COMIRNATY COVID-19 VACCIN medication leaflet 30mcg/dose x195 CONCENTRATE FOR INJECTION DISPERSION BIONT

J07BX03 COVID-19 mRNA vaccine (with modified nucleosides)

Medicine COMIRNATY COVID-19 VACCIN 30mcg/dose contains substance COVID-19 mRNA vaccine (with modified nucleosides) and classification given by the ATC (Anatomical Therapeutic Chemical) code J07BX03 is Antiinfectives for systemic use | Viral vaccines | Other viral vaccines.

COMIRNATY COVID-19 VACCIN 30mcg/dose x195 CONCENTRATE FOR INJECTION DISPERSION BIONT, COVID-19 mRNA vaccine (with modified nucleosides)
PDF file EMA leaflet
Published: 12/01/2021
Updated: 06/05/2022

General data about COMIRNATY COVID-19 VACCIN 30mcg/dose BIONT

Substance: COVID-19 mRNA vaccine (with modified nucleosides)

Date of last drug list: 01-02-2021

Commercial code: W67224002

Concentration: 30mcg/dose

Pharmaceutical form: CONCENTRATE FOR INJECTION DISPERSION

Packing volume: 0,45 ml

Product type: original

Prescription restrictions: P-RF - Medicines prescription that is retained in the pharmacy (not renewable).

Pharmaceutical forms available for COVID-19 mRNA vaccine (with modified nucleosides)

CONCENTRATE FOR INJECTION DISPERSION

Concentrations available for COVID-19 mRNA vaccine (with modified nucleosides)

100mcg/dose, 30mcg/dose

Marketing authorisation

Manufacturer: BIONTECH MANUFACTURING GMBH/ PFIZER MANUFACTURING - GERMANIA/BELGIA

Holder: BIONTECH MANUFACTURING GMBH - GERMANIA

Number: 1528/2020/01

Shelf life: 6 months- unopened bottle

Contents of the package leaflet for the medicine COMIRNATY COVID-19 VACCIN 30mcg/dose x195 CONCENTRATE FOR INJECTION DISPERSION BIONT

1. NAME OF THE MEDICINAL PRODUCT

Comirnaty 30 micrograms/dose concentrate for dispersion for injection
COVID-19 mRNA Vaccine (nucleoside modified)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

This is a multidose vial with a purple cap and must be diluted before use.

One vial (0.45 mL) contains 6 doses of 0.3 mL after dilution, see sections 4.2 and 6.6.

One dose (0.3 mL) contains 30 micrograms of tozinameran, a COVID-19 mRNA Vaccine (embedded in lipid nanoparticles).

Tozinameran is a single-stranded, 5’-capped messenger RNA (mRNA) produced using a cell-free in vitro transcription from the corresponding DNA templates, encoding the viral spike (S) protein of SARS-CoV-2.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Concentrate for dispersion for injection (sterile concentrate). The vaccine is a white to off-white frozen dispersion (pH: 6.9 - 7.9).

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Comirnaty 30 micrograms/dose concentrate for dispersion for injection is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 virus, in individuals 12 years of age and older.

The use of this vaccine should be in accordance with official recommendations.

4.2 Posology and method of administration

Posology
Primary vaccination course

Individuals 12 years of age and older
Comirnaty is administered intramuscularly after dilution as a primary course of 2 doses (0.3 mL each). It is recommended to administer the second dose 3 weeks after the first dose (see sections 4.4 and 5.1).

Severely immunocompromised aged 12 years and older
A third primary course dose may be administered intramuscularly at least 28 days after the second dose to individuals who are severely immunocompromised (see section 4.4).

Interchangeability
The interchangeability of Comirnaty with COVID-19 vaccines from other manufacturers to complete the primary course has not been established. Individuals who have received a dose of Comirnaty should continue to receive Comirnaty to complete the primary course.

Doses of Comirnaty 30 micrograms/dose concentrate for dispersion for injection after dilution (supplied in a vial with a purple cap) and Comirnaty 30 micrograms/dose dispersion for injection (supplied in a vial with a grey cap) are considered interchangeable.

Booster dose
A booster dose of Comirnaty should be administered intramuscularly as early as 3 months after the primary course with Comirnaty in individuals 12 years of age and older.

Comirnaty may also be given as a booster dose in individuals 18 years of age and older who have received a primary course comprised of another mRNA vaccine or adenoviral vector vaccine.

Paediatric population
There is a paediatric formulation available for children 5 to 11 years of age (i.e., 5 to less than 12 years of age). For details, please refer to the Summary of Product Characteristics for Comirnaty 10 micrograms/dose concentrate for dispersion for injection.

The safety and efficacy of Comirnaty in children aged less than 5 years have not yet been established.

Elderly population
No dosage adjustment is required in elderly individuals ≥ 65 years of age.

Method of administration
Comirnaty 30 micrograms/dose concentrate for dispersion for injection should be administered intramuscularly after dilution (see section 6.6).

After dilution, vials of Comirnaty contain 6 doses of 0.3 mL of vaccine. In order to extract 6 doses from a single vial, low dead-volume syringes and/or needles should be used. The low dead-volume syringe and needle combination should have a dead volume of no more than 35 microlitres. 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.

The preferred site is the deltoid muscle of the upper arm.

Do not inject the vaccine intravascularly, subcutaneously or intradermally.

The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products.

For precautions to be taken before administering the vaccine, see section 4.4.

For instructions regarding thawing, handling and disposal of the vaccine, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

General recommendations
Hypersensitivity and anaphylaxis
Events of anaphylaxis have been reported. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine.

