Last Updated: January 25, 2021
On this page:
- Key Literature
- Additional Literature
- Dilution, Dosing & Administration
- Distribution & Allocation
- Special Patient Populations/Settings
On December 11, 2020, the U.S. Food and Drug Administration issued the first emergency use authorization for a vaccine to prevent COVID-19. The vaccine, Pfizer-BioNTech’s BNT162b2, is authorized for use in individuals 16 years of age and older.
- Pfizer-BioNTech COVID-19 Vaccine EUA Letter of Authorization
- Pfizer-BioNTech COVID-19 Vaccine EUA Fact Sheet for Health Care Providers
- Pfizer-BioNTech COVID-19 Vaccine EUA Fact Sheet for Patients
- CDC Interim Recommendations for Use of Pfizer-BioNTech COVID-19 Vaccine
Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine (Polack, December 2020).
- BNT162b2 is an mRNA vaccine that is given in 2 doses, 21 days apart.
- In a Phase 2/3 multinational randomized placebo-controlled efficacy clinical trial, 43,538 participants over 16 years of age from 152 sites worldwide who were either healthy or had stable chronic medical conditions underwent 1:1 randomization.
- 43,448 received injections.
- 21,720 received 2 doses of BNT162b2, and 21,728 received a saline placebo.
- Patients with prior known COVID-19, on immunosuppressive therapy, who had an immunocompromising condition, or who were pregnant were excluded. People with well-controlled HIV infection were included.
- This publication is an interim analysis of the trial; additional publications with longer time to follow up and examining safety in specific groups are forthcoming.
- 3% of participants had serologic evidence of prior COVID-19 at the time of enrollment (but would have had asymptomatic disease, per enrollment exclusion criteria).
- Primary efficacy endpoints: The efficacy of BNT162b2 against confirmed COVID-19 with onset at least 7 days after the second dose in participants who had been without serologic or virologic evidence of SARS-CoV-2 infection up to 7 days after the second dose; efficacy in participants with and participants without evidence of prior infection.
- Confirmed COVID-19 was defined as having a positive RT-PCR respiratory specimen for SARS-CoV-2 AND at least one of the following: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea, or vomiting.
- Primary safety endpoints: Solicited local or systemic adverse events and use of an antipyretic or pain medication within 7 days of receiving either the vaccine or placebo via an electronic diary in a “reactogenicity” subset of patients; unsolicited adverse events reported through 1 month after the second dose of vaccine; unsolicited adverse events through 6 months after the second dose.
- 196 people living with HIV were included in the trial, but their safety data is being analyzed separately and has not yet been reported.
- 2-month follow-up data was available for 37,706 participants; in the reactogenicity subset, data was available for 8,183 participants.
- As of the writing of the report, 36,523 participants with no serologic or virologic evidence of existing or prior SARS-CoV-2 infection could be evaluated for efficacy at least 7 days after the second dose.
- As of the writing of the report, 40,137 participants with and without prior infection could be evaluated at least 7 days after the second dose.
- At the time of analysis, 3,614 participants had serologic evidence of COVID-19.
- Per information shared with the FDA, 1,747 people in the vaccinated group had positive serology for SARS-CoV-2, compared to 1,847 in the placebo group.
- At the time of analysis, 3,614 participants had serologic evidence of COVID-19.
- In the 37,706 participants who had a median of at least 2 months of safety data available after the second dose:
- The median age was 52 years, and 42% of participants were older than 55 years.
- 83% were white, 9% were Black or African American, and 28% were Hispanic or Latinx.
- 35% were obese (BMI>= 30.0 kg/m2), and 21% had at least one coexisting condition.
- Among 36,523 participants who had no serologic or virologic evidence of existing or prior SARS-CoV-2 infection, there were 8 cases of COVID-19 with onset at least 7 days after receiving the second dose of BNT162b2, and 162 cases with onset at least 7 days after receiving the second dose of placebo.
