WHAT IF the vaccine you received had not been in a clinical trial? For millions of people worldwide, this is precisely what happened when they unknowingly received a covid vaccine manufactured using a process where the end product had never been trialled in humans. This manufacturing shift resulted in significantly higher rates of adverse reactions – 13 times more in some cases – representing a regulatory failure with profound implications for public trust and safety. Yet, the UK Covid-19 Inquiry tasked with investigating these critical decisions has avoided addressing this issue, which lies at the heart of the controversy on regulatory failure.
Imagine a chef perfecting a recipe in a small kitchen, only to mass-produce it in a factory using different ingredients and techniques. In December 2020, the UK’s drug regulator, MHRA, gave a temporary authorisation to a mass-manufactured vaccine (Process 2 or P2) without requiring human trial data. Available safety and efficacy data were based solely on Process 1 (P1), the small-scale clinical trial method. MHRA relied on lab-based‘comparability’ studies to justify the switch, but these assessments failed to account for potential risks posed by even minor manufacturing changes.
This article delves into how the critical manufacturing switch occurred, why it went largely unchallenged, and implications for public health, safety, and regulatory accountability.
Crucial difference between P1 and P2
Even small changes in manufacturing can significantly affect a final product’s safety and effectiveness. Pfizer/BioNTech gave the public a different product to the one tested in clinical trials; it was a ‘bait and switch’. The industry uses the phrase ‘the process is the product’ because of wide variation in the end product can result from small changes in the manufacturing process.
Process 1 (P1) was used to produce vaccine administered in clinical trials. This small-scale, lab-controlled method relied on purified materials to create DNA and mRNA, ensuring minimal risk of contamination. MHRA relied on safety and efficacy data exclusively from P1-manufactured vaccines.
Process 2 (P2) by contrast, was designed for large-scale vaccine production. This method involved growing DNA templates in vats of E. coli bacteria – a faster but riskier approach that can introduce contaminants such as bacterial DNA fragments and endotoxins, substances that can trigger a vast range of pathology.
When mass manufactured batches were first given to humans, on 8th December 2020 in the UK, MHRA had seen no trial data of these products. The data they had seen analysed in the regulatory submission was up to the cutoff on 14th November 2020 and there was no data on P2. MHRA authorised a P2 batch (EJ0553), on December 2, 2020, based solely on laboratory-based ‘comparability assessments’ between P1 and P2; there was no human testing. MHRA justified making this decision based only on these comparability studies, by claiming there had been ‘full-scale validation’ of the manufacturing process, but this was focused entirely on quality and quantity of RNA.
MHRA also failed to ensure that the public was informed of this massive unknown and the potential risks involved. Informed consent would have been possible if there had been more honesty about uncertainties. Instead, the public was subjected to a barrage of ‘safe and effective’, including from the regulator themselves – the MHRA itself sets the terms for the advertising and promotion of medicines and effectively prohibited any caveats on the ‘safe and effective’ mantra.
Avoiding the Hard Questions
On January 22, Dr June Raine, the then CEO of MHRA, was questioned under oath about MHRA’s testing of covid vaccines. The convoluted way the question was phrased allowed for an evasive response. It is no wonder the inquiry failed to properly discuss this issue, as it would expose a monumental failing on the part of the regulator.
The question that should have been asked is, ‘Was the product given to the public manufactured using the same process as the product given in the trial?’ The answer to that would have been ‘no’.
Instead, Raine was asked about the difference between batches tested by MHRA and batches given to the public. MHRA did do limited testing of batches from the mass manufacturing process, but that is not the issue which is that there was no clinical trial of the P2 product used for the vaccination of the public!
The question, at 25:35 minutes:
‘Some have suggested that the batches, which were delivered to the United Kingdom for use amongst its population, […] were batches that were produced by a different manufacturing process […] as had been tested by the MHRA. So, bluntly, the suggestion has been made [that] you tested and authorised and certified a certain number of vaccines made by manufacturing process A, and then the manufacturers actually delivered vaccines to the British population produced as a result of a different manufacturing process, and one, by inference, which had not been tested.’
Raine replied,‘My understanding is that the manufacturing process would have been the same.’
Note that that Hugo Keith KC deliberately refers to process A and B to distinguish the manufacturing of different batches. This was a further obfuscation as Pfizer/BioNTech always refer to the clinical trial manufacturing as Process 1 and the mass production as Process 2.
When Ruth O’Rafferty of Scottish Vaccine Injury Group was questioned earlier in the week, her attempts to raise the issues (at 32:37 minutes) were quickly shut down with a claim that there was no time to discuss these topics in such detail. The failure to address these issues is because what happened is nothing like what should have happened. The regulator was relying on evidence that was entirely inadequate to demonstrate a sound safety case for the vaccines.
