Document text
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3 THAWING PRIOR TO DILUTION
• Thaw vial(s) of COMIRNATY before dilution either
by:
o Allowing vial(s) to thaw in the refrigerator [2ºC
to 8ºC (35ºF to 46ºF)]. A carton of vials may take up to 3 hours to thaw, and thawed vials can be stored in the refrigerator for up to 1 month.
o Allowing vial(s) to sit at room temperature [up to 25ºC (77ºF)] for 30 minutes.
• Using either thawing method, vials must reach room temperature before dilution and must be diluted
within 2 hours.
• Before dilution invert vaccine vial gently 10 times.
• Do not shake.
• Inspect the liquid in the vaccine vial prior to dilution. The liquid is a white to off- white
suspension and may contain white to off- white
opaque amorphous particles.
• Do not use if liquid is discolored or if other particles are observed.
DILUTION
• ONLY use sterile 0.9% Sodium Chloride Injection, USP as the diluent.
• Withdraw 1.8 mL of diluent into a transfer syringe
(21-gauge or narrower needle).
• Add 1.8 mL of sterile 0.9% Sodium Chloride
Injection, USP into the vaccine vial .
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5 PREPARATION OF INDIVIDUAL 0.3 mL DOSES OF COMIRNATY
• Withdraw 0.3 mL of COMIRNATY preferentially
using low dead-volume syringes and/or needles.
• Each dose must contain 0.3 mL of vaccine.
• If the amount of vaccine remaining in a single vial
cannot provide a full dose of 0.3 mL, discard the
vial and any excess volume.
• Administer immediately.
After dilution, vials of COMIRNATY contain 6 doses of 0.3 mL of vaccine. Low dead -volume syringes and/or
needles can be used to extract 6 doses from a single vial. If standard syringes and needles are used, there may not be sufficient volume to extract a sixth dose from a single vial. Irrespective of the type of syringe and needle,
• each dose must contain 0.3 mL of vaccine.
• if the amount of vaccine remaining in the vial cannot provide a full dose of 0.3 mL, discard the vial and
any excess volume.
• do not pool excess vaccine from multiple vials.
2.2 Administration Information
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The vaccine will be an off -white suspension. Do not
administer if vaccine is discolored or contains particulate matter.
Administer a single 0.3 mL dose of COMIRNATY intramuscularly. 2.3 Vaccination Schedule
COMIRNATY is administered intramuscularly as a series of 2 doses (0.3 mL each) 3 weeks apart.
There are no data available on the interchangeability of COMIRNATY with other COVID -19 vaccines to complete
the vaccination series. Individuals who have received 1 dose of COMIRNATY should receive a second dose of
COMIRNATY to complete the vaccination series.
3 DOSAGE FORMS AND STRENGTHS
COMIRNATY is a suspension for injection. After preparation, a single dose is 0.3 mL.
4 CONTRAINDICATIONS
Do not administer COMIRNATY to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the COMIRNATY [s ee Description (1 1)].
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9 Table 2: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Participants 16 Through 55 Years of
Age – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Fever
≥38.0℃ 119 (4.1) 25 (0.9) 440 (16.4) 11 (0.4)
≥38.0℃ to 38.4℃ 86 (3.0) 16 (0.6) 254 (9.5) 5 (0.2)
>38.4℃ to 38.9℃ 25 (0.9) 5 (0.2) 146 (5.4) 4 (0.1)
>38.9℃ to 40.0℃ 8 (0.3) 4 (0.1) 39 (1.5) 2 (0.1)
>40.0℃ 0 0 1 (0.0) 0
Fatiguec
Any 1431 (49.4) 960 (33.0) 1649 (61.5) 614 (22.9)
Mild 760 (26.2) 570 (19.6) 558 (20.8) 317 (11.8)
Moderate 630 (21.7) 372 (12.8) 949 (35.4) 283 (10.5)
Severe 41 (1.4) 18 (0.6) 142 (5.3) 14 (0.5)
Headachec
Any 1262 (43.5) 975 (33.5) 1448 (54.0) 652 (24.3)
Mild 785 (27.1) 633 (21.8) 699 (26.1) 404 (15.1)
