BNT162b2 COVID-19 Vaccine (BioNTech/Pfizer)

Kathryn Dzintars, Pharm.D., BCPS

VACCINE TYPE

  • On August 23, 2021, the FDA approved the Pfizer-BioNTech COVID-19 vaccine for individuals ≥ 16 years of age. It remains under the EUA for individuals aged 12 - 15 years, and was expanded to include children aged 5 - 11 years at a reduced dose.
  • The Pfizer-BioNTech COVID-19 vaccine (BNT162b2; Comirnaty) is a lipid nanoparticle-formulated, nucleoside-modified RNA (mRNA) vaccine encoding a prefusion-stabilized, membrane-anchored SARS-CoV-2 spike protein.
    • Primary series: two-dose series, given 21 days apart
      • A third dose can be administered to select immunocompromised patients a minimum of 28 days after the initial 2-dose series.
        • On August 12, 2021, the EUA was modified to include the administration of a third dose after the initial 2-dose primary series to certain immunocompromised patients (solid organ transplant, active treatment of solid or hematologic malignancies, CAR-T or prolonged immunosuppressive therapy, advanced/untreated HIV infection, active treatment with prednisone ≥20 mg/day)
          • The additional dose should be the same vaccine product as the original two-dose series.
          • Administer the additional dose at least 28 days after the completion of the initial two-dose series (this is based on expert opinion only).
    • Booster dose: currently advised for the following groups with graded recommendations, at least 6 months after completion of the initial 2-dose series:
      • Per CDC, people who should receive a booster 6 months after dose #2:

        • People ≥ 65 yrs
        • People aged 18 - 64 years with underlying medical conditions
        • People aged 18-64 years who are at increased risk for COVID-19 exposure and transmission because of living in a long-term care setting
        • People aged 18-64 years who work in high-risk settings (healthcare workers, first responders, education staff, food and agriculture workers, manufacturing workers, corrections workers, U.S. Postal Service workers, public transit workers, grocery store workers)
  • The Emergency for Use Authorization (EUA) remains in effect for the Pfizer-BioNTech COVID-19 vaccine for active immunization to prevent COVID-19 in individuals 5 - 15 years of age.
    • Mandatory requirements for the administration of BNT162b2 under the EUA are as follows:
      • The vaccination provider must give the individual receiving the Pfizer-BioNTech COVID-19 vaccine or their caregiver the “Fact Sheet for Recipients and Caregivers” before the individual receiving Pfizer-BioNTech COVID-19 vaccine.
      • Vaccine providers must include vaccine information to either the state’s or local jurisdiction’s Immunization Information System or other designated systems.
      • Vaccine providers are responsible for reporting certain events to the Vaccine Adverse Events Reporting System (VAERS):
        • Vaccine administration errors, whether or not associated with an adverse event
        • Serious adverse events include death, life-threatening adverse events, inpatient hospitalization/prolonged hospitalization, persistent or significant incapacity, congenital anomaly/birth defects
        • Cases of a multisystem inflammatory syndrome (MIS) in children and adults
        • Cases of COVID-19 that result in hospitalization and death
      • Vaccine providers are responsible for responding to FDA requests for information about vaccine administration errors, adverse events, cases of MIS in adults and children, and cases of COVID-19 that result in hospitalization or death following administration of Pfizer-BioNTech COVID-19 Vaccine to recipients.
  • There are limited data on the interchangeability of COVID-19 vaccines. If the primary series is initiated with the Pfizer-BioNTech product, the primary series should be completed with the Pfizer-BioNTech product.
    • Booster shots (6 months after the primary series) can be administered with any of the COVID-19 vaccines authorized in the U.S.

