ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

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 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

Spikevax dispersion for injection

COVID-19 mRNA Vaccine (nucleoside modified)

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

This is a multidose vial that contains 10 doses of 0.5 mL each or a maximum of 20 doses of 0.25 mL
each.

One dose (0.5 mL) contains 100 micrograms of messenger RNA (mRNA) (embedded in SM-102 lipid
nanoparticles).

One dose (0.25 mL) contains 50 micrograms of messenger RNA (mRNA) (embedded in SM-102 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.

3. PHARMACEUTICAL FORM

Dispersion for injection

White to off white dispersion (pH: 7.0 – 8.0).

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Spikevax is indicated for active immunisation to prevent COVID-19 caused by SARS-CoV-2 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 series
Individuals 12 years of age and older
Spikevax is administered as a course of 2 (two) 100 microgram doses (0.5 mL each). It is
recommended to administer the second dose 28 days after the first dose (see sections 4.4 and 5.1).

Booster dose
Individuals 18 years of age and older
A booster dose (0.25 mL, containing 50 micrograms mRNA, which is half of the primary dose) of
Spikevax may be administered intramuscularly at least 6 months after the second dose in individuals

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18 years of age and older. The decision when and for whom to implement a third dose of Spikevax
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 Spikevax with other COVID-19 vaccines to complete the primary
vaccination course or the booster dose (0.25 mL, 50 micrograms) has not been established. Individuals
who have received one dose of Spikevax (0.5 mL, 100 micrograms) should receive a second dose of
Spikevax (0.5 mL, 100 micrograms) to complete the primary vaccination course.

Severely immunocompromised aged 12 years and older

A third dose (0.5 mL, 100 micrograms) may be given at least 28 days after the second dose to
individuals who are severely immunocompromised (see section 4.4).

Paediatric population
The safety and efficacy of Spikevax in children and adolescents less than 12 years of age have not yet
been established. No data are available.

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

Method of administration

The vaccine should be administered intramuscularly. The preferred site is the deltoid muscle of the
upper arm.

Do not administer this 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.

Hypersensitivity and anaphylaxis

Anaphylaxis has been reported in individuals who have received Spikevax. Appropriate medical
treatment and supervision should always be readily available in case of an anaphylactic reaction
following administration of the vaccine.

Close observation for at least 15 minutes is recommended following vaccination. The second dose of
the vaccine should not be given to those who have experienced anaphylaxis to the first dose of
Spikevax.

Myocarditis and pericarditis

There is an increased risk for myocarditis and pericarditis following vaccination with Spikevax.
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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 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 (0.5 mL, 100 micrograms) or booster dose (0.25 mL,
50 micrograms) of Spikevax has not yet been characterised.

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

The recommendation to consider a third dose (0.5 mL) in severely immunocompromised individuals
(see section 4.2) is based on limited serological evidence with patients who are immunocompromised
after solid organ transplantation.

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

Individuals may not be fully protected until 14 days after their second dose. As with all vaccines,
vaccination with Spikevax may not protect all vaccine recipients.

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Excipients with known effect

Sodium
This vaccine contains less than 1 mmol sodium (23 mg) per 0.5 mL 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 Spikevax with other vaccines has not been studied.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is limited experience with use of Spikevax 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 Spikevax 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 Spikevax 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

Spikevax 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 the safety profile

Participants 18 years of age and older

The safety of Spikevax was evaluated in an ongoing Phase 3 randomised, placebo-controlled,

observer-blind clinical study conducted in the United States involving 30,351 participants 18 years of
age and older who received at least one dose of Spikevax (n=15,185) or placebo (n=15,166)
(NCT04470427). At the time of vaccination, the mean age of the population was 52 years (range 18-
95); 22,831 (75.2%) of participants were 18 to 64 years of age and 7,520 (24.8%) of participants were
65 years of age and older.

The most frequently reported adverse reactions were pain at the injection site (92%), fatigue (70%),
headache (64.7%), myalgia (61.5%), arthralgia (46.4%), chills (45.4%), nausea/vomiting (23%),
axillary swelling/tenderness (19.8%), fever (15.5%), injection site swelling (14.7%) and redness
(10%). Adverse reactions 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.

Overall, there was a higher incidence of some adverse reactions in younger age groups: the incidence
of axillary swelling/tenderness, fatigue, headache, myalgia, arthralgia, chills, nausea/vomiting
and fever was higher in adults aged 18 to < 65 years than in those aged 65 years and above.
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Local and systemic adverse reactions were more frequently reported after Dose 2 than after Dose 1.

