PREVENAR 20 suspension for injection in pre-filled syringe medication leaflet

Prevenar 20 suspension for injection in pre-filled syringe

Pneumococcal polysaccharide conjugate vaccine (20-valent, adsorbed)

One dose (0.5 mL) contains:

Pneumococcal polysaccharide serotype 11,2 2.2 µg

Pneumococcal polysaccharide serotype 31,2 2.2 µg

Pneumococcal polysaccharide serotype 41,2 2.2 µg

Pneumococcal polysaccharide serotype 51,2 2.2 µg

Pneumococcal polysaccharide serotype 6A1,2 2.2 µg

Pneumococcal polysaccharide serotype 6B1,2 4.4 µg

Pneumococcal polysaccharide serotype 7F1,2 2.2 µg

Pneumococcal polysaccharide serotype 81,2 2.2 µg

Pneumococcal polysaccharide serotype 9V1,2 2.2 µg

Pneumococcal polysaccharide serotype 10A1,2 2.2 µg

Pneumococcal polysaccharide serotype 11A1,2 2.2 µg

Pneumococcal polysaccharide serotype 12F1,2 2.2 µg

Pneumococcal polysaccharide serotype 141,2 2.2 µg

Pneumococcal polysaccharide serotype 15B1,2 2.2 µg

Pneumococcal polysaccharide serotype 18C1,2 2.2 µg

Pneumococcal polysaccharide serotype 19A1,2 2.2 µg

Pneumococcal polysaccharide serotype 19F1,2 2.2 µg

Pneumococcal polysaccharide serotype 22F1,2 2.2 µg

Pneumococcal polysaccharide serotype 23F1,2 2.2 µg

Pneumococcal polysaccharide serotype 33F1,2 2.2 µg1Conjugated to CRM197 carrier protein (approximately 51 µg per dose)2Adsorbed on aluminium phosphate (0.125 mg aluminium per dose)

Prevenar 20 contains 0.1 mg of polysorbate 80 in each 0.5 mL dose, which is equivalent to 0.2 mg/mLof polysorbate 80.

For the full list of excipients, see section 6.1.

Suspension for injection.

The vaccine is a homogeneous white suspension.

Active immunisation for the prevention of invasive disease, pneumonia, and acute otitis media causedby Streptococcus pneumoniae in infants, children, and adolescents from 6 weeks to less than 18 yearsof age.

Active immunisation for the prevention of invasive disease and pneumonia caused by Streptococcuspneumoniae in individuals 18 years of age and older.

See sections 4.4 and 5.1 for information on protection against specific pneumococcal serotypes.

Prevenar 20 should be used in accordance with official recommendations.

It is recommended that infants who receive a first dose of Prevenar 20 complete the vaccination coursewith Prevenar 20.

Vaccination schedule in infants and children 6 weeks to 15 months of age4-dose series (three-dose The primary infant series consists of three doses, each of 0.5 mL, withprimary series followed the first dose usually given at 2 months of age and with an interval of atby a booster dose) least 4 weeks between doses. The first dose may be given as early as6 weeks of age. The fourth (booster) dose is recommended between 11and 15 months of age (see section 5.1).

Vaccination schedule for individuals 18 years of age and older

Individuals 18 years of Prevenar 20 is to be administered as a single dose to individualsage and older 18 years of age and older.

The need for revaccination with a subsequent dose of Prevenar 20 hasnot been established.

No data on sequential vaccination with other pneumococcal vaccines ora booster dose are available for Prevenar 20. Based on the clinicalexperience with Prevenar 13 (a pneumococcal conjugate vaccineconsisting of 13 polysaccharide conjugates that are also in Prevenar 20),if the use of 23-valent pneumococcal polysaccharide vaccine(Pneumovax 23 [PPSV23]) is considered appropriate, Prevenar 20should be given first (see section 5.1).

No or only limited data are available for Prevenar 20 in infants below 6 weeks, preterm, olderunvaccinated, or partially vaccinated infants and children (see sections 4.4, pct. 4.8 and 5.1). The followingdosing recommendations are predominantly based on experience with Prevenar 13.

Infants below 6 weeks of age

The safety and efficacy of Prevenar 20 in infants below 6 weeks have not been established. No dataare available.

Preterm infants (less than 37 weeks of gestation)

The recommended immunisation series for Prevenar 20 consists of four doses, each of 0.5 mL. Theprimary infant series consists of three doses, with the first dose given at 2 months of age and with aninterval of at least 4 weeks between doses. The first dose may be given as early as 6 weeks of age. Thefourth (booster) dose is recommended between 11 and 15 months of age (see sections 4.4 and 5.1).

Unvaccinated infants 7 months to less than 12 months of age

Two doses, each of 0.5 mL, with an interval of at least 4 weeks between doses. A third dose isrecommended in the second year of life.

Unvaccinated children 12 months to less than 24 months of age

Two doses, each of 0.5 mL, with an interval of at least 8 weeks between doses.

Unvaccinated children 2 years to less than 5 years of age

One single dose of 0.5 mL.

Children 15 months to less than 5 years of age previously fully vaccinated with Prevenar 13

One single dose (0.5 mL) given on an individual basis according to official recommendations to elicitimmune responses to the additional serotypes.

If Prevenar 13 was administered, at least 8 weeks should elapse before administering Prevenar 20 (seesection 5.1).

Children and adolescents 5 years to less than 18 years of age regardless of prior Prevenar 13vaccination

One single dose (0.5 mL) given on an individual basis according to official recommendations.

If Prevenar 13 was administered, at least 8 weeks should elapse before administering Prevenar 20 (seesection 5.1).

There are no data with Prevenar 20 in special populations.

Experience from clinical studies with Prevenar 13 (a pneumococcal conjugate vaccine consisting of13 polysaccharide conjugates that are also in Prevenar 20) are available in children and adults athigher risk of pneumococcal infection including immunocompromised children and adults with humanimmunodeficiency virus (HIV) infection or haematopoietic stem cell transplant (HSCT), and childrenwith sickle cell disease (SCD) (see sections 4.4 and 5.1).

Based on these data, the following posology was recommended for Prevenar 13:

- Individuals at higher risk of pneumococcal infection (e.g., individuals with SCD or HIVinfection), including those previously vaccinated with 1 or more doses of PPSV23, wererecommended to receive at least 1 dose of Prevenar 13.

- In individuals with a HSCT, the recommended immunisation series with Prevenar 13consisted of 4 doses of 0.5 mL each. The primary series consisted of 3 doses, with the firstdose given 3 to 6 months after HSCT and with an interval of at least 4 weeks between doses.

A booster dose was recommended 6 months after the third dose (see section 5.1).

The recommended dosing of Prevenar 13 may be considered in guiding vaccination with Prevenar 20in high-risk populations. For information on responses to pneumococcal vaccines inimmunocompromised individuals, please also refer to sections 4.4. and 5.1.

For intramuscular use only.

The vaccine (0.5 mL) should be given by intramuscular injection. The preferred sites are theanterolateral aspect of the thigh (vastus lateralis muscle) in infants or the deltoid muscle of the upperarm in children and adults. Prevenar 20 should be administered, with care to avoid injection into ornear nerves and blood vessels.

For instructions on the handling of the vaccine before administration, see section 6.6.

Hypersensitivity to the active substances, to any of the excipients listed in section 6.1, or to diphtheriatoxoid.

Do not inject Prevenar 20 intravascularly.

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

As with all injectable vaccines, appropriate medical treatment and supervision must always be readilyavailable in case of a rare anaphylactic reaction following the administration of the vaccine.

Vaccination should be postponed in individuals suffering from acute severe febrile illness. However,the presence of a minor infection, such as a cold, should not result in the deferral of vaccination.

The vaccine must be administered with caution to individuals with thrombocytopenia or a bleedingdisorder since bleeding may occur following an intramuscular administration.

The risk of bleeding in patients with coagulation disorders needs to be carefully evaluated beforeintramuscular administration of any vaccine, and subcutaneous administration should be considered ifthe potential benefit clearly outweighs the risks.

Protection against pneumococcal disease

Prevenar 20 may only protect against Streptococcus pneumoniae serotypes included in the vaccine,and will not protect against other microorganisms that cause invasive disease, pneumonia or otitismedia (OM). As with any vaccine, Prevenar 20 may not protect all individuals receiving the vaccinefrom invasive pneumococcal disease (IPD), pneumonia or OM. For the most recent epidemiologicalinformation in your country, you should consult with the relevant national organisation.

Safety and immunogenicity data on Prevenar 20 are not available for individuals inimmunocompromised groups. Vaccination should be considered on an individual basis.

Based on experience with pneumococcal vaccines, some individuals with altered immunocompetencemay have reduced immune responses to Prevenar 20.

Individuals with impaired immune response, whether due to the use of immunosuppressive therapy, agenetic defect, HIV infection, or other causes, may have reduced antibody response to activeimmunisation. The clinical relevance of this is unknown.

Safety and immunogenicity data with Prevenar 13 (a pneumococcal conjugate vaccine consisting of13 polysaccharide conjugates that are also in Prevenar 20) are available for individuals with HIVinfection, SCD or with a HSCT (see sections 4.8 and 5.1). Prevenar 20 should be used in accordancewith official recommendations.

