Whether you're a pharmacist, a health care provider, or a patient, you probably have heard that vaccines must be kept in the fridge. But what does it mean exactly? At what precise temperatures must vaccines be kept? Do they all require the same storage conditions? And most importantly, what happens if a vaccine is left unrefrigerated?
Related article: How to travel with refrigerated medications?
What’s a Vaccine?
To understand why and how vaccines must be refrigerated, one first needs to understand what a vaccine is.
A vaccine is a pharmaceutical preparation used to stimulate the body’s immune response against viral or bacterial infections. There’s one vaccine per virus (or bacteria) or group of viruses (or bacteria). While most vaccines are injections, some can be administered via pills or nasal sprays.
Biological substances
Vaccines are inherently biological substances. Unlike chemically synthesized drugs, they contain living organisms or parts of living organisms, mainly from the virus or the bacteria itself (the antigen). Other ingredients commonly found in vaccines are preservatives, stabilizers, surfactants, diluents (sterile water), and sometimes adjuvants (aluminum salts).
Biologics are widely used in the pharmaceutical industry and include various products like vaccines, allergenics, somatic cells, tissues, and others. Typical biological medicines that also require refrigeration are insulin and other diabetes injections, arthritis medications like Humira or Enbrel, growth hormones, etc.
The recommended vaccinations in the United States include Chickenpox, Diphtheria, Tetanus, Pertussis, Hepatitis A, Hepatitis B, Hib, Papillomavirus, Flu, MMR, Meningococcal, Pneumococcal, Polio, Rotavirus, Dengue, and now COVID-19.
The fact that vaccines contain living organisms makes them extremely sensitive to storage conditions. Like any living thing you can think of (plants, fruits, animals, etc.), they can spoil quickly, deteriorate, and go bad if exposed to high temperatures or too much light. That’s why vaccines must be refrigerated and can only be left out of the fridge for a (very) limited time.
Related article: What drugs are refrigerated?
Vaccines storage temperatures
Like any biological substances, vaccines must be stored in the fridge and go through a breachless cold chain process from manufacturing to patient administration, passing by transportation, pharmaceutical storage, and healthcare services, among other steps.
Most vaccines must be refrigerated between 36°F and 46°F (2°C and 8°C), and ideally at 41°F (5°C) with as little temperature fluctuations as possible. Some vaccines even need to be stored at freezing temperatures between 5° F and -58°F (-15°C and -50°C).
Additionally, according to the Department of Health’s vaccine storage guidelines, they should be stored “in the middle of the fridge, two to three inches from the walls, ceiling, floor, door, and cold air vent. Do not store vaccine in doors or drawers”.
Each vaccine manufacturer must run laboratory tests and provide instructions about storing its specific biological product. Always read the vaccine’s storage instructions and double-check the required storage temperatures.
Related article: At what temperatures should you keep refrigerated medicines?
How long can vaccines stay out of the fridge?
Most vaccines have a very short shelf life. Usually, unpunctured vials can only be left at room temperature for a few hours maximum. And once a vaccine vial has been punctured, it must be administered quickly. However, the general rule does not apply to all vaccines, especially lyophilized ones (freeze-dried).
Here are some examples:
- The Moderna vaccine against COVID-19 can only stay at room temperature for 24 hours.
- The Pfizer-BioNTech COVID-19 vaccine may be stored at room temperature for up to 12 hours.
- The IPV vaccine (polio) is more stable and can be left unrefrigerated for up to one month with a maximum temperature of 77°F (25°C).
- Rabies vaccine can withstand temperatures as high as 140°F (60°C).
For detailed information about other vaccines, refer to their specific storage instructions. This World Health Organization’s study about the thermostability of vaccines is also a helpful resource. Researchers have analyzed the stability of the most common ones at different temperatures.
What happens if a vaccine is not refrigerated?
Like any biological substance, vaccines are very sensitive. They rarely go bad or contaminated, but they may lose their potency and effectiveness if not stored properly.
Several unsuitable storage conditions can affect a vaccine’s potency, including ultra-low temperatures, high temperatures, or exposure to light. As a result, the proteins in the vaccine may denature quickly, and the antigen may no longer be present, rendering the vaccination process pointless.
The denaturation of vaccines exposed to inadequate temperatures is progressive. For example, a study by Kumar et al. (1982) about the thermostability of the tetanus vaccine found that it could “survive temperatures of 35⁰C for several weeks, while at 45⁰C they experienced a 5% loss in potency per day (...). When exposed to temperatures of 60⁰C, the vaccine was rendered completely ineffective after three to five hours”.
Ultimately, when the cold chain is broken at any point, even for a short period of time, a vaccine can become less efficient or even completely inefficient.
Vaccinating a patient with a vaccine that has lost potency may put their health at risk because they won't be protected against future viral or bacterial attacks as much as they would have been with a full-potency vaccine.
References:
- Ozan S. Kumru, Sangeeta B. Joshi, Dawn E. Smith, C. Russell Middaugh, Ted Prusik, David B. Volkin,Vaccine instability in the cold chain: Mechanisms, analysis and formulation strategies, Biologicals, Volume 42, Issue 5, 2014, Pages 237-259, ISSN 1045-1056, https://doi.org/10.1016/j.biologicals.2014.05.007
- Sohail Ahmed, Ronald W. Ellis, Rino Rappuoli,66 - Technologies for Making New Vaccines, Editor(s): Stanley A. Plotkin, Walter A. Orenstein, Paul A. Offit, Kathryn M. Edwards, Plotkin's Vaccines (Seventh Edition), Elsevier, 2018, Pages 1283-1304.e7,ISBN 9780323357616,
- Powell BS, Andrianov AK, Fusco PC. Polyionic vaccine adjuvants: another look at aluminum salts and polyelectrolytes. Clin Exp Vaccine Res. 2015 Jan;4(1):23-45. doi: 10.7774/cevr.2015.4.1.23. Epub 2015 Jan 30. PMID: 25648619; PMCID: PMC4313107.
- Cao E, Chen Y, Cui Z, Foster PR. Effect of freezing and thawing rates on denaturation of proteins in aqueous solutions. Biotechnol Bioeng. 2003 Jun 20;82(6):684-90. doi: 10.1002/bit.10612. PMID: 12673768.