Adolescents 12 through 17 years of age

Safety data for Spikevax in adolescents were collected in an ongoing Phase 2/3 randomised,
placebo-controlled, observer-blind clinical study conducted in the United States involving
3,726 participants 12 through 17 years of age who received at least one dose of Spikevax (n=2,486) or
placebo (n=1,240) (NCT04649151). Demographic characteristics were similar among participants
who received Spikevax and those who received placebo.

The most frequent adverse reactions in adolescents 12 to 17 years of age were injection site pain
(97%), headache (78%), fatigue (75%), myalgia (54%), chills (49%), axillary swelling/tenderness
(35%), arthralgia (35%), nausea/vomiting (29%), injection site swelling (28%), injection site erythema
(26%), and fever (14%).

Participants 18 years of age and older (booster dose)

The safety, reactogenicity, and immunogenicity of a booster dose of Spikevax are evaluated in an
ongoing Phase 2, randomised, observer-blind, placebo-controlled, dose-confirmation study in
participants 18 years of age and older (NCT04405076). In this study, 198 participants received two
doses (0.5 mL, 100 micrograms 1 month apart) of the Spikevax vaccine primary series. In an open-
label phase of this study, 167 of those participants received a single booster dose (0.25 mL,
50 micrograms) at least 6 months after receiving the second dose of the primary series. The solicited
adverse reaction profile for the booster dose (0.25 mL, 50 micrograms) was similar to that after the
second dose in the primary series.

Tabulated list of adverse reactions from clinical studies and post authorisation experience in
individuals 12 years of age and older
The safety profile presented below is based on data generated in a placebo- controlled clinical
study on 30,351 adults ≥ 18 years of age, another placebo-controlled clinical study with 3,726
participants 12 through 17 years of age, and post-marketing experience.

Adverse reactions reported are listed according to the following frequency convention:

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)

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness
(Table 1).

Table 1: Adverse reactions from Spikevax clinical trials and post authorisation experience in
individuals 12 years of age and older

MedDRA system organ class Frequency Adverse reaction(s)

Blood and lymphatic system Very common Lymphadenopathy*
disorders
Immune system disorders Not known Anaphylaxis
Hypersensitivity
Nervous system disorders Very common Headache
Uncommon Dizziness
Rare Acute peripheral facial
paralysis**

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 Hypoaesthesia
Cardiac disorders Very rare Myocarditis
Pericarditis
Gastrointestinal disorders Very common Nausea/vomiting
Common Diarrhoea
Skin and subcutaneous tissue Common Rash
disorders Not known Erythema multiforme
Musculoskeletal and connective Very common Myalgia
tissue disorders Arthralgia
General disorders Very common Injection site pain
and administration site conditions Fatigue
Chills
Pyrexia
Injection site swelling
Common Injection site erythema
Injection site urticaria
Injection site rash
Delayed injection site
reaction***
Uncommon Injection site pruritus
Rare Facial swelling****
*Lymphadenopathy was captured as axillary lymphadenopathy on the same side as the injection site. Other lymph nodes
(e.g., cervical, supraclavicular) were affected in some cases.
**Throughout the safety follow-up period, acute peripheral facial paralysis (or palsy) was reported by three participants in the
Spikevax group and one participant in the placebo group. Onset in the vaccine group participants was 22 days, 28 days,
and 32 days after Dose 2.
***Median time to onset was 9 days after the first injection, and 11 days after the second injection. Median duration was
4 days after the first injection, and 4 days after the second injection.
****There were two serious adverse events of facial swelling in vaccine recipients with a history of injection of
dermatological fillers. The onset of swelling was reported on Day 1 and Day 3, respectively, relative to day of vaccination.

The reactogenicity and safety profile in 343 subjects receiving Spikevax, that were seropositive for
SARS-CoV-2 at baseline, was comparable to that in subjects seronegative for SARS-CoV-2 at
baseline.

Description of selected adverse reactions

Myocarditis

The increased risk of myocarditis after vaccination with Spikevax 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 Spikevax. One study showed that in a period of 7 days after the
second dose, there were about 1.316 (95% CI 1.299 – 1.333) extra cases of myocarditis in 12 to
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 1.88 (95% CI 0.956 – 2.804) extra cases of myocarditis in 16 to
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

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No case of overdose has been reported.