In adults across all studied age groups, formal non-inferiority criteria were met although numericallylower geometric mean titres (GMTs) were observed with Prevenar 20 for most of the serotypescompared to Prevenar 13 (see section 5.1), In children, numerically lower immunoglobulin G (IgG)geometric mean concentrations (GMCs) were observed for all shared serotypes compared with

Prevenar 13 (see section 5.1). The clinical relevance of these observations for immunocompromisedindividuals are unknown.

The potential risk of apnoea and the need for respiratory monitoring for 48 to 72 h should beconsidered when administering the primary immunisation series to very premature infants (born lessthan or equal to 28 weeks of gestation), and particularly for those with a previous history of respiratoryimmaturity. As the benefit of vaccination is high in this group of infants, vaccination should not bewithheld or delayed.

This medicinal product contains polysorbate 80 (see section 2). Polysorbate 80 may causehypersensitivity reactions.

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

Different injectable vaccines should always be administered at different vaccination sites.

Do not mix Prevenar 20 with other vaccines or medicinal products in the same syringe.

In infants and children, 6 weeks to less than 5 years of age, Prevenar 20 can be administeredconcomitantly with any of the following vaccine antigens, either as monovalent or combinationvaccines: diphtheria, tetanus, acellular pertussis, hepatitis B, Haemophilus influenzae type b,inactivated poliomyelitis, measles, mumps, rubella, and varicella vaccines. In clinical trials, rotavirusvaccines were permitted to be administered concomitantly with Prevenar 20 and no safety concernswere observed.

Prevenar 20 may be administered concomitantly with seasonal influenza vaccine (QIV; surfaceantigen, inactivated, adjuvanted). In subjects with underlying conditions associated with a high risk ofdeveloping life-threatening pneumococcal disease, consideration may be given to separatingadministrations of QIV and Prevenar 20 (e.g., by approximately 4 weeks). In a double-blind,randomised study (B7471004) in adults 65 years of age and older, the immune response was formallynon-inferior, however numerically lower titres were observed for all pneumococcal serotypes includedin Prevenar 20 when given concomitantly with seasonal influenza vaccine (QIV, surface antigen,inactivated, adjuvanted) compared to when Prevenar 20 was given alone. The clinical relevance of thisfinding is unknown.

Prevenar 20 can be administered concomitantly with COVID-19 mRNA vaccine (nucleosidemodified).

There are no data on the concomitant administration of Prevenar 20 with other vaccines.

There are no data on the use of Prevenar 20 in pregnant women.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Administration of Prevenar 20 in pregnancy should only be considered when the potential benefitsoutweigh any potential risks for the mother and foetus.

It is unknown whether Prevenar 20 is excreted in human milk.

No human data on the effect of Prevenar 20 on fertility are available. Animal studies do not indicatedirect or indirect harmful effects with respect to female fertility (see section 5.3).

Prevenar 20 has no or negligible influence on the ability to drive and use machines. However, some ofthe effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

The safety of Prevenar 20 was evaluated in 5,987 participants, 6 weeks of age to less than 18 years ofage, in five clinical trials (one Phase 2 and four Phase 3), four randomised, double-blind,active-controlled clinical trials and one single-arm clinical trial; 3,664 participants received at least 1dose of Prevenar 20, and 2,323 participants received Prevenar 13 (control vaccine).

Participants 6 weeks to less than 15 months of age

Clinical trials were conducted in healthy infants 6 weeks to less than 15 months of age using a 3-doseschedule or a 4-dose schedule (see section 5.1). In these infant trials, 5,156 participants received atleast 1 dose of vaccine: 2,833 received Prevenar 20, and 2,323 received Prevenar 13. Overall,approximately 90% of participants in each group received all doses through the study-specified toddlerdose. In all studies, local reactions and systemic events were collected after each dose, and adverseevents (AEs) were collected in all studies from the first dose through 1 month after the last infantvaccination and from the toddler dose through 1 month after the toddler dose. Serious adverse eventswere evaluated through 1 month after the last dose in the Phase 3 trial B7471012 (Study 1012) andthrough 6 months after the last dose in Phase 3 trials (Studies 1011, 1013) and Phase 2 trial(Study 1003).

Prevenar 20 was well tolerated, when administered in a 3-dose and a 4-dose series, in the infant studypopulations with low rates of severe local reactions and systemic events, and most reactions resolvingwithin 1 to 3 days. The percentages of participants with local reactions and systemic events after

Prevenar 20 were generally similar to those after Prevenar 13. The most frequently reported localreactions and systemic events after any dose of Prevenar 20 were irritability, drowsiness, and pain atinjection site. In these studies, Prevenar 20 was co-administered or permitted to be administered withcertain routine paediatric vaccines (see section 4.5).

Study 1012 was a pivotal, double-blind, randomised, active-controlled Phase 3 trial, in which601 healthy infants received Prevenar 20 in a 3-dose series. The most frequently reported (> 10%)adverse reactions after any dose of Prevenar 20 were irritability (71.0% to 71.9%),drowsiness/increased sleep (50.9% to 61.2%), pain at injection site (22.8% to 42.4%), decreasedappetite (24.7% to 39.3%), redness at the injection site (25.3% to 36.9%), swelling at the injection site(21.4% to 29.8%), and fever ≥ 38.0 ℃ (8.9% to 24.3%). Most adverse reactions occurred within 1 to 2days following vaccination and were mild or moderate in severity and of short duration (1 to 2 days).

Studies 1011, 1013 and 1003, were double-blind, randomised, active-controlled trials that included2,232 healthy infants, vaccinated with Prevenar 20 in a 4-dose series. The most frequently reported(> 10%) adverse reactions observed after any dose of Prevenar 20 in infants were irritability (58.5% to70.6%), drowsiness/increased sleep (37.7% to 66.2%), pain at injection site (32.8% to 45.5%),decreased appetite (23.0% to 26.4%), redness at the injection site (22.6% to 24.5%), and swelling atthe injection site (15.1% to 17.6%). Most adverse reactions were mild or moderate followingvaccination and most reactions resolving within 1 to 3 days. Severe reactions were reportedinfrequently.

In Study 1013, the local reactions and systemic events in the preterm subgroup (111 infants born at34 to less than 37 weeks of gestation) were similar to or lower than the term infants in the study. In thepreterm subgroup, the frequency of any reported local reaction was 31.7% to 55.3% in the Prevenar 20group, and any systemic event was 65.0% to 85.5% in the Prevenar 20 group.

Participants aged 15 months to less than 18 years of age

In the Phase 3 trial B7471014 (Study 1014), 831 participants 15 months to less than 18 years of agereceived a single dose of Prevenar 20 in four age groups (209 participants 15 to less than 24 months ofage; 216 participants 2 years to less than 5 years of age; 201 participants 5 years to less than 10 yearsage; and 205 participants 10 years to less than 18 years of age). The participants less than 5 years ofage had received at least 3 prior doses of Prevenar 13.

The most frequently reported (> 10%) adverse reactions observed after any dose of Prevenar 20 inparticipants less than 2 years of age were irritability (61.8%), pain at the injection site (52.5%),drowsiness/increased sleep (41.7%), redness at the injection site (37.7%), decreased appetite (25.0%),swelling at the injection site (22.1%), and fever ≥ 38.0 °C (11.8%). In participants aged 2 years andolder, the most frequently reported adverse reactions were pain at the injection site (66.0% to 82.9%),muscle pain (26.5% to 48.3%), redness at the injection site (15.1% to 39.1%), fatigue (27.8% to37.2%), headache (5.6% to 29.3%), and swelling at the injection site (15.6% to 27.1%).

The safety of Prevenar 20 was evaluated in 4,552 participants 18 years of age and older in six clinicaltrials (two Phase 1, one Phase 2, and three Phase 3), and 2,496 participants in the control groups.

In the Phase 3 trials, 4,263 participants received Prevenar 20. This, included 1,798 participants 18through 49 years of age, 334 participants 50 through 59 years of age, and 2,131 participants 60 yearsof age and older (1,138 were 65 years of age and older). Of the participants who received Prevenar 20in the Phase 3 trials, 3,639 were naïve to pneumococcal vaccines, 253 had previously received

Pneumovax 23 (pneumococcal polysaccharide vaccine [23-valent]; PPSV23) (≥ 1 to ≤ 5 years prior toenrollment), 246 had previously received Prevenar 13 only (≥ 6 months prior to enrollment), and 125had previously received Prevenar 13 followed by PPSV23 (the dose of PPSV23 ≥ 1-year prior toenrollment).

Participants in the Phase 3 trial B7471007 (Pivotal Study 1007) were evaluated for adverse events for1 month after vaccination, and serious adverse events through 6 months after vaccination. This studyincluded 447 participants 18 to 49 years of age, 445 participants 50 to 59 years of age,1,985 participants 60 to 64 years of age, 624 participants 65 to 69 years of age, 319 participants 70 to79 years of age, and 69 participants ≥ 80 years of age.

In participants 18 to 49 years of age in Studies 1007 and a Phase 3 trial B7471008 (Lot Consistency

Study 1008), the most frequently reported adverse reactions were pain at injection site (79.2%),muscle pain (62.9%), fatigue (46.7%), headache (36.7%), and joint pain (16.2%). In participants 50 to59 years of age in Study 1007, the most frequently reported adverse reactions were pain at injectionsite (72.5%), muscle pain (49.8%), fatigue (39.3%), headache (32.3%), and joint pain (15.4%). Inparticipants ≥ 60 years of age in Study 1007, the most frequently reported adverse reactions were painat injection site (55.4%), muscle pain (39.1%), fatigue (30.2%), headache (21.5%), and joint pain(12.6%). These were usually mild or moderate in intensity and resolved within a few days aftervaccination.

