8.1 Pregnancy

Risk Summary

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, miscarriage and pre-eclampsia in clinically recognized pregnancies is 2% to 4%, 15% to 20%, and 5% to 7%, respectively. There are no available data with COMIRNATY use in pregnant women before 24 weeks gestation to inform about risks for major birth defects and miscarriage.

A developmental toxicity study has been performed in female rats administered the equivalent of a single human dose of COMIRNATY [encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original)] on 4 occasions, twice prior to mating and twice during gestation. These studies revealed no evidence of harm to the fetus due to the vaccine (see Data).

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Pregnant individuals infected with SARS-CoV-2 are at increased risk of severe COVID-19 compared with non-pregnant individuals.

Data

Human Data

In Study 9, a randomized, placebo-controlled trial (NCT04754594), COVID-19 vaccine naïve, pregnant women 18 years of age and older received 2 doses of COMIRNATY (Original Monovalent) (n=173 received at least 1 dose) or placebo (n=173 received at least 1 dose), approximately 21 days apart, with the first dose administered at 24 to 34 weeks gestation (i.e., late second trimester and early third trimester of pregnancy). The trial was conducted in Brazil, South Africa, Spain, United Kingdom, and the US. The trial failed to reach target accrual (originally designed to be 4,000 participants), as it was terminated prematurely, resulting in uncertainty regarding differences in outcomes.

In an analysis which excluded participants with HIV infection, a numerical imbalance in pre-eclampsia in COMIRNATY recipients (6 of 161, 3.7%) compared with placebo recipients (2 of 163, 1.2%) was observed in this study. These data are insufficient to establish or exclude a causal relationship between COMIRNATY and pre-eclampsia.

Major or minor congenital anomalies or chromosomal abnormalities were reported in 10 of 156 (6.4%) infants born to women in the COMIRNATY group and 7 of 159 (4.4%) infants born to women in the placebo group (see Table 13). Some infants had more than one event listed in the table. The available trial data are insufficient to establish or exclude vaccine-associated risk of congenital anomalies because COMIRNATY was not administered in the first trimester (the period when the risk of major congenital anomalies is highest). In addition, predisposing factors including genetic risk factors and potential maternal risk factors were reported in some cases in the COMIRNATY group.

Descriptive immunogenicity analyses of geometric mean [neutralizing] titers (GMT) in pregnant participants compared with GMTs from non-pregnant participants enrolled in another study (Study 2) were inconclusive due to study limitations including a small sample size.

Animal Data

In a developmental toxicity study, 0.06 mL of a vaccine formulation containing the same quantity of nucleoside-modified messenger ribonucleic acid (mRNA) (30 mcg of modRNA) and other ingredients included in a single human dose of COMIRNATY [encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu-1 strain (Original)] was administered to female rats by the intramuscular route on 4 occasions: 21 and 14 days prior to mating, and on gestation days 9 and 20. No vaccine-related adverse effects on female fertility, fetal development, or postnatal development were reported in the study.

8.2 Lactation

Risk Summary

It is not known whether COMIRNATY is excreted in human milk. Data are not available to assess the effects of COMIRNATY on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for COMIRNATY and any potential adverse effects on the breastfed child from COMIRNATY or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.

8.4 Pediatric Use

Safety and effectiveness of COMIRNATY in individuals 5 years through 17 years of age with at least one underlying condition that puts them at high risk for severe outcomes from COVID-19 is based on safety and effectiveness data in this age group and in adults [see Adverse Reactions (6) and Clinical Studies (14)].

The safety and effectiveness of COMIRNATY in individuals younger than 5 years of age have not been established. Evidence from clinical studies in individuals 6 months through 4 years of age strongly suggests that a single dose of COMIRNATY would be ineffective in individuals younger than 6 months of age.