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

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

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

Mechanism of action

Spikevax contains mRNA encapsulated in lipid nanoparticles. The mRNA encodes for the full-length
SARS-CoV-2 spike protein modified with 2 proline substitutions within the heptad repeat 1 domain
(S-2P) to stabilise the spike protein into a prefusion conformation. After intramuscular injection, cells
at the injection site and the draining lymph nodes take up the lipid nanoparticle, effectively delivering
the mRNA sequence into cells for translation into viral protein. The delivered mRNA does not enter
the cellular nucleus or interact with the genome, is non-replicating, and is expressed transiently mainly
by dendritic cells and subcapsular sinus macrophages. The expressed, membrane-bound spike protein
of SARS-CoV-2 is then recognised by immune cells as a foreign antigen. This elicits both T-cell and
B-cell responses to generate neutralising antibodies, which may contribute to protection against
COVID-19.

Clinical efficacy in adults

The adult study was a randomised, placebo-controlled, observer-blind Phase 3 clinical study
(NCT04470427) that excluded individuals who were immunocompromised or had received
immunosuppressants within 6 months, as well as participants who were pregnant, or with a known
history of SARS-CoV-2 infection. Participants with stable HIV disease were not excluded. Influenza
vaccines could be administered 14 days before or 14 days after any dose of Spikevax. Participants
were also required to observe a minimum interval of 3 months after receipt of blood/plasma products
or immunoglobulins prior to the study in order to receive either placebo or Spikevax.

A total of 30,351 subjects were followed for a median of 92 days (range: 1-122) for the development
of COVID-19 disease.

The primary efficacy analysis population (referred to as the Per Protocol Set or PPS), included
28,207 subjects who received either Spikevax (n=14,134) or placebo (n=14,073) and had a negative
baseline SARS-CoV-2 status. The PPS study population included 47.4% female, 52.6% male, 79.5%
White, 9.7% African American, 4.6% Asian, and 6.2% other. 19.7% of participants identified as
Hispanic or Latino. The median age of subjects was 53 years (range 18-94). A dosing window of –7 to
+14 days for administration of the second dose (scheduled at day 29) was allowed for inclusion in the
PPS. 98% of vaccine recipients received the second dose 25 days to 35 days after dose 1
(corresponding to -3 to +7 days around the interval of 28 days).

COVID-19 cases were confirmed by Reverse Transcriptase Polymerase Chain Reaction (RT PCR) and
by a Clinical Adjudication Committee. Vaccine efficacy overall and by key age groups are presented
in Table 2.

Table 2: Vaccine efficacy analysis: confirmed COVID-19# regardless of severity starting 14 days
after the 2nd dose – per-protocol set

Spikevax Placebo

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 Incidence rate Incidence rate
COVID- COVID- % Vaccine
Age group Subjects of COVID-19 Subjects of COVID-19
19 cases 19 cases efficacy (95%
(years) N per 1,000 N per 1,000
n n CI)*
person-years person-years
Overall 94.1
14,134 11 3.328 14,073 185 56.510
(≥18) (89.3, 96.8)**
95.6
18 to <65 10,551 7 2.875 10,521 156 64.625
(90.6, 97.9)
86.4
≥65 3,583 4 4.595 3,552 29 33.728
(61.4, 95.2)
82.4%
≥65 to <75 2,953 4 5.586 2,864 22 31.744
(48.9, 93.9)
100%
≥75 630 0 0 688 7 41.968
(NE, 100)
#
COVID-19: symptomatic COVID-19 requiring positive RT-PCR result and at least 2 systemic symptoms or
1 respiratory symptom. Cases starting 14 days after the 2nd dose.
*Vaccine efficacy and 95% confidence interval (CI) from the stratified Cox proportional hazard model
** CI not adjusted for multiplicity. Multiplicity adjusted statistical analyses were carried out in an interim
analysis based on less COVID-19 cases, not reported here.

Among all subjects in the PPS, no cases of severe COVID-19 were reported in the vaccine group
compared with 30 of 185 (16%) cases reported in the placebo group. Of the 30 participants with severe
disease, 9 were hospitalised, 2 of which were admitted to an intensive care unit. The majority of the
remaining severe cases fulfilled only the oxygen saturation (SpO2) criterion for severe disease (≤ 93%
on room air).

The vaccine efficacy of Spikevax to prevent COVID-19, regardless of prior SARS-CoV-2 infection
(determined by baseline serology and nasopharyngeal swab sample testing) from 14 days after Dose 2
was 93.6% (95% confidence interval 88.6, 96.5%).

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.

Clinical efficacy in adolescents 12 through 17 years of age

The adolescent study is an ongoing Phase 2/3 randomised, placebo-controlled, observer-blind clinical
study (NCT04649151) to evaluate the safety, reactogenicity, and efficacy of Spikevax in adolescents
12 to 17 years of age. Participants with a known history of SARS-CoV-2 infection were excluded
from the study. A total of 3,732 participants were randomised 2:1 to receive 2 doses of Spikevax or
saline placebo 1 month apart.