Close observation for at least 15 minutes is recommended following vaccination. No further dose of the vaccine should be given to those who have experienced anaphylaxis after a prior dose of Comirnaty.

Myocarditis and pericarditis
There is an increased risk of myocarditis and pericarditis following vaccination with Comirnaty. These conditions can develop within just a few days after vaccination, and have primarily occurred within 14 days. They have been observed more often after the second vaccination, and more often in younger males (see section 4.8). Available data suggest that the course of myocarditis and pericarditis following vaccination is not different from myocarditis or pericarditis in general.

Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis.
Vaccinees (including parents or caregivers) should be instructed to seek immediate medical attention if they develop symptoms indicative of myocarditis or pericarditis such as (acute and persisting) chest pain, shortness of breath, or palpitations following vaccination.

Healthcare professionals should consult guidance and/or specialists to diagnose and treat this condition.

The risk of myocarditis after a third dose of Comirnaty has not yet been characterised.

Anxiety-related reactions
Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐related reactions (e.g. dizziness, palpitations, increases in heart rate, alterations in blood pressure, paraesthesia, hypoaesthesia and sweating) may occur in association with the vaccination process itself.
Stress-related reactions are temporary and resolve on their own. Individuals should be advised to bring symptoms to the attention of the vaccination provider for evaluation. It is important that precautions are in place to avoid injury from fainting.

Concurrent illness
Vaccination should be postponed in individuals suffering from acute severe febrile illness or acute infection. The presence of a minor infection and/or low-grade fever should not delay vaccination.

Thrombocytopenia and coagulation disorders
As with other intramuscular injections, the vaccine should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular administration in these individuals.

Immunocompromised individuals
The efficacy and safety of the vaccine has not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of Comirnaty may be lower in immunocompromised individuals.

The recommendation to consider a third dose in severely immunocompromised individuals is based on limited serological evidence from a case-series in the literature from the clinical management of patients with iatrogenic immunocompromisation after solid organ transplantation (see section 4.2).

Duration of protection
The duration of protection afforded by the vaccine is unknown as it is still being determined by ongoing clinical trials.

Limitations of vaccine effectiveness
As with any vaccine, vaccination with Comirnaty may not protect all vaccine recipients. Individuals may not be fully protected until 7 days after their second dose of vaccine.

Excipients
This vaccine contains less than 1 mmol potassium (39 mg) per dose, that is to say essentially ‘potassium-free’.

This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Concomitant administration of Comirnaty with other vaccines has not been studied.

4.6 Fertility, pregnancy and lactation

Pregnancy
A large amount of observational data from pregnant women vaccinated with Comirnaty during the second and third trimester have not shown an increase in adverse pregnancy outcomes. While data on pregnancy outcomes following vaccination during the first trimester are presently limited, no increased risk for miscarriage has been seen. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or post-natal development (see section 5.3). Comirnaty can be used during pregnancy.

Breast-feeding
No effects on the breast-fed newborn/infant are anticipated since the systemic exposure of breast-feeding woman to Comirnaty is negligible. Observational data from women who were breast-feeding after vaccination have not shown a risk for adverse effects in breast-fed newborns/infants. Comirnaty can be used during breast-feeding.

Fertility
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3).

4.7 Effects on ability to drive and use machines

Comirnaty has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

4.8 Undesirable effects

Summary of safety profile
Participants 16 years of age and older - after 2 doses
In Study 2, a total of 22,026 participants 16 years of age or older received at least 1 dose of Comirnaty and a total of 22,021 participants 16 years of age or older received placebo (including 138 and 145 adolescents 16 and 17 years of age in the vaccine and placebo groups, respectively). A total of 20,519 participants 16 years of age or older received 2 doses of Comirnaty.

At the time of the analysis of Study 2 with a data cut-off of 13 March 2021 for the placebo-controlled blinded follow-up period up to the participants’ unblinding dates, a total of 25,651 (58.2%) participants (13,031 Comirnaty and 12,620 placebo) 16 years of age and older were followed up for ≥ 4 months after the second dose. This included a total of 15,111 (7,704 Comirnaty and 7,407 placebo) participants 16 to 55 years of age and a total of 10,540 (5,327 Comirnaty and 5,213 placebo) participants 56 years of age and older.

The most frequent adverse reactions in participants 16 years of age and older that received 2 doses were injection site pain (> 80%), fatigue (> 60%), headache (> 50%), myalgia (> 40%), chills (> 30%), arthralgia (> 20%), pyrexia and injection site swelling (> 10%) and were usually mild or moderate in intensity and resolved within a few days after vaccination. A slightly lower frequency of reactogenicity events was associated with greater age.

The safety profile in 545 participants 16 years of age and older receiving Comirnaty, that were seropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.

Adolescents 12 to 15 years of age - after 2 doses
In an analysis of long-term safety follow-up in Study 2, 2,260 adolescents (1,131 Comirnaty and 1,129 placebo) were 12 to 15 years of age. Of these, 1,559 adolescents (786 Comirnaty and 773 placebo) have been followed for ≥ 4 months after the second dose of Comirnaty. The safety evaluation in Study 2 is ongoing.

The overall safety profile of Comirnaty in adolescents 12 to 15 years of age was similar to that seen in participants 16 years of age and older. The most frequent adverse reactions in adolescents 12 to 15 years of age that received 2 doses were injection site pain (> 90%), fatigue and headache (> 70%), myalgia and chills (> 40%), arthralgia and pyrexia (> 20%).

