Comirnaty Low-Temperature Storage Constraints Eased

22.02.2021 - For several days, the Pfizer-BioNTech Covid-19 vaccine Comirnaty (BNT162b2) has dominated international headlines. From the market’s perspective, the most significant news is that the partners, as hinted earlier, have been able to reformulate the doses to facilitate storage at a higher temperature.

The companies announced they had submitted new data to the Food and Drug Administration (FDA), asking it to update the Emergency Use Authorization to take account of a reformulation that allows the vaccine to remain stable when stored at minus 25°C to minus 15°. These temperatures are commonly found in pharmaceutical freezers and refrigerators.

Pfizer and BioNTech also announced plans for clinical trials of the vaccine with pregnant women, monitoring them and their newborns for an extended period. The news the public and political sectors were most interested in, however, came from a report published by the Israeli health ministry, which confirmed the shot’s already reported efficacy and even seemed to top that.

On the storage issue, the vaccine developers said new tweaks would allow vials to be kept at higher temperatures for up to two weeks as an alternative or a complement to storage in an ultra-low temperature freezer. This would be in addition to an option to store at standard refrigerator temperature for five days before mixing with a saline solution.

Current labels state that the vaccine must be stored in an ultra-cold freezer at temperatures between minus 80°C and minus 60° and that it can remain stored at these temperatures for up to six months. Pfizer has developed special thermal containers that can be used as temporary storage.

The American-German duo said the FDA submission includes stability data generated on batches manufactured over the past nine months, from the batches that supplied the earliest clinical trials through the commercial scale batches currently in production. The same data are to be submitted to global regulatory agencies within the next few weeks.

In a statement, BioNTech CEO Ugur Sahin said the companies will continue to leverage their expertise to develop potential new formulations that could make the vaccine easier to transport and use. The requirement to store the vials at an ultra-low temperature has been frequently cited as a drawback in distributing them to remote areas.

Clinical trials with pregnant women started

Pfizer and BioNTech announced also that the first participants have been dosed in a global Phase 2/3 study to further evaluate the safety, tolerability, and immunogenicity of Comirnaty (BNT162b2) in preventing COVID-19 in healthy pregnant women. This group has an increased risk of complications and developing severe Covid-19, which is why it is critical that we develop a vaccine that is safe and effective for this population,” the duo said.

The new trial is designed as a randomized, placebo-controlled, observer-blind study in approximately 4,000 healthy pregnant women aged 18 and older vaccinated during 24 to 34 weeks of gestation. The study will evaluate the safety, tolerability, and immunogenicity of two doses of the vaccine or placebo administered 21 days apart.

Each woman will participate in the study for seven to 10 months, depending on whether she was randomized to receive the vaccine or placebo. The study will assess safety in the newborns and the transfer of potentially protective antibodies to the infants, who will be monitored through approximately six months of age.

Prior to beginning the trial, Pfizer and BioNTech completed a developmental and reproductive toxicity (DART) study with BNT162b2, fulfilling the requirements of regulatory authorities. The results reportedly showed no evidence of fertility or reproductive toxicity in animals.  

A degree of protection against South African variant

The vaccine developers last week also reported on an in vitro study that they said sheds more light on the capability of sera from individuals immunized with BNT162b2 to neutralize Covid-19 with the South African variant spike protein. This study, which has not yet been peer reviewed but builds on previous work, was conducted by Pfizer and the University of Texas Medical Branch (UTMB).

Results of this test, published in the New England Journal of Medicine, are said to have shown a less than two-fold reduction in antibody titer levels. This would indicate that the vaccine may be effective in neutralizing a virus with the E484K and N501Y mutations found in the South African variant.

Pfizer and BioNTech added that the finding is consistent with recent reports of the neutralization of variant SARS-CoV-2 or corresponding pseudoviruses by convalescent or post-immunization sera. The companies are currently evaluating neutralization of Covid-19 with the Brazilian strain’s spike mutations, as well as mutations from other emerging variants in order to be in a position to develop and seek authorization for an updated mRNA vaccine or booster when needed.

Israeli study confirms efficacy claims

In preliminary trial results from Israel, the Comirnaty vaccine appeared to stop the vast majority of recipients becoming infected, according to a report by the national health ministry that has not yet been peer reviewed. The news was regarded as especially significant as it was the first evidence outside clinical trials that immunization could curb transmission of the virus.

The shot rolled out in the national immunization program begun on Dec. 20, 2021 was shown to be 89.4% effective at preventing laboratory-confirmed infections, according to a copy of a draft publication leaked to Twitter. Israeli authorities said also that the risk of illness from Covid-19 declined by 95.8% among those receiving both shots of the Pfizer-BioNTech vaccine and that it was also 98% effective in preventing fever or breathing problems as well as 98.9% effective in preventing hospitalizations and death.

Four-fifths of the virus cases reported in the country during the period of the study, which ran from Jan. 17 to Feb. 6, were identified as the more transmissible B.1.1.7 variant first identified in the UK.  As part of a deal with the Israeli government, the vaccine manufacturers supplied additional doses in exchange for the right to use data from the immunization campaign.

Author: Dede Williams, Freelance Journalist