A secondary efficacy analysis was performed in 3,181 participants who received 2 doses of either
Spikevax (n=2,139) or placebo (n=1,042) and had a negative baseline SARS-CoV-2 status in the Per
Protocol Set. Between participants who received Spikevax and those who received placebo, there were
no notable differences in demographics or pre-existing medical conditions.

COVID-19 was defined as symptomatic COVID-19 requiring positive RT-PCR result and at least
2 systemic symptoms or 1 respiratory symptom. Cases starting 14 days after the second dose.

There were zero symptomatic COVID-19 cases in the Spikevax group and 4 symptomatic COVID-19
cases in the placebo group.

Immunogenicity in adolescents 12 to 17 years of age

A non-inferiority analysis evaluating SARS-CoV-2 50% neutralising titers and seroresponse rates
28 days after Dose 2 was conducted in the Per-Protocol immunogenicity subsets of adolescents aged
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12 through 17 (n=340) in the adolescent study and in participants aged 18 through 25 (n=296) in the
adult study. Subjects had no immunologic or virologic evidence of prior SARS-CoV-2 infection at
baseline. The geometric mean ratio (GMR) of the neutralising antibody titers in adolescents 12 to
17 years of age compared to the 18- to 25-year-olds was 1.08 (95% CI: 0.94, 1.24). The difference in
seroresponse rate was 0.2% (95% CI: -1.8, 2.4). Non-inferiority criteria (lower bound of the 95% CI
for GMR > 0.67 and lower bound of the 95% CI of the seroresponse rate difference > -10%) were met.

Immunogenicity in participants 18 years of age and older – after booster dose (0.25 mL, 50
micrograms)

The safety, reactogenicity, and immunogenicity of a booster dose of Spikevax are evaluated in an
ongoing Phase 2, randomised, observer-blind, placebo-controlled, dose-confirmation study in
participants 18 years of age and older (NCT04405076). In this study, 198 participants received two
doses (0.5 mL, 100 micrograms 1 month apart) of the Spikevax vaccine as primary series. In an
open-label phase, 149 of those participants (Per-Protocol Set) received a single booster dose (0.25 mL,
50 micrograms) at least 6 months after receiving the second dose in the primary series. A single
booster dose (0.25 mL, 50 micrograms) was shown to result in a geometric mean fold rise (GMFR) of
12.99 (95% CI: 11.04, 15.29) in neutralising antibodies from pre-booster compared to 28 days after
the booster dose. The GMFR in neutralising antibodies was 1.53 (95% CI: 1.32, 1.77) when compared
28 days post dose 2 (primary series) to 28 days after the booster dose.

Elderly population

Spikevax was assessed in individuals 12 years of age and older, including 3,768 subjects 65 years of
age and older. The efficacy of Spikevax was consistent between elderly (≥65 years) and younger adult
subjects (18-64 years).

Paediatric population

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

Conditional approval

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
General toxicity studies were conducted in rats (intramuscularly receiving up to 4 doses exceeding the
human dose once every 2 weeks). Transient and reversible injection site oedema and erythema and
transient and reversible changes in laboratory tests (including increases in eosinophils, activated
partial thromboplastin time, and fibrinogen) were observed. Results suggests the toxicity potential to
humans is low.

Genotoxicity/carcinogenicity
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In vitro and in vivo genotoxicity studies were conducted with the novel lipid component SM-102 of
the vaccine. Results suggests the genotoxicity potential to humans is very low. Carcinogenicity studies
were not performed.

Reproductive toxicity
In a developmental toxicity study, 0.2 mL of a vaccine formulation containing the same quantity of
mRNA (100 micrograms) and other ingredients included in a single human dose of Spikevax was
administered to female rats by the intramuscular route on four occasions: 28 and 14 days prior to
mating, and on gestation days 1 and 13. SARS-CoV-2 antibody responses were present in maternal
animals from prior to mating to the end of the study on lactation day 21 as well as in foetuses and
offspring. There were no vaccine-related adverse effects on female fertility, pregnancy, embryo
foetal or offspring development or postnatal development. No data are available of Spikevax vaccine
placental transfer or excretion in milk.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Lipid SM-102 (heptadecan-9-yl 8-{(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino}octanoate)

Cholesterol
1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)
1,2-Dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000 DMG)
Trometamol
Trometamol hydrochloride
Acetic acid
Sodium acetate trihydrate
Sucrose
Water for injections

6.2 Incompatibilities

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

6.3 Shelf life

Unopened vial
9 months at -25ºC to -15ºC.