8.5 Geriatric Use

Of the total number of COMIRNATY recipients in Study 2 as of March 13, 2021 (N = 22,026), 20.7% (n = 4,552) were 65 years of age and older and 4.2% (n = 925) were 75 years of age and older [see Clinical Studies (14.1)]. In Study 4, of 5,081 recipients who received COMIRNATY as the first booster dose, 23.1% (n = 1,175) were 65 years of age and older and 5.2% (n = 265) were 75 years of age and older. In Study 5, of 726 recipients who received Pfizer-BioNTech COVID-19 Vaccine, Bivalent as the second booster dose, 21.9% (n = 159) were 65 years of age and older and 4.8% (n = 35) were 75 years of age and older [see Clinical Studies (14.1)]. No overall differences in safety or effectiveness were observed between these recipients and younger recipients.

8.6 Immunocompromised Individuals

In an open-label descriptive study (NCT04895982, Study 10), 87 immunocompromised participants 5 years of age and older received up to 4 age-appropriate doses of COMIRNATY (Original Monovalent) in a 4-dose regimen (an unapproved dosing regimen), with the first 2 doses separated by approximately 21 days, a third dose approximately 28 days after Dose 2, and a fourth dose administered approximately 3 to 6 months after Dose 3. The study evaluated safety and immunogenicity in participants 5 years through 11 years of age (n=65), 12 years through 17 years (n=15), and 18 years of age and older (n=7) with the following immunocompromising conditions: autoimmune inflammatory disorders on immunomodulatory therapy (n=31), solid organ transplant (n=25), stem cell transplant (n=29), non-small cell lung cancer (n=1), or hemodialysis (n=1). Study completion rates were 83.1% (54/65), 53.3% (8/15), and 57.1% (4/7) for the respective age groups. The trial was stopped early due to challenges with study enrollment.

Overall, 58.6% were male, 82.8% were White, 20.7% were Hispanic/Latino, 6.9% were Black or African American, 2.3% were Asian, 1.1% were American Indian or Alaska Native, 2.3% were Multiracial, and race and ethnicity was not reported by 4.6% of participants. The median age of participants in age groups 5 years through 11 years, 12 through 17 years, and 18 years of age and older was 9.0, 12.0, and 40.0 years, respectively.

The safety profile in immunocompromised participants 5 years of age and older who received COMIRNATY (Original Monovalent) was similar to that in immunocompetent participants in other clinical studies [see Adverse Reactions (6.1)]. There were no deaths in the study and no serious adverse events were assessed as related to vaccination.

Seroresponse rates (defined as achieving a ≥4-fold rise in neutralizing titers from baseline) were evaluated in all participants with at least one valid immunogenicity result after vaccination, regardless of prior SARS-CoV-2 infection status.

Among participants 5 years through 11 years of age: At 1 month after Dose 3, seroresponse rate was 81.7% [95% confidence interval (CI): 69.6%, 90.5%] (n=60). At 1 month after Dose 4, seroresponse rate was 96.0% (95% CI: 86.3%, 99.5%) (n=50). At 6 months after Dose 4, seroresponse rate was 87.8% (95% CI: 75.2%, 95.4%) (n=49).

Among participants 12 years through 17 years of age: At 1 month after Dose 3, seroresponse rate was 92.9% (95% CI: 66.1%, 99.8%) (n=14). At 1 month after Dose 4, seroresponse rate was 100.0% (95% CI: 66.4%, 100.0%) (n=9). At 6 months after Dose 4, seroresponse rate was 100.0% (95% CI: 63.1%, 100.0%) (n=8).

Among participants 18 years of age and older: At 1 month after Dose 3, seroresponse rate was 50.0% (95% CI: 11.8%, 88.2%) (n=6). At 1 month after Dose 4, seroresponse rate was 75.0% (95% CI: 19.4%, 99.4%) (n=4). At 6 months after Dose 4, seroresponse rate was 33.3% (95% CI: 0.8%, 90.6%) (n=3).

The limitations of the study data include small sample sizes, particularly in the 12 through 17 years and ≥18 years age groups, and early study termination due to enrollment challenges. The data from this study do not establish the effectiveness of COMIRNATY in immunocompromised individuals.

The Centers for Disease Control and Prevention has published considerations related to COVID-19 vaccination guidance for people who are immunocompromised.