Participants 16 years of age and older - after booster dose
A subset from Study 2 Phase 2/3 participants of 306 adults 18 to 55 years of age who completed the original Comirnaty 2-dose course, received a booster dose of Comirnaty approximately 6 months (range of 4.8 to 8.0 months) after receiving Dose 2.

The overall safety profile for the booster dose was similar to that seen after 2 doses. The most frequent adverse reactions in participants 18 to 55 years of age were injection site pain (> 80%), fatigue (> 60%), headache (> 40%), myalgia (> 30%), chills and arthralgia (> 20%).

In Study 4, a placebo-controlled booster study, participants 16 years of age and older recruited from
Study 2 received a booster dose of Comirnaty (5,081 participants), or placebo (5,044 participants) at least 6 months after the second dose of Comirnaty. Overall, participants who received a booster dose, had a median follow-up time of 2.5 months after the booster dose to the cut-off date (5 October 2021). No new adverse reactions of Comirnaty were identified.

Booster dose following primary vaccination with another authorised COVID-19 vaccine
In 5 independent studies on the use of a Comirnaty booster dose in individuals who had completed primary vaccination with another authorized COVID-19 vaccine (heterologous booster dose), no new safety issues were identified (see section 5.1).

Tabulated list of adverse reactions from clinical studies and post-authorisation experience in individuals 12 years of age and older

Adverse reactions observed during clinical studies are listed below according to the following frequency categories:

Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), Rare (≥ 1/10,000 to < 1/1,000), Very rare (< 1/10,000), Not known (cannot be estimated from the available data).

Table 1: Adverse reactions from Comirnaty clinical trials and post-authorisation experience

in individuals 12 years of age and older
Not known

Very Common Uncommon Rare (cannot be
System Organ

Class common (≥ 1/100 (≥ 1/1,000 to (≥ 1/10,000 Very rare estimated

(≥ 1/10) to < 1/10) < 1/100) to (< 1/10,000) from the < 1/1,000) available

data)
Blood and Lymphadenopathya lymphatic system disorders
Immune system Hypersensitivity Anaphylaxis disorders reactions (e.g. rash,

pruritus, urticariab, angioedemab)

Metabolism and Decreased appetite nutrition disorders
Psychiatric Insomnia disorders
Nervous system Headache Lethargy Acute Paraesthesiad;

disorders peripheral Hypoaesthesiad facial paralysisc

Cardiac Myocarditisd; disorders Pericarditisd
Gastrointestinal Diarrhoead Nausea; disorders Vomitingd
Skin and Hyperhidrosis; Erythema subcutaneous Night sweats multiformed tissue disorder
Musculoskeletal Arthralgia; Pain in extremitye and connective Myalgia tissue disorders

Not known

Very Common Uncommon Rare (cannot be
System Organ common (≥ 1/100 (≥ 1/1,000 to (≥ 1/10,000 Very rare estimated

Class (≥ 1/10) to < 1/10) < 1/100) to (< 1/10,000) from the < 1/1,000) available

data)
General Injection Injection Asthenia; Extensive disorders and site pain; site Malaise; swelling of administration Fatigue; redness Injection site vaccinated site conditions Chills; pruritus limbd;

Pyrexiaf; Facial
Injection swellingg site swelling

a. A higher frequency of lymphadenopathy (2.8% vs. 0.4%) was observed in participants receiving a booster dose in Study 4 compared to participants receiving 2 doses.

b. The frequency category for urticaria and angioedema was rare. c. Through the clinical trial safety follow-up period to 14 November 2020, acute peripheral facial paralysis (or

palsy) was reported by four participants in the COVID-19 mRNA Vaccine group. Onset was Day 37 after
Dose 1 (participant did not receive Dose 2) and Days 3, 9, and 48 after Dose 2. No cases of acute peripheral facial paralysis (or palsy) were reported in the placebo group.

d. Adverse reaction determined post-authorisation. e. Refers to vaccinated arm. f. A higher frequency of pyrexia was observed after the second dose compared to the first dose. g. Facial swelling in vaccine recipients with a history of injection of dermatological fillers has been reported in

the post-marketing phase.

Description of selected adverse reactions
Myocarditis
The increased risk of myocarditis after vaccination with Comirnaty is highest in younger males (see section 4.4).

Two large European pharmacoepidemiological studies have estimated the excess risk in younger males following the second dose of Comirnaty. One study showed that in a period of 7 days after the second dose there were about 0.265 (95% CI 0.255 - 0.275) extra cases of myocarditis in 12-29 year old males per 10,000 compared to unexposed persons. In another study, in a period of 28 days after the second dose there were 0.57 [95% CI 0.39 - 0.75] extra cases of myocarditis in 16-24 year old males per 10,000 compared to unexposed persons.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V and include batch/Lot number if available.

4.9 Overdose

Overdose data is available from 52 study participants included in the clinical trial that due to an error in dilution received 58 micrograms of Comirnaty. The vaccine recipients did not report an increase in reactogenicity or adverse reactions.

In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: vaccines, other viral vaccines, ATC code: J07BX03

Mechanism of action
The nucleoside-modified messenger RNA in Comirnaty is formulated in lipid nanoparticles, which enable delivery of the non-replicating RNA into host cells to direct transient expression of the
SARS-CoV-2 S antigen. The mRNA codes for membrane-anchored, full-length S with two point mutations within the central helix. Mutation of these two amino acids to proline locks S in an antigenically preferred prefusion conformation. The vaccine elicits both neutralizing antibody and cellular immune responses to the spike (S) antigen, which may contribute to protection against COVID-19.

