Pfizer Vaccine Report to FDA

Summary of Pfizer's FDA Report on the Vaccine Clinical Trials

Pfizer has just released a full detailed 53-page report to the FDA reviewing the results of the Phase I/II/III clinical study trials for their Covid-19 vaccine BNT162b2. What follows is a high-level 5-page summary of what’s known and not known based on the Pfizer report.


Study Participants:

  • 38,000 participants

  • Study Duration: 110 days

  • 50% vaccine group: 50% placebo group

Age Range:

  • 60% were under 55 years of age

  • 15% were 55-64 years of age

  • 25% were over 65 years of age

Health Conditions:

  • 35% Obese

  • 35% Overweight

  • 45% With Co-Morbidities


Vaccine Efficacy:

95% vaccine efficacy at least 7-days after the second dosage, where efficacy is defined as a reduction in confirmed mild to moderate symptomatic Covid-19 illness.

From the Pfizer report:

“For participants with and without evidence of SARS-CoV-2 infection before and during vaccination regimen, VE against confirmed COVID-19 occurring at least 7 days after Dose 2 was 94.6%, with 9 and 169 cases in the BNT162b2 and placebo groups respectively. The posterior probability was >99.99% for the true VE being greater than 30%. The 95% credible interval for the vaccine efficacy was 89.9% to 97.3%, indicating that the true VE is at least 89.9% with a 97.5% probability given the available data.”

This graph shows the cumulative cases of Covid-19 for the placebo group (red-line) and for the vaccine group (blue-line). So good efficacy even after just a single dose!


Vaccine Ingredients:

  1. VLP – virus-like particle (mRNA encapsulated in a shell of fat molecules)

    • Nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2

    • Lipids ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine, and cholesterol)

  2. Buffering Agents (to stabilize pH & provide an injection medium):

    • sodium chloride (basic table salt)

    • potassium chloride (an electrolyte found in sports drinks)

    • monobasic potassium phosphate (also often found in sports drinks)

    • dibasic sodium phosphate dihydrate (a common buffer salt)

  3. Stabilizing Agent (used to stabilize the vaccine during storage & transport):

    • sucrose (a common plant-derived sugar)

  4. What is NOT in the vaccine:

    • NO preservatives (not required for lipid-based VLPs)

    • NO adjuvants (the mRNA molecules act as their own adjuvant)


As modern vaccines go, this is an incredibly simple and basic ingredient list!


Adverse Effects:

Adverse effects were generally mild to moderate and of short-term duration and generally worse following the second dose.

Most common adverse reactions were:

  • Injection site reactions (84.1%)

  • Fatigue (62.9%)

  • Headache (55.1%)

  • Muscle pain (38.3%)

  • Chills (31.9%)

  • Joint pain (23.6%)

  • Fever (14.2%)


Handling & Dosage:

The Pfizer BNT162b2 COVID-19 Vaccine is administered intramuscularly (IM) as a series of two 30 μg doses (0.3 mL each) 21 days apart.

“The Pfizer-BioNTech COVID-19 Vaccine is supplied as a frozen [between -80°C to -60°C (-112°F to -76°F)] multi-dose (5-dose) vial. The vaccine must be thawed and diluted in its original vial with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to administration. After dilution, the vial contains 5 doses of 0.3 mL per dose. After dilution, the multiple-dose vials must be stored between 2°C to 25°C (35°F to 77°F) and used within 6 hours from the time of dilution.”


Risks & Unknowns - Summary:

  • Duration of Protection: Up to 2 months (study ran for only 110 days)

  • Immunocompromised individuals:  Unknown, no data - too few participants

  • Individuals previously infected: Unknown, those with existing antibodies were excluded from the study

  • Pediatric Patients (under 16): Unknown, those <16 were excluded from the study

  • Pregnant or lactating individuals: Unknown, excluded from the study

  • Future vaccine effectiveness due to virus mutations: Unknown, study period too short to see the effect of potential mutations

  • Long-term effects of COVID-19 disease: Unknown, not looked at in the study

  • Asymptomatic infection: Unknown, not looked at in the study

  • Effectiveness against mortality: Unknown, study size too small and too short in duration to determine vaccine impact on Covid-19 death rate

  • Vaccine effectiveness against transmission of SARS-CoV-2: Unkown
    Data are limited to assess the effect of the vaccine against transmission of SARS-CoV-2 from individuals who are infected despite vaccination.

    If efficacy against asymptomatic infection were lower than efficacy against symptomatic infection, asymptomatic cases in combination with reduced mask-wearing and social distancing could result in significant continued transmission.

  • Vaccine-Induced Disease Enhanced: Unknown
    Risk of vaccine-enhanced disease over time, potentially associated with waning immunity, remains unknown and needs to be evaluated further in ongoing clinical trials and in observational studies that could be conducted following authorization and/or licensure


Risks & Unknowns - Excerpts from the Pfizer Report:

Duration of protection

“As the interim and final analyses have a limited length of follow-up, it is not possible to assess sustained efficacy over a period longer than 2 months.”