Phase 3 Study B7471006 (Study 1006) evaluated Prevenar 20 in participants ≥ 65 years of age withvarying prior pneumococcal status (prior PPSV23, prior Prevenar 13 or prior Prevenar 13 followed by

PPSV23). In this study, the most frequently reported adverse reactions for participants were similar infrequency to those described for participants ≥ 60 years of age in Study 1007, with slightly higherinjection site pain (61.2%) in participants with prior Prevenar 13, and joint pain (16.8%) inparticipants with prior Prevenar 13 followed by PPSV23.

Tabulated lists of adverse reactions from the infant Phase 2, Phase 3 clinical trials in paediatric andadult populations, and postmarketing experience are presented below.

Adverse reactions from clinical trials

As Prevenar 20 contains the same 13 serotype-specific capsular polysaccharide conjugates and thesame vaccine excipients as Prevenar 13, the adverse reactions already identified for Prevenar 13 havebeen adopted for Prevenar 20. Table 1 presents adverse reactions reported in the Phase 2 infant trial,and the Phase 3 trials in paediatric and adult populations, based on the highest frequency amongadverse reactions, local reactions, or systemic events, after vaccination in an Prevenar 20 group orintegrated dataset. The data from clinical trials in infants reflect Prevenar 20 administeredsimultaneously with other routine childhood vaccines.

Adverse reactions are listed by 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 beestimated from available data).

Table 1. Tabulated Adverse Reactions From Prevenar 20 Clinical Trials

System Organ Adverse Reactions Frequency

Class

Infants/Children/Adolescents Adults6 weeks to less 5 years to lessthan 5 years of than 18 yearsage of age

Immune System Hypersensitivity Rarea - Uncommon

Disorders reaction includingface oedema,dyspnoea,bronchospasm

Metabolism and Decreased appetite Very common Very commona Very

Nutrition commona

Disorders

Psychiatric Irritability Very common Very commona -

Disorders Crying Uncommona - -

Nervous Drowsiness/increased Very common Very commona -

System sleep

Disorders Seizures (including Uncommon - -febrile seizures)

Hypotonic- Rarea - -hyporesponsiveepisode

Restless Very commona Very commona -sleep/decreased sleep

Headache - Very common Verycommon

Gastrointestinal Diarrhoea Common Commona Uncommonb

Disorders Nausea - - Uncommon

Vomiting Common Commona Uncommonb

Skin and Rash Common Commona Uncommonb

Subcutaneous Angioedema - - Uncommon

Tissue Urticaria or urticaria- Uncommon Uncommon -

Disorders like rash

Musculoskeletal Muscle pain - Very common Veryand connective commontissue Disorders Joint pain - Common Verycommon

Table 1. Tabulated Adverse Reactions From Prevenar 20 Clinical Trials

System Organ Adverse Reactions Frequency

Class

Infants/Children/Adolescents Adults6 weeks to less 5 years to lessthan 5 years of than 18 yearsage of age

General Fever (pyrexia) Very common Uncommon Common

Disorders and Fever greater than Common - -

Administration 38.9 °C

Site Conditions Fatigue - Very common Verycommon

Vaccination-site Very common Very common Commonberythema

Vaccination-site Very common Very common Commonbinduration/swelling

Vaccination-site Very common - -erythema or (after toddler doseinduration/swelling and in older(> 2.0-7.0 cm) children [age 2 to< 5 years])

Common (after - -infant series)

Vaccination-site Uncommon - -erythema orinduration/swelling(> 7.0 cm)

Vaccination-site Very common Very common Verypain/tenderness common

Vaccination-site Common Common Verypain/tenderness commonacausing limitation oflimb movement

Vaccination-site - - Uncommonpruritus

Lymphadenopathy - - Uncommon

Vaccination-site - - Uncommonurticaria

Chills - - Uncommonb

Vaccination-site Rarec - -hypersensitivity

a. These frequencies are based on adverse reactions (ARs) reported in clinical trials with Prevenar 13 as these ARswere not reported in Prevenar 20 trials of infants (Phase 2 and 3), children and adolescents less than 18 years of age,and adults 18 years and older (Phase 3); therefore, the frequency is not known.

b. Event reported from clinical trials in adults with Prevenar 13 with very common frequency (≥ 1/10).

c. AR not reported for Prevenar 13, although injection-site urticaria, injection-site pruritus, and injection-sitedermatitis were reported in Prevenar 13 postmarketing experience.

Safety with concomitant vaccine administration in adults

When Prevenar 20 was administered to adults aged ≥ 65 years together with the third (booster) dose ofa COVID-19 mRNA vaccine (nucleoside modified), the tolerability profile generally resembled that ofthe COVID-19 mRNA vaccine (nucleoside modified) administered alone. There were a fewdifferences in the safety profile when compared to administration of Prevenar 20 alone. In the phase 3trial B7471026 (Study 1026), pyrexia (13.0%) and chills (26.5%) were reported as “very common”with co-administration. There was also one report of dizziness (0.5%) in the co-administration group.

Adverse reactions from postmarketing experience

Table 2 includes adverse experiences that have been spontaneously reported during the postmarketinguse of Prevenar 13 in paediatric and adult populations, which may also occur with Prevenar 20. Thepostmarketing safety experience with Prevenar 13 is relevant to Prevenar 20, as Prevenar 20 containsall components (polysaccharide conjugates and excipients) of Prevenar 13. These events were reportedvoluntarily from a population of uncertain size. Therefore, it is not possible to reliably estimate theirfrequency or to establish, for all events, a causal relationship to vaccine exposure.

Table 2. Adverse Reactions From Prevenar 13 Postmarketing Experience

System Organ Class Frequency Not Known

Blood and lymphatic system disorders Lymphadenopathy localised to the region of thevaccination site

Immune system disorders Anaphylactic/anaphylactoid reaction, includingshock

Skin and subcutaneous tissue disorders Angioedema, Erythema multiforme

General disorders and administration site Vaccination-site dermatitis, Vaccination-siteconditions urticaria, Vaccination-site pruritus

Events reported spontaneously in Prevenar 13 postmarketing experience; therefore, the frequencies could not be estimatedfrom the available Prevenar 20 data and are considered as not known.

Additional information in special populations in studies with Prevenar 13

Participants 6 to < 18 years of age with HIV infection have similar frequencies of adverse reactions in

Table 1, except fever (11% to 19%), joint pain (24% to 42%), and vomiting (8% to 18%), which werevery common. Participants ≥ 18 years of age with HIV infection have similar frequencies of adversereactions in Table 1, except for pyrexia (5% to 18%) and vomiting (8% to 12%) which were verycommon and nausea (< 1% to 3%) which was common.

Participants 2 to < 18 years of age with HSCT have similar frequencies of adverse reactions in

Table 1, except vaccination-site pain causing limitation of limb movement (5% to 15%), vomiting (6%to 21%), diarrhoea (15% to 32%), and joint pain (25% to 32%), which were very common.

Participants ≥ 18 years of age with an HSCT have similar frequencies of adverse reactions in Table 1,except for pyrexia (4% to 15%), vomiting (6% to 21%), and diarrhoea (25% to 36%) which were verycommon.

Participants 6 to < 18 years of age with SCD have similar frequencies of adverse reactions in Table 1,except vaccination-site pain causing limitation of limb movement (11% to 16%), fever (21% to 22%),vomiting (13% to 15%), diarrhoea (13% to 25%), and joint pain (40% to 45%), which were verycommon.

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Overdose with Prevenar 20 is unlikely due to its presentation as a pre-filled syringe.

Pharmacotherapeutic group: vaccines, pneumococcal vaccines; ATC code: J07AL02

Prevenar 20 contains 20 pneumococcal capsular polysaccharides all conjugated to CRM197 carrierprotein, which modifies the immune response to the polysaccharide from a T-cell independentresponse to a T-cell dependent response. The T-cell dependent response leads to an enhanced antibodyresponse and induced functional antibodies (associated with opsonisation, phagocytosis and killing ofpneumococci) to protect against pneumococcal disease, as well as the generation of memory B cells,allowing for an anamnestic (booster) response on re-exposure to the bacterium.

Immune responses in children and adults, after exposure to Streptococcus pneumoniae or followingpneumococcal vaccination, can be determined by measuring IgG or opsonophagocytic activity (OPA)responses. OPA measures functional antibody activity and is considered to be an importantimmunologic surrogate measure of protection against pneumococcal disease in adults. In children,multiple immunogenicity criteria are used for the clinical evaluation of pneumococcal conjugatevaccines including the proportion of vaccinated children achieving a serotype-specific IgG antibodylevel corresponding to ≥ 0.35 µg/mL using the WHO enzyme linked immunosorbent assay (ELISA) oran equivalent assay-specific value.

Serotype-specific immune responses that correlate with individual protection against pneumococcaldisease have not been clearly defined.

No efficacy studies have been performed with Prevenar 20.

Immunogenicity data

Prevenar 20 clinical trials in infants, children and adolescents

Immunogenicity was assessed by serotype-specific IgG response rates (the proportion of participantsmeeting the serotype-specific IgG level of ≥ 0.35 μg/mL or equivalent assay-specific value) and IgG

GMCs at 1 month following the primary series and 1 month following the toddler dose. OPA GMTswere also measured 1 month following the primary series and following the toddler dose. Thepredefined concentration corresponding to 0.35 µg/mL in the WHO ELISA (or equivalentassay-specific threshold value) is only applicable at the population level and cannot be used to predictindividual or serotype-specific protection against IPD. No correlate of protection exists for pneumoniaand acute otitis media (AOM).