What should have happened
MHRA should have insisted on comprehensive data showing that conclusions drawn about P1 were comparable to P2 based on what happened in humans. For the purposes of this article, we shall leave aside the fact that the harm from P1 was not fully disclosed to MHRA and, even then, the risk of a serious adverse event of special interest (which were conditions identified in advance as being worth watching for) was 1 in 800 for Pfizer and Moderna combined and 1 in 990 for Pfizer.
Pfizer did set out a plan for a direct comparison between Process 1 and Process 2 products, but said it should be ‘post-approval’because of the‘urgency of the current pandemic’. Pfizer’s clinical trial aimed to compare P2 in 250 participants per lot. However, this comparison was abandoned on February 9, 2021. Only 252 people were given P2 as their first and second dose. Despite this, P2 products with known manufacturing differences were distributed to millions worldwide.
In September 2022, the trial was terminated. Pfizer said that‘given the number now administered worldwide, the originally planned comparison of manufacturing processes is no longer warranted.’ The trial records say that the FDA and EMA agreed to early completion of this trial having ‘removed the objective to describe the safety and immunogenicity of prophylactic BNT162b2 […] produced by manufacturing “Process 1” or “Process 2” because of the volume of BNT162b2 now distributed and administered globally using manufacturing “Process 2,” making this comparison unwarranted’.MHRA have stated, ‘this process comparison was not conducted as part of the formal documentation within the protocol amendment.’
Results comparing the 252 given P2 against those given P1 doses have never been disclosed. However, even without a control group, differences between Process 2 lots were stark, with the EU processing plant having twice as many adverse reactions as USA sites, 10.4 per cent vs 5.5 per cent.
Figure 1: Comparison of Adverse Events by Manufacturing Site for Process 2 (P2) Vaccines (mostly given as dose 3), December 2020–March 2021
This figure shows percentage of adverse events reported among individuals who received P2 vaccines, broken down by manufacturing site. The EU manufacturing site showed a significantly higher adverse reaction rate (10.4 per cent) compared to the USA site (5.5 per cent), illustrating inconsistencies in vaccine quality across production facilities.
December 2020 to March 2021
The first batch given in UK was EJ0553. On November 27, 2020, Commission on Human Medicines (CHM) said of the first two batches (which had been rejected by the MHRA labs*), ‘it is not currently feasible to compare these two batches to those given to subjects in clinical trials.’ That evening, these dud duo batches were switched for two alternative batches and then a third was added. They reconvened a meeting on the next morning. One of these contained visible particulate matter, and one had RNA that was the wrong size. The batch with floaters in it was the infamous EJ0553 – the first batch used in the UK.
The CHM feared they were not getting the best quality batches, and that ‘it may be the case that the batches the FDA are evaluating are further along the development lifecycle than those allocated for the UK.’ Later, their worst fears were realised. The company said the EJ0553 vial had failed to meet their own acceptance quality limit based on visual inspection. They did not know the ratio of lipids to RNA nor the overall potency (the measure of how much spike was likely to be produced). The minutes say,‘The company further explained that these particles did not alter the concentration of the drug product and they did not think this would have an impact on safety and efficacy of the product. However, as these were rejected vials [italics mine], they did not perform a potency test on these rejected vials.’The company explained that ‘the appearance of these lipid-associated particles increases at the end of the filling line’.Nucleic acids clump and lipid nanoparticles float; both could result in a higher concentration of product in the last batches to be filled.
The batches they were first offered may have been worse than these, but that does not excuse using these ones. The CMH minutes said that variable potency testing ‘makes interpretation of the available data difficult’. They noted that the potency test would be passed if between 30 and 100 per cent of cells produced spike, saying: ‘The limits for in vitro cell expression were also wide being set at 30 per cent or above. This could lead to large differences across batches.’ They added, ‘a concern was raised that if the product has less than 50 per cent RNA integrity, it may suggest that half of the product is not what it was laid out to be.’ However, they then declared it reassuring that ‘the later developmental batches have a higher level of RNA integrity that is more comparable with the earlier clinical batches.’
The focus throughout seemed to be a concern that junk vials might not have the same efficacy. There was minimal discussion on safety even though they had seen no data comparing these P2 products with P1.
The defence for using these vials was that they ‘were not understood to be associated with a change in concentration of RNA containing LNPs’.That claim did not appear to be based on data, nor should it have provided any reassurance regarding safety, which depends on factors beyond the concentration of the active ingredient.
Three days later, Lord Bethell signed a temporary use authorisation. EJ0553 became the template for all subsequent UK Pfizer batches, despite the absence of clinical safety data for P2. On 21st December, the EMA gave a conditional authorisation for Comirnaty (the brand name) and MHRA authorised for use in the UK both batches from the ‘dud duo’, EE8492 and EE8493, which were rejected in November. A later trial showed the true nature of EJ0553 was indeed very different to P1.