- BNT162b2 was 95% effective in preventing COVID-19 disease (95% CI, 90.3-97.6).
- Similar vaccine efficacy (generally 90 to 100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline body-mass index, and the presence of coexisting conditions.
- Among the 40,137 participants with and without evidence of prior infection, 9 cases occurred with onset at least 7 days after receiving the second dose of BNT162b2, and 169 cases occurred with onset at least 7 days after receiving the second dose of placebo.
- BNT162b2 was 94.6% effective in preventing COVID-19 disease in this group (95% CI 89.9-97.3).
- Of the 3,614 participants who had serologic evidence of COVID-19 at the time of analysis, there were 9 cases of COVID-19 disease in the placebo group and 10 in the vaccinated group.
- When examining rates of disease after the first dose of vaccine and before the second, there were 39 cases in the vaccinated group and 82 in the placebo group, resulting in a 52.4% efficacy rate after one dose (95% CI: 29.5-68.4).
- The safety analysis included all participants who had received at least one dose of the vaccine or placebo.
- In the reactogenicity subset, among those aged 16-55 years:
- Approximately 93% of those who received BNT162b2 had mild-to-moderate pain, redness or swelling at the infection site after dose 1 and 88% experienced these symptoms after dose 2. Approximately 15% of these events occurred in the placebo group after dose 1 and 13% after dose 2.
- In the reactogenicity subset, among those aged 55 years or more:
- Approximately 82% of those who received BNT162b2 had mild-to-moderate pain, redness or swelling at the infection site after dose 1; 79% experienced these symptoms after dose 2. Approximately 11% of these events occurred in the placebo group after dose 1 and 9% after dose 2.
- In vaccine recipients, the most commonly reported systemic events were fatigue and headache (59% after the first dose and 52% after the second dose among younger vaccine recipients; 51% after the first dose and 39% after the second dose among older recipients).
- Fatigue and headache were also reported by many placebo recipients (23% after the first dose and 24% after the second dose among younger vaccine recipients; 17% after the first dose and 14% after the second dose among older recipients).
- Fever (temperature ≥38 C) was reported after the second dose by 16% of younger vaccine recipients, and by 11% of older recipients.
- The incidence of serious adverse events was similar in the vaccine and placebo groups (0.6% and 0.5%, respectively).
- Among the 21,621 people in the trial who received BNT162b2, four related serious adverse events were reported: shoulder injury related to vaccine administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia and right leg paresthesia.
- Four participants in the clinical trial who received the vaccine later developed Bell’s palsy. These cases occurred at 3, 9, 37, and 48 days after vaccination. The observed frequency of reported Bell’s palsy in the vaccine group is consistent with the expected background rate in the general population, according to the FDA.
- No deaths were considered by the investigators to be related to the vaccine or placebo.
- The report includes 2 months of follow up after the second dose of the vaccine for only half of the trial participants.
- Due to the high efficacy found in the trial, the original plan of following placebo recipients for 2 years will not be followed due to ethical concerns. Therefore, there will be no placebo group with which to assess long-term efficacy and safety.
- The primary efficacy endpoint was clinical disease; asymptomatic infection was not assessed, although additional data utilizing a serologic endpoint is being collected.
- The trial did not include children, immunocompromised people or pregnant women, but trials are being developed to assess BNT162b2 in these groups.
- While there was a small group of people with evidence of prior COVID-19 infection at the time of analysis, the number of cases in this group was too small to draw any conclusions about the efficacy of the vaccine in individuals with prior infection; this may change as the trial continues.
- Serial RT-PCR testing was not performed, and so the efficacy of the vaccine in potentially preventing spread of SARS-CoV-2 could not be determined.
Overall, in this interim analysis of a Phase 2/3 randomized placebo-controlled efficacy trial, BNT162b2 was effective at preventing symptomatic COVID-19 disease and was safe at a median time to follow up of 2 months.
Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults (Mulligan, August 2020). Phase I/II safety, tolerability and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose-escalation study among 45 healthy adults (18–55 years of age), were randomized to receive 2 doses—separated by 21 days—of 10 μg, 30 μg or 100 μg of BNT162b1. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient, with pain at the injection site being the most frequent solicited local reaction. A second vaccination with 100 μg was not administered because of the increased reactogenicity and a lack of meaningfully increased immunogenicity after a single dose compared with the 30-μg dose. Geometric mean neutralizing titres reached 1.9-4.6-fold that of a panel of COVID-19 convalescent human sera, which were obtained at least 14 days after a positive SARS-CoV-2 PCR.
The Pfizer-BioNTech COVID-19 vaccination series consists of 2 intramuscular doses given 3 weeks apart.
Second doses administered within a grace period of ≤4 days from the recommended date for the second dose are considered valid; however, doses administered earlier do not need to be repeated. The second dose should be administered as close to the recommended interval as possible. However, there is no maximum interval between the first and second dose for either vaccine.
The Pfizer COVID-19 vaccine is not interchangeable with other COVID-19 vaccines to complete the vaccination series. The safety and efficacy of a mixed-product series have not been evaluated. Both doses of the series should be completed with the Pfizer COVID-19 vaccine. However, if two doses of different mRNA COVID-19 vaccine products are inadvertently administered, no additional doses of either product are recommended at this time.
Overall vaccine efficacy after one dose has not been studied. While there were patients in phase 3 trials who received one dose and vaccine efficacy was reported in these patients, the overall number of such patients was small and they were only followed for a short time period. The duration and degree of their immune responses to the single dose of the vaccine is not known; until such data is available and the efficacy of one dose has been studied, FDA recommends that all COVID-19 vaccine recipients receive two doses of vaccine.
Prior to Dilution
- The Pfizer-BioNTech COVID-19 Vaccine Multiple Dose Vial contains a frozen suspension that does not contain preservative and must be thawed and diluted prior to administration.
- Vials may be thawed in the refrigerator (2 C to 8 C [35 F to 46 F]) or at room temperature (up to 25 C [77 F]).
- If thawed in a refrigerator, vials can be stored in the refrigerator for up to 5 days.
- Vials thawed at room temperature must be used within 30 minutes.
- Dilute the vial contents using 1.8 mL of 0.9% sodium chloride injection, USP (not provided) to form the Pfizer-BioNTech COVID-19 vaccine.
- ONLY use 0.9% sodium chloride injection, USP as the diluent. This diluent is not packaged with the vaccine and must be sourced separately.
- Do not use bacteriostatic 0.9% sodium chloride injection or any other diluent.
- Once diluted, the vials must be used within 6 hours.
- Visually inspect each dose in the dosing syringe prior to administration. The vaccine will be an off-white suspension.
- During the visual inspection:
- Verify the final dosing volume of 0.3 mL;
- Confirm there are no particulates and that no discoloration is observed;
- Do not administer if vaccine is discolored or contains particulate matter.
- Administer the Pfizer-BioNTech COVID-19 vaccine intramuscularly.
According to FDA guidance, individuals should not get the Pfizer-BioNTech COVID-19 vaccine if they have:
- Had a severe allergic reaction after a previous dose of this vaccine, or
- Had a severe allergic reaction to any ingredient of the vaccine:
- 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);
- Potassium chloride;
- Monobasic potassium phosphate;
- Sodium chloride;
- Dibasic sodium phosphate dihydrate;
- Of note, an immediate allergic reaction to a vaccine or medication is defined as any hypersensitivity-related signs or symptoms such as urticaria, angioedema, respiratory distress (e.g., wheezing, stridor), or anaphylaxis that occur within four hours following administration.
- CDC considers a history of the following to be a contraindication to vaccination with the Pfizer COVID-19 vaccine:
- Severe allergic reaction (e.g., anaphylaxis) after a previous dose of an mRNA COVID-19 vaccine or any of its components.
