Pfizer/BioNTech’s COVID-19 Vaccine Formulation Tweaked to Improve Stability

SciCheck Digest

With the release of its pediatric COVID-19 vaccine, Pfizer switched the buffer used in its formulation to increase the stability of the product, allowing it to remain at refrigerator temperatures for longer. The Food and Drug Administration OK’d the change, which is also being made to some doses for teens and adults. Social media posts, however, misleadingly suggest that the ingredient swap is dangerous or was added to prevent heart attacks in children.

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A minor change to Pfizer/BioNTech’s COVID-19 vaccine, done to make doses easier to store at warmer temperatures, is being misconstrued online as a safety hazard or as a sign that the vaccines are not safe for kids. There is no evidence to support either claim.

The ingredient in question is Tris, or tromethamine, which is used as a buffer in the children’s vaccine — and will soon be available in some adult and teen formulations as well — to keep doses at the correct pH, neither too acidic nor too basic. The original iteration of the Pfizer/BioNTech vaccine used phosphate buffered saline, or PBS.

Pfizer and the FDA have said the switch was made to improve the stability of its mRNA vaccine, which previously had to be kept ultracold for long-term storage and lasted a month in a fridge once thawed; the newer version can last in the fridge for up to 10 weeks. Other experts back up that notion.

Furthermore, Tris has safely been used in other vaccines and other products.

Less stringent cold chain requirements are especially helpful for the pediatric vaccine, which is being administered more in doctor’s offices.

But social media posts have zeroed in on the formulation change to misleadingly suggest that Tris is dangerous — and simultaneously, that Tris was added to conceal cardiac side effects of the vaccine.

Alex Jones’ Infowars, for example, falsely claims that tromethamine is a “heart attack drug” that was “secretly added” to the pediatric vaccine.

“Is Tris being added to these children’s vials to try to cover up the cardiovascular events that they cause, or at least minimize them?” suggestively asks an article from Natural News, another dubious website that has previously spread COVID-19 misinformation and has repeatedly been banned by Facebook.

Other posts, some subsequently shared on Instagram, make similarly suggestive claims, pointing out the switch to Tris and calling it a “disturbing nugget” “buried” in paperwork submitted to the FDA. They describe Tris as a “blood acid reducer which is used to stabilize people with heart attacks” and list a bunch of scary-sounding side effects, including respiratory depression and IV thrombosis.

Experts, however, say these claims are false or misleading. In large quantities, Tris can be used as a drug, but here, as in other vaccines and medicines, the compound is present in only a very small amount as an inactive ingredient to help keep the vaccine stable.

“It’s a really different use,” Dr. Kawsar R. Talaat, an infectious disease physician and vaccine scientist at the Johns Hopkins Bloomberg School of Public Health, told us of Tris being used therapeutically. “That’s put into somebody’s vein, it’s put in at larger concentrations. This is an infinitesimal amount of this buffer that goes into 0.2 milliliters of a vaccine just to keep the vaccine stable.”

According to FDA documents, each 0.2 milliliter pediatric dose contains 0.02 milligrams tromethamine and 0.13 milligrams of tromethamine hydrochloride.

Tris in vaccines, Talaat said, has “absolutely nothing to do” with Tris being given to people who are having heart attacks. In those situations, she said, individuals might not be getting enough oxygen, leading to acidosis, or an increase of acid, in the blood. That can then be countered with much larger volumes and higher concentrations of Tris than what is present in the vaccine.

The implication from some of the posts that Tris was added to reduce heart attacks in children is groundless. The Pfizer/BioNTech COVID-19 vaccine is not known to increase the risk of a heart attack in any population. Instead, the cardiac concern that has been identified for the two mRNA vaccines is an increased risk of myocarditis, or inflammation of the heart muscle, and pericarditis, or inflammation of the lining surrounding the heart, particularly in young men. But these adverse events are rare, and as a buffer, Tris would not be expected to modify the risk in either direction.