Two Phase 3 clinical trials (Study 1011, Study 1012) and one Phase 2 clinical trial (Study 1003)evaluated the immunogenicity of Prevenar 20 in a 3-dose or a 4-dose series in infants. One Phase 3

Study B7471027 (Study 1027) evaluated the immunogenicity of a single booster dose or 2 doses of

Prevenar 20 in toddlers 12 months to less than 24 months of age after 2 prior infant doses of

Prevenar 13. One Phase 3 study (Study 1014) of children 15 months to less than 18 years of ageevaluated a single dose of Prevenar 20.

Immune responses following 3 and 4 doses in a 4-dose infant vaccination series

In Study 1011, conducted in the United States and Puerto Rico, 1,991 healthy infants aged 2 months(≥ 42 to ≤ 98 days) at the time of consent and born at > 36 weeks of gestation, were randomised (1:1)and vaccinated with either Prevenar 20 or Prevenar 13 at approximately 2, 4, 6, and 12 to 15 months ofage. Participants also received other paediatric vaccines including a combination vaccine containingdiphtheria, tetanus, pertussis (acellular), hepatitis B (rDNA), poliomyelitis (inactivated), and a

Haemophilus influenzae type b conjugate vaccine (adsorbed) with all 3 doses, and measles, mumps,rubella combination vaccine, and varicella vaccine at the toddler dose. Rotavirus and influenzavaccines were permitted to be co-administered in the study.

One month after the third infant dose, NI for the difference in percentages of participants withspecified serotype-specific IgG concentrations (with a 10% NI criterion) was met for 9 of the 13matched serotypes and missed for 4 serotypes (serotypes 3, 4, 9V, and 23F) (Table 3). Six of the7 additional serotypes also met the non-inferiority criterion when compared to the lowest result for avaccine serotype in the Prevenar 13 group (excluding serotype 3); serotype 12F missed the statisticalnon-inferiority criterion. IgG GMCs 1 month after dose 3 of Prevenar 20 were non-inferior (with a0.5 NI criterion for IgG geometric mean ratio (GMR)) to those in the Prevenar 13 group for all 13matched serotypes. The NI criterion was also met for the 7 additional serotypes to the lowest IgG

GMC (excluding serotype 3) among the vaccine serotypes in the Prevenar 13 group (Table 3).

The antibody levels for all 7 additional serotypes were significantly higher than the correspondingserotype in the Prevenar 13 group (Tables 3 and 4).

One month after the toddler dose, NI for IgG GMCs (with a 0.5 NI criterion for IgG GMR) was metfor all 13 matched serotypes. The NI criterion was also met for the 7 additional serotypes to the lowest

IgG GMC (excluding serotype 3) among the vaccine serotypes in the Prevenar 13 group (Table 4).

Although non-inferiority was not formally tested for this endpoint, the observed differences(Prevenar 20 - Prevenar 13) in percentages of participants with specified serotype-specific IgGconcentrations 1 month after dose 4 were greater than -10% for all 13 matched serotypes exceptserotype 3 (-16.4%, CI -21.0%, -11.8%). For the 7 additional serotypes, the observed differences inpercentage of participants with specified serotype-specific IgG concentrations 1 month after dose 4ranged from -11.5% (serotype 12F) to 1.8% (serotype 15B, 22F, and 33F) (Table 4).

Table 3. Percentage of Participants With Specified Pneumococcal IgG Concentrations and

Pneumococcal IgG GMCs (µg/mL) One Month After Dose 3 of a 4-Dose Series,

Study 1011a

Percentages of Participants With

Specified IgG Concentrationsb IgG GMCs

Difference(Prevenar 20

Prevenar 20 Prevenar 13 - Prevenar Prevenar 20 Prevenar 13 Prevenar 20

Nc = 831-833 Nc = 801-802 13) Nc = 831-833 Nc = 801-802 /Prevenar 13% GMR% % (95% CId) GMCe GMCe (95% CIe)

Serotypes

- 6.3 0.651 84.9 91.1 (-9.4, -3.1) 0.74 1.14 (0.59, 0.72)

- 14.8 0.703 40.5 55.2 (-19.5, -10.0) 0.36 0.51 (0.64, 0.76)

- 9.4 0.704 78.2 87.5 (-13.0, -5.8) 0.75 1.08 (0.63, 0.78)

- 4.3 0.695 86.2 90.5 (-7.5, -1.2) 0.66 0.96 (0.61, 0.77)

- 1.9 0.726A 94.2 96.1 (-4.0, 0.2) 1.95 2.69 (0.65, 0.81)

- 4.1 0.606B 88.3 92.4 (-7.0, -1.2) 0.61 1.02 (0.51, 0.70)

- 0.9 0.757F 96.4 97.3 (-2.6, 0.9) 1.71 2.29 (0.69, 0.81)

Table 3. Percentage of Participants With Specified Pneumococcal IgG Concentrations and

Pneumococcal IgG GMCs (µg/mL) One Month After Dose 3 of a 4-Dose Series,

Study 1011a

Percentages of Participants With

Specified IgG Concentrationsb IgG GMCs

Difference(Prevenar 20

Prevenar 20 Prevenar 13 - Prevenar Prevenar 20 Prevenar 13 Prevenar 20

Nc = 831-833 Nc = 801-802 13) Nc = 831-833 Nc = 801-802 /Prevenar 13% GMR% % (95% CId) GMCe GMCe (95% CIe)

Serotypes

- 8.5 0.729V 80.3 88.8 (-12.0, -5.0) 0.87 1.21 (0.65, 0.80)

- 1.2 0.7914 94.2 95.4 (-3.4, 1.0) 2.16 2.72 (0.71, 0.89)

- 2.1 0.7718C 87.3 89.4 (-5.3, 1.0) 1.31 1.71 (0.70, 0.84)

- 1.7 0.7919A 96.3 98.0 (-3.4, -0.1) 0.72 0.91 (0.72, 0.86)0.2 0.7919F 96.0 95.9 (-1.8, 2.1) 1.59 2.00 (0.73, 0.86)

- 8.9 0.6623F 74.3 83.2 (-12.8, -4.9) 0.82 1.25 (0.58, 0.75)

Additional Serotypesf12.6 1.988 95.8 83.2f (9.8, 15.6) 1.80 0.91g (1.81, 2.16)4.8 1.3210A 88.0 83.2f (1.4, 8.3) 1.21 0.91g (1.18, 1.49)6.9 1.5211A 90.0 83.2f (3.6, 10.2) 1.39 0.91g (1.39, 1.67)

- 35.1 0.6012F 48.0 83.2f (-39.4, -30.8) 0.55 0.91g (0.54, 0.67)13.8 4.8215B 97.0 83.2f (11.1, 16.8) 4.40 0.91g (4.39, 5.30)15.5 4.0622F 98.7 83.2f (12.9, 18.3) 3.71 0.91g (3.68, pct. 4.48)6.1 1.6433F 89.3 83.2f (2.8, 9.5) 1.49 0.91g (1.46, 1.83)

Abbreviations: CI = confidence interval; dLIA = Luminex-based direct immunoassay; ELISA = enzyme-linkedimmunosorbent assay; GMC = geometric mean concentration; GMR = geometric mean ratio; IgG = immunoglobulin G;

LLOQ = lower limit of quantitation.

Note: Non-inferiority for a serotype was concluded if the lower bound of the 2-sided 95% CI for the percentage difference(Prevenar 20 - Prevenar 13) was > -10% or the lower bound of the 2-sided 95% CI for the GMR (Prevenar 20 to Prevenar13) was > 0.5 for that serotype.

Note: Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.

a. Study 1011 was conducted in the United States and the territory of Puerto Rico (NCT04382326).

b. Specified levels for the Prevenar 13 serotypes are from a published bridging study (Tan CY, et al. 2018) using resultsfrom after primary infant doses, before toddler dose, and after toddler dose (schedule of 3 infant doses followed by atoddler dose) except for serotype 19A, which used results from after primary infant doses only. For the additional 7serotypes, specified levels are from a concordance evaluation (clinical dLIA to re-test ELISA) of data from a Phase 2

Study B7471003, which also uses the schedule of 3 infant doses followed by a toddler dose.

c. N = Number of participants with valid IgG concentrations.

d. Two-sided CI based on the Miettinen and Nurminen method.

e. GMCs, GMRs and the associated 2-sided CIs were calculated by exponentiating the means and the mean differences(PREVENAR 20 - Prevenar 13) of the logarithm of the concentrations and the corresponding CIs (based on the

Student’s t distribution).

f. For the percentage differences of the 7 additional serotypes, the IgG results from serotype 23F (Prevenar 13 serotypewith the lowest percentage, excluding serotype 3) in the Prevenar 13 group was used in the comparisons for

Table 3. Percentage of Participants With Specified Pneumococcal IgG Concentrations and

Pneumococcal IgG GMCs (µg/mL) One Month After Dose 3 of a 4-Dose Series,

Study 1011a

Percentages of Participants With

Specified IgG Concentrationsb IgG GMCs

Difference(Prevenar 20

Prevenar 20 Prevenar 13 - Prevenar Prevenar 20 Prevenar 13 Prevenar 20

Nc = 831-833 Nc = 801-802 13) Nc = 831-833 Nc = 801-802 /Prevenar 13% GMR% % (95% CId) GMCe GMCe (95% CIe)

Serotypesnon-inferiority. Percentages of participants with specified IgG concentrations to serotypes 8, 10A, 11A, 12F, 15B, 22Fand 33F in the Prevenar 13 group were 1.4%, 1.9%, 1.4%, 0.1%, 1.2%, 1.4% and 1.5%, respectively.

g. For the GMRs of the 7 additional serotypes, the IgG results from serotype 19A (Prevenar 13 serotype with the lowest

GMC, excluding serotype 3) in the Prevenar 13 group was used in the comparisons for non-inferiority. IgG GMCs toserotypes 8, 10A, 11A, 12F, 15B, 22F and 33F in the Prevenar 13 group were 0.02 µg/mL, 0.01 µg/mL, 0.02 µg/mL,0.01 µg/mL, 0.03 µg/mL, 0.01 µg/mL and 0.02 µg/mL, respectively.