Moderate 444 (15.3) 318 (10.9) 658 (24.5) 230 (8.6)
Severe 33 (1.1) 24 (0.8) 91 (3.4) 18 (0.7)
Chillsc
Any 479 (16.5) 199 (6.8) 1015 (37.8) 114 (4.2)
Mild 338 (11.7) 148 (5.1) 477 (17.8) 89 (3.3)
Moderate 126 (4.3) 49 (1.7) 469 (17.5) 23 (0.9)
Severe 15 (0.5) 2 (0.1) 69 (2.6) 2 (0.1)
Vomitingd
Any 34 (1.2) 36 (1.2) 58 (2.2) 30 (1.1)
Mild 29 (1.0) 30 (1.0) 42 (1.6) 20 (0.7)
Moderate 5 (0.2) 5 (0.2) 12 (0.4) 10 (0.4)
Severe 0 1 (0.0) 4 (0.1) 0
Diarrheae
Any 309 (10.7) 323 (11.1) 269 (10.0) 205 (7.6)
Mild 251 (8.7) 264 (9.1) 219 (8.2) 169 (6.3)
Moderate 55 (1.9) 58 (2.0) 44 (1.6) 35 (1.3)
Severe 3 (0.1) 1 (0.0) 6 (0.2) 1 (0.0)
New or worsened muscle painc
Any 664 (22.9) 329 (11.3) 1055 (39.3) 237 (8.8)
Mild 353 (12.2) 231 (7.9) 441 (16.4) 150 (5.6)
Moderate 296 (10.2) 96 (3.3) 552 (20.6) 84 (3.1)
Severe 15 (0.5) 2 (0.1) 62 (2.3) 3 (0.1)
New or worsened joint painc
Any 342 (11.8) 168 (5.8) 638 (23.8) 147 (5.5)
Mild 200 (6.9) 112 (3.9) 291 (10.9) 82 (3.1)
Moderate 137 (4.7) 55 (1.9) 320 (11.9) 61 (2.3)
Severe 5 (0.2) 1 (0.0) 27 (1.0) 4 (0.1)
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10 COMIRNATY
Dose 1
Na=2899
nb (%) Placebo
Dose 1
Na=2908
nb (%) COMIRNATY
Dose 2
Na=2682
nb (%) Placebo
Dose 2
Na=2684
nb (%)
Use of antipyretic or
pain medicationf 805 (27.8) 398 (13.7) 1213 (45.2) 320 (11.9)
Note s: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 to Day 7 after
each dose
No Grade 4 solicited systemic reactions were reported in participants 16 through 55 years of age
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention Participants
with chronic, stable HIV infection were excluded
a N = N umber of participants reporting at least 1 yes or no response for the specified reaction after the specified dose The N for
each reaction or use of antipyretic or pain medication was the same, therefore, this information was included in the column
header
b n = Number of participants with the specified reaction
c Mild: does not interfere with activity; M oderate: some interference with activity; S evere: prevents daily activity
d Mild: 1 to 2 times in 24 hours; M oderate: >2 times in 24 hours; S evere: requires intravenous hydration
e Mild: 2 to 3 loose stools in 24 hours; M oderate: 4 to 5 loose stools in 24 hours; S evere: 6 or more loose stools in 24 hours
f Severity was not collected for use of antipyretic or pain medication
Table 3: Study 2 – Frequency and Percentages of Participants with Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and Older – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Rednessc
Any (>2 .0 cm) 106 (5.3) 20 (1.0) 133 (7.2) 14 (0.8)
Mild 71 (3.5) 13 (0.7) 65 (3.5) 10 (0.5)
Moderate 30 (1.5) 5 (0.3) 58 (3.1) 3 (0.2)
Severe 5 (0.2) 2 (0.1) 10 (0.5) 1 (0.1)
Swellingc
Any (>2 .0 cm) 141 (7.0) 23 (1.2) 145 (7.8) 13 (0.7)
Mild 87 (4.3) 11 (0.6) 80 (4.3) 5 (0.3)
Moderate 52 (2.6) 12 (0.6) 61 (3.3) 7 (0.4)
Severe 2 (0.1) 0 4 (0.2) 1 (0.1)
Pain at the injection sited
Any (>2 .0 cm) 1408 (70.1) 185 (9.3) 1230 (66.1) 143 (7.8)
Mild 1108 (55.2) 177 (8.9) 873 (46.9) 138 (7.5)
Moderate 296 (14.7) 8 (0.4) 347 (18.7) 5 (0.3)
Severe 4 (0.2) 0 10 (0.5) 0
Note s: Reactions were collected in the electronic diary (e -diary) from Day 1 to Day 7 after vaccination
No Grade 4 solicited local reactions were reported in participants 56 years of age and older
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention Participants
with chronic, stable HIV infection were excluded
a N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose The N for
each reaction was the same, therefore, the information was included in the column header
b n = Number of participants with the specified reaction
c Mild: >2 0 to ≤5 0 cm; M oderate: >5 0 to ≤ 10 0 cm; S evere: >10 0 cm
d Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity
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11 Table 4: Study 2 – Frequency and Percentages of Participants with Solicited Systemic Reactions, by
Maximum Severity, Within 7 Days After Each Dose – Participants 56 Years of Age and Older – Reactogenicity Subset of the Safety Population*
COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
Fever
≥38.0℃ 26 (1.3) 8 (0.4) 219 (11.8) 4 (0.2)
≥38.0℃ to 38.4℃ 23 (1.1) 3 (0.2) 158 (8.5) 2 (0.1)
>38.4℃ to 38.9℃ 2 (0.1) 3 (0.2) 54 (2.9) 1 (0.1)
>38.9℃ to 40.0℃ 1 (0.0) 2 (0.1) 7 (0.4) 1 (0.1)
>40.0℃ 0 0 0 0
Fatiguec
Any 677 (33.7) 447 (22.5) 949 (51.0) 306 (16.7)
Mild 415 (20.7) 281 (14.1) 391 (21.0) 183 (10.0)
Moderate 259 (12.9) 163 (8.2) 497 (26.7) 121 (6.6)
Severe 3 (0.1) 3 (0.2) 60 (3.2) 2 (0.1)
Grade 4 0 0 1 (0.1) 0
Headachec
Any 503 (25.0) 363 (18.3) 733 (39.4) 259 (14.1)
Mild 381 (19.0) 267 (13.4) 464 (24.9) 189 (10.3)
Moderate 120 (6.0) 93 (4.7) 256 (13.8) 65 (3.5)
Severe 2 (0.1) 3 (0.2) 13 (0.7) 5 (0.3)
Chillsc
Any 130 (6.5) 69 (3.5) 435 (23.4) 57 (3.1)
Mild 102 (5.1) 49 (2.5) 229 (12.3) 45 (2.5)
Moderate 28 (1.4) 19 (1.0) 185 (9.9) 12 (0.7)
Severe 0 1 (0.1) 21 (1.1) 0
Vomitingd
Any 10 (0.5) 9 (0.5) 13 (0.7) 5 (0.3)
Mild 9 (0.4) 9 (0.5) 10 (0.5) 5 (0.3)
Moderate 1 (0.0) 0 1 (0.1) 0
Severe 0 0 2 (0.1) 0
Diarrheae
Any 168 (8.4) 130 (6.5) 152 (8.2) 102 (5.6)
Mild 137 (6.8) 109 (5.5) 125 (6.7) 76 (4.1)
Moderate 27 (1.3) 20 (1.0) 25 (1.3) 22 (1.2)
Severe 4 (0.2) 1 (0.1) 2 (0.1) 4 (0.2)
New or worsened muscle painc
Any 274 (13.6) 165 (8.3) 537 (28.9) 99 (5.4)
Mild 183 (9.1) 111 (5.6) 229 (12.3) 65 (3.5)
Moderate 90 (4.5) 51 (2.6) 288 (15.5) 33 (1.8)
Severe 1 (0.0) 3 (0.2) 20 (1.1) 1 (0.1)
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12 COMIRNATY
Dose 1
Na=2008
nb (%) Placebo
Dose 1
Na=1989
nb (%) COMIRNATY
Dose 2
Na=1860
nb (%) Placebo
Dose 2
Na=1833
nb (%)
New or worsened joint painc
Any 175 (8.7) 124 (6.2) 353 (19.0) 72 (3.9)
Mild 119 (5.9) 78 (3.9) 183 (9.8) 44 (2.4)
Moderate 53 (2.6) 45 (2.3) 161 (8.7) 27 (1.5)
Severe 3 (0.1) 1 (0.1) 9 (0.5) 1 (0.1)
Use of antipyretic or
pain medicationf 382 (19.0) 224 (11.3) 688 (37.0) 170 (9.3)
Note s: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e -diary) from Day 1 to Day 7 after
each dose
The only Grade 4 solicited systemic reaction reported in participants 56 years of age and older was fatigue
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention Participants
with chronic, stable HIV infection were excluded
a N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose N for each
reaction or use of antipyretic or pain medication was the same, therefore was included in the column header
b n = Number of participants with the specified reaction
c Mild: does not interfere with activity; M oderate: some interference with activity; S evere: prevents daily activity ; Grade 4
reactions were defined in the clinical study protocol as emergency room visit or hospitalization for severe fatigue, severe
headache, severe chills, severe muscle pain, or severe joint pain
d Mild: 1 to 2 times in 24 hours; M oderate: >2 times in 24 hours; S evere: requires intravenous hydration; Grade 4 emergency visit
or hospitalization for severe vomiting
e Mild: 2 to 3 loose stools in 24 hours; M oderat e: 4 to 5 loose stools in 24 hours; S evere: 6 or more loose stools in 24 hours ;
Grade 4: emergency room or hospitalization for severe diarrhea
f Severity was not collected for use of antipyretic or pain medication
In participants with chronic, stable HIV infection the frequencies of solicited local and systemic adverse
reactions were similar to or lower than those observed for all participants 16 years of age and older .