INDICATIONS

ACIP RECOMMENDATIONS

  • On December 12, 2020, ACIP voted 11–0 (three recusals) in favor of the interim recommendation for the use of the Pfizer-BioNTech COVID-19 vaccine for individuals ≥ 16 years of age.
    • On May 10, 2021, ACIP voted to lower the recipient age to individuals ≥ 12 years of age.
    • FDA approved vaccine ages 16 and older, ACIP update 8/12/21
    • On November 2, 2021, ACIP unanimously voted to recommend vaccination to children 5 - 11 years of age at a reduced dose (10 mcg/0.2mL) in a 2-dose series administered 3 weeks apart.
  • The EUA fact sheet for recipients and caregivers should be provided to vaccine recipients, and recipients should be counseled on local and systemic reactions.

FORMS

Brand Name

Preparation

Manufacturer

Route

Form

Dosage

Cost

Comirnaty (full-dose, purple cap)

SARS-Cov-2 S-protein 30µg encoded mRNA + lipid nanoparticle vaccine

Pfizer-BioNTech

IM

Vial

0.3 mL IM on Day 0 and Day 21

N/A

Comirnaty (reduced-dose, orange cap)

SARS-Cov-2 S-protein 10µg encoded mRNA + lipid nanoparticle vaccine

Pfizer-BioNTech

IM

Vial

0.2 mL IM on Day 0 and Day 21

N/A

PATHOGEN DIRECTED PROTECTION

  • COVID-19

DOSE/ADMINISTRATION

Adult PRIMARY SERIES

  • This is a series of 2 vaccines given 3 weeks apart.
    • The first dose (0.3 mL) should be given on Day 0 and the second dose (0.3 mL) on Day 21.
    • A third dose can be administered to select immunocompromised patients a minimum of 28 days after the initial 2-dose series (see below)
    • A booster dose is recommended for all other individuals beginning 8 months after completing the initial 2-dose series.
  • There are no data on the interchangeability of the vaccines.
    • If you receive the Pfizer-BioNTech vaccine on Day 0, the series should be completed with the Pfizer-BioNTech product.
  • Cartons of Pfizer-BioNTech COVID-19 Vaccine Multiple Dose Vials arrive in thermal containers with dry ice. Once received, remove the vial cartons immediately from the thermal container and store them in an ultra-low temperature freezer between -80ºC to -60ºC (-112ºF to -76ºF). Vials must be kept frozen between -80ºC to -60ºC (-112ºF to -76ºF) and protected from light until ready to use.
    • Alternatively, vials can be stored at -25ºC to -15ºC (-13ºF to 5ºF) for up to 2 weeks. These vials may be returned to -80ºC to -60ºC (-112ºF to -76ºF) one time, but the total cumulative time the vials are stored at -25ºC to -15ºC (-13ºF to 5ºF) is a maximum of 2 weeks.
    • If an ultra-low-temperature freezer is not available, the thermal container can be used as temporary storage as long as it is continually filled with dry ice. Refer to the insert provided in the shipping container for re-icing instructions.
  • Thaw instructions for undiluted vials:
    • Refrigerator: Once in the refrigerator, the vial(s) will thaw in 2-3 hours. Thawed vials can be stored at 2ºC to 8ºC (35ºF to 46ºF) for up to 5 days (120 hours).
    • Room temperature: For immediate use, thaw undiluted vials at room temperature [up to 25ºC (77ºF)] for 30 minutes. Once thawed, vials are stable for 2 hours only.
    • Once vials have been thawed, they cannot be refrozen.
  • Stability once diluted:
    • After dilution, store vials between 2°C to 25°C (35°F to 77°F) and use within 6 hours from the time of dilution.
    • During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.
    • Any vaccine remaining in vials must be discarded after 6 hours.
    • Do not refreeze.

Adult BOOSTER

  • A booster dose is recommended for the following individuals beginning 6 months after completion of the initial 2-dose series
    • Individuals over the age of 65
    • Individuals 18 years and older living in long-term care facilities, nursing homes, etc.
    • Individuals 18 years and older with underlying conditions including pregnancy, HIV, cancer, diabetes, obesity, or heart disease
    • Individuals 18 years and older with high risk of exposure due to workplace or institutional setting (e.g. front-line healthcare workers, teachers, etc.)