Table 4. Percentage of Participants With Specified Pneumococcal IgG Concentrationsand Pneumococcal IgG GMCs (µg/mL) One Month After Dose 4 of a 4-Dose

Series, Study 1011a

Percentages of Participants With

Specified IgG Concentrationsb IgG GMCs

Difference(Prevenar 20

Prevenar 20 Prevenar 13 - Prevenar Prevenar 20 Prevenar 13 Prevenar 20

Nc = 753-755 Nc = 744-745 13) Nc = 753-755 Nc = 744-745 /Prevenar 13% GMR% % (95% CId) GMCe GMCe (95% CIe)

Serotypes

- 2.6 0.691 95.5 98.1 (-4.5, -0.9) 1.47 2.12 (0.63, 0.76)

- 16.4 0.663 60.8 77.2 (-21.0, -11.8) 0.56 0.85 (0.61, 0.73)

- 0.1 0.784 98.8 98.9 (-1.3, 1.1) 3.77 4.84 (0.70, 0.86)0.2 0.745 98.8 98.7 (-1.1, 1.4) 1.87 2.51 (0.67, 0.82)

- 0.4 0.776A 99.5 99.9 (-1.2, 0.3) 9.01 11.69 (0.70, 0.85)

- 0.4 0.706B 99.1 99.5 (-1.4, 0.6) 4.01 5.74 (0.62, 0.79)

- 0.4 0.767F 99.5 99.9 (-1.2, 0.3) 3.91 5.18 (0.70, 0.82)

- 0.6 0.809V 98.3 98.9 (-2.0, 0.6) 3.44 4.30 (0.73, 0.88)

- 0.4 0.9014 99.2 99.6 (-1.4, 0.5) 5.68 6.34 (0.81, 1.00)

- 0.2 0.7418C 97.6 97.9 (-1.8, 1.3) 3.46 4.69 (0.67, 0.82)0.1 0.8519A 99.9 99.7 (-0.5, 0.9) 3.53 4.13 (0.77, 0.94)0.2 0.8619F 98.8 98.7 (-1.1, 1.4) 5.01 5.79 (0.78, 0.96)23F 96.6 97.9 -1.3 3.95 6.18 0.64

Table 4. Percentage of Participants With Specified Pneumococcal IgG Concentrationsand Pneumococcal IgG GMCs (µg/mL) One Month After Dose 4 of a 4-Dose

Series, Study 1011a

Percentages of Participants With

Specified IgG Concentrationsb IgG GMCs

Difference(Prevenar 20

Prevenar 20 Prevenar 13 - Prevenar Prevenar 20 Prevenar 13 Prevenar 20

Nc = 753-755 Nc = 744-745 13) Nc = 753-755 Nc = 744-745 /Prevenar 13% GMR% % (95% CId) GMCe GMCe (95% CIe)(-3.1, 0.4) (0.57, 0.72)

Additional Serotypes1.4 1.878 99.2 97.9f (0.1, 2.8) 3.97 2.12g (1.71, 2.06)0.8 2.9410A 98.7 97.9f (-0.5, 2.3) 6.22 2.12g (2.64, 3.26)0.8 1.6711A 98.7 97.9f (-0.5, 2.3) 3.53 2.12g (1.51, 1.84)

- 11.5 0.8812F 86.4 97.9f (-14.3, -8.9) 1.85 2.12g (0.79, 0.97)1.8 5.9515B 99.6 97.9f (0.7, 3.1) 12.59 2.12g (5.39, 6.55)1.8 5.0122F 99.6 97.9f (0.7, 3.1) 10.60 2.12g (4.54, 5.52)1.8 4.4033F 99.6 97.9f (0.7, 3.1) 9.31 2.12g (3.99, pct. 4.85)

Abbreviations: CI = confidence interval; dLIA = Luminex-based direct immunoassay; ELISA = enzyme-linkedimmunosorbent assay; GMC = geometric mean concentration; GMR = geometric mean ratio; IgG = immunoglobulin

G; LLOQ = lower limit of quantitation.

Note: Non-inferiority for a serotype was concluded if the lower bound of the 2-sided 95% CI for the GMR(Prevenar 20 to Prevenar 13) was > 0.5 for that serotype.

Note: Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.

a. Study 1011 was conducted in the United States and the territory of Puerto Rico (NCT04382326).

b. Specified levels for the Prevenar 13 serotypes are from a published bridging study (Tan CY, et al. 2018) usingresults from after primary infant doses, before toddler dose, and after toddler dose (schedule of 3 infant dosesfollowed by a toddler dose) except for serotype 19A, which used results from after primary infant doses only. Forthe additional 7 serotypes, specified levels are from a concordance evaluation (clinical dLIA to re-test ELISA) ofdata from a Phase 2 Study B7471003, which also uses the schedule of 3 infant doses followed by a toddler dose.

c. N = Number of participants with valid IgG concentrations.

d. Two-sided CI based on the Miettinen and Nurminen method.

e. GMCs, GMRs and the associated 2-sided CIs were calculated by exponentiating the means and the meandifferences (Prevenar 20 - Prevenar 13) of the logarithm of the concentrations and the corresponding CIs (basedon the Student’s t distribution).

f. For the percentage differences of the 7 additional serotypes, the IgG results from serotype 18C or 23F (Prevenar13 serotype with the lowest percentage excluding serotype 3) in the Prevenar 13 group was used in thecomparisons for non-inferiority. Percentages of participants with specified IgG concentrations to serotypes 8,10A, 11A, 12F, 15B, 22F and 33F in the Prevenar 13 group were 4.2%, 2.2%, 3.8%, 0.1%, 3.1%, 1.7% and 2.3%,respectively.

g. For the GMRs of the 7 additional serotypes, the IgG results from serotype 1 (Prevenar 13 serotype with the lowest

GMC excluding serotype 3) in the Prevenar 13 group was used in the comparisons for non-inferiority. IgG GMCsto serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F in the Prevenar 13 group were 0.03 µg/mL, 0.01 µg/mL, 0.02µg/mL, 0.01 µg/mL, 0.02 µg/mL, 0.00 µg/mL and 0.01 µg/mL, respectively.

OPA GMTs for the 13 matched serotypes in the Prevenar 20 group were generally comparable to the

OPA GMTs in the Prevenar 13 group 1 month after the third infant dose, and they were slightly lowerthan in the Prevenar 13 group for most serotypes after the toddler dose. There is variability of the OPAdata due to small sample sizes, while interpretation of the clinical relevance of slightly lower OPA

GMTs is unknown. The observed OPA GMTs for the 7 additional serotypes were substantially higherin the Prevenar 20 group than the Prevenar 13 group. Prevenar 20 immune responses also showboosting of IgG concentrations and OPA GMTs after the toddler dose, indicating that a memoryresponse was elicited by the 3 infant doses.

Pneumococcal IgG immune responses following 2 and 3 doses of 3-dose vaccination series

In Study 1012, 1,204 infants 2 months (≥ 42 to ≤ 112 days) of age at the time of consent and born at> 36 weeks of gestation were randomised (1:1) and vaccinated with either Prevenar 20 or Prevenar 13.

The first dose was given at enrollment, a second dose approximately 2 months later, and the third doseat approximately 11 to 12 months of age.

One month after 2 infant doses, the observed IgG GMCs for 9 of the 13 matched serotypes were non-inferior to those in the Prevenar 13 group, and 4 of the 13 matched serotypes (6A, 6B, 9V, and 23F)did not meet the 2-fold statistical criterion for non-inferiority. The percentages of participants withspecified serotype-specific IgG concentrations 1 month after Dose 2 of Prevenar 20 for 4 of the 13matched serotypes were non-inferior to those of the Prevenar 13 group based on a 10% differencenon-inferiority criteria; and 9 of the 13 matched serotypes (1, 3, 4, 5, 6A, 6B, 9V, 18C and 23F) didnot meet noninferiority.