Unsolicited Adverse Events
Overall , 11,253 ( 51.1% ) participants in the COMIRNATY group and 11,316 ( 51.4% ) participants in the
placebo group had follow- up time between ≥4 months to <6 months after Dose 2 in the blinded
placebo -controlled follow-up period with an additional 1,778 ( 8.1% ) and 1,304 ( 5.9% ) with ≥6 months of
blinded follow-up time in the COMIRNATY and placebo groups, respectively.
A total of 12,006 ( 54.5% ) participants originally randomized to COMIRNATY had ≥6 months total (blinded
and unblinded) follow-up after Dose 2.
In an analysis of all unsolicited adverse events reported following any dose, through 1 month after Dose 2, in
participants 16 years of age and older (N=43,847; 21,926 COMIRNATY group vs. 21,921 placebo group),
those assessed as adverse reactions not already cap tured by solicited local and systemic reactions were nausea
(274 vs. 87), malaise ( 130 vs. 22), lymphadenopathy (83 vs. 7), asthenia ( 76 vs. 25), decreased appetite
(39 vs. 9), hyperhidrosis (31 vs. 9), lethargy (25 vs. 6), and night sweats ( 17 vs. 3).
In analyses of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date,
58.2% of study participants had at least 4 months of follow -up after Dose 2. Among participants 16 through
55 years of age who received at least one dose of study vaccine, 12,995 of whom received COMIRNATY and
13,026 of whom received placebo , unsolicited adverse events were reported by 4,396 (33.8%) participants in
the COMIRNATY group and 2,136 (16.4%) participants in the pla cebo group. In a similar analysis in
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15 COMIRNATY
Dose 1
Na=1127
nb (%) Placebo
Dose 1
Na=1127
nb (%) COMIRNATY
Dose 2
Na=1097
nb (%) Placebo
Dose 2
Na=1078
nb (%)
Fatiguec
Any 677 (60.1) 457 (40.6) 726 (66.2) 264 (24.5)
Mild 278 (24.7) 250 (22.2) 232 (21.1) 133 (12.3)
Moderate 384 (34.1) 199 (17.7) 468 (42.7) 127 (11.8)
Severe 15 (1.3) 8 (0.7) 26 (2.4) 4 (0.4)
Headachec
Any 623 (55.3) 396 (35.1) 708 (64.5) 263 (24.4)
Mild 361 (32.0) 256 (22.7) 302 (27.5) 169 (15.7)
Moderate 251 (22.3) 131 (11.6) 384 (35.0) 93 (8.6)
Severe 11 (1.0) 9 (0.8) 22 (2.0) 1 (0.1)
Chillsc
Any 311 (27.6) 109 (9.7) 455 (41.5) 73 (6.8)
Mild 195 (17.3) 82 (7.3) 221 (20.1) 52 (4.8)
Moderate 111 (9.8) 25 (2.2) 214 (19.5) 21 (1.9)
Severe 5 (0.4) 2 (0.2) 20 (1.8) 0 (0.0)
Vomitingd
Any 31 (2.8) 10 (0.9) 29 (2.6) 12 (1.1)
Mild 30 (2.7) 8 (0.7) 25 (2.3) 11 (1.0)
Moderate 0 (0.0) 2 (0.2) 4 (0.4) 1 (0.1)
Severe 1 (0.1) 0 (0.0) 0 (0.0) 0 (0.0)
Diarrheae
Any 90 (8.0) 82 (7.3) 65 (5.9) 43 (4.0)
Mild 77 (6.8) 72 (6.4) 59 (5.4) 38 (3.5)
Moderate 13 (1.2) 10 (0.9) 6 (0.5) 5 (0.5)
Severe 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)
New or worsened muscle painc
Any 272 (24.1) 148 (13.1) 355 (32.4) 90 (8.3)
Mild 125 (11.1) 88 (7.8) 152 (13.9) 51 (4.7)
Moderate 145 (12.9) 60 (5.3) 197 (18.0) 37 (3.4)
Severe 2 (0.2) 0 (0.0) 6 (0.5) 2 (0.2)
New or worsened joint painc
Any 109 (9.7) 77 (6.8) 173 (15.8) 51 (4.7)
Mild 66 (5.9) 50 (4.4) 91 (8.3) 30 (2.8)
Moderate 42 (3.7) 27 (2.4) 78 (7.1) 21 (1.9)
Severe 1 (0.1) 0 (0.0) 4 (0.4) 0 (0.0)
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17 6.2 Postmarketing Experience
The following adverse reactions have been identified during postmarketing use of COMIRNATY, including
under Emergency Use Authorization. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.