Effectiveness in certain populations at high risk of severe COVID-19

“Although the proportion of participants at high risk of severe COVID-19 is adequate for the overall evaluation of safety in the available follow-up period, the subset of certain groups such as immunocompromised individuals (e.g., those with HIV/AIDS) is too small to evaluate efficacy outcomes.“


Effectiveness in individuals previously infected with SARS-CoV-2

“Therefore, available data are insufficient to make conclusions about benefit in individuals with prior SARS-CoV-2 infection. However, available data, while limited, do suggest that previously infected individuals can be at risk of COVID-19 (i.e., reinfection) and could benefit from vaccination.”


Effectiveness in pediatric populations

“The representation of pediatric participants in the study population is too limited to adequately evaluate efficacy in pediatric age groups younger than 16 years. No efficacy data are available from participants ages 15 years and younger.”


Future vaccine effectiveness as influenced by characteristics of the pandemic, changes in the virus, and/or potential effects of co-infections

“The study enrollment and follow-up occurred during the period of July 27 to November 14, 2020, in various geographical locations. The evolution of the pandemic characteristics, such as increased attack rates, increased exposure of subpopulations, as well as potential changes in the virus infectivity,  antigenically significant mutations to the S protein, and/or the effect of coinfections may potentially limit the generalizability of the efficacy conclusions over time.”


Vaccine effectiveness against asymptomatic infection

“Data are limited to assess the effect of the vaccine against asymptomatic infection as measured by detection of the virus and/or detection of antibodies against non-vaccine antigens that would indicate infection rather than an immune response induced by the vaccine.

Additional evaluations will be needed to assess the effect of the vaccine in preventing asymptomatic infection, including data from clinical trials and from the vaccine’s use post-authorization.“


Vaccine effectiveness against long-term effects of COVID-19 disease

“COVID-19 disease may have long-term effects on certain organs, and at present it is not possible to assess whether the vaccine will have an impact on specific long-term sequelae of COVID-19 disease in individuals who are infected despite vaccination.

Demonstrated high efficacy against symptomatic COVID-19 should translate to overall prevention of COVID-19-related sequelae in vaccinated populations, though it is possible that asymptomatic infections may not be prevented as effectively as symptomatic infections and may be associated with sequelae that are either late-onset or undetected at the time of infection (e.g., myocarditis).”


Vaccine effectiveness against mortality

“A larger number of individuals at high risk of COVID-19 and higher attack rates would be needed to confirm efficacy of the vaccine against mortality. However, non-COVID vaccines (e.g., influenza) that are efficacious against disease have also been shown to prevent disease associated death.11-14 Benefits in preventing death should be evaluated in large observational studies following authorization.”


Vaccine effectiveness against transmission of SARS-CoV-2

“Data are limited to assess the effect of the vaccine against transmission of SARS-CoV-2 from individuals who are infected despite vaccination. Demonstrated high efficacy against symptomatic COVID-19 may translate to overall prevention of transmission in populations with high enough vaccine uptake, though it is possible that if efficacy against asymptomatic infection were lower than efficacy against symptomatic infection, asymptomatic cases in combination with reduced mask-wearing and social distancing could result in significant continued transmission.

Additional evaluations including data from clinical trials and from vaccine use post-authorization will be needed to assess the effect of the vaccine in preventing virus shedding and transmission, in particular in individuals with asymptomatic infection.”


Vaccine-enhanced disease

“Available data do not indicate a risk of vaccine-enhanced disease, and conversely suggest effectiveness against severe disease within the available follow-up period. However, risk of vaccine-enhanced disease over time, potentially associated with waning immunity, remains unknown and needs to be evaluated further in ongoing clinical trials and in observational studies that could be conducted following authorization and/or licensure.”


Phase 3 Follow-up

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile. From a safety perspective, a 2-month median follow-up following completion of the full vaccination regimen will allow identification of potential adverse events that were not apparent in the immediate postvaccination period.

Adverse events considered plausibly linked to vaccination generally start within 6 weeks of vaccine receipt.7 Therefore, a 2- month follow-up period may allow for identification of potential immune-mediated adverse events that began within 6 weeks of vaccination. From the perspective of vaccine efficacy, it is important to assess whether protection mediated by early responses has not started to wane.

A 2-month median follow-up is the shortest follow-up period to achieve some confidence that any protection against COVID-19 is likely to be more than short-lived.

The EUA request should include a plan for active follow-up for safety (including deaths, hospitalizations, and other serious or clinically significant adverse events) among individuals administered the vaccine under an EUA in order to inform ongoing benefit-risk determinations to support continuation of the EUA.”


Links to Pfizer FDA Report & Original Clinical Study Protocol:


About the author:

I am a scientist with 20+ years in the biotech industry. I currently work as a consultant with companies involved in developing molecular diagnostics platforms, including some of the key testing platforms used to detect the SarsCoV2 virus.

So I bring an insider’s perspective that is scientifically oriented but directed to a general audience trying to make sense of the conflicting stories surrounding the Covid pandemic.

To learn more: https://www.linkedin.com/in/dalewharrison/


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