Efficacy
Study 2 is a multicentre, multinational, Phase 1/2/3 randomised, placebo-controlled, observer-blind dose-finding, vaccine candidate selection and efficacy study in participants 12 years of age and older.
Randomisation was stratified by age: 12 to 15 years of age, 16 to 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 COVID-19. Participants with pre-existing stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrolment, were included as were participants with known stable infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV).

Efficacy in participants 16 years of age and older - after 2 doses
In the Phase 2/3 portion of Study 2, based on data accrued through 14 November 2020, approximately 44,000 participants were randomised equally and were to receive 2 doses of COVID-19 mRNA
Vaccine or placebo. The efficacy analyses included participants that received their second vaccination within 19 to 42 days after their first vaccination. The majority (93.1%) of vaccine recipients received the second dose 19 days to 23 days after Dose 1. Participants are planned to be followed for up to 24 months after Dose 2, for assessments of safety and efficacy against COVID-19. In the clinical study, participants were required to observe a minimum interval of 14 days before and after administration of an influenza vaccine in order to receive either placebo or COVID-19 mRNA
Vaccine. In the clinical study, participants were required to observe a minimum interval of 60 days before or after receipt of blood/plasma products or immunoglobulins within through conclusion of the study in order to receive either placebo or COVID-19 mRNA Vaccine.

The population for the analysis of the primary efficacy endpoint included, 36,621 participants 12 years of age and older (18,242 in the COVID-19 mRNA Vaccine 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.
In addition, 134 participants were between the ages of 16 to 17 years of age (66 in the COVID-19 mRNA Vaccine group and 68 in the placebo group) and 1,616 participants 75 years of age and older (804 in the COVID-19 mRNA Vaccine group and 812 in the placebo group).

At the time of the primary efficacy analysis, participants had been followed for symptomatic
COVID-19 for in total 2,214 person-years for the COVID-19 mRNA Vaccine and in total 2,222 person-years in the placebo group.

There were no meaningful clinical differences in overall vaccine efficacy in participants who were at risk of severe COVID-19 including those with 1 or more comorbidities that increase the risk of severe
COVID-19 (e.g. asthma, body mass index (BMI) ≥ 30 kg/m2, chronic pulmonary disease, diabetes mellitus, hypertension).

The vaccine efficacy information is presented in Table 2.

Table 2: Vaccine efficacy - First COVID-19 occurrence from 7 days after Dose 2, by age

subgroup - participants without evidence of infection prior to 7 days after
Dose 2 - evaluable efficacy (7 days) population

First COVID-19 occurrence from 7 days after Dose 2 in participants without evidence of prior
SARS-CoV-2 infection*

COVID-19 mRNA
Vaccine Placebo

Na = 18,198 Na = 18,325
Cases Cases

n1b n1b Vaccine efficacy %
Subgroup Surveillance timec (n2d) Surveillance timec (n2d) (95% CI)e

8 162 95.0
All participants 2.214 (17,411) 2.222 (17,511) (90.0, 97.9)

7 143 95.1 16 to 64 years 1.706 (13,549) 1.710 (13,618) (89.6, 98.1)

1 19 94.7 65 years and older 0.508 (3848) 0.511 (3880) (66.7, 99.9)

1 14 92.9 65 to 74 years 0.406 (3074) 0.406 (3095) (53.1, 99.8) 75 years and 0 5 100.0 older 0.102 (774) 0.106 (785) (-13.1, 100.0)

Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom consistent with COVID-19 [*Case definition: (at least 1 of) 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, diarrhoea or vomiting.] * Participants who had no serological or virological evidence (prior to 7 days after receipt of the last dose) of

past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 not detected by nucleic acid amplification tests (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.

a. N = Number of participants in the specified group. b. n1 = Number of participants meeting the endpoint definition. c. Total surveillance time in 1,000 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. CI not adjusted for multiplicity.

Efficacy of COVID-19 mRNA Vaccine in preventing first COVID-19 occurrence from 7 days after
Dose 2 compared to placebo was 94.6% (95% confidence interval of 89.6% to 97.6%) in participants 16 years of age and older with or without evidence of prior infection with SARS-CoV-2.

Additionally, subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates across genders, ethnic groups, and participants with medical comorbidities associated with high risk of severe COVID-19.

Updated efficacy analyses were performed with additional confirmed COVID-19 cases accrued during blinded placebo-controlled follow-up, representing up to 6 months after Dose 2 in the efficacy population.

The updated vaccine efficacy information is presented in Table 3.

Table 3: Vaccine efficacy - First COVID-19 occurrence from 7 days after Dose 2, by age subgroup - participants without evidence of prior SARS-CoV-2 infection* prior to 7 days after Dose 2 - evaluable efficacy (7 days) population during the placebo-controlled follow-up period

COVID-19 mRNA
Vaccine Placebo

Na=20,998 Na=21,096
Cases Cases

n1b n1b
Surveillance timec Surveillance timec Vaccine efficacy %

Subgroup (n2d) (n2d) (95% CIe) 77 850 91.3

All participantsf 6.247 (20,712) 6.003 (20,713) (89.0, 93.2)

70 710 90.6 16 to 64 years 4.859 (15,519) 4.654 (15,515) (87.9, 92.7)

7 124 94.5 65 years and older 1.233 (4192) 1.202 (4226) (88.3, 97.8)

6 98 94.1 65 to 74 years 0.994 (3350) 0.966 (3379) (86.6, 97.9)

1 26 96.2 75 years and older 0.239 (842) 0.237 (847) (76.9, 99.9)

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 muscle pain; new loss of taste or smell; sore throat; diarrhoea; 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.

a. N = Number of participants in the specified group. b. n1 = Number of participants meeting the endpoint definition. c. Total surveillance time in 1,000 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 95% confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson

method adjusted to the surveillance time. f. Included confirmed cases in participants 12 to 15 years of age: 0 in the COVID-19 mRNA Vaccine group;

16 in the placebo group.