Cardiac Disorders: myocarditis, pericarditis
Gastrointestinal Disorders: diarrhea, vomiting
Immune System Disorders: severe allergic reactions, including anaphylaxis , and other hypersensitivity reactions
(e.g., rash, pruritus, urticaria, angioedema)
Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to COMIRNATY during pregnancy. Women who are vaccinated with COMIRNATY during pregnancy are encouraged to enroll in the registry by visiting https://mothertobaby.org/ongoing-study/covid19- vaccines/
.
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 and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on COMIRNATY administe red to pregnant women are
insufficient to inform vaccine-associated risks in pregnancy. A developmental toxicity stud y has been performed in female rats administered the equivalent of a single
human dose of COMIRNATY 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 Animal Data) .
Data
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) and other ingredients included in a single human dose of COMIRNATY 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
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18 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 16 12 through 17 years of age is based on safety and
effectiveness data in this age group and in adults [see Adverse Reactions (6) and Clinical Studies (14.1)] .
The safety and effectiveness of COMIRNATY in individuals younger than 16 12 years of age have not been
established.
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)] . No overall differences in safety or effectiveness were observed between these
recipients and younger recipients.
11 DESCRIPTION
COMIRNATY (COVID -19 V accine, mRNA) is a sterile suspension for injection for intramuscular use.
COMIRNATY is supplied as a frozen suspension in multiple dose vials; each vial must be diluted with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine. Each dose of COMIRNATY
contains 30 mcg of a nucleoside- modified messenger RNA ( mRNA) encoding the viral spike (S) glycoprotein
of SARS -CoV-2.
Each 0.3 mL dose of the COMIRNATY also includes the following ingredients: lipids (0.43 mg
((4-hydroxybutyl)azanediyl)bis(hexane-6,1- diyl)bis(2 -hexyldecanoate), 0.05 mg 2-(polyethylene
glycol 2000)- N,N-ditetradecylacetamide, 0.09 mg 1,2-distearoyl- sn-glycero-3-phosphocholine, and 0.2 mg
cholesterol), 0.01 mg potassium chloride, 0.01 mg monobasic potassium phosphate, 0.36 mg sodium chloride, 0.07 mg dibasic sodium phosphate dihydrate, and 6 mg sucrose. The diluent (0.9% Sodium Chloride Injection, USP) contributes an additional 2.16 mg sodium chloride per dose.
COMIRNATY does not contain preservative. The vial stoppers are not made with natural rubber latex.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The nucleoside-modified m RNA in COMIRNATY is formulated in lipid particles, which enable delivery of the
mRNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.
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19 13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
COMIRNATY has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of
male fertility. In a developmental toxicity study in rats with COMIRNATY t here were no vaccine- related
effects on female fertility [see Use in Specific Populations (8.1)] .
14 CLINICAL STUDIES
14.1 Efficacy in Participants 16 Years of Age and Older
Study 2 is a n ongoing, multicenter, multinational, randomized, placebo-controlled, observer-blind, dose-finding,
vaccine candidate–selection, and efficacy study in participants 12 years of age and older. Randomization was stratified by age: 12 through 15 years of age, 16 through 55 years of age, or 56 years of age and older, with a minimum of 40% of participants in the ≥56-year stratum. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID19.
