Medieval to Modern: Refrigeration's Impact on Vaccine Degradation

The magic of medicine has blossomed over time to become what it is today, but modern medicine came into existence long before now. The 19th and 20th century were full of invention and discovery to help us get from where we were, when severe illnesses were often believed to be supernatural in origin, to today. It’s been a plethora of breakthroughs in science and technology that have led the way.

From Morbid to Modern:  A look at Medicine Through Time 

  • 1816 - stethoscope was invented
  • 1834 - First working vapor-compression refrigeration system was built
  • 1847 - discovered that clean hands reduce illness
  • 1854 - first commercial ice-making machine was invented
  • 1879 - first laboratory-developed vaccine
  • 1882 - The first rabies vaccine by post-exposure vaccination.
  • 1889 - Arrhenius equation showed relationship between temperature and chemical reaction
  • 1901 - Different human blood types were discovered
  • 1906 - Vitamins were discovered
  • 1913 - Refrigerators for home use were invented
  • 1921 - The technique of epidural anesthesia was pioneered
  • 1928 - Penicillin was discovered
  • 1946 - The first effective cancer chemotherapy drug was discovered
  • 1948 - Acetaminophen (Tylenol) was invented
  • 1958 - The first implantable pacemaker was developed
  • 1963 - The first human liver/lung transplants were performed
  • 1967 - The first human heart transplant was successfully performed
  • 1985 - Surgical robots were created
  • 2000 - The Human Genome Project (HGP) draft was completed.

Temperature control has been a major factor in the growth of not just modern medicine, but in modern society as a whole. It allows us to live comfortably, eat safely, and be appropriately cared for by the advancements that have been made in health and wellness. That’s because of what is known as the Arrhenius equation. In 1889 Swedish scientist Svante Arrhenius proved a mathematical equation that suggested a reaction rate was dependent on the environmental conditions.

A reaction can involve any number of criteria, like the oxidation of iron or the combustion of cellulose in a fire, but has been extremely important in industries like food and medicine. That’s because it has helped the food industry better understand spoilage and the world of pharmaceuticals to predict the shelf life of their reagents and medications. In both cases, the shelf life decreases as the temperature elevates. According to an article in the 2014 issue of Biologicals, this makes it imperative to monitor the environment in the world of healthcare whenever a vaccine is involved.

“It is always necessary, whatever the nature of an antigen, to conduct extensive stability studies, both under accelerated conditions (e.g., pH, temperature, ionic strength, mechanical, and freeze/thaw) as part of vaccine formulation development, as well as under actual storage conditions to establish shelf-life and expiry dating at the recommended storage temperature.”

That storage temperature is dependent upon the type of vaccine and the medium it’s in. Some vaccines are freeze dried. Lyophilization, or freeze drying, was developed during World War II to make unrefrigerated transportation possible from the US to Europe. In the 75 years since, the freeze-dry process has been expanded to other products and is now often used when a reasonable temperature-stable shelf life cannot be achieved in a liquid product form.

Once a vaccine is freeze dried it can withstand extreme temperatures for an extended period of time. According to research published by the World Health Organization, the stability of measles vaccines is pronounced at high temperatures.

“At room temperature (20°C to 25°C) modern measles vaccines show low degradation rates, of about 0.17 and 0.33 CCID50 loss respectively after two and four weeks’ storage. The minimum required infectivity titre is still retained after two to four months’ storage at room temperatures.”

In order to be given to a patient, the freeze dried vaccine has to go through a reconstitution process. It requires a specific set of diluents to ready the vial for inoculation. Substituting a separate fluid, including normal saline or sterile water, in order to dilute the freeze dried medicine can render it ineffective. According to Path, an international nonprofit on health innovation, deaths have resulted when vaccines were incorrectly mixed with medications other than diluents that were approved for use by the manufacturer. Once a vial has been reconstituted it needs to be kept cool and away from sunlight in a temperature between 35° and 45°F. Even in refrigeration, reconstituted vaccines must be tossed six hours after the reconstitution process because they lack preservatives to limit the growth of bacteria.

A number of vaccines are unable to be freeze dried however and need to be kept as close to 40°F as possible. These vaccines have been the topic of numerous testing to determine the potency of the medicine after freezing and the results haven’t been promising. A freeze-thaw test on four batches of tetanus showed a 14.5% regression in potency following a single freeze-thaw and a 61.5% regression after two rounds of freezing. Similar tests have shown comparable results across a variety of different inoculations.

The Arrhenius equation holds true on vaccines that can’t be frozen. Vaccines that would normally last two years when kept refrigerated, can last as little as days when warmed. The BCG vaccine that is primarily used against tuberculosis becomes fully degraded after 48 hours at room temperature. As you can imagine, it’s important to keep all vaccines in peak condition for patient safety, but the rising costs of the drugs makes it imperative for offices to get as much out of them as they can.

A 2014 story from the New York Times looked into the rising costs of vaccines and found that some vaccine refrigerators can hold $70,000 worth of product or more. As Dr. Lindsay Irvin remembered in the story, that was “more than I paid for four years of medical school.”

Over the last two decades, vaccine prices have skyrocketed from one digit to three digit costs.It’s forced some doctors across the country to stop offering immunizations because they say they simply cannot afford it. Case in point, since 1986, the cost to fully vaccinate a child with private insurance until their 18th birthday has risen by nearly 2200%, up to $2,192 from the $100 it used to be. Increased costs mean an increased pressure to maximize a clinic’s investment on the medicine, and it isn’t just a concern for clinics either.

According to Dr. Lance Rodewald, the director of immunization services at the Center for Disease Control and Prevention in Atlanta, waste costs the $2 billion-a-year federal Vaccines for Children Program about $20 million a year. The biggest single cause? That would be improper refrigeration. Dr. Patricia Quinlisk, Iowa epidemiologist, echoed this sentiment.

"We will get months and months and months of vaccine refrigerator logs where the refrigerator is out of the temperature and nobody has done anything except every day mark down it's out of temperature," she said.

The moral of the story? Don’t just monitor your temperature, understand it and be able to act accordingly. Otherwise the magic of medicine will fail you and even the marvel of refrigeration won’t be able to help you keep your cool.

If you’d like to learn more about products to help you manage and maintain your temperature sensitive materials visit or call (630) 543-3747 to speak to a Dickson certified product expert today.