The unopened vaccine may be stored refrigerated at 2°C to 8°C, protected from light, for maximum
30 days. Within this period, up to 12 hours may be used for transportation.

Once thawed the vaccine should not be re-frozen.

The unopened vaccine may be stored at 8°C to 25°C up to 24 hours after removal from refrigerated
conditions.

Punctured vial
Chemical and physical in-use stability has been demonstrated for 19 hours at 2°C to 25ºC after initial
puncture (within the allowed use period of 30 days at 2°C to 8ºC and 24 hours at 8°C to 25ºC). From a
microbiological point of view, the product should be used immediately. If the vaccine is not used
immediately, in-use storage times and conditions are the responsibility of the user.

6.4 Special precautions for storage

Store frozen between -25ºC to -15ºC.

Store in the original carton to protect from light.
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Do not store below -50ºC.
For storage conditions after thawing and first opening see section 6.3.

Transportation of thawed vials in liquid state at 2°C to 8°C

If transport at -50°C to -15°C is not feasible, available data support transportation of one or more
thawed vials in liquid state for up to 12 hours at 2°C to 8°C (within the 30 days shelf life at 2°C to
8°C). Once thawed and transported in liquid state at 2°C to 8°C, vials should not be refrozen and
should be stored at 2°C to 8°C until use.

6.5 Nature and contents of container

5 mL dispersion in a vial (type 1 or type 1 equivalent glass) with a stopper (chlorobutyl rubber) and a
flip-off plastic cap with seal (aluminium seal).

Each vial contains 5 mL.

Pack size: 10 multidose vials

6.6 Special precautions for disposal and other handling

The vaccine should be prepared and administered by a trained healthcare professional using aseptic
techniques to ensure sterility of the dispersion.

The vaccine comes ready to use once thawed.

Do not shake or dilute. Swirl the vial gently after thawing and before each withdrawal.

Spikevax vials are multidose.

Ten (10) doses (of 0.5 mL each) or a maximum of twenty (20) doses (of 0.25 mL each) can be
withdrawn from each vial.

Pierce the stopper preferably at a different site each time. Do not puncture the vial more than 20 times.

An additional overfill is included in each vial to ensure that 10 doses of 0.5 mL or a maximum of 20
doses of 0.25 mL can be delivered.

Thawed vials and filled syringes can be handled in room light conditions.

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7. MARKETING AUTHORISATION HOLDER

MODERNA BIOTECH SPAIN, S.L.

Calle Monte Esquinza 30
28010 Madrid
Spain

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/20/1507/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 06 January 2021

Date of latest renewal: 04 October 2021

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines
Agency [Link]

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 ANNEX II

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE

SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR
BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY

AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE

MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL
PRODUCT

E. SPECIFIC OBLIGATION TO COMPLETE POST-

AUTHORISATION MEASURES FOR THE CONDITIONAL
MARKETING AUTHORISATION

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A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer of the biological active substance

LONZA AG
Lonzastrasse 2
Visp 3930
Switzerland

LONZA AG
Ibex Solutions
Rottenstrasse 6
Visp 3930
Switzerland

ModernaTX, Inc.
One Moderna Way
Norwood, MA 02062
USA

Lonza Biologics, Inc.

101 International Drive Portsmouth, NH 03801
USA

Name and address of the manufacturer responsible for batch release

Rovi Pharma Industrial Services, S.A.

Paseo de Europa, 50
28703. San Sebastián de los Reyes
Madrid, Spain

Recipharm Monts
18 Rue de Montbazon
Monts, France 37260

In view of the declared Public Health Emergency of International Concern and in order to ensure early
supply this medicinal product is subject to a time-limited exemption allowing reliance on batch control
testing conducted in the registered site(s) that are located in a third country. This exemption ceases to
be valid on 31 July 2022. Implementation of EU based batch control arrangements, including the
necessary variations to the terms of the marketing authorisation, has to be completed by 31 July 2022
at the latest, in line with the agreed plan for this transfer of testing.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

Official batch release

In accordance with Article 114 of Directive 2001/83/EC, the official batch release will be undertaken
by a state laboratory or a laboratory designated for that purpose.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING

AUTHORISATION

16
Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC
and any subsequent updates published on the European medicines web-portal.

The marketing authorisation holder (MAH) shall submit the first PSUR for this product within
6 months following authorisation.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND

EFFECTIVE USE OF THE MEDICINAL PRODUCT

Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the
marketing authorisation and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:

• At the request of the European Medicines Agency;
• Whenever the risk management system is modified, especially as the result of new information
being received that may lead to a significant change to the benefit/risk profile or as the result of
an important (pharmacovigilance or risk minimisation) milestone being reached.