Particip ants with preexisting stable disease, defined as disease not requiring significant change in therapy or
hospitalization for worsening disease during the 6 weeks- before enrollment, were included as were participants with known stable infection with HIV, he patitis C virus (HCV), or hepatitis B virus (HBV).
In Study 2, based on data accrued through March 13, 2021, approximately 44,000 participants 1612 years of age
and older were randomized equally and received 2 doses of COMIRNATY or placebo. Participants are planned to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19.
Overall, among the total participants who received COMIRNATY or placebo, 51.4% or 50.3% were male and 48.6% or 49.7% were female, 79.1% or 79.2% were 16 through 64 years of age, 20.9% or 20.8% were 65 years
of age and older, 81.9% or 82.1% were White, 9.5% or 9.6% were Black or African American, 1.0 % or 0.9%
were American Indian or Alaska Native, 4. 4% or 4.3% were Asian, 0.3% or 0.2% Native Hawaiian or other
Pacific Islander, 2 5.6% or 2 5.4% were Hispanic/Latino, 73.9% or 74.1% were non- Hispanic/Latino, 0.5% or
0.5% did not report ethnicity, 46.0% or 45.7% had comorbidities [participants who have 1 or more comorbidities that increase the risk of severe COVID -19 disease: defined as subjects who had at least one of the
Charlson comorbidity index category or body mass index (BMI) ≥30 kg/m
2], respectively. The mean age at
vaccination was 4 9.8 or 4 9.7 years and median age was 5 1.0 or 51.0 in participants who received
COMIRNATY or placebo, respectively.
Efficacy Against COVID-19
The population for the analysis of the protocol pre- specified primary efficacy endpoint included
36,621 participants 12 years of age and older (18,242 in the C OMIRNATY group and 18,379 in the placebo
group) who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose. The population in the protocol pre- specified primary efficacy analysis included all participants 12 years of age
and older who had been enrolled from July 27, 2020, and followed for the development of COVID-19 through November 14, 2020. Participants 18 through 55 years of age and 56 years of age and older began enrollment from July 27, 2020, 16 through 17 years of age began enrollment from September 16, 2020, and 12 through 15 years of age began enrollment from October 15, 2020.
For participants without evidence of SARS-CoV-2 infection prior to 7 days after Dose 2, vaccine efficacy
against confirmed C OVID- 19 occurring at least 7 days after Dose 2 was 95.0% (95% credible interval: 90.3,
FDA-CBER-2022-5812-0220487
20 97.6), which met the pre- specified success criterion. The case split was 8 COVID -19 cases in the
COMIRNATY group compared to 162 COVID-19 cases in the placebo group.
The population for the updated vaccine efficacy analysis included participants 16 years of age and older who had been enrolled from July 27, 2020, and followed for the development of COVID19 during blinded
placebo -controlled follow-up through March 13, 2021, representing up to 6 months of follow-up after Dose 2.
There were 12,796 (60.8%) participants in the COMIRNATY group and 12,449 ( 58.7%) in the plac ebo group
followed for ≥4 months after Dose 2 in the blinded placebo-controlled follow-up period.
SARS -CoV-2 variants of concern identified from COVID-19 cases in this study include B.1.1.7 (Alpha) and
B.1.351 ( Beta).
Representation of identified variants among cases in vaccine versus placebo recipients did not
suggest decreased vaccine effectiveness against these variants.
The updated vaccine efficacy information is presented in Table 57.