In the updated efficacy analysis, efficacy of COVID-19 mRNA Vaccine in preventing first COVID-19 occurrence from 7 days after Dose 2 compared to placebo was 91.1% (95% CI of 88.8% to 93.0%) in participants in the evaluable efficacy population with or without evidence of prior infection with SARS-CoV-2.

Additionally, the updated efficacy analyses by subgroup showed similar efficacy point estimates across sexes, ethnic groups, geography and participants with medical comorbidities and obesity associated with high risk of severe COVID-19.

Efficacy against severe COVID-19
Updated efficacy analyses of secondary efficacy endpoints supported benefit of the COVID-19 mRNA Vaccine in preventing severe COVID‑19.

As of 13 March 2021, vaccine efficacy against severe COVID-19 is presented only for participants with or without prior SARS-CoV-2 infection (Table 4) 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 COVID-19 mRNA Vaccine and placebo groups.

Table 4: Vaccine efficacy - First severe COVID-19 occurrence in participants with or without prior SARS-CoV-2 infection based on the Food and Drug Administration (FDA)* after Dose 1 or from 7 days after Dose 2 in the placebo-controlled follow-up

COVID-19 mRNA
Vaccine Placebo
Cases Cases

n1a n1a
Surveillance time Surveillance time Vaccine efficacy %

(n2b) (n2b) (95% CIc) 1 30 96.7

After Dose 1d 8.439e (22,505) 8.288e (22,435) (80.3, 99.9) 1 21 95.3

7 days after Dose 2f 6.522g (21,649) 6.404g (21,730) (70.9, 99.9)
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 muscle pain; new loss of taste or smell; sore throat; diarrhoea; vomiting). * Severe illness from COVID-19 as defined by FDA is 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 arterial 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; * Death.

a. n1 = Number of participants meeting the endpoint definition. b. n2 = Number of participants at risk for the endpoint. c. Two-side confidence interval (CI) for vaccine efficacy is derived based on the Clopper and Pearson method

adjusted to the surveillance time. d. Efficacy assessed based on the Dose 1 all available efficacy (modified intention-to-treat) population that

included all randomised participants who received at least 1 dose of study intervention. e. Total surveillance time in 1,000 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 Dose 1 to the end of the surveillance period.

f. Efficacy assessed based on the evaluable efficacy (7 Days) population that included all eligible randomised participants who receive all dose(s) of study intervention as randomised within the predefined window, have no other important protocol deviations as determined by the clinician.

g. Total surveillance time in 1,000 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.

Efficacy and immunogenicity in adolescents 12 to 15 years of age - after 2 doses
In an initial analysis of Study 2 in adolescents 12 to 15 years of age (representing a median follow-up duration of > 2 months after Dose 2) without evidence of prior infection, there were no cases in 1,005 participants who received the vaccine and 16 cases out of 978 who received placebo. The point estimate for efficacy is 100% (95% confidence interval 75.3, 100.0). In participants with or without evidence of prior infection there were 0 cases in the 1,119 who received vaccine and 18 cases in 1,110 participants who received placebo. This also indicates the point estimate for efficacy is 100% (95% confidence interval 78.1, 100.0).

Updated efficacy analyses were performed with additional confirmed COVID-19 cases accrued during blinded placebo-controlled follow-up, representing up to 6 months after Dose 2 in the efficacy population.

In the updated efficacy analysis of Study 2 in adolescents 12 to 15 years of age without evidence of prior infection, there were no cases in 1,057 participants who received the vaccine and 28 cases out of 1,030 who received placebo. The point estimate for efficacy is 100% (95% confidence interval 86.8, 100.0). In participants with or without evidence of prior infection there were 0 cases in the 1,119 who received vaccine and 30 cases in 1,109 participants who received placebo. This also indicates the point estimate for efficacy is 100% (95% confidence interval 87.5, 100.0).

In Study 2, an analysis of SARS-CoV-2 neutralising titres 1 month after Dose 2 was conducted in a randomly selected subset of participants who had no serological or virological evidence of past
SARS-CoV-2 infection up to 1 month after Dose 2, comparing the response in adolescents 12 to 15 years of age (n = 190) to participants 16 to 25 years of age (n = 170).

The ratio of the geometric mean titres (GMT) in the 12 to 15 years of age group to the 16 to 25 years of age group was 1.76, with a 2-sided 95% CI of 1.47 to 2.10. Therefore, the 1.5-fold noninferiority criterion was met as the lower bound of the 2-sided 95% CI for the geometric mean ratio [GMR] was > 0.67.

Immunogenicity in participants 18 years of age and older - after booster dose
Effectiveness of a booster dose of Comirnaty was based on an assessment of 50% neutralizing antibody titres (NT50) against SARS-CoV-2 (USA_WA1/2020) in Study 2. In this study, the booster dose was administered 5 to 8 months (median 7 months) after the second dose. In Study 2, analyses of
NT50 1 month after the booster dose compared to 1 month after the primary series in individuals 18 through 55 years of age who had no serological or virological evidence of past SARS-CoV-2 infection up to 1 month after the booster vaccination demonstrated noninferiority for both geometric mean ratio (GMR) and difference in seroresponse rates. Seroresponse for a participant was defined as achieving a ≥ 4-fold rise in NT50 from baseline (before primary series). These analyses are summarized in Table 5.

