Europe’s drug regulator was worried about the efficacy and safety of the Pfizer-BioNTech vaccine early in the treatment’s review, according to a new article in The BMJ, a British medical journal.
The article cites classified information from the European Medicines Agency (EMA), which reviewed the Pfizer-BioNTech Covid-19 vaccine for distribution within the European Union. EMA officials specifically expressed concerns about differences between the clinical and commercial batches of the vaccine.
“Regulators had major concerns over unexpectedly low quantities of intact mRNA in batches of the vaccine developed for commercial production,” the peer-reviewed article found.
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The disclosure comes as a long list of pandemic-hit countries are receiving the first mass deployment of mRNA vaccines, a novel technology that pharmaceutical companies have invested heavily in throughout the past decade. Some corners of the internet have swirled with false claims that these vaccines alter human DNA and are toxic.
Messenger RNA (mRNA) is a single-strand molecule of RNA, short for ribonucleic acid. While traditional vaccines create immunity from a virus by inserting a human with a small quantity of the inactivated pathogen, mRNA vaccines bypass this step by directly “instructing” human cells how to make a viral or bacterial protein, which then allows the body to develop immunity.
Chinese Covid-19 vaccine manufacturers like SinoVac and CanSino have opted for the more traditional method; US pharmaceutical companies like Pfizer and Moderna have developed mRNA-based Covid-19 vaccines.
Because mRNA vaccines do not rely on inserting any pathogen or bacteria into the human body, they carry no risk of infection, while being easier to scale up, as well as more effective and malleable, according to a 2018 peer-reviewed article published in the journal Nature Reviews: Drug Discovery.
However, mRNA is also very fragile, causing it to degrade unless stored at very low temperatures. The less intact the mRNA, the lower its potency as a vaccine.
“The integrity of RNA vaccine is important to ensure that sufficient spike protein is produced in the body to train the immune system to react early against Sars-CoV-2 and prevent Covid-19,” said Professor Ooi Eng Eong of the microbiology and immunology department at the National University of Singapore.
According to leaked information cited by the BMJ article, an EMA official said in November that the percentage of intact mRNA in the commercial batches of the Pfizer-BioNTech Covid-19 vaccine was much lower than the clinical batch – 55 per cent compared to 78 per cent.
Even so, one month later, the EMA approved the vaccine. The BMJ article cited a leaked email suggesting that the percentage of mRNA was subsequently increased after the EMA expressed concern.
The EMA and BioNTech did not respond to requests for comment from the South China Morning Post.
Pfizer said in a statement that the EMA’s decision to approve the vaccine on December 21 meant that any questions raised during the review procedure had been answered. However, it did not provide further details about the reason for the discrepancy in intact mRNA percentages that the EMA had flagged.
“It’s important to note that each batch of vaccines is tested by the official medicinal control laboratory – the Paul-Ehrlich Institute in Germany – before final product release. As a result, the quality of all vaccine doses that are placed on the market in Europe has been double tested to ensure compliance with the specifications agreed upon with the regulatory authorities. Should a batch not meet these required specifications, the product wouldn’t be released for use in Europe,” Pfizer said.
Jacob Wes Ulm, a researcher in medical genetics at the University of Pittsburgh in the US, told The BMJ that RNA-based vaccines like those developed by Pfizer-BioNTech and Moderna use a lipid nanoparticle to encase the mRNA to reduce the molecule’s inherent instability.
He praised Pfizer-BioNTech and Moderna for scaling up the manufacture of mRNA technology but noted that long-term drug studies were necessary to ascertain whether any toxicity resulted from the immune response triggered by their Covid-19 vaccines.
Ooi in Singapore said that non-intact mRNA, also called truncated mRNA, is not a safety risk because it is even more unstable than intact mRNA, making it easier for human cells to remove them.
“Improperly produced proteins happen in our cells constantly and our cells have the machinery to sieve out the faulty proteins from the properly produced versions. There is thus no elevated safety risk from truncated mRNA,” he said.
Ooi, who is co-developing a mRNA-based Covid-19 vaccine, added that the latest research from Israel – which has the world’s Covid-19 vaccination rate – shows that commercial batches of the Pfizer-BioNTech vaccine were producing the same results in the real world as the clinical batches did during phase 3 trials.
A peer-reviewed study published in the New England Journal of Medicine last month compared almost 600,000 Pfizer-BioNTech vaccinations in Israel to unvaccinated controls. The results were clear: two doses of the mRNA vaccine reduced cases by 94 per cent in Israel – roughly the 95 per cent efficacy rate announced by Pfizer after concluding phase 3 clinical trials.
The article in The BMJ is coloured by the source of the leaks. In December, the EMA, based in Amsterdam, suffered a cybersecurity breach, reportedly conducted by Russian hackers. The leaked information sent to The BMJ was also published on the dark web; the identity of the senders remains unknown.
“The perpetrators primarily targeted data related to Covid-19 medicines and vaccines and unlawfully accessed documents belonging to third parties,” the EMA said then.
While the EMA has not identified the culprits behind the hack, the US has previously accused Russia of conducting disinformation campaigns against Pfizer and other Western Covid-19 vaccines.
Ned Price, the State Department‘s chief spokesman, said on Monday that the US had identified four online platforms, all serving as fronts for Russian intelligence.
“It is very clear that Russia is up to its old tricks, and in doing so is potentially putting people at risk by spreading disinformation about vaccines that we know to be saving lives every day,” he said.
The EMA said in January that the leaked information, some of it cited in the BMJ article, was not published in full and may have been taken out of context.
“Whilst individual emails are authentic, data from different users were selected and aggregated, screenshots from multiple folders and mailboxes have been created and additional titles were added by the perpetrators in a way which could undermine trust in vaccines.”
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