Pediatric PRIMARY SERIES

  • For patients ≥ 12 years of age, per the current EUA:
    • This is a series of 2 vaccines given 3 weeks apart. The first dose (0.3 mL) should be given on Day 0 and the second dose (0.3 mL) on Day 21.
  • For patients 5 - 11 years of age, per the current EUA:
    • This is a series of 2 vaccines given 3 weeks apart. The first dose (0.2 mL) should be given on Day 0 and the second dose (0.2 mL) on Day 21. This is a reduced dose compared to those ≥ 12 years of age and older.

Pediatric BOOSTER

  • No booster dose is authorized for 18 yrs and younger.

ADVERSE DRUG REACTIONS

GENERAL

  • Overall, the Pfizer-BioNTech vaccine is well-tolerated without serious adverse events reported to the FDA in the preliminary phase 3 trial information.
  • The incidence of adverse events is higher with the administration of the second dose of the vaccine.

COMMON

  • Pain, redness, and swelling at the injection site.
  • Fever
  • Fatigue
  • Headache
  • Chills
  • Diarrhea
  • Muscle and joint pain

RARE

  • At least 226 cases of myocarditis or pericarditis have been reported in patients ≤ 30 years of age and are investigating at least 250 more reports.
    • Occurs after administration of the second dose of the vaccine
    • This adverse event remains rare, but the incidence rate is higher than expected in those ages 16 - 24 years.
    • Cases have been predominantly in males, and the median age was 24 years.
    • Greater than 80% of cases have been resolved.
    • Myocarditis or pericarditis should be considered in patients developing acute chest pain, shortness of breath or heart palpitations within a week after vaccination.

VACCINE/DRUG INTERACTIONS

  • No vaccine/drug interactions have been identified at this time.

CONTRAINDICATIONS

  • Do not administer Pfizer-BioNTech COVID-19 vaccine to individuals with a known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer-BioNTech COVID-19 Vaccine.

IMMUNE RESPONSE

  • The highest neutralization titers were obtained at day 28 and day 35, confirming the need for two-dose series. Dose #2 elicited a robust immune response.
  • Geometric mean titers (GMT) on day 28 or day 35 ranged from 1.7 to 4.6 times the GMT of convalescent serum in those aged 18 - 55 years, and 1.1 to 2.2 times the GMT in those aged 65 - 85 years.
  • The complete immune response is still being elucidated.
  • While vaccine effectiveness has been sustained against the need for hospitalization, reporting from the New York City area suggests vaccine effectiveness against infection has declined from 92% to 80%. These decreases were significantly worse in nursing home residents (74.7% to 53.1%).

CLINICAL EFFICACY

  • An ongoing, multinational, placebo-controlled, observer-blinded safety and efficacy trial in individuals ≥ 16 years of age were randomized 1:1 to receive 2 doses, 21 days apart, of either placebo or the BNT162b2 vaccine.
    • The primary endpoints were vaccine efficacy against COVID-19 and safety.
    • 43,448 patients received injections (21,720 in the vaccine group; 21,728 in the placebo group).
    • There were 8 cases of COVID-19 disease onset at least 7 days after the second dose in those receiving active vaccine compared to 162 cases of COVID-19 disease in those patients assigned placebo.
      • This translates to 95% vaccine efficacy in preventing COVID-19 disease.
    • Similar vaccine efficacy was noted among subgroups, including age, sex, race, ethnicity and baseline body mass index.
      • It should be noted that despite no differences seen in these subgroups, 83% of the overall population in this trial were Caucasian.
    • The most common adverse effects were injection site pain, fatigue and headache.
    • The overall incidence of adverse effects was low, and similar between the vaccine and placebo groups.
  • 2260 adolescents (12 - 15 years of age) were enrolled in a clinical trial to receive either BNT162b2 (n = 1,129) or placebo (n = 1,131).
    • 18 cases of COVID-19 were diagnosed in the placebo group compared to none in the vaccine group.
    • Geometric mean titers (GMTs) and adverse effects were similar to the 16- to 25-year-old age group in the above analysis.
  • A clinical trial evaluating the vaccine in children 6 months to 11 years was initiated in March 2021.

