In December 2020, Pfizer-BioNTech's Comirnaty became the first mRNA vaccine approved for human use, based on just two months of clinical trial data. This analysis examines the evidence supporting its rapid deployment, subsequent safety monitoring, and the evolution of claims about its efficacy.
Development and classification
The classification of Comirnaty itself has been subject to regulatory divergence. While many authorities categorised it as a biological product, Japan's Pharmaceuticals and Medical Devices Agency (PMDA) took a different stance, considering it a 'powerful drug' with tozinameran as its active ingredient, rather than a biologic.
This classification difference reflects broader uncertainty about the novel technology platform. At its core, Comirnaty delivers messenger RNA (mRNA) via lipid nanoparticles (LNPs). According to analyses by Trust The Evidence, regulatory documents note 'limited experience' with these delivery compounds, particularly regarding their distribution within the human body.
Trial data and evidence base
The evidence supporting Comirnaty's initial emergency authorisation came primarily from trial C4591001, with additional data from a smaller German trial (Pfizer's subsidiary BioNTech, which manufacures the vaccine, is based in Mainz, Germany), BNT16201. The larger C4591001 trial enrolled 44,165 participants aged 16 or older and 2,264 participants aged 12-15 years, who received either two 30-μg doses of BNT162b2 or placebo, 21 days apart.
Efficacy claims
The trial reported:
- 91.3% overall efficacy (95% CI: 89.0-93.2) through 6 months
- 96.7% efficacy against severe disease (95% CI: 80.3-99.9)
- 100% efficacy in South Africa against the Beta variant (95% CI: 53.5-100)
However, several important caveats apply:
- These results only included participants without evidence of previous SARS-CoV-2 infection
- The researchers noted a 'gradual decline in vaccine efficacy' over the study period
- The trial did not assess prevention of asymptomatic infection or transmission
Demographics and representation
The trial's demographic reporting raises questions about transparency and representation. While the published data indicates that 40.7% of participants were over 55 years old (8,957 participants), with ages ranging from 16-89 years, Trust The Evidence's analysis of regulatory documents indicates that only twelve participants aged 65-85 were included in crucial early phases. This apparent discrepancy highlights the importance of careful examination of trial phases and regulatory submissions.
Notable exclusions from the trial included:
- Pregnant and lactating mothers
- Immunosuppressed individuals
- People with multiple pathologies
- Those with autoimmune diseases
Regulatory decisions and policy
The timeline of regulatory decisions is particularly noteworthy. Emergency use authorization was granted based on just two months of clinical trial data, with six-month follow-up data published later in support of full approval. This rapid authorization process was unprecedented for a vaccine using novel mRNA technology.
The UK government issued its first authorisation to Pfizer BioNTech for the supply of Comirnaty in Decemmber 2020, based on data provided from 1 October to 2 December 2020.
The US FDA issued a licence to Pfizer BioNTech to manufacture Comirnaty on 23 August 2021. Comirnaty received a conditional marketing authorisation valid throughout the EU on 21 December 2020. This was switched to a standard marketing authorisation on 10 October 2022.
Safety monitoring and compensation schemes
Documentation reveals that UK government preparations for vaccine injury compensation were explicitly calibrated against previous experience with the H1N1 influenza vaccine Pandemrix. Internal documents show authorities planned for claim rates 'double the rate in H1N1', with some scenarios assuming 2.5 times higher rates due to the need for multiple boosters.
This advance planning for adverse events appears to contrast with public messaging about safety. Further questions about transparency emerged when Dr Jenny Harries, head of the UK Health Security Authority, declined to release death data by dose number to Parliament, citing 'commercial confidentiality'.
Current data shows the UK government is spending more on managing vaccine injury claims than on settling them, raising questions about the efficiency and accessibility of the compensation process.
Current status and retrospective analysis
Since its marketing authorisation in the European Union (EU) on 21 December 2020 until 29 October 2021, almost 428 million doses of Comirnaty have been administered in the EU/EEA. The EU's Pharmacovigilance Risk Assessment Committee is currently investigating data on the risk of myocarditis and pericarditis (serious heart disease) following vaccination with Comirnaty.
After Pfizer BioNTech's temporary licence to supply Comirnaty was issued by the UK government in December 2020, it was converted to a full marketing authorisation on 10 October 2022.
