global policies and recommendations regarding off-label vaccine use, researchers support boosting awareness and strengthening dialogue surrounding this type of vaccine administration.

“Numerous reasons exist for making off-label recommendations for vaccines,” wrote authors of the study.¹ “These reasons may include specific age groups or sub-populations that may be at heightened risk for complications arising from the disease, such as administering influenza vaccinations to immunocompromised patients and pregnant women who were not included in pre-licensure clinical trials, and therefore may not be listed in the product labelling information.”

Similar to that of medications used off-label, vaccines can be administered for reasons other than their approved functions. The FDA firmly stands behind the safety and efficacy of using prescription products for their approved use only. However, they too acknowledge the fact that many providers may be forced to prescribe medications or vaccines off-label if there are no other approved options, or if a specific patient has had little success with the available options.²

READ MORE: Increased Vaccination Could Curb Burden of Community-Acquired Pneumonia

With vaccines for infectious diseases, however, off-label immunization has the potential to impact communities across the world as well as individuals who even decided against getting vaccinated. This sentiment was apparent during the COVID-19 pandemic, a public health emergency impacting global populations.

“In countries such as in North America, off-label use is more accepted as prescribers are responsible for their prescriptions, including off-label use of a particular drug,” wrote authors of a previous study.³ “For vaccines, public health recommendations set the standard of care and even if off-label, these recommendations should be and most often are followed by those delivering vaccines.”

The World Health Organization’s (WHO) National Immunization Technical Advisory Groups (NITAGs) are one example of authorities on public health, providing recommendations for all health care professionals administering vaccines. However, since the COVID-19 pandemic has waned, researchers wanted to understand how off-label vaccines have evolved.

“The present study aimed to examine the adoption and trends in off-label vaccine recommendations by NITAGs in low-, middle-, and high-income countries, with a specific focus on changes observed since the COVID-19 pandemic,” continued authors of the current study.¹ “Furthermore, the study sought to identify the evidence requirements, legal implications, enabling factors, and policy frameworks that support the integration of off-label vaccine use into immunization programs.”

Among NITAG representatives from all 6 WHO regions, researchers distributed online surveys focusing on the off-label vaccine policies, procedures, legislation, and regulations of various NITAGs throughout the world. The analysis was conducted to include data for off-label vaccine use before 2020; during the pandemic, from 2020 to 2022; and following the pandemic, after 2022.

Survey respondents were asked a series of questions that explored the evidence and enablers used when considering off-label vaccine use. They were also asked about the review and implementation processes regarding off-label vaccine distribution. Finally, on the legal and regulatory side, NITAG representatives were asked about the policies, procedures, and concerns surrounding off-label vaccine recommendations.

While any country a part of WHO with a NITAG was invited to participate, the researchers concluded their analysis with a total of 76 survey responses from NITAG or immunization program managers across the world.¹

Of the 76 survey responses, 52 (68%) reported that off-label vaccine decisions are being made, leaving 43% of NITAGs and immunization managers that have not made off-label recommendations. And, despite these responses showing a lack of recommendations provided, many were from countries that had specifically mandated off-label vaccine use.

Overall, among responses from countries where off-label vaccination is prominent or not, researchers supported the idea that off-label vaccine use is significantly nuanced across the world.

“In some instances, the reason for off-label recommendations may be mostly related to logistics such as supply issues (COVID-19 vaccines) that occurred during that timeframe,” they continued.¹ “It is possible that activities related to the COVID-19 pandemic have influenced how NITAGs perceive and approach off-label recommendations, resulting in greater acceptance and comfort with this practice. Interestingly, while most countries identified making off-label recommendations, few countries indicated having policies and procedures for implementation and evaluation.”

Based on trends in the past decade or so, the COVID-19 pandemic has served as a significant catalyst for increased off-label vaccine use around the world. Rather than curbing these efforts amid a post-pandemic landscape, researchers suggest that further development and understanding of off-label vaccinations is necessary.

“Although WHO broadly provides guidance on the mandate and core functions of NITAGs, globally, they have differing mandates and operational capacities related to off-label vaccine use,” concluded the authors.¹ “These findings suggest the need for increased awareness of off-label vaccine recommendations and strengthened dialogue around implementation of off-label recommendations.”

READ MORE: Immunization Resource Center

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References

1. Roberts C, Top KA, Henaff L, et al. Exploring off-label vaccine use: a survey of the global national immunization technical advisory group network. Vaccine. 2025;62:127581. https://doi.org/10.1016/j.vaccine.2025.127581

2. Understanding unapproved use of approved drugs “off-label.” FDA. February 3, 2018. Accessed August 14, 2025. https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/understanding-unapproved-use-approved-drugs-label

3. Neels P, Southern J, Abramson J, et al. Off-label use of vaccines. Vaccine. 2017;35(18):2329-2337. https://doi.org/10.1016/j.vaccine.2017.02.056