Addressing the Cold Reality of mRNA Vaccine Stability

J Pharm Sci. 2021 Mar;110(3):997-1001. doi: 10.1016/j.xphs.2020.12.006. Epub 2020 Dec 13.

Abstract

As mRNA vaccines became the frontrunners in late-stage clinical trials to fight the COVID-19 pandemic, challenges surrounding their formulation and stability became readily apparent. In this commentary, we first describe company proposals, based on available public information, for the (frozen) storage of mRNA vaccine drug products across the vaccine supply chain. We then review the literature on the pharmaceutical stability of mRNA vaccine candidates, including attempts to improve their stability, analytical techniques to monitor their stability, and regulatory guidelines covering product characterization and storage stability. We conclude that systematic approaches to identify the key physicochemical degradation mechanism(s) of formulated mRNA vaccine candidates are currently lacking. Rational design of optimally stabilized mRNA vaccine formulations during storage, transport, and administration at refrigerated or ambient temperatures should thus have top priority in the pharmaceutical development community. In addition to evidence of human immunogenicity against multiple viral pathogens, including compelling efficacy results against COVID-19, another key strength of the mRNA vaccine approach is that it is readily adaptable to rapidly address future outbreaks of new emerging infectious diseases. Consequently, we should not wait for the next pandemic to address and solve the challenges associated with the stability and storage of formulated mRNA vaccines.

Keywords: COVID-19; Cold chain; Formulation; Lipid nanoparticles; Shelf life; Stability; Vaccine; mRNA.

MeSH terms

  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / chemistry*
  • COVID-19 Vaccines / immunology
  • Cold Temperature
  • Drug Stability
  • Drug Storage / methods
  • Humans
  • RNA Stability
  • RNA, Messenger / chemistry
  • RNA, Messenger / immunology
  • SARS-CoV-2 / immunology
  • Vaccine Potency*
  • Vaccines, Synthetic / chemistry*
  • Vaccines, Synthetic / immunology

Substances

  • COVID-19 Vaccines
  • RNA, Messenger
  • Vaccines, Synthetic
  • mRNA Vaccine
  • mRNA-1273 vaccine
  • BNT162 vaccine