The idea that Tris is dangerous is also not supported. The FDA said in an email to FactCheck.org that the buffer is used in other approved vaccines, including those for dengue, smallpox and monkeypox, and Ebola. Tris is also used in the insulin Humalog and the autoimmune disease drug Enbrel, both of which are prescribed to children.

Also, contrary to many of the posts, the switch to Tris from PBS was not a secret, as it was noted in Pfizer and FDA documentation prior to authorization and was covered in the publicly streamed FDA advisory meeting. It was also mentioned in the FDA’s press release and press briefing announcing the agency’s decision to authorize the pediatric vaccine for kids 5 to 11 years old. Additionally, the ingredients are listed in agency vaccine fact sheets.

Pfizer has said that the buffer swap was done for improved stability and doesn’t change anything about the vaccine’s manufacturing.

“The manufacturing processes involved in producing the pediatric doses remain unchanged from the adult and adolescent doses. There are also no changes in raw materials, mRNA, lipids or suppliers in the manufacturing of the drug substance and lipid nanoparticles,” the company said in an email to us in response to an earlier inquiry about the claim (emphasis is Pfizer’s). “To enable extended storage time an alternative buffer is being leveraged, known as a ‘tris buffer’. Simply put, this allows the mRNA to resist being degraded for a longer period of time before administration — meaning the pediatric vaccine can be stored for 2-8°C [35.6-46.4°F] in commonly available refrigerators for up to 10 weeks. This buffer will also be used in the updated adult/adolescent 30mcg doses in due course, helping to ensure simplified handling of the vaccine across age groups.”

Andrew Geall, a co-founder and chief development officer of Replicate Bioscience, a biotech company focused on using self-replicating RNAs in vaccines and therapeutics, told us there is a logical basis for the buffer switch.

“I can tell you that PBS is a problem when you freeze it with RNA,” he said, citing his 13 years in the RNA vaccine field. “You see a huge drop in pH during that freezing process, and it impacts the stability of the RNA. And Tris does not have that, largely … it’s a much better buffer for these types of systems.”

While Geall said he had not seen data from Pfizer — and therefore his comments were speculative — he said it made sense that improved stability would be why the company swapped buffers. “It’s well known,” he said, of the challenges with PBS and the benefits of using Tris.

As for why Tris wasn’t used in the first place, as it was with Moderna’s COVID-19 vaccine, Geall said that wasn’t too surprising.

“Typically, in prototype formulations people will use phosphate buffered saline,” he said, since they aren’t being frozen much. “And then, at a later date, they start to do long-term stability studies, testing different buffers and pHs.”

Given the effort to get a COVID-19 vaccine as quickly as possible, Geall said, the company probably didn’t have time to work on optimizing the buffer, and moved forward with what they knew worked first, before returning to the issue.

As we’ve explained before, the pediatric clinical trials did not use the Tris formulation, but lab tests were performed to make sure the buffer change did not affect the shot’s safety or effectiveness.

These included analytical comparability tests showing that the size of the lipid nanoparticles, for example, wasn’t altered, and that the modified mRNA that acts as the active ingredient in the vaccine remained the same, according to the FDA. The agency has said the buffer exchange is “not considered clinically significant.”

Dr. H. Cody Meissner, chief of pediatric infectious disease at Tufts Children’s Hospital, and a member of the committee advising the FDA, also told us for an earlier article that he didn’t think the change in buffers would “make much of a difference at all.”

Talaat, who was an investigator at a trial site for the Pfizer/BioNTech vaccine in adults and children, said the lack of clinical testing with this specific formulation was not worrisome.

“Formulations do change, and they don’t usually require clinical trials for minor changes like this,” she said. “We’re always trying to improve on things, and make them more stable and make them more functional.”

“I had no concern about this at all,” she added, saying that her 10-year-old got his first dose of the vaccine the first Saturday it was available. “I was so excited to give him the vaccine.”

Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over FactCheck.org’s editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.

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