Posted by Curt on 30 January, 2023 at 9:09 am. 1 comment.


by Sasha Latypova

Lack of mRNA integrity and product impurities (fragmented nucleic acid chains) were found in Pfizer’s product days before it was authorized for market.  mRNA integrity, and conversely, its instability, is one of the most important variables relevant to all mRNA vaccines.  Pfizer and BioNTech repeatedly stated that the efficacy of the product is highly dependent on the quantity of the sufficiently intact mRNA molecule.  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.
I reported on this issue about a year ago, but since I have larger audience now I am re-publishing my analysis here. The integrity of key active ingredient – mRNA molecule as measured by the %mRNA integrity and % of fragments (Late Migrating Species, LMS) in each manufactured batch is highly and unacceptably variable.  This was identified by the regulatory reviewers at EMA and FDA.  The discussions around this issue are recorded in numerous documents that were released from EMA, at the end of November 2020, including email exchanges between EMA staff and senior executives.  The “solution” to this issue was to lower the acceptance standard for the %mRNA integrity in the active substance for shelf live to just >50%.  In other words, the “other” 50% of the nucleic acid chains and other impurities can be present in the active substance, do not need to be characterized (no matter the length or composition of the RNA molecules) and the product is still deemed “acceptable”.
An extremely wide variation of the integrity of the active substance in bulk material of the product and abundant presence of uncharacterized nucleic acid impurities means that batches of different formulation – and thus different potency and safety profiles – are being produced.  This variation is further amplified when hundreds of liters of the bulk material is filled in small quantities into 0.45 ml vials and subsequently manually divided into doses by untrained and unsupervised staff at the vaccination centers.
Both the regulators and Pfizer to date have not disclosed the acceptable ranges or testing methods for the key ingredients of the vaccine product, neither in bulk product nor in a vial or a dose (as dispensed), and claim “commercial secrets” prevent them from doing so.
33 Commercial Batches Manufactured Prior to December 2020:
Records released by the EMA leak contain some manufacturing and testing details for 33 commercial scale batches made by Pfizer between August and late November 2020. The fact that commercial batches were manufactured prior to the regulatory review and prior to any safety or efficacy data available for the product is a violation of CFR21 – current Good Manufacturing Practices. To clarify, a company can manufacture a volume of product prior to approval, but once the regulatory review finds significant problems in the submission (as was found here) – shipping these batches commercially without demonstrating that whatever issues were found did not affect the product safety and efficacy is a big problem. Given the number of significant and major objections and the short span of time (about 2 weeks before product was shipped) it is not possible that these problems were resolved. That’s why no sane and well-intentioned manufacturer would ever do such a thing – produce millions of doses of expensive product “at risk” before finding whether it is actually safe. However, geniuses at BARDA believe this is hip, cool and “innovative” and only the losers in the private sector should follow laws and regulations. When the government is in the business of “saving lives”, no laws apply and nobody is concerned with boring regulations:

Back to the 33 “pre-authorization” batches:
Specifically, these batches and all information used in my analysis were listed in the document titled: “COVID-19 Vaccine (BNT162, PF-07302048) BB-IND 19736 Response to CBER Comments Received on 20 November 2020 Regarding Overall CMC Information.” The document is dated November 25, 2020. It was part of the documents that were leaked from the EMA. Here’s the title page:

At the time of issue of this document, the manufacturing facilities were deemed not in acceptable compliance with the current Good Manufacturing Practices by the regulatory authorities (both EMA and FDA). CGMP a set of regulatory requirements guiding quality, purity, stability and reproducibility and labeling of mass-produced drugs and vaccines. The cGMP regulations for drugs contain minimum requirements for the methods, facilities, and controls used in manufacturing, processing, and packing of a drug product.  The regulations make sure that a product is safe for use, and that it has the ingredients and strength it claims to have.
The non-compliance with cGMP was recorded as Major Objection #1 by the EMA reviewers, and in addition, the issue of lack of mRNA integrity and presence of significant uncharacterized impurities in the form of nucleic acid chains (LMS) was raised and recorded as Major Objection #2.  Here are the slides from EMA-BioNTech meeting discussing the “comparability” issue, i.e., the batches used to manufacture clinical trial material (using Process 1) were very substantially different from the batches manufactured at commercial scale (Process 2) and there was no way to reconcile this without re-running a clinical trial. But of course that’s not what they decided to do. The response was to simply lower the acceptance standard, which was arbitrarily set to begin with, from >70% to >50% of the batch would need to conform to the specification for it’s key active ingredient – an intact, full length mRNA molecule of certain specification.

The regulators and manufacturer knew there were going to be “truncated” molecules, and had no idea what mutant proteins that would create…

They had the tests showing significant profile differences between Process 1 and Process 2 batches (note the “bumps” before the main spike)…

The %mRNA integrity was not comparable between Process 1 and Process 2 (and strictly speaking, within each process, too)…

The “Applicant’s Reply Strategy” was to simply lower acceptance threshold without any data showing that any of this is ok…

It was clear that the mRNA breaks and degrades during production (drug substance manufactured into drug product), and subsequently during shelf storage. Of course this process continues during transportation and manual dose preparation, because those “moving at the speed of $ience! (TM)” are not concerned with any of this pedestrian stuff…

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