Drareg
Member
- Joined
- Feb 18, 2016
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- 4,772
Anyone hear about this hack in MSM? I didn’t, probably another back page story while they hyped something woke on the front page.
It’s not just mRNA to worry about it’s now potentially modified mRNA from poor production quality.
Peat spoke about the carrier lipids months ago, this data leak highlights concerns about said lipids.
People are putting this crap in their body, the authoritarians won’t let you socialize/pass again unless you take it, let’s not forget the pandemrix vaccine, you know the one that caused mass narcolepsy-https://www.bmj.com/content/362/bmj.k3948
But hey, take the vaccine and post it on social media for normie likes!
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, writes Serena Tinari
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. They came from anonymous email accounts and most efforts to interact with the senders were unsuccessful. None of the senders revealed their identity, and the EMA says it is pursuing a criminal investigation.
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.
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.”2
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.
But the documents offer the broader medical community a chance to reflect on the complexities of quality assurance for novel mRNA vaccines, which include everything from the quantification and integrity of mRNA and carrier lipids to measuring the distribution of particle sizes and encapsulation efficiency. Of particular concern is RNA instability, one of the most important variables relevant to all mRNA vaccines that has thus far received scant attention in the clinical community. It is an issue relevant not just to Pfizer-BioNTech’s vaccine but also to those produced by Moderna, CureVac, and others,4 as well as a “second generation” mRNA vaccine being pursued by Imperial College London.5
RNA instability is one of the biggest hurdles for researchers developing nucleic acid based vaccines. It is the primary reason for the technology’s stringent cold chain requirements and has been addressed by encapsulating the mRNA in lipid nanoparticles (box).
“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.”6
Crommelin and colleagues note that specific regulatory guidance for mRNA based vaccines has yet to be developed, and The BMJ’s attempts to clarify current standards were unsuccessful.
Over the years, researchers attempted to resolve intrinsic instability by encapsulating mRNA in nanocarriers made of polymers, lipids, or inorganic materials. Lipid nanoparticles (LNPs) were chosen by Moderna, Pfizer-BioNTech, CureVac, and Imperial College London for their covid-19 vaccines. This has attracted the attention of specialists in the field of pharmaceutical biotechnology, some of whom have raised concerns about further unknowns.
In a rapid response posted on bmj.com, JW Ulm, a gene therapy specialist who has published on tissue targeting of therapeutic vectors,13 raised concerns about the biodistribution of LNPs: “At present, relatively little has been reported on the tissue localisation of the LNPs used to encase the SARS-CoV-2 spike protein-encoding messenger RNA, and it is vital to have more specific information on precisely where the liposomal nanoparticles are going after injection.”14
It is an unknown that Ulm worries could have implications for vaccine safety.
Ulm told The BMJ: “Pfizer-BioNTech and Moderna did a remarkable job of rapidly scaling up manufacturing of such a novel system in swift fashion, which is genuinely a landmark technological achievement. However, pharmacokinetic studies, with independent laboratory confirmation, are essential to ascertain potential cytotoxicity and macroscopic toxicity, especially given the likelihood of booster injections over months or years, since the tissue trafficking patterns of the mRNA vaccine payload will determine which cells and tissues are killed by cytotoxic T-cells in each round.” Given the variation in LNP formulations, it is unclear how relevant previous animal experiments are to answering this question.
Regulators and manufacturers contacted by The BMJ for this article did not wish to address any of the questions raised by Ulm’s rapid response.
It’s not just mRNA to worry about it’s now potentially modified mRNA from poor production quality.
Peat spoke about the carrier lipids months ago, this data leak highlights concerns about said lipids.
People are putting this crap in their body, the authoritarians won’t let you socialize/pass again unless you take it, let’s not forget the pandemrix vaccine, you know the one that caused mass narcolepsy-https://www.bmj.com/content/362/bmj.k3948
But hey, take the vaccine and post it on social media for normie likes!
The EMA covid-19 data leak, and what it tells us about mRNA instability
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, writes Serena Tinari As it conducted its analysis of the Pfizer-BioNTech...
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, writes Serena Tinari
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. They came from anonymous email accounts and most efforts to interact with the senders were unsuccessful. None of the senders revealed their identity, and the EMA says it is pursuing a criminal investigation.
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.
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.”2
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.
But the documents offer the broader medical community a chance to reflect on the complexities of quality assurance for novel mRNA vaccines, which include everything from the quantification and integrity of mRNA and carrier lipids to measuring the distribution of particle sizes and encapsulation efficiency. Of particular concern is RNA instability, one of the most important variables relevant to all mRNA vaccines that has thus far received scant attention in the clinical community. It is an issue relevant not just to Pfizer-BioNTech’s vaccine but also to those produced by Moderna, CureVac, and others,4 as well as a “second generation” mRNA vaccine being pursued by Imperial College London.5
RNA instability is one of the biggest hurdles for researchers developing nucleic acid based vaccines. It is the primary reason for the technology’s stringent cold chain requirements and has been addressed by encapsulating the mRNA in lipid nanoparticles (box).
“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.”6
Crommelin and colleagues note that specific regulatory guidance for mRNA based vaccines has yet to be developed, and The BMJ’s attempts to clarify current standards were unsuccessful.
Lipid nanoparticles—where do they go and what do they do?
Conceived three decades ago, RNA based therapeutics11 have long inspired imaginations for their theoretical potential to transform cells of the body into “an on-demand drug factory.”12 But despite heavy investment by the biotech industry, bench-to-bedside translation was constantly hindered by the fragility of mRNA.Over the years, researchers attempted to resolve intrinsic instability by encapsulating mRNA in nanocarriers made of polymers, lipids, or inorganic materials. Lipid nanoparticles (LNPs) were chosen by Moderna, Pfizer-BioNTech, CureVac, and Imperial College London for their covid-19 vaccines. This has attracted the attention of specialists in the field of pharmaceutical biotechnology, some of whom have raised concerns about further unknowns.
In a rapid response posted on bmj.com, JW Ulm, a gene therapy specialist who has published on tissue targeting of therapeutic vectors,13 raised concerns about the biodistribution of LNPs: “At present, relatively little has been reported on the tissue localisation of the LNPs used to encase the SARS-CoV-2 spike protein-encoding messenger RNA, and it is vital to have more specific information on precisely where the liposomal nanoparticles are going after injection.”14
It is an unknown that Ulm worries could have implications for vaccine safety.
Ulm told The BMJ: “Pfizer-BioNTech and Moderna did a remarkable job of rapidly scaling up manufacturing of such a novel system in swift fashion, which is genuinely a landmark technological achievement. However, pharmacokinetic studies, with independent laboratory confirmation, are essential to ascertain potential cytotoxicity and macroscopic toxicity, especially given the likelihood of booster injections over months or years, since the tissue trafficking patterns of the mRNA vaccine payload will determine which cells and tissues are killed by cytotoxic T-cells in each round.” Given the variation in LNP formulations, it is unclear how relevant previous animal experiments are to answering this question.
Regulators and manufacturers contacted by The BMJ for this article did not wish to address any of the questions raised by Ulm’s rapid response.
