COMIRNATY 30 MICROGRAMS / DOSE DISPERSION FOR INJECTION COVID-19 MRNA VACCINE (NUCLEOSIDE MODIFIED) - summary of medicine characteristics

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions

1. NAME OF THE MEDICINAL PRODUCT

Comirnaty 30 micrograms/dose dispersion for injection

COVID-19 mRNA Vaccine (nucleoside modified)

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

This is a multidose vial. Do not dilute prior to use.

One vial (2.25 mL) contains 6 doses of 0.3 mL, 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.

Dispersion for injection.

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 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

Individuals 12 years of age and older

Comirnaty is administered intramuscularly 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).

A booster dose (third dose) of Comirnaty may be administered intramuscularly at least 6 months after the second dose in individuals 18 years of age and older. The decision when and for whom to implement a third dose of Comirnaty should be made based on available vaccine effectiveness data, taking into account limited safety data (see sections 4.4 and 5.1).

The interchangeability of Comirnaty with COVID-19 vaccines from other manufacturers to complete the primary vaccination course or the booster dose (third dose) has not been established. Individuals who have received 1 dose of Comirnaty should receive a second dose of Comirnaty to complete the primary vaccination course and for any additional doses. Doses of Comirnaty 30 micrograms/dose concentrate for dispersion for injection after dilution and Comirnaty 30 micrograms/dose dispersion for injection are considered interchangeable.

Severely immunocompromised aged 12 years and older

A third dose may be given at least 28 days after the second dose to individuals who are severely immunocompromised (see section 4.4).

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.

Elderly population

No dosage adjustment is required in elderly individuals > 65 years of age. The safety and immunogenicity of a booster dose (third dose) of Comirnaty in individuals 65 years of age and older is based on safety and immunogenicity data in adults 18 to 55 years of age.

Method of administration

Comirnaty 30 micrograms/dose dispersion for injection should be administered intramuscularly (see section 6.6). Do not dilute prior to use.

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. A second dose of the vaccine should not be given to those who have experienced anaphylaxis to the first 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, tingling sensations 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.

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

The safety of Comirnaty was evaluated in participants 12 years of age and older in 2 clinical studies that included 23,205 participants (comprised of 22,074 participants 16 years of age and older and 1,131 adolescents 12 to 15 years of age) that have received at least one dose of Comirnaty.

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.

Additionally, 306 existing Phase 3 participants 18 to 55 years of age received a booster dose (third dose) of Comirnaty approximately 6 months after the second dose. The overall safety profile for the booster dose (third dose) was similar to that seen after 2 doses.

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 Study 2, based on data up to the cut-off date of 13 March 2021, 2,260 adolescents (1,131 Comirnaty and 1,129 placebo) were 12 to 15 years of age. Of these, 1,308 adolescents (660 Comirnaty and 648 placebo) have been followed for at least 2 months after the second dose of Comirnaty. The safety evaluation in Study 2 is ongoing.

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 18 years of age and older – after booster dose (third 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 (third dose) of Comirnaty approximately 6 months (range of 4.8 to 8.0 months) after receiving Dose 2.

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%).

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 experienced individuals 12 years of age and older

a. A higher frequency of lymphadenopathy (5.2% vs 0.4%) was observed in participants receiving a booster dose (third dose) 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 compare 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 If you are concerned about an adverse event, it should be reported on a Yellow card. Reporting forms and information can be found at https://coronavirus-yellowcard.mhra.gov.uk/ or search for MHRA Yellow Card in the Google Play or Apple App Store. When reporting please include the vaccine brand and batch/Lot number if available.

Alternatively, adverse events of concern in association with Comirnaty can be reported to Pfizer Medical Information on 01304 616161 or via www.pfizersafetyreporting.com.

Please do not report the same adverse event(s) to both systems as all reports will be shared between Pfizer and MHRA (in an anonymized form) and dual reporting will create unnecessary duplicates.

4.9 Overdose

5   PHARMACOLOGICAL PROPERTIES

5.1   Pharmacodynamic properties

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

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

Trometamol

Trometamol hydrochloride

Sucrose

Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

Unopened vial

Frozen vial

9 months when stored at –90 °C to –60 °C.

The vaccine will be received frozen at –90 °C to –60 °C. Frozen vaccine can be stored either at –90 °C to –60 °C or 2 °C to 8 °C upon receipt.

When stored frozen at –90 °C to –60 °C, 10-vial packs of the vaccine can be thawed at 2 °C to 8 °C for 6 hours or individual vials can be stored at room temperature (up to 30 °C) for 30 minutes.

Thawed vial

10 weeks storage and transportation at 2 °C to 8 °C within the 9-month shelf life.

Upon moving the product to 2 °C to 8 °C storage, the updated expiry date must be written on the outer carton and the vaccine should be used or discarded by the updated expiry date. The original expiry date should be crossed out.

If the vaccine is received at 2 °C to 8 °C it should be stored at 2 °C to

8 °C. Check that the expiry date on the outer carton has been updated to reflect the refrigerated expiry date and that the original expiry date has been crossed out.

Prior to use, the unopened vials can be stored for up to 12 hours at temperatures between 8 °C and 30 °C.

Thawed vials can be handled in room light conditions.

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

Handling of temperature excursions during refrigerated storage

Stability data indicate that the unopened vial is stable for up to 10 weeks when stored at temperatures from –2 °C to 2 °C, within the 10-week storage period between 2 °C and 8 °C.

Stability data indicate the vial can be stored for up to 24 hours at temperatures of 8 °C to 30 °C, including up to 12 hours following first puncture.

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

Opened vial

Chemical and physical in-use stability has been demonstrated for12 hours at 2 °C to 30 °C. From a microbiological point of view, unless the method of opening precludes the risks 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 first opening, see section 6.3.

6.5 Nature and contents of container

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

Pack sizes: 195 vials or 10 vials

Not all pack sizes may be marketed.

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.

DOSE VERIFICATION OF COMIRNATY 30 MICROGRAMS/DOSE

DISPERSION FOR INJECTION (12 YEARS AND OLDER)

Verify that the vial has a grey plastic cap.

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

If the vial has an orange plastic cap, please make reference to the Summary of Product Characteristics for Comirnaty 10 micrograms/dose concentrate for dispersion for

__injection.

HANDLING PRIOR TO USE OF COMIRNATY 30

MICROGRAMS/DOSE DISPERSION FOR INJECTION (12 YEARS AND OLDER)

If the multidose vial is stored

frozen it must be thawed prior to use. Frozen vials should be _     _ transferred to an environment

Store for up to f 2 °c to 8 °c to thaw; a 10 weeks at 2 Cio vial pack may take 6 hours to 8 C, updateto thaw. Ensure vials are expiry on cartoiCompletely thawed prior to

use.

Upon moving vials to 2 °C to

8 °C storage, update the expiry date on the carton.

Unopened vials can be stored for up to 10 weeks at 2 °C to 8 °C within the 9-month shelf life.

Alternatively, individual frozen vials may be thawed for 30 minutes at temperatures up to 30 °C.

Prior to use, the unopened vial can be stored for up to 12 hours at temperatures up to 30 °C. Thawed vials can be handled in room light conditions.

Gently x 10

Gently mix by inverting vials 10 times prior to use. Do not shake.

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

After mixing, the vaccine should present as a white to off-white dispersion with no particulates visible. Do not use the vaccine if particulates or discolouration are present.

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

0.3 mL vaccine

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 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 12 hours after first puncture. Record the appropriate date/time on the vial.

Disposal

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