Table 5: SARS-CoV-2 neutralization assay - NT50 (titre)† (SARS-CoV-2 USA_WA1/2020) -

GMT and seroresponse rate comparison of 1 month after booster dose to 1 month after primary series - participants 18 through 55 years of age without evidence of infection up to 1 month after booster dose* - booster dose evaluable immunogenicity population±

1 month after booster dose/- 1 month after Met

1 month after 1 month after primary noninferiority booster dose primary series series objective

N (95% CI) (95% CI) (97.5% CI) (Y/N)
Geometric mean 50% neutralizing 2466.0b 750.6b 3.29c titre (GMTb) 212a (2202.6, 2760.8) (656.2, 858.6) (2.77, 3.90) Yd
Seroresponse rate 199f 196f (%) for 50% 99.5% 98.0% 1.5%g neutralizing titre† 200e (97.2%, 100.0%) (95.0%, 99.5%) (-0.7%, 3.7%h) Yi
Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titre;
LLOQ = lower limit of quantitation; N-binding = SARS-CoV-2 nucleoprotein-binding; NAAT = nucleic acid amplification test; NT50 = 50% neutralizing titre; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; Y/N = yes/no. † SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralization

Assay. The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virus neutralization is read on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized.

* Participants who had no serological or virological evidence (up to 1 month after receipt of a booster dose of Comirnaty) of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative and
SARS-CoV-2 not detected by NAAT [nasal swab]) and had a negative NAAT (nasal swab) at any unscheduled visit up to 1 month after the booster dose were included in the analysis.

± All eligible participants who had received 2 doses of Comirnaty as initially randomized, with Dose 2 received within the predefined window (within 19 to 42 days after Dose 1), received a booster dose of
Comirnaty, had at least 1 valid and determinate immunogenicity result after booster dose from a blood collection within an appropriate window (within 28 to 42 days after the booster dose), and had no other important protocol deviations as determined by the clinician.

a. n = Number of participants with valid and determinate assay results at both sampling time points within specified window.

b. GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titres and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ.

c. GMRs and 2-sided 97.5% CIs were calculated by exponentiating the mean differences in the logarithms of the assay and the corresponding CIs (based on the Student t distribution).

d. Noninferiority is declared if the lower bound of the 2-sided 97.5% CI for the GMR is > 0.67 and the point estimate of the GMR is ≥ 0.80.

e. n = Number of participants with valid and determinate assay results for the specified assay at baseline, 1 month after Dose 2 and 1 month after the booster dose within specified window. These values are the denominators for the percentage calculations.

f. Number of participants with seroresponse for the given assay at the given dose/sampling time point. Exact 2-sided CI based on the Clopper and Pearson method.

g. Difference in proportions, expressed as a percentage (1 month after booster dose - 1 month after Dose 2). h. Adjusted Wald 2-sided CI for the difference in proportions, expressed as a percentage. i. Noninferiority is declared if the lower bound of the 2-sided 97.5% CI for the percentage difference is

> -10%.

Relative vaccine efficacy in participants 16 years of age and older - after booster dose
An interim efficacy analysis of Study 4, a placebo-controlled booster study performed in approximately 10,000 participants 16 years of age and older who were recruited from Study 2, evaluated confirmed COVID-19 cases accrued from at least 7 days after booster vaccination up to a data cut-off date of 5 October 2021, which represents a median of 2.5 months post-booster follow-up.
The booster dose was administered 5 to 13 months (median 11 months) after the second dose. Vaccine efficacy of the Comirnaty booster dose after the primary series relative to the placebo booster group who only received the primary series dose was assessed.

The relative vaccine efficacy information for participants 16 years of age and older without prior evidence of SARS-CoV-2 infection is presented in Table 6. Relative vaccine efficacy in participants with or without evidence of prior SARS-CoV-2 infection was 94.6% (95% confidence interval of 88.5% to 97.9%), similar to that seen in those participants without evidence of prior infection. Primary
COVID-19 cases observed from 7 days after booster vaccination were 7 primary cases in the Comirnaty group, and 124 primary cases in the placebo group.

Table 6: Vaccine efficacy - First COVID-19 occurrence from 7 days after booster

vaccination - participants 16 years of age and older without evidence of infection - evaluable efficacy population

First COVID-19 occurrence from 7 days after booster dose in participants without evidence of prior SARS-CoV-2 infection*

Comirnaty Placebo
Na=4695 Na=4671

Cases Cases Relative Vaccine n1b n1b Efficacye %

Surveillance Timec (n2d) Surveillance Timec (n2d) (95% CIf)
First COVID-19 occurrence from 7 days after booster 6 123 95.3 vaccination 0.823 (4659) 0.792 (4614) (89.5, 98.3)

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 muscle pain; new loss of taste or smell; sore throat; diarrhoea; vomiting).

* Participants who had no serological or virological evidence (prior to 7 days after receipt of the booster vaccination) 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 Visit 1, and had a negative NAAT [nasal swab] at any unscheduled visit prior to 7 days after booster vaccination) were included in the analysis.

a. N = Number of participants in the specified group. b. n1 = Number of participants meeting the endpoint definition. c. Total surveillance time in 1,000 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 the booster vaccination to the end of the surveillance period.

d. n2 = Number of participants at risk for the endpoint. e. Relative vaccine efficacy of the Comirnaty booster group relative to the placebo group (non-booster). f. Two-sided confidence interval (CI) for relative vaccine efficacy is derived based on the Clopper and Pearson

method adjusted for surveillance time.

