REG 174 INFORMATION FOR UK HEALTHCARE PROFESSIONALS

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This medicinal product does not have a UK marketing authorisation but has been given
authorisation for temporary supply by the UK Department of Health and Social Care and the
Medicines & Healthcare products Regulatory Agency for active immunization to prevent
COVID-19 disease caused by SARS-CoV-2 virus in individuals aged 16 years of age and over.

As with any new medicine in the UK, this product will be closely monitored to 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

COVID-19 mRNA Vaccine BNT162b2 concentrate for solution for injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

This is a multidose vial and must be diluted before use. 1 vial (0.45 mL) contains 5 doses of
30 micrograms of BNT162b2 RNA (embedded in lipid nanoparticles).

COVID-19 mRNA Vaccine BNT162b2 is highly purified single-stranded, 5’-capped messenger RNA
(mRNA) produced by cell-free in vitro transcription from the corresponding DNA templates, encoding
the viral spike (S) protein of SARS-CoV-2.

Excipients with known effect:

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Concentrate for solution for injection.

The vaccine is a white to off-white frozen solution.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Active immunisation to prevent COVID-19 caused by SARS-CoV-2 virus, in individuals 16 years of

age and older.

The use of COVID-19 mRNA Vaccine BNT162b2 should be in accordance with official guidance.

4.2 Posology and method of administration

Posology
Individuals 16 years of age and older
COVID-19 mRNA Vaccine BNT162b2 is administered intramuscularly after dilution as a series of
two doses (0.3 mL each) 21 days apart (see section 5.1).

There are no data available on the interchangeability of COVID-19 mRNA Vaccine BNT162b2 with
other COVID-19 vaccines to complete the vaccination series. Individuals who have received one dose
of COVID-19 mRNA Vaccine BNT162b2 should receive a second dose of COVID-19 mRNA
Vaccine BNT162b2 to complete the vaccination series.

Individuals may not be protected until at least 7 days after their second dose of the vaccine.

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For further information on efficacy, see section 5.1.

Paediatric population
The safety and efficacy of COVID-19 mRNA Vaccine BNT162b2 in children under 16 years of age
have not yet been established.

Method of administration
Administer the COVID-19 mRNA Vaccine BNT162b2 vaccine intramuscularly in the deltoid muscle
after dilution.

Do not inject the vaccine intravascularly, subcutaneously or intradermally.

Preparation: The multidose vial is stored frozen and must be thawed prior to dilution.

Frozen vials should be transferred to 2 °C to

8 °C to thaw; a 195 vial pack may take 3 hours
to thaw (see section 6.4). Alternatively, frozen
vials may also be thawed for 30 minutes at
temperatures up to 25 °C for immediate use.
Once thawed, the undiluted vaccine can be
stored for up to 5 days at 2 °C to 8 °C, and up to
2 hours.at temperatures up to 25 °C.

Allow the thawed vial to come to room

temperature and gently invert 10 times prior to
dilution. Do not shake. Prior to dilution the
vaccine should present as an off-white solution
with no particulates visible. Discard the vaccine
if particulates or discolouration are present.

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.

Warning: Unpreserved sodium chloride

9 mg/mL (0.9%) solution for injection is the
only diluent that should be used. This diluent is
not provided in the vaccine carton.

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Equalise vial pressure before removing the
needle from the vial by withdrawing 1.8 mL air
into the empty diluent syringe.

Gently invert the diluted solution 10 times. Do

not shake.

The diluted vaccine should present as an off-

white solution with no particulates visible.
Discard the diluted vaccine if particulates or
discolouration are present.

The diluted vials should be marked with the

dilution date and time and stored between 2 °C
to 25 °C.

Use immediately, and within 6 hours after

dilution.

After dilution, the vial contains 5 doses of

0.3 mL. Withdraw the required 0.3 mL dose of
diluted vaccine using a sterile needle and
syringe and discard any unused vaccine within
6 hours after dilution.

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For instructions on disposal 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
As with all injectable vaccines, appropriate medical treatment and supervision should always be
readily available in case of a rare anaphylactic event following the administration of the vaccine.

The administration of COVID-19 mRNA Vaccine BNT162b2 should be postponed in individuals

suffering from acute severe febrile illness.

Individuals receiving anticoagulant therapy or those with a bleeding disorder that would contraindicate
intramuscular injection, should not be given the vaccine unless the potential benefit clearly outweighs
the risk of administration.

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have

a diminished immune response to the vaccine. No data are available about concomitant use of
immunosuppressants.

As with any vaccine, vaccination with COVID-19 mRNA Vaccine BNT162b2 may not protect all
vaccine recipients.

No data are available on the use of COVID-19 mRNA Vaccine BNT162b2 in persons that have
previously received a full or partial vaccine series with another COVID-19 vaccine.

