Virus World

(Reuters) - Pfizer Inc and BioNTech SE have submitted new temperature data to the U.S. health regulator which they said on Friday could allow their COVID-19 vaccine to be stored in pharmacy freezers rather than in ultra-cold storage facilities.  If approved, the less onerous storage requirements would provide a significant logistical relief for the roll-out of the vaccine, particularly in lower-income countries that do not have the necessary infrastructure. Pfizer/BioNTech's vaccine, along with Moderna Inc's two-dose shot, won the U.S. emergency use authorization (EUA) and is being widely distributed as part of the country's mass vaccination efforts. The new data has been submitted to the U.S. Food and Drug Administration to support a proposed update to the current EUA label that would allow vaccine vials to be stored at -25 to -15 degrees Celsius (-13°F to 5°F) for a total of two weeks as an alternative for storage in an ultra-low temperature freezer.

"The data submitted may facilitate the handling of our vaccine in pharmacies and provide vaccination centers an even greater flexibility," BioNTech Chief Executive Officer Ugur Sahin said. Pfizer/BioNTech's current label requires the vaccine to be stored in an ultra-cold freezer at temperatures between -80ºC and -60ºC (-112ºF to -76ºF), calling for it to be shipped in specially designed containers. The new data also will be submitted to global regulatory agencies within the next few weeks, the two companies said. A BioNTech spokeswoman declined to provide more details on the timing and which agencies would be contacted.

For now, novel vaccine type needs to be frozen for storage and transport, with one requiring ultracold temperatures of –70°C. Today’s dramatic news that Moderna’s COVID-19 vaccine might work as well as one made by Pfizer and BioNTech means the world could have two powerful weapons to fight the COVID-19 pandemic. Now, the next hot vaccine topic is, well, heat. Both vaccines use a novel technology—strands of messenger RNA (mRNA), held within lipid particles—that is vulnerable to degradation at room temperature and requires doses to be frozen for transportation, then thawed for use. That’s where the Moderna vaccine may have an edge: Unlike Pfizer’s and BioNTech’s offering, it does not have to be stored at –70°C, but can tolerate a much warmer –20°C, which is standard for most hospital and pharmacy freezers. That difference means Moderna’s vaccine should be easier to distribute and store, particularly in the rural United States and developing countries that lack ultracold freezers. Moderna says years of development work enabled its vaccine to be stored at higher temperatures, but last week another mRNA vaccine company announced it is testing a COVID-19 vaccine that early studies suggest can survive at the even warmer temperatures of 2°C to 8°C found in refrigerators.  

Many types of vaccines must be stored and transported frozen, via a cold supply chain. Public health officials have even found ways to keep a vaccine ultracold, between –60°C to –80°C, in places like sub-Saharan Africa. There, for the past 5 years, a high-tech thermos called Arktek has helped distribute Ebola vaccines that must be kept ultracold. “In all likelihood, we’ll need a wide range of supply chain tools” to distribute COVID-19 vaccines, says Daniel Lieberman, a mechanical engineer with Global Health Labs in Seattle, a nonprofit created by the Bill & Melinda Gates Foundation, which funded Arktek’s development, and by a venture capital firm started by Bill Gates. Still, relying on an ultracold chain is expensive, and in some places it may make more sense to distribute a vaccine that can tolerate warmer temperatures even if it’s less effective. Both the Moderna and Pfizer/BioNTech vaccines give the body’s cells an mRNA template for making the spike protein of SARS-CoV-2, the virus that causes COVID-19. The protein then moves to the cell’s surface and triggers an immune response. This mRNA is relatively fragile compared with the proteins or protein fragments that often make up conventional vaccines, and it cleaves easily at room temperature, says Alana Gerhardt, who studies vaccine product development at the nonprofit Infectious Disease Research Institute (IDRI) in Seattle. Also, enzymes called ribonucleases that chew up mRNAs “are everywhere, even in the controlled environment of the lab,” from sources such as lab workers’ breath and skin, Gerhardt says.

The companies give the mRNA some protection during production and storage by inserting it into a carrier, a fatlike substance called a lipid nanoparticle. The lipid also shields the mRNA from enzymes in the blood once it has been injected. But the nanoparticle is deliberately designed to slowly degrade, so it won’t build up in the liver and cause harm, says Massachusetts Institute of Technology geneticist and chemical engineer Daniel Anderson.  Although the companies’ exact formulations are proprietary, Pfizer and BioNTech have so far said their vaccine has to be kept ultracold. But Barney Graham, a vaccine researcher at the U.S. National Institute of Allergy and Infectious Diseases who designed the mRNA used by both Moderna and Pfizer/BioNTech, says the temperature requirements are actually unclear. Pfizer and BioNtech started with –70°C when they first asked regulators to test their vaccine in humans, and Graham says the companies might ultimately be able to document that the mRNA survives warmer temperatures. In the meantime, at sites in Kalamazoo, Michigan, and Puurs, Belgium, Pfizer will pack shipments of 200 to 1000 vials each containing five doses in insulated boxes with thermal sensors on dry ice to provide the necessary chill. Pharmacies and doctor’s offices that lack $15,000 ultracold freezers can store it in the thermal box for about 2 weeks by refilling the dry ice every 5 days; once removed, the vaccine can be refrigerated for 5 days. Moderna’s vaccine, however, is stable for 6 months at –20°C, or in a standard freezer, and the company announced today its product can be kept at normal refrigerator temperatures for up to 30 days, longer than the 7 days initially expected....