- Immediate allergic reaction of any severity to a previous dose of an mRNA COVID-19 vaccine or any of its components (including polyethylene glycol [PEG])*.
- Immediate allergic reaction of any severity to polysorbate (due to potential cross-reactive hypersensitivity with the vaccine ingredient PEG)*.
- * These persons should not receive mRNA COVID-19 vaccination at this time unless they have been evaluated by an allergist-immunologist and it is determined that the person can safely receive the vaccine (e.g., under observation, in a setting with advanced medical care available).
- According to a December 19th CDC presentation, persons with a history of anaphylaxis to any other vaccine or injectable therapy can still receive the Pfizer-BioNTech COVID-19 vaccine, but should be counseled about the unknown risks of developing a severe allergic reaction.
- The following persons do NOT have a contraindication or precaution to receiving the Pfizer-BioNTech COVID-19 vaccine: persons who have a history of food, pet, insect, venom, environmental, or latex allergy; persons with an allergy to an oral medication; persons with a non-serious allergy to other vaccines or injectables; persons with a family history of anaphylaxis; persons with any other history of anaphylaxis unrelated to a vaccine or injectable.
- Persons with no history of anaphylaxis should be monitored for 15 minutes after vaccination; persons with a history of anaphylaxis should be monitored for 30 minutes.
CDC has provided considerations after administration of mRNA vaccines in health care personnel with systemic signs and symptoms following COVID-19 vaccination, as well as interim clinical considerations on preparing for the initial assessment and management of anaphylaxis following COVID-19 vaccination.
Post-Market Safety Monitoring
The FDA Pfizer-BioNTech EUA includes specific instructions on continuous safety monitoring (see “Conditions of Authorization” on pages 5-7) in accordance with its requirement that all EUA sponsors “plan for active follow-up for safety, including deaths, hospitalizations and other serious or clinically significant adverse events, among individuals who receive the vaccine under an EUA, to inform ongoing benefit-risk determinations to support continuation of the EUA.”
The federal government uses multiple vaccine safety monitoring systems to monitor COVID-19 vaccines in the post-authorization/approval period, including the Vaccine Adverse Event Reporting System, the Vaccine Safety Datalink, the Biologics Effectiveness and Safety Initiative and Medicare claims data.
Resources to monitor initial supply distribution include:
Interim ACIP Recommendation for Allocating Initial Vaccine Supplies
Guidance for federal, state, and local COVID-19 vaccination planning and implementation from CDC’s Advisory Committee on Immunization Practices.
State Plans for Vaccinating Populations Against COVID-19
Chart- and map-based overview developed by the National Academy for State Health Policy.
Previous or Current SARS-CoV-2 Infection
Data is limited on the efficacy of the vaccine in people who have previously had SARS-CoV-2.
Vaccination should be offered to persons regardless of history of prior symptomatic or asymptomatic SARS-CoV-2 infection. Viral testing to assess for acute SARS-CoV-2 infection or serologic testing to assess for prior infection solely for the purposes of vaccine decision-making is not recommended.
Vaccination of persons with known current SARS-CoV-2 infection should be deferred until the person has recovered from the acute illness (if the person had symptoms) and criteria have been met for them to discontinue isolation. This recommendation applies to persons who develop SARS-CoV-2 infection before receiving any vaccine doses as well as those who develop SARS-CoV-2 infection after the first dose but before receipt of the second dose.
At study enrollment in the Phase 3 clinical trial detailed above, 3% of participants had serologic evidence of prior infection. Among this population, the attack rate of infection was low in both groups over the course of the study (9 in the placebo group and 10 in the vaccinated group), according to a briefing document presented to FDA.
At the time of the interim analysis, 1,747 people in the vaccinated group had positive serology for SARS-CoV-2, compared to 1847 in the placebo group. There was one symptomatic infection in the vaccinated group and seven in the placebo group, which would imply vaccine efficacy, but the number of events are too small to draw conclusions.