Table 57: Vaccine Efficacy – First COVID-19 Occurrence From 7 Days After Dose 2, by Age
Subgroup – Participants 16 Years of Age and Older Without Evidence of Infection and
Participants With or Without Evidence of Infection Prior to 7 Days After Dose 2 – Evaluable
Efficacy (7 Days) Population Dur ing the Placebo -Controlled Follow- up Period
First COVID -19 occurrence from 7 days after Dose 2 in particip ants without evidence of prior
SARS -CoV -2 infection*
Subgroup COMIRNATY
Na=19,993
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=20,118
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CIe)
All participantsf 77
6.092 ( 19,711) 833
5.857 ( 19,741) 91.1
(88.8, 93.1)
16 through 64 years 70
4.859 (15,519) 709
4.654 (15,515) 90.5
(87.9, 92.7)
65 years and older 7
1.233 (4192) 124
1.202 (4226) 94.5
(88.3, 97.8)
First COVID -19 occurrence from 7 days after Dose 2 in participants with or without* evidence of prior
SARS -CoV -2 infection
Subgroup COMIRNATY
Na=21,047
Cases
n1b
Surveillance Timec (n2d) Placebo
Na=21,210
Cases
n1b
Surveillance Timec (n2d) Vaccine Efficacy %
(95% CIe)
All participants 81
6.340 ( 20,533) 854
6.110 (20 ,595) 90.9
(88.5, 92.8)
16 through 64 years 74
5.073 (16,218) 726
4.879 ( 16,269) 90.2
(87.5, 92.4)
65 years and older 7
1.267 (4315) 128
1.232 (4326) 94.7
(88.7, 97.9)
Note: Confirmed cases were determined by Reverse Transcription -Polymerase Chain Reaction (RT -PCR) and at least 1 symptom
consistent with COVID -19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or
increased muscl e pain; new loss of taste or smell; sore throat; diarrhea; vomiting)
* Participants who had no evidence of past SARS -CoV-2 infection (i e , N -binding antibody [serum] negative at Visit 1 and
SARS -CoV -2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis
FDA-CBER-2022-5812-0220488
21 a N = Number of participants in the specified group
b n1 = Number of participants meeting the endpoint definition
c Total surveillance time in 1000 person -years for the given endpoint across all participants within each group at risk for the endpoint
Time period for COVID -19 case accrual is from 7 days after Dose 2 to the end of the surveillance period
d n2 = Number of participants at risk for the endpoint
e Two-sided confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method adjusted to the
surveillance time
Subgroup analyses of vaccine efficacy (although limited by small numbers of cases in some subgroups) did not
suggest meaningful differences in efficacy across genders, ethnic groups, geographies, or for participan ts with
obesity or medical comorbidities associated with high risk of severe COVID-19.
Efficacy Against S evere COVID -19
Efficacy analyses of secondary efficacy endpoints supported benefit of COMIRNATY in preventing severe
COVID- 19. Vaccine efficacy against severe COVID -19 is presented only for participants with or without prior
SARS -CoV-2 infection (Table 68) as the COVID -19 case counts in participants without prior SARS-CoV-2
infection were the same as those in participants with or without prior SARS-CoV-2 infection in both the COMIRNATY and placebo groups.
Table 68: Vaccine Efficacy – First Severe COVID- 19 Occurrence in Participants 16 Years of Age and
Older With or Without* Prior SARS- CoV-2 Infection Based on Protocol† or Centers for
Disease Control and Prevention (CDC)‡ Definition From 7 Days After Dose 2 – Evaluable
Efficacy (7 Days) Population D uring the Placebo -Controlled Follow- up
Vaccine Efficacy – First Severe COVID -19 Occurrence
COMIRNATY
Cases
n1a
Surveillance Timeb (n2c) Placebo
Cases
n1a
Surveillance Timeb (n2c) Vaccine Efficacy %
(95% CId)
7 days after Dose 2d 1
6.353 (20 ,540) 21
6.237 (20 ,629) 95.3
(70.9, 99.9)
Vaccine Efficacy – First Severe COVID -19 Occurrence Based on CDC Definition
COMIRNATY
Cases
n1a
Surveillance Timeb (n2c) Placebo
Cases
n1a
Surveillance Timeb (n2c) Vaccine Efficacy %
(95% CId)
7 days after Dose 2d 0
6.345 ( 20,513) 31
6.225 ( 20,593) 100
(87.6, 100.0)
Note: Confirmed cases were determined by Reverse Transcription -Polymerase Chain Reaction (RT -PCR) and at least 1 symptom
consistent with COVID -19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or
increased mu scle pain; new loss of taste or smell; sore throat; diarrhea; vomiting)
* Participants who had no evidence of past SARS -CoV-2 infection (i e , N -binding antibody [serum] negative at Visit 1 and
SARS -CoV -2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit
prior to 7 days after Dose 2 were included in the analysis
† Severe illness from COVID -19 is defined in the protocol as confirmed COVID -19 and presence of at least 1 of the following:
• Clinical signs at rest indicative of severe systemic illness (respiratory rate ≥30 breaths per minute, heart rate ≥125 beats per
minute, saturation of oxygen ≤93% on room air at sea level, or ratio of arteri al oxygen partial pressure to fractional inspired
oxygen <300 mm Hg);
• Respiratory failure [defined as needing high -flow oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal
membrane oxygenation (ECMO)];
• Evidence of shock (systolic blood pressure <90 mm Hg, diastolic blood pressure <60 mm Hg, or requiring vasopressors);
• Significant acute renal, hepatic, or neurologic dysfunction;
• Admission to an Intensive Care Unit;
FDA-CBER-2022-5812-0220489
FDA-CBER-2022-5812-0220490
FDA-CBER-2022-5812-0220491
24
After dilution, 1 vial contains 6 doses of 0.3 mL.
