According to The BMJ’s recent news investigation, the documents revealed that regulators reviewing vaccine candidates had concerns about truncated messenger RNA (mRNA) in early batches of Pfizer-BioNTech’s COVID-19 vaccine. These early batches developed for commercial production had about 55% intact mRNA, a lower percentage than in clinical trial batches, with uncertain implications.
According to the news story’s author, journalist Serena Tinari, Pfizer, the EMA, and Health Canada, as well as the US Food and Drug Administration and COVID-19 vaccine developers Moderna and CureVac, did not provide specifics about the percentage of mRNA integrity acceptable for a vaccine.
After a cyberattack late last year against the European Medicines Agency (EMA), anonymous emails dispatched a trove of classified documents to academics and journalists. In a January 25 statement, the EMA said some of the hacked documents—which mainly concerned COVID-19 medicines and vaccines—were altered in a way that “could undermine trust in vaccines.”
More than 40 megabytes of classified information from the agency’s review were published on the dark web, and several journalists—including from The BMJ—and academics worldwide were sent copies of the leaks. They came from anonymous email accounts and most efforts to interact with the senders were unsuccessful. The email identified “a significant difference in % RNA integrity/truncated species” between the clinical batches and proposed commercial batches—from around 78% to 55%. The root cause was unknown and the impact of this loss of RNA integrity on safety and efficacy of the vaccine was “yet to be defined,” the email said.
Ultimately, on 21 December, EMA authorised Pfizer-BioNTech’s vaccine. The agency’s public assessment report, a technical document published on its website, noted, “the quality of this medicinal product, submitted in the emergency context of the current (covid-19) pandemic, is considered to be sufficiently consistent and acceptable.” It’s unclear how the agency’s concerns were satisfied. According to one of the leaked emails dated 25 November, positive news had come from an undisclosed source in the US: “The latest lots indicate that % intact RNA are back at around 70-75%, which leaves us cautiously optimistic that additional data could address the issue,” the email said.
The BMJ asked Pfizer, Moderna, and CureVac, as well as several regulators, what percentage mRNA integrity they consider acceptable for vaccines against covid-19. None offered any specifics.
The Medicines and Healthcare products Regulatory Agency, the UK’s medicines regulator, acknowledged the lack of a specified percentage RNA integrity, but declined to provide further detail. “The specification limit acceptance criteria are commercially confidential,” the agency said in an email.
The US Food and Drug Administration (FDA) directed The BMJ to read its guidance documents78 and its review of Pfizer’s vaccine, but none of these specify the percentage RNA the agency is requiring. Asked to comment, the regulator pointed to Pfizer: “information that you seek that is not addressed in the FDA Review Memorandum should be directed to Pfizer.”