The immune responses to the additional 7 serotypes after Prevenar 20 were non-inferior to the lowest

IgG GMC among the 13 serotypes (serotype 6B) in Prevenar 13. For the 7 additional serotypes, thepercentages of participants with specified serotype-specific IgG concentrations 1 month after Dose 2of Prevenar 20 for 5 of the 7 additional serotypes were non-inferior to the serotype with the lowestpercentage among the 13 serotypes (serotype 6B) in the Prevenar 13 group and serotypes 10A and 12Fdid not meet the statistical noninferiority criterion. The clinical relevance of these findings isunknown. Additionally, the IgG GMCs for the 7 additional serotypes were higher compared with the

IgG GMCs from the corresponding serotypes in the Prevenar 13 group after two infant doses. Onemonth after the third (toddler) dose, the observed IgG GMCs of Prevenar 20 were non-inferior to the

Prevenar 13 group for 12 of 13 matched serotypes except for serotype 6B and all 7 additionalserotypes were non-inferior to the lowest IgG GMC in the Prevenar 13 group. Additionally, the IgG

GMCs for the 7 additional serotypes were higher compared with the IgG GMCs from thecorresponding serotypes in the Prevenar 13 group after the toddler dose.

Functional responses, as measured by OPA GMTs, for the 13 matched serotypes at 1 month after thesecond infant dose and 1 month after the toddler dose in the Prevenar 20 group were generally similarto the observed OPA GMTs in the Prevenar 13 group for most serotypes and the observed OPA GMTswere substantially higher for the 7 additional serotypes at both timepoints in the Prevenar 20 groupthan in the Prevenar 13 group. Increases in IgG and OPA antibody responses after Prevenar 20following Dose 2 to after Dose 3 were observed for all 20 serotypes including those that missednon-inferiority, indicative of immunological memory.

Children 12 months to less than 18 years of age (Studies 1027 and 1014)

Children 12 months to less than 24 months of age previously vaccinated with Prevenar 13(Study 1027)

In a multicentre, randomised, partially double-blinded trial (Study 1027), 356 participants 12 monthsto less than 24 months of age with 2 prior infant doses of Prevenar 13 were enrolled and randomised toreceive either 1 or 2 toddler doses of Prevenar 20, or a single dose of Prevenar 13 (control). In thegroup receiving 2 doses of Prevenar 20, the second dose was given approximately 2 months after

Dose 1.

IgG immune responses to the 13 matched serotypes were observed after 1 or 2 doses of Prevenar 20with the observed IgG GMCs numerically higher for most of the 13 matched serotypes after 1 dose of

Prevenar 20 than after 2 doses of Prevenar 20. The observed IgG GMCs 1 month after last vaccinationfor the 13 matched serotypes were lower after 1 or 2 doses of Prevenar 20 than after 1 dose of

Prevenar 13. IgG immune responses to all 7 additional serotypes were observed after 1 or 2 doses of

Prevenar 20, with numerically higher IgG responses after 2 doses of Prevenar 20 than after a singledose. The observed IgG GMCs for all 7 additional serotypes (not covered by Prevenar 13) were low 1month after a single toddler dose of Prevenar 13.

OPA responses were elicited for all 20 serotypes with similar tendencies as described above for IgG

GMCs.

Children and adolescents 15 months to less than 18 years of age (Study 1014)

In a multicentre, single-arm trial (Study 1014), participants were enrolled into the study by age group(approximately 200 participants per group) to receive a single dose of Prevenar 20 as described below.

Children 15 months to less than 24 months of age previously vaccinated with Prevenar 13

In 15 months to less than 24 months age group, participants had been previously vaccinated with 3 or4 doses of Prevenar 13. Increases in IgG concentrations from before to 1 month after Prevenar 20 wereobserved for all 20 vaccine serotypes. The observed IgG geometric mean fold rises (GMFRs) to the 7additional serotypes ranged from 27.9 to 1847.7.

Children 24 months to less than 5 years of age previously vaccinated with Prevenar 13

In 24 months to less than 5 years age group, participants had been previously vaccinated with 3 or 4doses of Prevenar 13. Increases in IgG concentrations from before to 1 month after Prevenar 20 wereobserved for all 20 vaccine serotypes. The observed IgG GMFRs to the 7 additional serotypes rangedfrom 36.6 to 796.2. For the 7 additional serotypes, 71.2% to 94.6% had ≥ 4-fold rise in OPA titres.

Children and adolescents 5 years to less than 18 years of age previously unvaccinated or vaccinatedwith Prevenar 13

In participants 5 years to less than 10 years and 10 years to less than 18 years of age, irrespective ofprior vaccination history with Prevenar 13. Prevenar 20 elicited robust IgG and OPA immuneresponses to the 20 vaccine serotypes after a single dose in participants 5 to less than 18 years of age.

OPA GMFRs ranged from 11.5 to 499.0 to the 7 additional serotypes and increases in OPA GMTswere observed for all 20 vaccine serotypes.

Preterm infants

No immunogenicity data is available with Prevenar 20 in preterm infants. Based on experience with

Prevenar and Prevenar 13, immune responses are elicited in preterm infants, although they may belower than in term infants. The safety and tolerability of Prevenar 20 were evaluated in Phase 3 study(Study 1013), which included 111 late preterm infants (infants born at 34 to less than 37 weeks ofgestational age) among the total study population. Participants were randomised to receive a 4-doseseries of either Prevenar 20 (N=77) or Prevenar 13 (N=34).

Prevenar 20 clinical trials in adults

Three Phase 3 clinical trials, B7471006, B7471007 and B7471008 (Study 1006, Study 1007, and

Study 1008), were conducted in the United States and Sweden evaluating the immunogenicity of

Prevenar 20 in different adult age groups, and in participants who were either pneumococcalvaccine-naïve, or previously vaccinated with Prevenar 13, PPSV23, or both.

Each study included participants who were healthy or immunocompetent with stable underlyingconditions, including chronic cardiovascular disease, chronic pulmonary disease, renal disorders,diabetes mellitus, chronic liver disease, and medical risk conditions and behaviours (e.g., smoking)that are known to increase the risk of serious pneumococcal pneumonia and IPD. In the pivotal study(Study 1007), these risk factors were identified in 34%, 32%, and 26% of participants 60 years of ageand over, 50 to 59 years of age, and 18 to 49 years of age, respectively. A stable medical conditionwas defined as a medical condition not requiring significant change in therapy in the previous 6 weeks(i.e., change to new therapy category due to worsening disease), or any hospitalization for worseningdisease within 12 weeks before receiving the study vaccine.

In each study, immune responses elicited by Prevenar 20 and the control pneumococcal vaccines weremeasured by an opsonophagocytic activity (OPA) assay. OPA assays measure functional antibodies to

S. pneumoniae.

Comparison of immune responses of Prevenar 20 to Prevenar 13 and PPSV23

In a randomised, active-controlled, double-blind, non-inferiority clinical trial (Pivotal Study 1007) of

Prevenar 20 in the United States and Sweden, pneumococcal vaccine-naïve participants 18 years ofage and older were enrolled into 1 of 3 cohorts based on their age at enrollment (18 to 49, 50 to 59,and ≥ 60 years of age), and randomised to receive Prevenar 20 or control. Participants 60 years of ageand older were randomised in a 1:1 ratio to receive Prevenar 20 (n = 1,507) followed 1 month laterwith the administration of saline placebo or Prevenar 13 (n = 1,490), and with the administration of

PPSV23 1 month later. Participants 18 to 49 years of age and 50 to 59 years of age were randomlyassigned (3:1 ratio); they received a dose of Prevenar 20 (18 to 49 years of age: n = 335; 50 to 59 yearsof age: n = 334) or Prevenar 13 (18 to 49 years of age: n = 112; 50 to 59 years of age: n = 111).

Serotype-specific OPA GMTs were measured before the first vaccination and 1 month after eachvaccination. Non-inferiority of immune responses, OPA GMTs 1 month after vaccination, with

Prevenar 20 to a control vaccine for a serotype was declared if the lower bound of the 2-sided 95% CIfor the GMT ratio (Prevenar 20/Prevenar 13; Prevenar 20/PPSV23) for that serotype was greater than0.5.

In participants 60 years of age and older, the immune responses to all 13 matched serotypes elicited by

Prevenar 20 were non-inferior to those elicited by Prevenar 13 for the same serotypes 1 month aftervaccination. In general, numerically lower geometric mean titres were observed with Prevenar 20 inthe matched serotypes compared to Prevenar 13 (Table 5), however the clinical relevance of thesefindings is unknown.

The immune responses induced by Prevenar 20 to 6/7 additional serotypes were non-inferior to thoseinduced by PPSV23 to the same serotypes 1 month after vaccination. The response to serotype 8missed the pre-specified statistical non-inferiority criterion (the lower bound of the 2-sided 95% CI forthe GMT ratio is 0.49 instead of > 0.50) (Table 5). The clinical relevance of this observation isunknown. Supportive analyses for other serotype 8 endpoints in the Prevenar 20 group showedfavourable outcomes. These include a GMFR of 22.1 from before vaccination to 1 monthpost-vaccination, 77.8% of participants achieved a ≥ 4-fold rise in OPA titres from before vaccinationto 1 month after vaccination, and 92.9% of participants achieved OPA titres ≥ LLOQ 1 month aftervaccination.