What is unknown about this data is when these people were infected, which would have bearing on their antibody titers. In addition, by definition these were people who had never had symptomatic COVID-19 disease, and thus were asymptomatic; given data suggests people with milder illness may have a less robust antibody response, this data cannot be extrapolated to people with prior symptomatic disease. The trial did collect serum and notes they will be reporting on the efficacy of the vaccine in seropositive people in the future.
In the interim, CDC recommends offering vaccination to individuals regardless of history of prior symptomatic or asymptomatic SARS-CoV-2 infection. Viral testing to assess for acute SARS-CoV-2 infection or serologic testing to assess for prior infection solely for the purposes of vaccine decision-making is not recommended. Vaccination of individuals with known current SARS-CoV-2 infection should be deferred until the person has recovered from the acute illness (if the person had symptoms) and criteria have been met for them to discontinue isolation.
As current evidence suggests that reinfection is uncommon in the 90 days after initial infection, CDC states that individuals with documented acute SARS-CoV-2 infection in the preceding 90 days may delay vaccination until near the end of this period, if desired.
Passive Antibody Therapy Recipients
No clinical trial data exists on the use of the Pfizer-BioNTech vaccine in people who have previously received monoclonal antibodies or convalescent plasma for COVID-19.
Based on the estimated half-life of such therapies as well as evidence suggesting that reinfection is uncommon in the 90 days after initial infection, vaccination should be deferred for at least 90 days, as a precautionary measure until additional information becomes available, to avoid interference of the antibody treatment with vaccine-induced immune responses.
For persons receiving antibody therapies not specific to COVID-19 treatment (e.g., intravenous immunoglobulin, RhoGAM), administration of mRNA COVID-19 vaccines either simultaneously with or at any interval before or after receipt of an antibody-containing product is unlikely to substantially impair development of a protective antibody response. Thus, there is no recommended minimum interval between other antibody therapies (i.e., those that are not specific to COVID-19 treatment) and mRNA COVID-19 vaccination.
People Living with HIV/Immunocompromised
One hundred and ninety-six individuals with stable HIV disease were included in the Phase 2/3 trial of the Pfizer-BioNTech COVID-19 vaccine. The safety data on this group is to be reported separately. People with significant immunocompromise were not included in the trial. As such, there is currently not data on vaccine efficacy or safety in these groups.
Persons with HIV infection or other immunocompromising conditions, or who take immunosuppressive medications or therapies might be at increased risk for severe COVID-19. Data are not currently available to establish vaccine safety and efficacy in these groups. Persons with stable HIV infection were included in mRNA COVID-19 vaccine clinical trials, though data remain limited. Immunocompromised individuals may receive COVID-19 vaccination if they have no contraindications to vaccination. However, they should be counseled about the unknown vaccine safety profile and effectiveness in immunocompromised populations, as well as the potential for reduced immune responses and the need to continue to follow all current guidance to protect themselves against COVID-19. Antibody testing is not recommended to assess for immunity to COVID-19 following mRNA COVID-19 vaccination.
At this time, re-vaccination is not recommended after immune competence is regained in persons who received mRNA COVID-19 vaccines during chemotherapy or treatment with other immunosuppressive drugs. Recommendations on re-vaccination or additional doses of mRNA COVID-19 vaccines may be updated as additional information is available.
Regarding use of the vaccine in pregnant people, safety information provided by Pfizer (pages 24-25) states: “All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.”
Of note, women were screened for pregnancy prior to each trial vaccination, according to a Pfizer-BioNTech briefing document. A total of 23 pregnancies occurred, some after vaccination and some that occurred prior to vaccination but were not detected via screening. Twelve pregnant individuals received the vaccine, and 11 received placebo. No unsolicited adverse events, including spontaneous abortion, occurred. Trials of the vaccine including pregnant people are planned. It is also noteworthy that mRNA vaccines are not live vaccines, that normal cellular processes degrade the mRNA quickly and that the mRNA does not enter the nucleus of cells.