E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES

FOR THE CONDITIONAL MARKETING AUTHORISATION

This being a conditional marketing authorisation and pursuant to Article 14-a of Regulation (EC) No
726/2004, the MAH shall complete, within the stated timeframe, the following measures:

Description Due date

In order to complete the characterisation of the active substance and 31 July 2021
finished product manufacturing processes, the MAH should provide
additional data.

In order to confirm the consistency of the active substance and finished 15 November 2021
product manufacturing process (Initial and final scales), the MAH should
provide additional comparability and validation data.
In order to ensure consistent product quality, the MAH should provide 15 July 2021
additional information on stability of the active substance and finished
product and review the active substance and finished product
specifications following further manufacturing experience.

In order to confirm the efficacy and safety of Spikevax, the MAH should December 2022
submit the final Clinical Study Report for the randomised, placebo-
controlled, observer-blind study mRNA-1273-P301.

In order to confirm the efficacy and safety of Spikevax, the MAH should 30 September 2022
submit the final Clinical Study Report for the randomised, placebo-
controlled, observer-blind study mRNA-1273-P203, including the full
bioanalytical report.

17
 ANNEX III

LABELLING AND PACKAGE LEAFLET

18
A. LABELLING

19
PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Spikevax dispersion for injection

COVID-19 mRNA Vaccine (nucleoside modified)

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each multidose vial contains 5 mL.

3. LIST OF EXCIPIENTS

Excipients: Lipid SM-102, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-

Dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000 DMG), trometamol,
trometamol hydrochloride, acetic acid, sodium acetate trihydrate, sucrose, water for injections.

4. PHARMACEUTICAL FORM AND CONTENTS

Dispersion for injection

10 multidose vials

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Intramuscular use.
Read the package leaflet before use.

Scan here for package leaflet or visit [Link].

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT

OF THE SIGHT AND REACH OF CHILDREN

Keep out of sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

20
8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store frozen at -25°C to -15°C.

Read the package leaflet for the shelf life after first opening and for additional storage information.
Keep the vial in the outer carton to protect from light

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE

Dispose of in accordance with local requirement.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

MODERNA BIOTECH SPAIN, S.L.

Calle Monte Esquinza, 30
28010 Madrid
Spain

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/20/1507/001

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted.

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

21
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC
SN
NN

22
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL LABEL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Spikevax dispersion for injection

COVID-19 mRNA Vaccine (nucleoside modified)
IM

2. METHOD OF ADMINISTRATION

Intramuscular use

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

Multidose vial
(5 mL)

6. OTHER

Scan here for package leaflet or visit [Link].

Discard date/time:

23
 ANNEX III

B. PACKAGE LEAFLET

24
 Package leaflet: Information for the user

Spikevax dispersion for injection

COVID-19 mRNA Vaccine (nucleoside modified)

This medicine is subject to additional monitoring. This will allow quick identification of new
safety information. You can help by reporting any side effects you may get. See the end of section 4
for how to report side effects.

Read all of this leaflet carefully before you receive this vaccine because it contains important
information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor, pharmacist or nurse.
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Spikevax is and what it is used for

2. What you need to know before you are given Spikevax
3. How Spikevax is given
4. Possible side effects
5. How to store Spikevax
6. Contents of the pack and other information

1. What Spikevax is and what it is used for

Spikevax is a vaccine used to prevent COVID-19 caused by SARS-CoV-2. It is given to adults and
children aged 12 years and older. The active substance in Spikevax is mRNA encoding the SARS-
CoV-2 Spike protein. The mRNA is embedded in SM-102 lipid nanoparticles.

As Spikevax does not contain the virus, it cannot give you COVID-19.

How the vaccine works

Spikevax stimulates the body’s natural defences (immune system). The vaccine works by causing the
body to produce protection (antibodies) against the virus that causes COVID-19. Spikevax uses a
substance called messenger ribonucleic acid (mRNA) to carry instructions that cells in the body can
use to make the spike protein that is also on the virus. The cells then make antibodies against the spike
protein to help fight off the virus. This will help to protect you against COVID-19.

2. What you need to know before you are given Spikevax

The vaccine must not be given if you are allergic to the active substance or any of the other
ingredients of this vaccine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you are given Spikevax if:

- you have previously had a severe, life-threatening allergic reaction after any other vaccine
injection or after you were given Spikevax in the past.
- you have a very weak or compromised immune system
- you have ever fainted following any needle injection.
- you have a bleeding disorder
- you have a high fever or severe infection; however, you can have your vaccination if you have a
mild fever or upper airway infection like a cold
25
- you have any serious illness
- if you have anxiety related to injections

There is an increased risk of myocarditis (inflammation of the heart muscle) and pericarditis
(inflammation of the lining outside the heart) after vaccination with Spikevax (see section 4).