Evidence emerges
As P2 was used and people were affected, MHRA should have been alarmed by the signals. From the first day of rollout, doses of EJ0553 coincided with three cases of anaphylaxis among 400 initial recipients, affecting those with a clinical history of anaphylaxis. By March 2021, breast screening programs noted 11 per cent of dose 1 recipients and 16 per cent of dose 2 recipients exhibited lymphadenopathy, a ‘swelling of lymph nodes’ that ‘usually settles within a few days’ – a dramatic increase compared to the trial’s P1 product rate of 0.4 per cent. Adjustments to breast screening protocols were required to avoid false cancer diagnoses.
In April 2021, Pfizer submitted evidence showing significantly higher rates of adverse reactions among clinical trial participants who received P2 (see Figure 2). These participants were originally part of the placebo group and had not previously received the P1 vaccine used during the initial clinical trial. Following the temporary authorizations, most participants in the placebo group were promptly vaccinated with the P2 product, making medium- and long-term safety analysis impossible. Despite the stark increase in adverse reactions among these individuals, Pfizer dismissed the findings, stating that the excess reactions wereas expected.
Figure 2: Adverse Reactions in P1 vs. P2 Recipients in Clinical Trials, Pre- and Post-Unblinding This figure presents data from Pfizer’s FDA submission, comparing adverse reactions between individuals who received P1 vaccines during the blinded trial phase (roughly around December 2020) (Table 60) and those who were given P2 vaccines as a third dose after two placebo doses up to March 2021 (Table 65). Adverse reaction rates were notably higher in the P2 group, despite the relatively short follow-up.
Despite this, MHRA did not re-evaluate the trial findings in light of this, nor did they respond to signals in Yellow Card reporting. Furthermore, they ignored a disproportionately high rate of adverse events in women given P2 compared to near-equal rates in those given P1 in clinical trials. Pfizer’s June 2021 Periodic Safety Update Report (figure 3) detailed this stark gender disparity. This was reinforced by Lareb’s finding that 48 women and 19 men experienced prolonged lymphadenopathy.
Figure 3: Gender Disparity in Adverse Reactions: P1 vs. P2 Vaccines This table highlights a stark gender disparity in adverse reaction rates between clinical trial data (P1) and real-world data (P2). While P1 showed higher adverse reactions in males (middle column), P2 data from real-world administration revealed significantly higher rates in females (first column), suggesting a fundamental difference in the reactogenicity of P2 vaccines.
In September 2021, MHRA was first presented with trial data on P2. This was not data regarding the 252 participants given it as dose 1 and 2, but was on just 306 trial participants who received P2 as a booster. Both the original batch from the UK rollout and one of the batches rejected outright by USA and UK were two of the three batches (EJ0553 and EE8493) used in Pfizer’s booster trial. The recipients of these P2 boosters had a 5.2% lymphadenopathy rate. In comparison this was 4.3 per cent for those receiving P2 in the adolescent trial and 0.4 per cent for P1. These findings indicate a 10- to 13-fold increase in reactogenicity. Did they act? No. They said nothing until December, then on Christmas Eve 2021, they added this fact as a footnote to a table saying that ‘a higher frequency of lymphadenopathy (5.2% vs 0.4%) was observed in participants receiving a booster dose (third dose) compared to participants receiving 2 doses’. This statement misleadingly framed reactogenicity as booster-related rather than acknowledging its roots in the P2 manufacturing process. Lymphadenopathy was just as common with dose 1 when P2 was given. In reality, 85 per cent of lymphadenopathy cases occurred after the first two doses, with some persisting beyond six months. The difference was not the dose; it was because P2 was given.
The elevated rate of lymphadenopathy and other adverse events is indicative of a marked inflammatory process likely linked to P2 manufacturing processes. Contaminants such as endotoxins or residual plasmid DNA may contribute to these signals. It could be something else or a combination of factors – the exact cause is as yet unproven. Unlike largely endotoxin-free P1 batches, risk of endotoxin in P2 using E. coli to produce key materials is higher.
Conclusion
MHRA’s failure to address differences between P1 and P2 in their safety analysis undermined public trust. Millions of people received a product with a 13-fold higher reactogenicity than P1. Key safety signals – such as lymphadenopathy, gender disparities, and reactogenicity – were overlooked, raising serious questions about regulatory accountability. These decisions have had lasting consequences, from deaths and injury to denial of high adverse reaction rates and widespread public confusion and concern. It is long past time for an overhaul of our regulator, MHRA.
* N.B. These first two batches were called EE8492 or CTM12 and EE8493 or CTM13 and had also been rejected for emergency use in the USA on 20th November 2020.The rejection was because of ‘differences in applied label’.
