Prior to the COVID-19 pandemic, most people outside the scientific community hadn’t heard of mRNA vaccines or ultra-low temperature (ULT) freezers. Fast forward to October 2020, and everyone from your neighbor to mainstream media is talking about how the first potential COVID-19 mRNA vaccine from Pfizer needs to be kept in an ULT freezer at -80˚C.
When Pfizer’s vaccine was first approved for Emergency Use Authorization, it needed to be kept at -70˚C to -80˚C, a temperature only offered by ULT freezers. Anticipating that most facilities were not equipped with such infrastructure, the pharmaceutical giant designed suitcase-sized, temperature-controlled shipping packages that used dry ice to keep the vaccine vials at -75˚C for 10 days.
However, as of Feb. 25, 2021, Pfizer was approved to store the BNT162b2 vaccine between -25°C and -15°C, a common temperature that almost all facilities can accommodate. Still, the conversation about the first-available COVID-19 vaccine and its cold chain requirements thrust ULT freezers into a spotlight they don’t ordinarily enjoy.
“We’re getting over the horizon here soon relative to the pandemic, but as you start to take a look at future biologic development, whether that be vaccines or other types of cancer therapies, I think mRNA vaccines will be here to stay,” said Dusty Tenney, president and COO of BioLife Solutions.
The Impact of mRNA Vaccines
Traditional vaccines contain small or inactivated doses of the disease-causing organism, which are introduced into the body to provoke the immune system into mounting a response. In contrast, mRNA vaccines contain a synthetic version of the mRNA that a virus uses to build its infectious proteins. This mRNA is delivered into the human body, whose cells read it as instructions to build that viral protein, creating some of the virus’ molecules themselves. The immune system then detects these viral proteins and starts to produce a defensive response to them.
Scientists have been working on mRNA vaccines for decades; but, the technology was often considered far-fetched, a moonshot or even “before its time.” The emergence of COVID-19 changed that, and Pfizer and BioNTech's BNT162b2 vaccine became the first mRNA-based vaccine to be approved for use in December 2020. Moderna’s mRNA-1273 vaccine was approved for emergency use authorization just a week later. Consequently, the world went from zero mRNA vaccines to two effective, safe options in less than 12 months.
“The requirements for ULTs for the pandemic may be over, but we’re at the starting point in relationship to the next revolution in personalized medicine,” said Tenney. “With the advances that have been made here and the confidence that has been built around mRNA vaccines, I think that will continue to accentuate these.”
For example, a research team from IAVI and Scripps Research Institute recently tested a vaccine to prevent HIV in a Phase 1 clinical trial. The vaccine demonstrated great success, actively stimulating production of the immune cells needed to generate antibodies in 97%of the participants who received it. Now, the team is partnering with Moderna to develop and test an mRNA-based version of the vaccine. If successful, the team says they believe this vaccination method could also be applied to other challenging pathogens, such as influenza, dengue, Zika, hepatitis C viruses and malaria.
Additionally, Van Morris, M.D., a professor in the department of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, is leading a clinical trial to test whether mRNA technology could prevent colorectal cancer from recurring.
The Phase 2 clinical trial is following high-risk patients with stage II or stage III colorectal cancer who test positive for circulating tumor DNA (ctDNA). After surgery, tumor tissue is removed from the patient’s body and tested for genetic mutations that fuel cancer growth. As with COVID-19 vaccines, this mRNA vaccine instructs a patient’s cells to produce protein fragments based off the genetic mutations identified during testing. The immune system then searches for other cells with the mutated proteins and clears out any remaining circulating tumor cells.
“Each patient receives a personalized mRNA vaccine based on the individual mutation test results from their tumor,” Morris says. “We’re hopeful that with the personalized vaccine, we’re priming the immune system to go after the residual tumor cells, clear them out and cure the patient.”
‘Need for Speed’
Pre-pandemic, the approval process for drugs and vaccines was long and arduous. If anything, COVID-19 has proven that the cycle can be shortened. That, in addition to the fact that ULT infrastructure is now in place, leads Tenney to believe there is going to be a “need for speed” in the near future.
“Given what happened during the pandemic, there will be a drive to bring vaccines and therapies to market much faster,” he said. “Cold chain will play an important part in the longevity for maintaining those vaccines to ensure maximum efficacy.”
Even if future mRNA vaccines do not need to be stored short-term in ULTs, the freezers are still required for shelf-life purposes and long-term storage. Additionally, drugs, enzymes, chemicals, viruses, bacteria, cell preparations, tissue samples, and more are stored at a minimum of 45˚C. In fact, blood and urine samples are stored at -80˚C for research and clinical purposes.
“Just by virtue of having ULT infrastructure in place, that will enable respective therapies to get to market much faster than they have in the past,” said Tenney.
While market reports do expect a slight dip in the ULT freezer market going into 2022 as companies stabilize their purchasing post-COVID-19 requirements, the overall market is expected to continue to grow—ResearchandMarkets values it at $1 billion come 2025, increasing at a compound annual growth rate of 5.7%.
“The pandemic really accentuated the acronym ULT,” concluded Tenney. “ULTs before were used primarily in research. It was a staple, growing market in many respects, but now there is a true realization that having ULT infrastructure down to -80˚C is needed.”