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.

Following vaccination, you should be alert to signs of myocarditis and pericarditis, such as
breathlessness, palpitations and chest pain, and seek immediate medical attention should these occur.

If any of the above apply to you (or you are not sure), talk to your doctor, pharmacist or
nurse before you are given Spikevax.

As with any vaccine, the primary 2-dose vaccination course of Spikevax may not fully protect all those
who receive it and it is not known how long you will be protected.

Children
Spikevax is not recommended for children aged under 12 years.

Other medicines and Spikevax

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines. Spikevax may affect the way other medicines work, and other medicines may affect how
Spikevax works.

Immunocompromised individuals
If you are immunocompromised, you may receive a third dose of Spikevax. The efficacy of Spikevax
even after a third dose may be lower in people who are immunocompromised. In these cases, you
should continue to maintain physical precautions to help prevent COVID-19. In addition, your close
contacts should be vaccinated as appropriate. Discuss appropriate individual recommendations with
your doctor.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, tell
your doctor, pharmacist or nurse before being vaccinated.

Driving and using machines

Do not drive or use machines if you are feeling unwell after vaccination. Wait until any effects of the
vaccine have worn off before you drive or use machines.

Spikevax contains sodium

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

3. How you will be given Spikevax

Spikevax will be given to you as two 0.5 mL injections. It is recommended to administer the second
dose of the same vaccine 28 days after the first dose to complete the vaccination course.

If you miss an appointment for your primary 2nd dose of Spikevax

- If you miss an appointment, arrange another visit as soon as possible with your doctor, pharmacist
or nurse.
- If you miss a scheduled injection, you may not be fully protected against COVID-19.

26
A booster dose (0.25 mL) of Spikevax may be given at least 6 months after the second dose in
individuals 18 years of age and older.

If you are immunocompromised, you may receive a third dose (0.5 mL) of Spikevax at least 1 month
after the second dose.

Your doctor, pharmacist or nurse will inject the vaccine into a muscle (intramuscular injection) in your
upper arm.

After each injection of the vaccine, your doctor, pharmacist or nurse will watch over you for at least
15 minutes to monitor for signs of an allergic reaction.

If you have any further questions on the use of this vaccine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this vaccine can cause side effects, although not everybody gets them.

Get urgent medical attention if you get any of the following signs and symptoms of an allergic
reaction:
- feeling faint or light-headed;
- changes in your heartbeat;
- shortness of breath;
- wheezing;
- swelling of your lips, face, or throat;
- hives or rash;
- nausea or vomiting;
- stomach pain.

Talk to your doctor or nurse if you develop any other side effects. These can include:

Very common (may affect more than 1 in 10 people):

- swelling/tenderness in the underarm
- headache
- nausea
- vomiting
- muscle ache, joint aches, and stiffness
- pain or swelling at the injection site
- feeling very tired
- chills
- fever

Common (may affect up to 1 in 10 people):

- diarrhoea
- rash
- rash, redness, or hives at the injection site (some of which may occur at a median of 4 to
11 days after the injection)

Uncommon (may affect up to 1 in 100 people):

- itchiness at the injection site

Rare (may affect up to 1 in 1,000 people)

- temporary one-sided facial drooping (Bell’s palsy)
- swelling of the face (swelling of the face may occur in patients who have had facial cosmetic
injections.)
27
 - dizziness
- decreased sense of touch or sensation

Very rare (may affect up to 1 in 10,000 people)

- inflammation of the heart muscle (myocarditis) or inflammation of the lining outside the heart
(pericarditis) which can result in breathlessness, palpitations or chest pain

Frequency unknown
- severe allergic reactions with breathing difficulties (anaphylaxis)
- reaction of increased sensitivity or intolerance by the immune system (hypersensitivity)
- a skin reaction that causes red spots or patches on the skin that may look like a target or
“bulls-eye” with a dark red centre surrounded by paler red rings (erythema multiforme)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the national reporting
system listed in Appendix V. By reporting side effects you can help provide more information on the
safety of this vaccine.

5. How to store Spikevax

Keep this vaccine out of the sight and reach of children.

Do not use this vaccine after the expiry date which is stated on the label after EXP. The expiry date
refers to the last day of that month.

