A thread on Pfizer's Process 1 & Process 2. And why it matters that their vaccine was tested only.. on 252 persons - inconvenient truth revealed thanks to Josh Guetzkow & Retsef Levi As a preamble, let's let Paul Offit explain the rule of the industry: "The process is... the product". 1/show more

The rule emerged in the 70s, due to the high complexity of biopharmaceutical & became widely adopted in the 90s, with p.e the 1987 FDA's guidelines on General principles of Process Validation, in order to reduce the risk of variability in drugs quality. 2/

In the development of its COVID-19 vaccine candidate, BNT162b2 (commercially known as Comirnaty), Pfizer/BioNTech used two distinct manufacturing methods, which they referred to as “Process 1” ("P1") and “Process 2” ("P2"). 3/

The differences between P1 & P2 aren't trivial. A document from the TGA details some key changes performed. In P1, the DNA template for mRNA transcription was produced via PCR-amplification; P2 uses linearized plasmid DNA cultured in E. coli bacteria. 4/

So, who during the trial received this process 2? A document made public by the TGA, FOI 3659 doc. 4, titled “BNT162b2 (PF-07302048) Comparability Report for PPQ Drug Product Lots”, lists the lots distributed, their use and their corresponding production processes. 5/

Another document released by the FDA details which lots had been shipped to which clinical research site at approximately 6 months into the trial. It is dated March 17, 2021 and titled “125742_S1_M5_5351_c4591001-interim-mth6-patient-batches.pdf”. 6/

Two Process 2 lots are identified in the 6-month patient batches document cited: EE8493 & EJ0553. EE8493 is listed as a P2 lot in Table 1 of the TGA’s “Comparability Report for PPQ Drug Product Lots” document cited above. EJ0553 is listed in the TGA comparability report. 7/

There are 2 ways to identify P2 lots used as part of the planned comparison study between P1 & P2 described in the protocol. The 1st is by identifying which P2 lots were shipped to which sites & count how many treatment subjects were enrolled from P2 deployment. 8/

The second is to show that the randomization numbers of a subset of participants was distinct from all the others. These independent methods converge on the same result: only 252 subjects were given vaccine doses from lot EE8493 & enrolled as part of the planned comparison. 9/

In a reply to FOI request 23/510, the United Kingdom’s Medicines & Healthcare products Regulatory Agency (MHRA) attested that “the first clinical batch which contained process 2 drug substance was dosed 19th October 2020 in US”. 10/

Back to the doc. which lists the lots supplied to each site as of Nov. 19, 2020. In that document, the only P2 lot listed is EE8493. Therefore, EE8493 was the only P2 lot that had been distributed to the study sites when the comparison of P1 vs. P2 began on Oct. 19, 2020. 11/

It was supplied to sites 1133, 1135, 1146 and 1170 according to both the interim and 6-month batch docs. Analysis of the subjects who received their first dose on or after Oct. 19, 2020 shows a total of 252 subjects administered the vaccine and 250 administered the placebo. 12/

You can reproduce and verify this analysis yourself by executing the following R scripts: Download: Extract: Randomised population: Process 2 recipients: 13/

The dataset and documents used for this analysis provide a second means for identifying the subjects involved in the comparison study: the subject "randomization" number. A small subset of 502 subjects have a unique range of randomization numbers between 400002 and 401509. 14/

This can be verified with this R script: Of these, 252 are the same treatment subjects identified above, at the 4 sites that received P2 lots prior to Nov. 2020. The others 250 are Placebo recipients, the same than those at the four sites identified. 15/

This shows independent corroboration of that these 252 subjects from sites that received lot EE8493 were the only ones who were intended for the comparison between processes 1 and 2. The comparison of process 1 vs process 2 recruitment has been represented on a weekly chart. 16/

In FOI request 23/510, cited above, the MHRA states that the data from the study were expected in Feb. 2021 (p. 2). However, the planned comparison was “removed and documented in Protocol amendment 20 in Sept. 2022. Thus, this process comparison was not conducted” (p. 5). 17/

The motive for not comparing the products ? We had "extensive usage of vaccines manufactured". Otherwise said, you were the guinea-pigs, to whom we told that the product had been extensively tested, when it was pushed to pregnant women without a shadow of real safety data. 18/

We modeled the impact of being a recipient of Process 2 compared to other variables on the number of adverse effects registered by subjects in the USA, 55 or under, using a Poisson regression, & found that an increase in adverse events by 264.33%. 19/

Comparing exclusively the 95 non-obese male recipients male recipients in the USA, Process 2 results in a 211.77% increase, with an impact 4.84 times larger than comorbidity. The evaluation is similar (214.49% increase) using a negative binomial regression. 20/

Differences in the reported rate of lymphadenopathy between the first two vaccine doses in the clinical trial (C4591001) & the rates from the third (booster) dose are also indicative of the different adverse event profiles of process 1 versus process 2 vaccine product. 21/

The reason is that the first two doses in the clinical trial were overwhelmingly from vaccine doses made with process 1, whereas booster doses given many months later would have been manufactured using the process 2 for commercial supply. 22/

The “MHRA’s Public Assessment Report for the Authorisation for Temporary Supply” of Pfizer/BioNTech’s COVID-19 mRNA Vaccine BNT162b2 describes the rate of lymphadenopathy based on the preliminary report from clinical trial C4591001. 23/

Although the public assessment report (MHRA’s PAR) was updated for adolescent vaccination in June, 2021, the cover page states that it “summarises the initial assessment at the time of approval in December 2020. The text in the original report remains unchanged.” 24/

The lymphadenopathy rates from clinical trial C4591001 are listed on page 42 of the MHRA’s PAR as 0.3% and classed on page 50 as “uncommon,” defined as occurring greater than 0.1% of the time but less than 1%. 25/

In the MHRA’s June, 2023, “Information for Health. Pro. on COVID-19 Vaccine Pfzr/BNT”, the lymphadenopathy rate is given in Table 1125: “A higher frequency of lymphadenopathy (5.2% vs 0.4%) was observed in participants receiving a booster dose compared to .. 2 doses.” 26/

It can be concluded with very high confidence that the increase in the rate of lymphadenopathy reported by the MHRA is due to the switch from process 1 doses used in the clinical trial to process 2 doses used later for booster doses. 27/

Posterior studies found high rates of Menorrhagia ; for example 12+%in a study on female students and staff at a university in Saudi Arabia. A meta-analysis138, by Al Kadri, found a pooled prevalence of 24.24 % (95 % CI: 12.8–35.6 %). 28/

By opposition, only 4 cases of Menorrhagia had been reported as Adverse events during the trial - 2 among the BNT162b2 recipients (0.065% of the 3087 women 16 to 39). 29/

This is very far from the post-study rates, and leads us to conclude that the very high rates of Menorrhagia in the post-marketing studies are another consequence of the switch to Process 2. 30/

Therefore, this concludes this demonstration. Pfizer, while marketing and presenting to the public a product as having been tested on 22.000+ persons, in fact had tested it on 252 persons, and deployed a more dangerous, hazardous, and untested manufacturing process. 31/

Dr. Tal Patalon explores how AI mega initiatives like the $500B Stargate project & AI-powered genomic analysis by Illumina & NVIDIA are transforming healthcare. @TalPatalon @forbes @edengallery_ #AIinHealthcare #PrecisionMedicine #Multiomics #HealthTech