OTHER INFORMATION

  • It is MANDATORY for vaccination providers to report to the Vaccine Adverse Event Reporting System (VAERS) all vaccine administration errors, all serious adverse events, cases of the multisystem inflammatory syndrome (MIS) in adults and children, and hospitalized or fatal cases of COVID-19 following vaccination with the Pfizer-BioNTech COVID-19 Vaccine.
  • Frozen vials MUST be stored in ultra-low-temperature freezers. Once thawed, stability is limited.
  • More than 200 cases of myocarditis or pericarditis have been reported within one week of receiving the second vaccine dose of the mRNA vaccines. It most often occurs in males, and the median age is 24 years. While the incidence is rare, these rates are higher than expected. Anyone developing chest pain, shortness of breath or heart palpitations within 1 week of receiving the second dose of the mRNA vaccine should be evaluated.
  • Full dose vaccine (0.3 mL) dose is recommended for individuals > 12 years of age. These vials contain purple caps. Reduced dose (0.2 mL) is recommended for individuals 5 - 11 years of age. These vials contain orange caps.

Basis for recommendation

  1. https://www.fda.gov/media/144413/download (11/10/2021 accessed)

    Comment:

    Fact Sheet for Providers administering vaccine: Emergency Use Authorization (EUA) of the Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus Disease 2019.

References

  1. Rosenblum HG, Hadler SC, Moulia D, et al. Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson & Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices - United States, July 2021. MMWR Morb Mortal Wkly Rep. 2021;70(32):1094-1099.  [PMID:34383735]

    Comment: ACIP update deals with the rare issues described after COVID-19 immunization including GBS and TTS after Janssen/JNJ vaccine, and myocarditis/pericarditis after mRNA vaccines.

  2. Walsh EE, Frenck RW, Falsey AR, et al. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med. 2020.  [PMID:33053279]

    Comment: This is the phase I, placebo-controlled, observer-blinded, dose-escalation trial conducted in the United States in which participants aged 18 - 55 or 65 - 85 were randomized to receive either placebo or one of two vaccine candidates (BNT162b1 or BNT162b2). The primary endpoint was safety, and immunogenicity was the secondary outcome. Vaccine responses elicited in both groups were similar in terms of dose-dependent SARS-CoV-2–neutralizing geometric mean titers, which were similar to or higher than the geometric mean titer of a panel of SARS-CoV-2 convalescent serum samples. The incidence of adverse effects was lower in the BNT162b2 subset, and this was chosen to move forward in the phase 2/3 study.

  3. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020.  [PMID:33301246]

    Comment: In this ongoing, multinational, placebo-controlled, observer-blinded efficacy trial, participants 16 years of age or older were randomized to receive 2 doses given 21 days apart of BNT162b2 or placebo. The primary endpoint was the efficacy of the vaccine against lab-confirmed COVID-19, as well as safety. 21,720 participants received the vaccine candidate while 21,728 received placebo. There were only 8 cases of COVID-19 disease that occured at least 7 days after the second dose of the vaccine compared to 162 cases in the group who received placebo, translating to 95% efficacy. Similar vaccine efficacy was observed across subgroups (age, sex, race, ethnicity, baseline BMI), although it should be noted that 83% of all participants were Caucasian. The incidence of adverse events was similar between groups, with the most frequently reported adverse events being injection site pain, fatigue, headache and diarrhea.

  4. Oliver S, Gargano J, Marin M, et al. The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine — United States, December 2020. MMWR Morb Mortal Wkly Rep. ePub: 13 December 2020. DOI: http://dx.doi.org/10.15585/mmwr.mm6950e2

    Comment: MMWR report providing ACIP interim recommendations endorsing the Pfizer-BioNTech EUA from the FDA. The committee agreed that robust clinical trial data support the administration of the two-dose vaccine series on Day 0 and Day 21 for the prevention of COVID-19 disease in those 16 years of age and older.


