FDA Advisory Committee Vote to Simplify COVID-19 Regimen

COVID-19 vaccines have been available for only approximately 2 years and have already undergone multiple revisions to the recommended vaccine schedule. Vaccine dosing timelines and composition can vary widely depending on age, immune status, and type of SARS-CoV-2 vaccine received. 1 It is perhaps one of the most complex schedules for a vaccine directed towards a single preventable disease that the average pharmacist has ever had to manage. For this reason, some health care providers have developed and/or are using tables or flowcharts to remain oriented to the intricacies of COVID-19 vaccine dosing. It’s been suggested that that these complexities have, at least partially, contributed to difficulties in communication about vaccine benefit and vaccine uptake throughout the country.² However, there is hope that a simplified COVID-19 vaccine dosing and administration structure will become a reality.

On January 26, 2023, the FDA’s Vaccines and Related Biological Products Advisory Committee voted to recommend harmonizing the SARS-CoV-2 vaccine strain composition of both the primary series and booster doses to a single composition and with the consideration that all vaccines administered within the United States be a bivalent vaccine. The advisory committee spent over 9 hours listening to data presented by experts from the FDA, the CDC, and from the manufacturers of currently available COVID-19 vaccines. Although exact details of a simplified COVID-19 have not been finalized, the conversation on moving to a consistent strain composition for all vaccine doses was generally supportive.

Jerry Weir, PhD, director of the Division of Viral Products at the FDA, presented to the committee several benefits that simplification and alignment of the vaccine would produce. These include improved antibody response with bivalent vaccine, a simplified immunization schedule applicable to all COVID-19 vaccines, increased ability to use immunogenicity and efficacy data to modify future versions of the vaccine based on evolving variants if needed, and alignment with recommendations from the European Medicines Agency Emergency Task Force.²

While the advisory committee’s vote might be viewed as a step forward, a lot of uncertainties remain. The coronavirus continues to do what comes naturally and evolve, with new variants continuing to emerge. Almost all the variants that have emerged in recent months have been versions of the Omicron variant, but that does not necessarily translate into cross-immunity among the subvariants.³ Currently, primary series for COVID-19 vaccines remains monovalent and encode or contain ancestral SARS-CoV-2 spike protein; bivalent vaccines were introduced to provide protection against the Omicron variant.

Literature published through the end of 2022 suggested an indeterminate benefit of a bivalent vaccine compared to monovalent vaccines for the BA.4 and BA.5 strains.⁴ However, these 2 subvariants have mostly been replaced with strains who are more able to evade the immune system.

For the SARS-CoV-2 Omicron sublineage XBB, a recent report evaluating patients through mid-January 2023 suggested that the bivalent booster dose provide protection against symptomatic infection caused by XBB-related viruses for at least 3 months following the booster administration in patients previously receiving 2 to 4 monovalent vaccine doses.⁵ Continued vaccine efficacy for future variants and lineages remains uncertain. During the advisory committee meeting, manufacturers indicated that a shift to a single composition would still allow them to alter the vaccine in accordance with the virus’ evolution, analogous to the way the influenza vaccine is adjusted to changes in circulating strains.² Advisory committee members questioned what the FDA’s response would be if a manufacturer did not update their vaccine product based on expert recommendation(s); though the FDA indicated that specific response had not yet been determined, the agency acknowledged that a plan for such a scenario would need to be addressed in the process of COVID-19 vaccine simplification.²

Other questions and discussion points brought forward by advisory committee members during the meeting included whether the vaccines should continue to use the ancestral strain and ideal timing of any future doses in both vaccinated and unvaccinated people. It was also suggested that alternative strategies be explored such as higher doses, which has proven to be beneficial in geriatric patients for the influenza vaccine.² Answers to these questions were not addressed during the meeting and it remains unclear when proposals could be expected.

The clinical impact of COVID-19 vaccine simplification is difficult to predict with so many questions still unanswered. However, there are several logistical and practical benefits for pharmacies, such as supply and inventory logistics, administration standardization, and more straightforward patient counseling approaches. The indeterminacy of when and if the advisory committee’s recommendation will come to fruition makes advanced planning almost impossible from the pharmacy perspective. Until the process determined and finalized, pharmacies are still bound to the current cumbersome process. Still, the advisory committee’s vote does provide hope that an easier strategy could be on the horizon.

References

1. CDC. Stay Up to Date with COVID-19 Vaccines Including Boosters. CDC website. Updated January 25, 2023. Accessed February 1, 2023. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/stay-up-to-date.html#recommendations
2. FDA. Vaccines and Related Biological Products Advisory Committee January 26, 2023 Meeting Announcement. FDA website. January 26, 2023. Accessed February 1, 2023. https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-january-26-2023-meeting-announcement#event-materials
3. COVID Data Tracker. Atlanta, GA: CDC; January 30, 2023. Accessed February 1, 2023. https://covid.cdc.gov/covid-data-tracker
4. Offit PA. Bivalent COVID-19 vaccines – a cautionary tale. N Eng J Med. 2023. doi:10.1056/NEJMp2215780
5. Link-Gelles R, Ciesla AA, Roper LE, et al. Early Estimates of Bivalent mRNA Booster Dose Vaccine Effectiveness in Preventing Symptomatic SARS-CoV-2 Infection Attributable to Omicron BA.5– and XBB/XBB.1.5–Related Sublineages Among Immunocompetent Adults — Increasing Community Access to Testing Program, United States, December 2022–January 2023. MMWR Morb Mortal Wkly Rep. ePub:January 25, 2023. doi:10.15585/mmwr.mm7205e1