EMA covid-19 data leak, and what it tells us about mRNA instability

So, some leaked documents from the Euroean Medical Agency were analyzed by the British Medical Journal who found there were significant concerns over the quantities of intact mRNA in commercial batches of Pfizer's vaccine.

Despite these concerns, the EMA approved the vaccine citing

in the emergency context of the current (covid-19) pandemic, is considered to be sufficiently consistent and acceptable.”

According to the leaked documents, the EMA was assured by anonymous sources the batches were up to 70%-75% in the US, leading the EMA to approve the vaccine.

An, incomplete mRNA molecule with even a minor degradation can cause incomplete antigen expression causing a lack of vaccine efficacy or worse.

Furthermore, the article mentions a lack of any clarification on changes Pfizer made to their batches from the FDA, Canada Health and other global health organizations that approved the vaccines based on Pfizer's promise that it fixed the problem. It seems as though no further testing was actually done by those countries however.

www.bmj.com...

Leaked documents show that some early commercial batches of Pfizer-BioNTech’s covid-19 vaccine had lower than expected levels of intact mRNA, prompting wider questions about how to assess this novel vaccine platform.

As it conducted its analysis of the Pfizer-BioNTech covid-19 vaccine in December, the European Medicines Agency (EMA) was the victim of a cyberattack.1 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.

The BMJ has reviewed the documents, which show that regulators had major concerns over unexpectedly low quantities of intact mRNA in batches of the vaccine developed for commercial production.

EMA scientists tasked with ensuring manufacturing quality—the chemistry, manufacturing, and control aspects of Pfizer’s submission to the EMA—worried about “truncated and modified mRNA species present in the finished product.” Among the many files leaked to The BMJ, an email dated 23 November by a high ranking EMA official outlined a raft of issues. In short, commercial manufacturing was not producing vaccines to the specifications expected, and regulators were unsure of the implications. EMA responded by filing two “major objections” with Pfizer, along with a host of other questions it wanted addressed.

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.

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 complete, intact mRNA molecule is essential to its potency as a vaccine,” professor of biopharmaceutics Daan J.A. Crommelin and colleagues wrote in a review article in The Journal of Pharmaceutical Sciences late last year. “Even a minor degradation reaction, anywhere along a mRNA strand, can severely slow or stop proper translation performance of that strand and thus result in the incomplete expression of the target antigen.”

If they could guarantee the mRNA was degraded, they might have more takers for that vaccine.
I'll pass either way.

a reply to: dug88

This is interesting news. It speaks to the uniformity of manufacture (and distribution) of the vaccine.

It could be that it doesn't adversely affect the efficacy of the vaccine in practice, but I wonder if any of the vaccine that was used to establish the claimed 95% effectiveness was degraded? Probably not.

Also, the article does suggest that the situation has been remedied. It could have been that the manufacturing process was being 'tweaked' at the time.

I'll be interested in seeing where this leads, as New Zealand, where I reside, has purchased enough of the Pfizer vaccine to immunize the country.

a reply to: chr0naut

Also, the article does suggest that the situation has been remedied. It could have been that the manufacturing process was being 'tweaked' at the time.

It does suggest this, but it also mentions a lack of clarification on how it's been 'tweaked' and a lack of data on the efficacy of those tweaks apart from some assurances from undisclosed sources.

originally posted by: chr0naut
a reply to: dug88

This is interesting news. It speaks to the uniformity of manufacture (and distribution) of the vaccine.

It could be that it doesn't adversely affect the efficacy of the vaccine in practice, but I wonder if any of the vaccine that was used to establish the claimed 95% effectiveness was degraded? Probably not.

Also, the article does suggest that the situation has been remedied. It could have been that the manufacturing process was being 'tweaked' at the time.

I'll be interested in seeing where this leads, as New Zealand, where I reside, has purchased enough of the Pfizer vaccine to immunize the country.

That's a good call, after all, other vaccines, (in their trials) don't have the like with like claims, and all the vaccines claims must surely be a percentage of the numbers of persons used in those trials, included in that will likely have unknown factors, maybe someone died after vaccination with no specific reason for dying, perhaps another for observed reasons like blood clots as in some Astrazeneca reports, and at least one person dying from a previously, and rare, unknown head tumor. In all those examples, it would be irrational to make attribution to any vaccines efficacy per se.

Of course though, there should be some investigation of death vis-à-vis any vaccination trials, in any case to attempt to establish a true cause of death, but that may not yet be possible in the ultimate. Even so, it doesn't take away from the efficacy rate which will never be 100% anyway.

originally posted by: dug88
a reply to: chr0naut
It does suggest this, but it also mentions a lack of clarification on how it's been 'tweaked' and a lack of data on the efficacy of those tweaks apart from some assurances from undisclosed sources.

Yeah... tweaked...

Considering how this new mRNA technology is not a vaccine, but more along the lines of a human software update, and knowing just how badly almost all programs are coded, I will be taking a hard pass on any and all of these...

Unless... maybe, just maybe, I night consider it, if these firms employed the engineering expertise of Wietse Venema and Victor Duchovny (postfix being the absolute gold standard for how coding should be done), and they fully open-sourced all of the 'code' that was used in these things.

Well... on second thought, probably not, because there would be no way to prove that what they shipped was actually what is on the label.

Nope, I'll just rely on good ole mother nature's immune system I was born with, it's served me well these last 60 years.

a reply to: dug88

Well done;

Also worth reading;

www.sciencemag.org...

a reply to: steaming

Hmmm that is interesting

A similar mRNA vaccine developed by Moderna, which was authorized for emergency use in the United States on Friday, also contains the compound, polyethylene glycol (PEG).

PEG has never been used before in an approved vaccine, but it is found in many drugs that have occasionally triggered anaphylaxis—a potentially life-threatening reaction that can cause rashes, a plummeting blood pressure, shortness of breath, and a fast heartbeat. Some allergists and immunologists believe a small number of people previously exposed to PEG may have high levels of antibodies against PEG, putting them at risk of an anaphylactic reaction to the vaccine. 

PEG is used in vape pens. All those young people vaping..