  5. Rosenberg ES, Holtgrave DR, Dorabawila V, et al. New COVID-19 Cases and Hospitalizations Among Adults, by Vaccination Status — New York, May 3–July 25, 2021. MMWR Morb Mortal Wkly Rep. ePub: 18 August 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7034e1



    Comment: In an evaluation of vaccine effectiveness in the state of New York, the overall age-adjusted vaccine effectiveness against hospitalization remained stable (91.9% - 95.3%) while the age-adjusted vaccine effectivemess against infection decreased from 91.7% to 79.8%. This evaluation provides evidence for the need for a booster dose of the vaccination.



  6. Tenforde MW, Self WH, Naioti EA, et al. Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults — United States, March–July 2021. MMWR Morb Mortal Wkly Rep. ePub: 18 August 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7034e2



    Comment:
    An evaluation of 1,129 patients who completed the 2-dose vaccine series had sustained vaccine effectiveness against hospitalization over a 24 week period. Effectiveness was 86% through 2 - 12 weeks and fell to 84% from 13 - 24 weeks. Investigators noted, though, that ongoing monitoring is necessary as new variants continue to emerge.


  7. Tenforde MW, Self WH, Naioti EA, et al. Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults — United States, March–July 2021. MMWR Morb Mortal Wkly Rep. ePub: 18 August 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7034e2



    Comment:
    An evaluation of 1,129 patients who completed the 2-dose vaccine series had sustained vaccine effectiveness against hospitalization over a 24 week period. Effectiveness was 86% through 2 - 12 weeks and fell to 84% from 13 - 24 weeks. Investigators noted, though, that ongoing monitoring is necessary as new variants continue to emerge.


  8. Nanduri S, Pilishvili T, Derado G, et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant — National Healthcare Safety Network, March 1–August 1, 2021. MMWR Morb Mortal Wkly Rep. ePub: 18 August 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7034e3



    Comment:
    Evidence that vaccine effectiveness declined significantly with the emergence of the delta variant in nursing home residents. From March - May 2021, vaccine effectiveness was 74.7% compared to only 53.1% during June-July 2021. An additional dose of the COVID-19 vaccine is recommended to boost immunity.


  9. Nanduri S, Pilishvili T, Derado G, et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant — National Healthcare Safety Network, March 1–August 1, 2021. MMWR Morb Mortal Wkly Rep. ePub: 18 August 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7034e3



    Comment:
    Evidence that vaccine effectiveness declined significantly with the emergence of the delta variant in nursing home residents. From March - May 2021, vaccine effectiveness was 74.7% compared to only 53.1% during June-July 2021. An additional dose of the COVID-19 vaccine is recommended to boost immunity.




  10. Woodworth KR, Moulia D, Collins JP, et al. The Advisory Committee on Immunization Practices’ Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine in Children Aged 5–11 Years — United States, November 2021. MMWR Morb Mortal Wkly Rep. ePub: 5 November 2021. DOI: http://dx.doi.org/10.15585/mmwr.mm7045e1

    Comment:
    ACIP recommendations on the use of the Pfizer-BioNTech COVID-19 vaccine in the use of children aged 5 - 11.The EUA was amended on 10/29/21 that children aged 5 - 11 years receive 2 doses (10 mcg/0.2 mL) 3 weeks apart.


  11. https://www.aappublications.org/news/2021/06/10/covid-vaccine-myocarditis-.... Accesses 11/10/21.

    Comment: American Academy of Pediatrics discussion on the CDC confirmation of more than 220 cases of myocarditis or pericarditis in those age 30 and younger occurring within 1 week of receiving the second dose of the COVID-19 mRNA vaccines. Although this incidence is rare, it is higher than what is expected. Greater than 80% of patients have made a full recovery. The CDC recommends that myocarditis or pericarditis be considered in any patient who develops acute chest pain, heart palpitations, and/or shortness of breath within 1 week of receiving their second vaccine dose.

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Last updated: November 13, 2021