This is a multidose vial 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.

1 dose (0.3 mL) contains 30 micrograms of COVID-19 mRNA Vaccine (embedded in lipid nanoparticles).

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.

4.1 Therapeutic indications

Comirnaty is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 virus, in individuals 16 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 16 years of age and older
Comirnaty is administered intramuscularly after dilution as a 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).

There are no data available on the interchangeability of Comirnaty with other COVID-19 vaccines to complete the vaccination course. Individuals who have received 1 dose of Comirnaty should receive a second dose of Comirnaty to complete the vaccination course. 

Paediatric population
The safety and efficacy of Comirnaty in children and adolescents aged less than 16 years of age have not yet been established. Limited data are available.

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

Method of administration

Comirnaty should be administered intramuscularly after dilution (see section 6.6).

After dilution, vials of Comirnaty contain six doses of 0.3 mL of vaccine. In order to extract six 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.

Anxiety-related reactions

Anxiety-related reactions, including vasovagal reactions (syncope), hyperventilation or stress‐related reactions may occur in association with vaccination as a psychogenic response to the needle injection. 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, safety and immunogenicity of the vaccine has not been assessed in immunocompromised individuals, including those receiving immunosuppressant therapy. The efficacy of Comirnaty may be lower in immunosuppressed individuals.

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

There is limited experience with use of Comirnaty in pregnant women. 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). Administration of Comirnaty in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and foetus.

Breast-feeding

It is unknown whether Comirnaty is excreted in human milk. 

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 16 years of age and older in 2 clinical studies that included 21,744 participants that have received at least one dose of Comirnaty. 

In Study 2, a total of 21,720 participants 16 years of age or older received at least 1 dose of Comirnaty and a total of 21,728 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, a total of 19,067 (9,531 Comirnaty and 9,536 placebo) participants 16 years of age or older were evaluated for safety for at least 2 months after the second dose of Comirnaty. This included a total of 10,727 (5,350 Comirnaty and 5,377 placebo) participants 16 to 55 years of age and a total of 8,340 (4,181 Comirnaty and 4,159 placebo) participants 56 years and older.

The most frequent adverse reactions in participants 16 years of age and older were injection site pain (> 80%), fatigue (> 60%), headache (> 50%), myalgia and 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.

Tabulated list of adverse reactions from clinical studies and post authorisation experience
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).

The safety profile in 545 subjects receiving Comirnaty, that were seropositive for SARS-CoV-2 at baseline, was similar to that seen in the general population.

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 www.signalement-sante.gouv.fr 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.

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

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
6 months at -90 °C to -60 °C
Within the 6 months 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.

Thawed vial
5 days at 2 °C to 8 °C
Within the 5 days shelf-life at 2 °C to 8 °C, up to 12 hours may be used for transportation.
Prior to use, the unopened vaccine can be stored for up to 2 hours at temperatures up to 30 °C.

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, 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.
Thawed vials can be handled in room light conditions.

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

6.5 Nature and contents of container

2 mL clear multidose vial (type I glass) with a stopper (synthetic bromobutyl rubber) and a 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.

THAWING PRIOR TO DILUTION
	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 thaw; a 195 vial pack may take 3 hours to thaw. Alternatively, frozen vials may also be thawed for 30 minutes at temperatures up to 30 °C for immediate use. The unopened vial can be stored for up to 5 days at 2 °C to 8 °C. Within the 5 days 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 and gently invert it 10 times prior to dilution. Do not shake. Prior to dilution, the thawed dispersion may contain white to off-white opaque amorphous particles.
DILUTION
	The thawed vaccine must be diluted in its original vial with 1.8 mL sodium chloride 9 mg/mL (0.9%) solution for injection, using a 21 gauge or narrower needle and aseptic techniques.
	Equalise vial pressure before removing the needle from the vial stopper by withdrawing 1.8 mL air into the empty diluent syringe.
	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.
	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.
PREPARATION OF INDIVIDUAL 0.3 mL DOSES OF COMIRNATY
	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 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.