Excipient information
This vaccine contains potassium, less than 1 mmol (39 mg) per dose, i.e. essentially ‘potassium-free’.
This vaccine contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium‑free’.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

Concomitant administration of COVID-19 mRNA Vaccine BNT162b2 with other vaccines has not
been studied (see section 5.1).

Do not mix COVID-19 mRNA Vaccine BNT162b2 with other vaccines/products in the same syringe.

4.6 Fertility, pregnancy and lactation

Pregnancy
There are no or limited amount of data from the use of COVID-19 mRNA Vaccine BNT162b2.
Animal reproductive toxicity studies have not been completed. COVID-19 mRNA Vaccine
BNT162b2 is not recommended during pregnancy.

For women of childbearing age, pregnancy should be excluded before vaccination. In addition, women
of childbearing age should be advised to avoid pregnancy for at least 2 months after their second dose.

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Breast-feeding
It is unknown whether COVID-19 mRNA Vaccine BNT162b2 is excreted in human milk. A risk to
the newborns/infants cannot be excluded. COVID-19 mRNA Vaccine BNT162b2 should not be used
during breast-feeding.

Fertility
It is unknown whether COVID-19 mRNA Vaccine BNT162b2 has an impact on fertility.

4.7 Effects on ability to drive and use machines

COVID-19 mRNA Vaccine BNT162b2 has no or negligible influence on the ability to drive and use
machines. However, some of the adverse reactions 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 COVID-19 mRNA Vaccine BNT162b2 was evaluated in participants 16 years of age
and older in two clinical studies conducted in the United States, Europe, Turkey, South Africa, and
South America. Study BNT162-01 (Study 1) enrolled 60 participants, 18 through 55 years of age.
Study C4591001 (Study 2) enrolled approximately 44,000 participants, 12 years of age or older.
In Study 2, a total of 21,720 participants 16 years of age or older received at least one dose of COVID-
19 mRNA Vaccine BNT162b and 21,728 participants 16 years of age or older received placebo. Out
of these, at the time of the analysis, 19,067 (9531 COVID-19 mRNA Vaccine BNT162b2 and
9536 placebo) were evaluated for safety 2 months after the second dose of COVID-19 mRNA Vaccine
BNT162b2.

Demographic characteristics were generally similar with regard to age, gender, race and ethnicity
among participants who received COVID-19 mRNA Vaccine and those who received placebo.
Overall, among the participants who received COVID-19 mRNA Vaccine BNT162b2, 51.5% were
male and 48.5% were female, 82.1% were White, 9.6% were Black or African American, 26.1% were
Hispanic/Latino, 4.3% were Asian and 0.7% were Native American/Alaskan native.

The most frequent adverse reactions in participants 16 years of age and older were pain at the injection
site (> 80%), fatigue (> 60%), headache (> 50%), myalgia (> 30%), chills (> 30%), arthralgia (> 20%)
and pyrexia (> 10%) and were usually mild or moderate in intensity and resolved within a few days
after vaccination. If required, symptomatic treatment with analgesic and/or anti-pyretic medicinal
products (e.g. paracetamol-containing products) may be used.

Adverse reactions from clinical studies

Adverse reactions reported in clinical studies are listed in this section per MedDRA system organ
class, in decreasing order of frequency and seriousness. The frequency is defined as follows: 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 available data).

Blood and lymphatic system disorders

Uncommon: Lymphadenopathy

Nervous system disorders

Very common: Headache

Musculoskeletal and connective tissue disorders

Very common: Arthralgia; myalgia

General disorders and administration site conditions

Very common: Injection-site pain; fatigue; chills; pyrexia

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Common: Redness at injection site; injection site swelling
Uncommon: Malaise

Gastrointestinal disorders
Common Nausea

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 Coronavirus Yellow Card
reporting site https://coronavirus-yellowcard.mhra.gov.uk/
or search for MHRA Yellow Card in the Google Play or Apple App Store
and include the vaccine brand and batch/Lot number if available.

4.9 Overdose

Participants who received 58 micrograms of COVID-19 mRNA Vaccine in clinical trials did not
report an increase in reactogenicity or adverse events.

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

5. PHARMACODYNAMIC PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: {group}, ATC code: not yet assigned

Mechanism of action
The nucleoside-modified messenger RNA in COVID-19 mRNA Vaccine BNT162b2 is formulated in
lipid nanoparticles, which enable delivery of the RNA into host cells to allow expression of the SARS-
CoV-2 S antigen. The vaccine elicits both neutralizing antibody and cellular immune responses to the
spike (S) antigen, which may contribute to protection against COVID-19 disease.