Table 5. OPA GMTs 1 Month After Vaccination in Participants 60 Years of Age and Older

Given Prevenar 20 Compared to Prevenar 13 for the 13 Matched Serotypes and to

PPSV23 for the 7 Additional Serotypes (Study 1007)a,b,c,d

Prevenar 13 PPSV23

Prevenar 20 (N = 1390- (N = 1201- Vaccine Comparison(N = 1157-1430) 1419) 1319)

GMT Ratioe 95% CIe

GMTe GMTe GMTe

Serotype1 123 154 0.80 0.71, 0.903 41 48 0.85 0.78, 0.934 509 627 0.81 0.71, 0.935 92 110 0.83 0.74, 0.946A 889 1165 0.76 0.66, 0.886B 1115 1341 0.83 0.73, 0.957F 969 1129 0.86 0.77, 0.969V 1456 1568 0.93 0.82, 1.0514 747 747 1.00 0.89, 1.1318C 1253 1482 0.85 0.74, 0.9719A 518 645 0.80 0.71, 0.9019F 266 333 0.80 0.70, 0.9123F 277 335 0.83 0.70, 0.97

Additional Serotypes8 466 848 0.55 0.49, 0.6210A 2008 1080 1.86 1.63, 2.1211A 4427 2535 1.75 1.52, 2.0112F 2539 1717 1.48 1.27, 1.7215B 2398 769 3.12 2.62, 3.7122F 3666 1846 1.99 1.70, 2.3233F 5126 3721 1.38 1.21, 1.57

Abbreviations: CI = confidence interval; GMT = geometric mean titre; LLOQ = lower limit ofquantitation; N = number of participants; OPA = opsonophagocytic activity; PPSV23 = pneumococcalpolysaccharide vaccine (23-valent).

a. Study 1007 was conducted in the United States and in Sweden.

b. Non-inferiority for a serotype was met if the lower bound of the 2-sided 95% CI for the GMT ratio(ratio of Prevenar 20/comparator) was greater than 0.5 (2-fold criterion for non-inferiority).

c. Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.

d. Evaluable immunogenicity population.

e. GMTs and GMT ratios as well as the associated 2-sided CIs were based on analysis of log-transformed

OPA titres using a regression model with vaccine group, sex, smoking status, age at vaccination inyears, and baseline log transformed OPA titres.

Immunogenicity in participants 18 through 59 years of age

In Study 1007, participants 50 through 59 years of age and participants 18 through 49 years of agewere randomly assigned (3:1 ratio) to receive 1 vaccination with Prevenar 20 or Prevenar 13.

Serotype-specific OPA GMTs were measured before vaccination and 1 month after vaccination. Withboth vaccines, higher immune responses were observed in younger participants compared with olderparticipants. A non-inferiority analysis of Prevenar 20 in the younger age group versus Prevenar 20 inparticipants 60 through 64 years of age per serotype was performed to support the indication in adults18 through 49 years of age and 50 through 59 years of age. Non-inferiority was declared if the lowerbound of the 2-sided 95% CI for the GMT ratio (Prevenar 20 in participants 18 through 49 years ofage/60 through 64 years of age and in 50 through 59 years of age/60 through 64 years of age) foreach of the 20 serotypes was > 0.5. Prevenar 20 elicited immune responses to all 20 vaccine serotypesin the two of the younger age groups that were non-inferior to responses in participants 60 through64 years of age 1 month after vaccination (Table 6).

While not planned as an active control for immunogenicity evaluations in the study, a post hocdescriptive analysis showed generally numerically lower OPA GMTs 1 month after Prevenar 20 forthe matched serotypes compared to Prevenar 13 in participants 18 through 59 years of age, howeverthe clinical relevance of these findings is unknown.

As noted above, individuals with risk factors were included in this study. Across all the age groupsstudied, in general, a numerically lower immune response was observed in participants with riskfactors compared to participants without risk factors. The clinical relevance of this observation isunknown.

Table 6. Comparisons of OPA GMTs 1 Month After Prevenar 20 in Participants 18 Through49 or 50 Through 59 Years of Age to Participants 60 Through 64 Years of Age(Study 1007)a,b,c,d18-49 Years 60-64 Years 50-59 Years18-49 Years 60-64 Years Relative to 50-59 Years (N = 765- Relative to(N = 251-317) (N = 765-941) 60-64 Years (N = 266-320) 941) 60-64 Years

GMT Ratioe GMT Ratioe

GMTe GMTe (95% CI)e GMTe GMTe (95% CI)e

Serotype1.23 1.031 163 132 (1.01, 1.50) 136 132 (0.84, 1.26)1.00 1.063 42 42 (0.87, 1.16) 43 41 (0.92, 1.22)3.31 1.104 1967 594 (2.65, 4.13) 633 578 (0.87, 1.38)1.11 0.885 108 97 (0.91, 1.36) 85 97 (0.72, 1.07)3.84 1.216A 3931 1023 (3.06, pct. 4.83) 1204 997 (0.95, 1.53)3.41 1.256B 4260 1250 (2.73, 4.26) 1503 1199 (1.00, 1.56)1.58 0.897F 1873 1187 (1.30, 1.91) 1047 1173 (0.74, 1.07)3.50 1.029V 6041 1727 (2.83, pct. 4.33) 1726 1688 (0.83, 1.26)2.39 1.2514 1848 773 (1.93, 2.96) 926 742 (1.01, 1.54)3.20 1.3318C 4460 1395 (2.53, 4.04) 1805 1355 (1.06, 1.68)2.31 1.0319A 1415 611 (1.91, 2.81) 618 600 (0.85, 1.25)2.17 0.9919F 655 301 (1.76, 2.68) 287 290 (0.80, 1.22)4.80 1.6823F 1559 325 (3.65, 6.32) 549 328 (1.27, 2.22)

Additional Serotypes1.71 0.978 867 508 (1.38, 2.12) 487 502 (0.78, 1.20)1.62 1.0310A 4157 2570 (1.31, 2.00) 2520 2437 (0.84, 1.28)1.32 1.2211A 7169 5420 (1.04, 1.68) 6417 5249 (0.96, 1.56)1.91 1.1112F 5875 3075 (1.51, 2.41) 3445 3105 (0.88, 1.39)1.52 1.1715B 4601 3019 (1.13, 2.05) 3356 2874 (0.88, 1.56)

Table 6. Comparisons of OPA GMTs 1 Month After Prevenar 20 in Participants 18 Through49 or 50 Through 59 Years of Age to Participants 60 Through 64 Years of Age(Study 1007)a,b,c,d18-49 Years 60-64 Years 50-59 Years18-49 Years 60-64 Years Relative to 50-59 Years (N = 765- Relative to(N = 251-317) (N = 765-941) 60-64 Years (N = 266-320) 941) 60-64 Years

GMT Ratioe GMT Ratioe

GMTe GMTe (95% CI)e GMTe GMTe (95% CI)e1.69 0.9022F 7568 4482 (1.30, 2.20) 3808 4228 (0.69, 1.17)1.40 1.0233F 7977 5693 (1.10, 1.79) 5571 5445 (0.81, 1.30)

Abbreviations: CI = confidence interval; GMT = geometric mean titre; LLOQ = lower limit of quantitation; N = number ofparticipants; OPA = opsonophagocytic activity; PPSV23 = pneumococcal polysaccharide vaccine (23-valent).

a. Study 1007 was conducted in the United States and in Sweden.

b. Non-inferiority for a serotype was met if the lower bound of the 2-sided 95% CI for the GMT ratio (ratio of younger agegroup/60 through 64 years of age group) was greater than 0.5 (2-fold criterion for non-inferiority).

c. Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.

d. Evaluable immunogenicity population.

e. GMTs, GMT ratios, and the associated 2-sided CIs were based on analysis of log-transformed OPA titres using aregression model with age group, sex, smoking status, and baseline log transformed OPA titres. The comparisonsbetween participants 18 through 49 years of age and participants 60 through 64 years of age and between participants 50through 59 years of age and participants 60 through 64 years of age were based on separate regression models.

Immunogenicity of Prevenar 20 in adults previously vaccinated with pneumococcal vaccine

A Phase 3 randomised, open-label clinical trial (Study 1006) described immune responses to

Prevenar 20 in participants 65 years of age and older previously vaccinated with PPSV23, with

Prevenar 13, or with Prevenar 13 followed by PPSV23. Participants previously vaccinated with

Prevenar 13 (Prevenar 13 only or followed by PPSV23) were enrolled at sites in the United States,whereas participants and previously vaccinated with PPSV23 only were also enrolled from Swedishsites (35.5% in that category).

Prevenar 20 elicited immune responses to all 20 vaccine serotypes in participants 65 years of age andolder with prior pneumococcal vaccination (Table 7). Immune responses were lower in participants inboth groups who received prior PPSV23 vaccinations.