Information about storage, expiry, and use and handling are described in the section intended for
healthcare professionals at the end of the package leaflet.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Spikevax contains

- This is a multidose vial that contains 10 doses of 0.5 mL each or a maximum of 20 doses of
0.25 mL each.
- One dose (0.5 mL) contains 100 micrograms of messenger RNA (mRNA) (embedded in SM-102
lipid nanoparticles).
- One dose (0.25 mL) contains 50 micrograms of messenger RNA (mRNA) (embedded in SM-102
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.
- The other ingredients are lipid SM-102 (heptadecan-9-yl 8-{(2-hydroxyethyl)[6-oxo-6-
(undecyloxy)hexyl]amino}octanoate), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine
(DSPC), 1,2-Dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (PEG2000 DMG),
trometamol, trometamol hydrochloride, acetic acid, sodium acetate trihydrate, sucrose, water for
injections.

What Spikevax looks like and contents of the pack

Spikevax is a white to off white dispersion supplied in a glass vial with a rubber stopper and
aluminium seal.

28
Pack size: 10 multidose vials

Marketing Authorisation Holder:

MODERNA BIOTECH SPAIN, S.L.
Calle Monte Esquinza 30
28010 Madrid
Spain

Manufacturer:
Rovi Pharma Industrial Services, S.A.
Paseo de Europa, 50
28703. San Sebastián de los Reyes
Madrid, Spain

Recipharm Monts
18 Rue de Montbazon
Monts, France 37260

For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder.

België/Belgique/Belgien Lietuva
Tél/Tel: 3280038405 Tel: (8 5) 214 1995

България Luxembourg/Luxemburg
Teл: 008002100471 Tél/Tel: 35280026532

Česká republika Magyarország

Tel: 800050719 Tel: 3680088442

Danmark Malta
Tlf: 80 83 01 53 Tel: 80062397

Deutschland Nederland
Tel: 08001009632 Tel: 08004090001

Eesti Norge
Tel: 8000032166 Tlf: 4780031401

Ελλάδα Österreich
Τηλ: 21 1 199 3571 Tel: 43800232927

España Polska
Tel: 900031015 Tel: 008003211487

France Portugal
Tél: 0805543016 Tel: 800210256

Hrvatska România
Tel: 08009614 Tel: 40800630047

Ireland Slovenija
Tel: 1800 851 200 Tel: 080488802

Ísland Slovenská republika

Sími: 8004382 Tel: 421800105207

29
 Italia Suomi/Finland
Tel: +39 800141758 Puh/Tel: 358800413854

Κύπρος Sverige
Τηλ: 35780077065 Tel: 020127022

Latvija United Kingdom (Northern Ireland)

Tel: 37180005882 Tel: 08000857562

This leaflet was last revised in {DD month YYYY}.

This vaccine has been given ‘conditional approval’. This means that there is more evidence to come
about this vaccine.

The European Medicines Agency will review new information on this vaccine at least every year and
this leaflet will be updated as necessary.

Scan the code with a mobile device to get the package leaflet in different languages.

Or visit the URL [Link]

Detailed information on this vaccine is available on the European Medicines Agency web site:
[Link]

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

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.

Spikevax should be administered by a trained healthcare professional.

The vaccine comes ready to use once thawed.

Do not shake or dilute.

Spikevax vials are multidose. Ten (10) doses (of 0.5 mL each) or a maximum of twenty (20) doses (of
0.25 mL each) can be withdrawn from each multidose vial.

Pierce the stopper preferably at a different site each time. Do not puncture the vial more than 20 times.

An additional overfill is included in each vial to ensure that 10 doses of 0.5 mL or a maximum of 20
doses of 0.25 mL can be delivered.
30
Thawed vials and filled syringes can be handled in room light conditions.

For the primary series, Spikevax should be administered as two 0.5 mL (100 microgram) doses. It is
recommended to administer the second dose 28 days after the first dose. A third dose (0.5 mL,
100 micrograms) may be given at least 1 month after the second dose to individuals who are severely
immunocompromised.

A booster dose (0.25 mL, 50 micrograms) of Spikevax may be given at least 6 months after a primary
series in individuals 18 years of age and older.

As with all injectable vaccines, appropriate medical treatment and supervision must always be readily
available in the event of an anaphylactic reaction following the administration of Spikevax.

Individuals should be observed by a healthcare professional for at least 15 minutes after vaccination.

There are no data to assess the concomitant administration of Spikevax with other vaccines. Spikevax
must not be mixed with other vaccines or medicinal products in the same syringe.

The vaccine must be administered intramuscularly. The preferred site is the deltoid muscle of the
upper arm. Do not administer this vaccine intravascularly, subcutaneously or intradermally.

31
Information about storage and handling

32
33