[ad_1]
Some of the early commercial batches of the Pfizer / BioNTech COVID-19 vaccine had less intact mRNA than expected, according to leaked documents that raise concerns about companies’ quality assurance control.
A cyber attack on the European Medicines Agency (EMA) while reviewing the Pfizer-BioNTech COVID-19 vaccine in December captured a large amount of data, subsequently published on the dark web and sent to various journalists and academics by as-yet-unidentified entities. .
“In summary, commercial manufacturing did not produce vaccines to the expected specifications and regulators were not sure of the implications,” summarized investigative reporter Serena Tinari in The BMJ, which received the leaked documents.
A leaked email from an EMA official identified a problem with the integrity of the mRNA, which had been around 78% in clinical batches, but 55% in proposed commercial batches. Why this happened and what it would mean for the safety and efficacy of the vaccine is unknown, according to the email.
The problem appears to have affected the US as well, and one of the leaked emails citing an undisclosed US source reads: “Latest batches indicate% intact RNA is back at around 70-75%, which leaves us cautiously optimistic that the additional data could fix the problem. “
EMA responded to The BMJ say that mRNA problems in affected commercial lots would not constitute a safety risk, although it did not address how efficacy might be affected. “The issue was successfully addressed, the agency stressed, when the manufacturer provided more information,” Tinari wrote.
Health Canada told him, however, that “changes were made to their processes to ensure that integrity was improved and aligned with what was seen in clinical trial batches” and that they, along with the EMA and the FDA subsequently They agreed “there was no concern there with the integrity of the RNA or any other product specification.”
The agencies finally granted emergency use authorization for the Pfizer-BioNTech vaccine.
The EMA did not deny the veracity of the information in the individual emails, although it did warn that the overall leak was “partially manipulated”, for example by selecting and aggregating data from different users.
The fragility of the mRNA is not a surprise: it is the key factor behind the encapsulation of lipid nanoparticles and the extreme cold storage requirements for the Pfizer vaccine. It’s a problem for all mRNA vaccines, not just Pfizer’s, Tinari noted.
It’s also what kept RNA-based drugs from entering the clinic despite decades of great development. Any loss in the mRNA strand, even minor, can slow or prevent you from making the protein it encodes, potentially hampering immunity.
Pfizer did not say what happened or what percentage of mRNA integrity to target, “leaving open the question of whether it could happen again,” Tinari noted.
Moderna, CureVac, the FDA, EMA, and Canadian and British regulators responded to the The BMJresearch without comment or that the specific percentage of RNA integrity required is commercially confidential information.
An article in the March issue of the Journal of Pharmaceutical Sciences noted that there is still no specific regulatory guide for mRNA-based vaccines.
However, it is clear that mRNA applications are unlikely to end the pandemic.
The technology is expected to “continue to break down barriers in the pharmaceutical industry, with the oncology market likely to benefit the most,” according to data and analytics company GlobalData. He noted that at least 44 clinical trials of mRNA vaccines are underway, and about half are phase I or II trials in oncology.
Therefore, Tinari noted that the papers offer “an opportunity to reflect on the complexities of quality assurance for new mRNA vaccines, including everything from quantification and integrity of mRNA and carrier lipids to measurement of the particle size distribution and encapsulation efficiency “.
Disclosures
Tinari revealed that he has no relevant relationships with the industry.