Immunogenicity of a booster dose following primary vaccination with another authorised COVID-19 vaccine
Effectiveness of a Comirnaty booster dose (30 mcg) in individuals who completed primary vaccination with another authorised COVID-19 vaccine (heterologous booster dose) is inferred from immunogenicity data from an independent National Institutes of Health (NIH) study phase 1/2 open-label clinical trial (NCT04889209) conducted in the United States. In this study, adults (range 19 to 80 years of age) who had completed primary vaccination with Moderna 100 mcg 2-dose series (N = 51, mean age 54±17), Janssen single dose (N = 53, mean age 48±14), or Comirnaty 30 mcg 2-dose series (N = 50, mean age 50±18) at least 12 weeks prior to enrolment and who reported no history of SARS-CoV-2 infection received a booster dose of Comirnaty (30 mcg). The boost with Comirnaty induced a 36, 12, and 20 GMR-fold rise in neutralising titres following the Janssen, Moderna, and Comirnaty primary doses, respectively.

Heterologous boosting with Comirnaty was also evaluated in the CoV-BOOST study (EudraCT 2021-002175-19), a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19, in which 107 adult participants (median age 71 years of age, interquartile range 54 to 77 years of age) were randomised at least 70 days post 2 doses of AstraZeneca COVID-19 Vaccine. After the AstraZeneca COVID‑19 Vaccine primary series, pseudovirus (wild-type), neutralising antibody NT50 GMR-fold change increased 21.6-fold with heterologous Comirnaty booster (n = 95).

Paediatric population
The European Medicines Agency has deferred the obligation to submit the results of studies with
Comirnaty in the paediatric population in prevention of COVID-19 (see section 4.2 for information on paediatric use).

This medicinal product has been authorised under a so-called ‘conditional approval’ scheme. This means that further evidence on this medicinal product is awaited. The European Medicines Agency will review new information on this medicinal product at least every year and this SmPC will be updated as necessary.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of repeat dose toxicity and reproductive and developmental toxicity.

General toxicity
Rats intramuscularly administered Comirnaty (receiving 3 full human doses once weekly, generating relatively higher levels in rats due to body weight differences) demonstrated some injection site oedema and erythema and increases in white blood cells (including basophils and eosinophils) consistent with an inflammatory response as well as vacuolation of portal hepatocytes without evidence of liver injury. All effects were reversible.

Genotoxicity/Carcinogenicity
Neither genotoxicity nor carcinogenicity studies were performed. The components of the vaccine (lipids and mRNA) are not expected to have genotoxic potential.

Reproductive toxicity
Reproductive and developmental toxicity were investigated in rats in a combined fertility and developmental toxicity study where female rats were intramuscularly administered Comirnaty prior to mating and during gestation (receiving 4 full human doses that generate relatively higher levels in rat due to body weight differences, spanning between pre-mating day 21 and gestational day 20).
SARS-CoV-2 neutralizing antibody responses were present in maternal animals from prior to mating to the end of the study on postnatal day 21 as well as in foetuses and offspring. There were no vaccine-related effects on female fertility, pregnancy, or embryo-foetal or offspring development. No Comirnaty data are available on vaccine placental transfer or excretion in milk.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate) (ALC-0315) 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide (ALC-0159) 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC)
Cholesterol
Potassium chloride
Potassium dihydrogen phosphate
Sodium chloride
Disodium phosphate dihydrate
Sucrose
Water for injections
Sodium hydroxide (for pH adjustment)
Hydrochloric acid (for pH adjustment)

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3 Shelf life

Unopened vial
Frozen vial 12 months when stored at -90 °C to -60 °C.
Within the 12-month shelf life unopened vials may be stored and transported at -25 °C to -15 °C for a single period of up to 2 weeks and can be returned to -90 °C to -60 °C.

When stored frozen at -90 °C to -60 °C, 195-vial packs of the vaccine can be thawed at 2 °C to 8 °C for 3 hours or individual vials can be thawed at room temperature (up to 30 °C) for 30 minutes.

Thawed vial 1 month at 2 °C to 8 °C within the 12-month shelf life. Within the 1-month shelf life at 2 °C to 8 °C, up to 12 hours may be used for transportation. Prior to use, the unopened vial can be stored for up to 2 hours at temperatures up to 30 °C. Thawed vials can be handled in room light conditions.

Once thawed, the vaccine should not be re-frozen.

Handling of temperature excursions once removed from the freezer
Stability data indicate that the unopened vial is stable for up to: * 24 hours when stored at temperatures from -3 °C to 2 °C * a total of 4 hours when stored at temperatures from 8 °C to 30 °C; this includes the 2 hours at up

to 30 °C detailed above

This information is intended to guide healthcare professionals only in case of temporary temperature excursion.

Transfers of frozen vials stored at ultra-low temperature (< -60 °C) * Closed-lid vial trays containing 195 vials removed from ultra-low temperature frozen storage

(< -60 °C) may be at temperatures up to 25 °C for up to 5 minutes. * Open-lid vial trays, or vial trays containing less than 195 vials, removed from ultra-low

temperature frozen storage (< -60 °C) may be at temperatures up to 25 °C for up to 3 minutes. * After vial trays are returned to frozen storage following temperature exposure up to 25 °C, they

must remain in frozen storage for at least 2 hours before they can be removed again.