The EUA does not exclude pregnant people; providers who wish to offer BNT162b2 to pregnant people may do so. Based on current knowledge, experts believe that mRNA vaccines are unlikely to pose a risk to the pregnant person or the fetus because mRNA vaccines are not live vaccines. The mRNA in the vaccine is degraded quickly by normal cellular processes and does not enter the nucleus of the cell. However, the potential risks of mRNA vaccines to the pregnant person and the fetus are unknown because these vaccines have not been studied in pregnant people.
If pregnant people are part of a group that is recommended to receive a COVID-19 vaccine (e.g., healthcare personnel), they may choose to be vaccinated. A conversation between the patient and their clinical team may assist with decisions regarding the use of a mRNA COVID-19 vaccine, though a conversation with a healthcare provider is not required prior to vaccination. When making a decision, pregnant people and their healthcare providers should consider the level of COVID-19 community transmission, the patient’s personal risk of contracting COVID-19, the risks of COVID-19 to the patient and potential risks to the fetus, the efficacy of the vaccine, the side effects of the vaccine, and the lack of data about the vaccine during pregnancy.
Side effects can occur with COVID-19 vaccine use in pregnant people, similar to those expected among non-pregnant people. Pregnant people who experience fever following vaccination may be counseled to take acetaminophen as fever has been associated with adverse pregnancy outcomes. Acetaminophen may be offered as an option for pregnant people experiencing other post-vaccination symptoms as well.
In December 2020, the American College of Obstetricians and Gynecologists (ACOG) recommended that COVID-19 vaccines should not be withheld from pregnant individuals who meet criteria for vaccination based on ACIP-recommended priority groups. The Society for Maternal Fetal Medicine stated that the safety risk of mRNA vaccination for pregnant or lactating people appears low, recommended pregnant women be offered vaccination and noted the decision to receive the vaccine should be guided by an individual’s risk of contracting COVID-19 and other individual factors.
Regarding use of the vaccine in lactating people, safety information provided by Pfizer (pages 24-25) states: “Data are not available to assess the effects of Pfizer-BioNTech COVID-19 Vaccine on the breastfed infant or on milk production/excretion.”
According to a December 2020 CDC presentation, mRNA vaccines are not considered live virus vaccines and are not thought to be a risk to a breastfeeding infant. If a lactating person is part of a group (e.g., healthcare personnel) who is recommended for COVID-19 vaccination, they may choose to be vaccinated.
ACOG recommends COVID-19 vaccines be offered to lactating individuals similarly to non-lactating individuals when they meet criteria for receipt of the vaccine based on prioritization groups outlined by ACIP. While lactating individuals were not included in most clinical trials, ACOG recommends that COVID-19 vaccines not be withheld from lactating individuals who otherwise meet criteria for vaccination.
Clinical studies of the Pfizer-BioNTech COVID-19 Vaccine included older participants, but they are grouped into a category of persons aged 55 years or more (that is, not everyone in this category was geriatric). Data from this group contributed to the overall assessment of safety and efficacy (see Key Literature above).
In subgroup analysis in persons aged 65-74, there was 1 case of COVID-19 out of 3,255 participants in the vaccinated group and 14 cases out of 3,255 in the placebo group, with a vaccine efficacy of 92.9 (95% CI 53.2-99.8). In people 75 years of age or older there were 0 cases out of 805 participants in the vaccinated group and 5 cases out of 812 participants in the placebo group, with a vaccine efficacy of 100%, although this was not statistically significant (95% CI -12.1-100). Due to the small numbers in these subgroups, the results should be interpreted with caution.
Information on additional special populations, including people who have been exposed to SARS-CoV-2 and adolescents, can be found on the CDC website.