About a month before Pfizer and BioNTech won the head of emergency for the COVID-19 vaccine in Europe, regulators raised flags on intact mRNA levels lower than expected in commercial batches, BMJ reports.
The European Medicines Agency outlined “a significant difference” in RNA in proposed clinical and commercial batches, according to leaked information from an EMA cyberattack in December, which the BMJ subsequently revised.
Although the production problem has since been resolved – and the Pfizer vaccine has been approved in Europe – the leaks show the “complexity of quality assurance” of mRNA vaccines. especially in terms of RNA instability, the BMJ said. It is a problem that affects all mRNA developers, including Moderna and CureVac. This instability is the reason for the cold chain requirements and the need to encapsulate mRNA in lipid nanoparticles, BMJ said.
The problem boils down to whether the commercial manufacturing of Pfizer and BioNTech was up to par. EMA scientists had doubts about “the truncated and modified mRNA species present in the finished product” and, as a result, raised two important objections with Pfizer and raised a number of additional questions, according to the report.
In an email to Fierce Pharma, Pfizer noted that discussions with regulators about vaccine quality are a “normal component of the regulatory review process.”
RELATED: US focus on Pfizer production could delay manufacturing of other COVID-19 vaccines, warns Serum Institute CEO
Having a complete and intact mRNA molecule is essential for the performance of an mRNA vaccine and “[even] a minor degradation reaction, anywhere along an mRNA strand, can slow or stop the correct translation performance of that strand and therefore result in incomplete expression of the target antigen. ” , wrote Daan JA Crommelin, a professor of biopharmaceuticals at The Journal of Pharmaceutical Sciences last year, citing BMJ.
For the Pfizer product, mRNA integrity for clinical batches reached around 78%, compared to 55% for the proposed commercial batches, according to an EMA email from November 23. This difference sparked concerns that Pfizer and regulators worked.
The effectiveness of the vaccine depends on the presence of adequate levels of intact mRNA, according to the EMA. Regulators and Pfizer have not said what level of mRNA integrity is acceptable.
“It is important to note that each batch of vaccines is tested by the official drug control laboratory (OMCL) – the Paul-Ehrlich Institute in Germany – before the final product is released,” Pfizer said in a statement. electronic.
“As a result, the quality of all doses of vaccines marketed in Europe has been tested twice as high to ensure compliance with the specifications agreed with the regulatory authorities. If a batch does not meet these required specifications, the product will not be will launch for use in Europe “.
RELATED: Pfizer, BioNTech vaccine addresses 3 worrisome COVID-19 variants in a laboratory study
In another leaked email on Nov. 25, an undisclosed U.S. source said that “the latest batches indicate that the percentage of intact RNA returns to 70-75%, which leaves us cautiously optimistic that the additional data can solve the problem “.
Meanwhile, Pfizer told Fierce Pharma that its EMA authorization indicates “that all issues raised during the procedure were satisfactorily addressed and that the efficacy, safety and quality of the vaccine could be demonstrated in the data submitted.” Regulators in Canada, the United States and many other countries have also authorized the shooting.