Transfers of frozen vials stored at -25 °C to -15 °C * Closed-lid vial trays containing 195 vials removed from frozen storage (-25 °C to -15 °C) may

be at temperatures up to 25 °C for up to 3 minutes. * Open-lid vial trays, or vial trays containing less than 195 vials, removed from frozen storage

(-25 °C to -15 °C) may be at temperatures up to 25 °C for up to 1 minute.

Once a vial is removed from the vial tray, it should be thawed for use.

Diluted medicinal product
Chemical and physical in-use stability, including during transportation, has been demonstrated for 6 hours at 2 ºC to 30 ºC after dilution in sodium chloride 9 mg/mL (0.9%) solution for injection. From a microbiological point of view, unless the method of dilution precludes the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4 Special precautions for storage

Store in a freezer at -90 °C to -60 °C. Store in the original package in order to protect from light.
During storage, minimise exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.

For storage conditions after thawing and dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

0.45 mL concentrate in a 2 mL clear multidose vial (type I glass) with a stopper (synthetic bromobutyl rubber) and a purple flip-off plastic cap with aluminium seal. Each vial contains 6 doses, see section 6.6.

Pack size: 195 vials

6.6 Special precautions for disposal and other handling

Handling instructions
Comirnaty should be prepared by a healthcare professional using aseptic technique to ensure the sterility of the prepared dispersion.

VIAL VERIFICATION OF COMIRNATY 30 MICROGRAMS/DOSE CONCENTRATE
FOR DISPERSION FOR INJECTION (12 YEARS AND OLDER)

* Verify that the vial has a purple Purple cap plastic cap.

* If the vial has a grey plastic cap, please make reference to the
Summary of Product Characteristics for Comirnaty 30 micrograms/dose dispersion for injection.

* If the vial has an orange plastic cap,
After Dilution please make reference to the

Summary of Product Characteristics for Comirnaty 10 micrograms/dose concentrate for dispersion for injection.

THAWING PRIOR TO DILUTION OF COMIRNATY 30 MICROGRAMS/DOSE
CONCENTRATE FOR DISPERSION FOR INJECTION (12 YEARS AND OLDER) * The multidose vial is stored frozen

and must be thawed prior to dilution.
Frozen vials should be transferred to an environment of 2 °C to 8 °C to

No m ore than thaw; a 195 vial pack may take 2 hours at room 3 hours to thaw. Alternatively, frozen

temperature vials may also be thawed for (up to 30 °C). 30 minutes at temperatures up to

30 °C for immediate use. * The unopened vial can be stored for

up to 1 month at 2 °C to 8 °C; not exceeding the printed expiry date

(EXP). Within the 1-month shelf life at 2 °C to 8 °C, up to 12 hours may be used for transportation.

* Allow the thawed vial to come to room temperature. Prior to use, the unopened vial can be stored for up to 2 hours at temperatures up to 30 °C.
Thawed vials can be handled in room light conditions.

* Gently invert the vial 10 times prior to dilution. Do not shake.

* Prior to dilution, the thawed dispersion may contain white to off- white opaque amorphous particles.

DILUTION OF COMIRNATY 30 MICROGRAMS/DOSE CONCENTRATE FOR
DISPERSION FOR INJECTION (12 YEARS AND OLDER) * The thawed vaccine must be diluted

in its original vial with 1.8 mL of sodium chloride 9 mg/mL (0.9%) solution for injection, using a 21 gauge or narrower needle and aseptic techniques.

1.8 mL of sodium chloride 9 mg/mL (0.9%) solution for injection.

* Equalise vial pressure before

removing the needle from the vial stopper by withdrawing 1.8 mL air into the empty diluent syringe.

Pull back plunger to 1.8 mL to remove air from vial.

* Gently invert the diluted dispersion 10 times. Do not shake.

* The diluted vaccine should present as an off-white dispersion with no particulates visible. Do not use the diluted vaccine if particulates or discolouration are present.

Gently × 10

* The diluted vials should be marked with the appropriate date and time.

* After dilution, store at 2 ºC to 30 ºC and use within 6 hours, including any transportation time.

* Do not freeze or shake the diluted dispersion. If refrigerated, allow the diluted dispersion to come to room temperature prior to use.

Discard Time

Record appropriate date and time. Use within 6 hours after dilution.

PREPARATION OF INDIVIDUAL 0.3 mL DOSES OF COMIRNATY 30 MICROGRAMS/DOSE CONCENTRATE FOR DISPERSION FOR INJECTION (12 YEARS AND OLDER)

* After dilution, the vial contains 2.25 mL from which 6 doses of 0.3 mL can be extracted.

* Using aseptic technique, cleanse the vial stopper with a single-use antiseptic swab.

* Withdraw 0.3 mL of Comirnaty.

Low dead-volume syringes and/or needles should be used in order to extract 6 doses from a single vial.
The low dead-volume syringe and needle combination should have a dead volume of no more than 35 microlitres.

If standard syringes and needles are used, there may not be sufficient

0.3 mL diluted vaccine volume to extract a sixth dose from a single vial.

* 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.

* Discard any unused vaccine within 6 hours after dilution.

Disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

BioNTech Manufacturing GmbH
An der Goldgrube 12 55131 Mainz
Germany
Phone: +49 6131 9084-0
Fax: +49 6131 9084-2121 service@biontech.de

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/20/1528/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 21 December 2020
Date of latest renewal: 03 November 2021

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.