Efficacy in participants 16 years of age and older

The efficacy of COVID-19 mRNA Vaccine BNT162b2 was evaluated in participants 16 years of age
and older in two clinical studies conducted in the United States, Europe, Turkey, South Africa and
South America. Study 1 enrolled 60 participants, 18 through 55 years of age. Study 2 is a multicentre,
placebo-controlled efficacy study in participants 12 years of age and older. Randomisation was
stratified by age: 12 through 15 years of age, 16 through 55 years of age, or 56 years of age and older,
with a minimum of 40% of participants in the ≥ 56-year stratum. The study excluded participants who
were immunocompromised and those who had previous clinical or microbiological diagnosis of
COVID-19 disease. 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). There was no
requirement for prophylactic use of paracetamol or analgesics. Influenza vaccines could be
administered outside a window ± 14 days of the vaccine doses.

In Study 2, approximately 44,000 participants 12 years of age and older were randomised equally and
received 2 doses of COVID-19 mRNA Vaccine or placebo with a planned interval of 21 days. The
efficacy analyses included participants that received their second vaccination within 19 to 42 days
after their first vaccination. Participants are planned to be followed for up to 24 months, for
assessments of safety and efficacy against COVID-19 disease.

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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.

Demographic characteristics were generally similar with regard to age, gender, race and ethnicity
among participants who received COVID-19 mRNA BNT162b2 vaccine and those who received
placebo. Overall, among the participants who received COVID-19 mRNA vaccine, 51.1% were male
and 48.9% were female, 82.8% were White, 8.9% were Black or African American, 26.8% were
Hispanic/Latino, 4.5% were Asian and 0.6% were Native American/Alaskan native. 57.2% were aged
16-55 years, 42.6% were aged > 55 years and 21.8% were ≥ 65 years.

Efficacy against COVID-19 disease

At the time of the analysis of Study 2, information presented is based on participants 16 years and
older. Participants had been followed for symptomatic COVID-19 disease for at least 2,214
person-years for the COVID-19 mRNA Vaccine and at least 2,222 person-years in the placebo group.
There were 8 confirmed COVID-19 cases identified in the COVID-19 mRNA Vaccine group and 162
cases in the placebo group, respectively. In this analysis, compared to placebo, efficacy of COVID-19
mRNA Vaccine BNT162b2 from first COVID-19 occurrence from 7 days after Dose 2 in participants
without evidence of prior infection with SARS-CoV-2 was 95.0% (95% credible interval of 90.3% to
97.6%). In participants 65 years of age and older and 75 years of age and older without evidence of
prior infections with SARS-CoV-2, efficacy of COVID-19 mRNA Vaccine BNT162b2 was 94.7%
(two-sided 95% confidence interval of 66.7% to 99.9%) and 100% (two-sided 95% confidence
interval of -13.1% to 100.0%) respectively.

In a separate analysis, compared to placebo, efficacy of COVID-19 mRNA Vaccine from first
COVID-19 occurrence from 7 days after Dose 2 in participants with or without evidence of prior
infection with SARS-CoV-2 was 94.6% (95% credible interval of 89.9% to 97.3%).

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

Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR)

and at least 1 symptom consistent with COVID-19 disease*.

*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.

5.2 Pharmacokinetic properties

Not applicable.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on a conventional study of repeat dose
toxicity. Animal studies into potential toxicity to reproduction and development have not been
completed.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

ALC-0315 = (4-hydroxybutyl) azanediyl)bis (hexane-6,1-diyl)bis(2-hexyldecanoate),

ALC-0159 = 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide,

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1,2-Distearoyl-sn-glycero-3-phosphocholine,
cholesterol,
potassium chloride,
potassium dihydrogen phosphate,
sodium chloride,
disodium hydrogen phosphate dihydrate,
sucrose,
water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal
products.

6.3 Shelf life

6 months at -80 °C to -60 °C.

6.4 Special precautions for storage

Store in a freezer at -80 °C to -60 °C.

Store in the thermal container at -90 ºC to -60 ºC.

Store in the original package in order to protect from light.

After thawing, the vaccine should be diluted and used immediately. However, in-use stability data
have demonstrated that once thawed, the undiluted vaccine can be stored for up to 5 days at 2 °C to
8 °C, or up to 2 hours at temperatures up to 25 °C, prior to use. 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.

After dilution, store the vaccine at 2 °C to 25 °C and use immediately and within 6 hours. The vaccine
does not contain a preservative. Discard any unused vaccine.

Once diluted, the vials should be marked with the dilution date and time. Once thawed, the vaccine
cannot be re-frozen.

6.5 Nature and contents of container

Concentrate for solution for injection for 5 doses in a 2 mL clear vial (type I glass) with a stopper
(bromobutyl) and a flip-off plastic cap with aluminium seal.

Pack size: 195 vials

6.6 Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.
For instructions on dose preparation of the medicinal product before administration, see section 4.2.

7. MARKETING AUTHORISATION HOLDER

Not applicable.

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8. MARKETING AUTHORISATION NUMBER(S)

Not applicable.

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Not applicable.

10. DATE OF REVISION OF THE TEXT

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