During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light. Do not refreeze thawed vials.
Frozen Vials Prior to Use
Cartons of COMIRNATY Multiple Dose Vials arrive in thermal containers with dry ice. Once received, remove the vial cartons i mmediately from the thermal container and preferably store in an ultra- low temperature freezer
between -90ºC to -60ºC (-130ºF to -76ºF) until the expiry date printed on the label. Alternatively, vials may be stored at -25°C to - 15°C ( -13°F to 5°F) for up to 2 weeks . Vials must be kept frozen and protected from light, in
the original cartons, until ready to use. Vials stored at -25°C to -15 °C (-13°F to 5°F) for up to 2 weeks may be
returned 1 time to the recommended storage condition of -90ºC to -60ºC (-130ºF to -76ºF). Total cumulative
time the vials are stored at -25°C to - 15°C ( -13°F to 5°F) should be tracked and should not exceed 2 weeks .
If an ultra -low temperature freezer is not available, the thermal container in which COMIRNATY arrives may
be used as temporary storage when consistently re-filled to the top of the container with dry ice. Refer to the
re-icing guidelines packed in the original thermal container for instructions regarding the use of the thermal
container for temporary storage. The thermal container maintains a temperature range of -90ºC to -60ºC (-130ºF
to -76ºF). Storage of the vials between -96°C to - 60°C ( -141°F to -76°F) is not considered an excursion from
the recommended storage condition.
Transportation of Frozen Vials
If local redistribution is needed and full cartons containing vials cannot be transported at -90°C to -60°C (-130°F to -76°F), vials may be transported at -25°C to - 15°C ( -13°F to 5°F). Any hours used for transport
at -25°C to - 15°C ( -13°F to 5°F) count against the 2- week limit for storage at -25°C to - 15°C ( -13°F to 5°F).
Frozen vials transported at -25°C to - 15°C ( -13°F to 5°F) may be returned 1 time to the recommended storage
condition of -90ºC to -60ºC (-130ºF to -76ºF).
Thawed Vials Before Dilution
Thawed Under Refrigeration
Thaw and then store undiluted vials in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] for up to 1 month. A carton of 25 vials or 195 vials may take up to 2 or 3 hours , respectively, to thaw in the refrigerator, whereas a fewer
number of vials will thaw in less time. Thawed at Room Temperature For immediate use, thaw undiluted vials at room temperature [up to 25ºC (77ºF)] for 30 minutes. Thawed vials
can be handled in room light conditions. Vials must reach room temperature before dilution.
Undiluted vials may be stored at room temperature for no more than 2 hours.
FDA-CBER-2022-5812-0220492
25 Transportation of Thawed Vials
Available data support transportation of 1 or more thawed vials at 2°C to 8°C (35°F to 46°F) for up to 12 hours.
Vials After Dilution
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.
17 PATIENT COUNSELING INFORMATION
Inform vaccine recipient of the potential benefits and risks of vaccination with COMIRNATY. Inform vaccine recipient of the importance of completing the two dose vaccination series. There is a pregnancy exposure registry for COMIRNATY. Encourage individuals exposed to COMIRNATY around the time of conception or during pregnancy to register by visiting
https://mothertobaby.org/ongoing-
study/covid19- vaccines/ .
Advise vaccine recipient to report any adverse events to their healthcare provider or to the Vaccine Adverse Event Reporting System at 1-800-822- 7967 and www.vaers hhs.gov
.
This product’s labeling may have been updated. For the most recent prescribing information, please visit
https://dailymed nlm nih.gov/dailymed/ .
Manufactured for BioNTech Manufacturing GmbH An der Goldgrube 12 55131 Mainz, Germany
Manufactured by Pfizer Inc., New York, NY 10017
LAB -1448-1.01b
US Govt. License No. 2229
FDA-CBER-2022-5812-0220493