Table 7. Pneumococcal OPA GMTs Before and 1 Month After Prevenar 20 in Participants65 Years of Age and Older With Prior Pneumococcal Vaccination (Study 1006)a,b,c,d

Prior Prevenar 13 and

Prior PPSV23 only Prior Prevenar 13 only PPSV23

Before After Before After Before Aftervaccination vaccination vaccination vaccination vaccination vaccination(N = 208-247) (N = 216-246) (N = 210-243) (N = 201-243) (N = 106-121) (N = 102-121)

GMT GMT GMT GMT GMT GMT(95% CI)e (95% CI)e (95% CI)e (95% CI)e (95% CI)e (95% CI)e

Serotype24 51 34 115 42 821 (20, 28) (42, 62) (28, 41) (96, 138) (32, 56) (61, 110)13 31 15 54 20 393 (11, 15) (27, 36) (13, 18) (47, 63) (17, 25) (32, 48)29 150 67 335 73 1944 (23, 35) (118, 190) (53, 84) (274, 410) (53, 101) (143, 262)27 63 38 87 47 835 (24, 31) (53, 75) (32, 44) (73, 104) (37, 59) (65, 108)57 749 125 1081 161 10856A (46, 70) (577, 972) (99, 158) (880, 1327) (116, 224) (797, 1478)

Table 7. Pneumococcal OPA GMTs Before and 1 Month After Prevenar 20 in Participants65 Years of Age and Older With Prior Pneumococcal Vaccination (Study 1006)a,b,c,d

Prior Prevenar 13 and

Prior PPSV23 only Prior Prevenar 13 only PPSV23

Before After Before After Before Aftervaccination vaccination vaccination vaccination vaccination vaccination(N = 208-247) (N = 216-246) (N = 210-243) (N = 201-243) (N = 106-121) (N = 102-121)

GMT GMT GMT GMT GMT GMT(95% CI)e (95% CI)e (95% CI)e (95% CI)e (95% CI)e (95% CI)e107 727 174 1159 259 10336B (86, 133) (574, 922) (138, 219) (951, 1414) (191, 352) (755, 1415)156 378 210 555 206 3467F (132, 184) (316, 452) (175, 251) (467, 661) (164, 258) (277, 432)203 550 339 1085 352 7239V (171, 241) (454, 667) (282, 408) (893, 1318) (270, 459) (558, 938)212 391 282 665 336 58114 (166, 270) (315, 486) (224, 356) (554, 798) (238, 473) (434, 777)173 552 219 846 278 62118C (137, 218) (445, 684) (177, 272) (693, 1033) (209, 369) (470, 821)82 239 124 365 182 34119A (66, 100) (197, 288) (100, 153) (303, 440) (141, 235) (264, 439)61 159 89 242 120 21819F (52, 71) (131, 192) (74, 107) (199, 294) (94, 154) (168, 282)23 152 48 450 66 29323F (18, 28) (115, 199) (37, 62) (358, 566) (46, 94) (204, 420)

Additional Serotypes55 212 28 603 139 2948 (45, 67) (172, 261) (24, 33) (483, 753) (99, 195) (220, 392)212 1012 141 2005 400 158010A (166, 269) (807, 1270) (113, 177) (1586, 2536) (281, 568) (1176, 2124)510 1473 269 1908 550 156711A (396, 656) (1192, 1820) (211, 343) (1541, 2362) (386, 785) (1141, 2151)147 1054 53 1763 368 140112F (112, 193) (822, 1353) (43, 65) (1372, 2267) (236, 573) (1002, 1960)140 647 74 1480 190 106715B (104, 189) (491, 853) (56, 98) (1093, 2003) (124, 291) (721, 1578)167 1773 60 4157 286 271822F (122, 230) (1355, 2320) (45, 82) (3244, 5326) (180, 456) (1978, 3733)1129 2026 606 3175 1353 218333F (936, 1362) (1684, 2437) (507, 723) (2579, 3908) (1037, 1765) (1639, 2908)

Abbreviations: CI = confidence interval; GMT = geometric mean titre; LLOQ = lower limit of quantitation; N = number ofparticipants; OPA = opsonophagocytic activity; PPSV23 = pneumococcal polysaccharide vaccine (23-valent).

a. Study 1006 was conducted in the United States and in Sweden.

b. Assay results below the LLOQ were set to 0.5 × LLOQ in the analysis.

c. Evaluable immunogenicity population.

d. Open-label administration of Prevenar 20.

e. 2-sided CIs based on the Student t distribution.

Immune responses in special populations

Individuals with the conditions described below have an increased risk of pneumococcal disease.

Studies in individuals with SCD, HIV, and HSCT have not been conducted with Prevenar 20.

Experience from clinical studies with Prevenar 13 (a pneumococcal conjugate vaccine consisting of 13polysaccharide conjugates that are also in Prevenar 20) are available in children and adults at higherrisk of pneumococcal infection including immunocompromised children and adults with HIV infectionor HSCT, and children with SCD.

Participants who were healthy, or with stable non-immunocompromising chronic medical conditions,in all the age groups analysed had a lower immune response with Prevenar 20 compared with

Prevenar 13 in spite of meeting the predefined non-inferiority margins. The clinical relevance of thisobservation is unknown.

Sickle cell disease (SCD)

An open-label single-arm study with 2 doses of Prevenar 13 given 6 months apart was conducted in158 children and adolescents 6 to < 18 years of age with SCD who were previously vaccinated withone or more doses of 23-valent pneumococcal polysaccharide vaccine at least 6 months prior toenrollment. After the first vaccination, Prevenar 13 elicited antibody levels measured by both IgG

GMCs and OPA GMTs that were statistically significantly higher when compared with levels prior tovaccination. After the second dose, immune responses were comparable to those after the first dose.

One year after the second dose, antibody levels measured by both IgG GMCs and OPA GMTs werehigher than levels prior to the first dose of Prevenar 13, except for the IgG GMCs for serotypes 3 and5 that were numerically similar.

HIV infection

Children and adults not previously vaccinated with a pneumococcal vaccine

In Study 6115A1-3002 (B1851021), 151 participants 6 to < 18 years of age and 152 participants≥ 18 years of age infected with HIV (CD4 ≥ 200 cells/µL, viral load < 50,000 copies/mL and free ofactive acquired immunodeficiency syndrome [AIDS]-related illness) not previously vaccinated with apneumococcal vaccine were enrolled to receive 3 doses of Prevenar 13. As per the generalrecommendations, a single dose of PPSV23 was subsequently administered. The vaccines wereadministered at 1-month intervals. Immune responses were assessed in 128 to 133 evaluableparticipants 6 to < 18 years of age and in 131 to 137 evaluable participants ≥ 18 years of ageapproximately 1 month after each dose of the vaccine. After the first dose, Prevenar 13 elicitedantibody levels, measured by IgGGMCs and OPA GMTs, that were statistically significantly highercompared with levels prior to vaccination. After the second and third dose of Prevenar 13, immuneresponses were similar to or higher than those after the first dose.

Adults previously vaccinated with PPSV23

In Study 6115A1-3017 (B1851028), immune responses were assessed in 329 HIV-infectedparticipants ≥ 18 years of age (CD4+ T-cell count ≥ 200 cells/µL and viral load < 50,000 copies/mL)previously vaccinated with PPSV23 administered at least 6 months prior to enrollment. Participantsreceived 3 doses of Prevenar 13: at enrollment, 6 months, and 12 months after the first dose of

Prevenar 13. After the first vaccination, Prevenar 13 elicited antibody levels measured by IgG GMCsand OPA GMTs that were statistically significantly higher compared with levels prior to vaccination.

After the second and third dose of Prevenar 13, immune responses were comparable to or higher thanthose after the first dose. Participants who received previously 2 or more doses of PPSV23 showed asimilar immune response compared to participants who previously received a single dose.

Haematopoietic stem cell transplant (HSCT)

In Study 6115A1-3003 (B1851022), 61 participants 2 to < 18 years of age and 190 participants≥ 18 years of age with an allogeneic HSCT were enrolled to receive 3 doses of Prevenar 13 with aninterval of at least 1 month between doses. The first dose was administered at 3 to 6 months after

HSCT. A fourth (booster) dose of Prevenar 13 was administered 6 months after the third dose. As perthe general recommendations, a single dose of PPSV23 was administered 1 month after the fourthdose of Prevenar 13. Immune responses, as measured by IgG GMCs, were assessed in 41 to52 evaluable participants 2 to < 18 years of age and in 127 to 159 evaluable participants ≥ 18 years ofage approximately 1 month after vaccination. Prevenar 13 elicited increased antibody levels after eachdose. Immune responses after the fourth dose of Prevenar 13 were significantly increased for allserotypes compared with those after the third dose with the exception of serotype 3 in the 2 to< 18 years age group. Overall, participants 2 to < 18 years of age had generally higherserotype-specific immune responses compared with those ≥ 18 years of age.

This study demonstrated that 4 doses of Prevenar 13 elicited serum IgG concentrations similar to thoseinduced by a single dose in healthy participants of the same age group.

Invasive pneumococcal disease (IPD)

Vaccine effectiveness of Prevenar 13 against vaccine-serotype IPD was evaluated in the SpIDnetstudy, a multi-country enhanced IPD surveillance project in Europe. Based on data over a 6-yearperiod (2012-2018) from 10 sites in 7 European countries using Prevenar 13, the effectiveness against

IPD caused by serotypes in the vaccine among children < 5 years of age was 84.2% (95% CI,79.0-88.1) and 88.7% (95% CI, 81.7-92.7) in children receiving ≥ 1 Prevenar 13 dose and a completevaccination schedule, respectively.

Not applicable.

Non-clinical data revealed no special hazard for humans based on conventional studies ofrepeated-dose toxicity and reproduction and developmental toxicity.

Sodium chloride

Succinic acid

Polysorbate 80

Water for injections

For adjuvant, see section 2.

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

2 years

Store in a refrigerator (2 °C to 8 °C). Pre-filled syringes should be stored in the refrigeratorhorizontally to minimise the resuspension time.

Do not freeze. Discard if the vaccine has been frozen.

From a microbiological point of view, once removed from the refrigerator, the vaccine should be usedimmediately.

Stability data indicate that the vaccine is stable for 96 hours when stored at temperatures from 8 °C to25 °C, or 72 hours when stored at temperatures from 0 °C to 2 °C. At the end of these time periods

Prevenar 20 should be used or discarded. These data are intended to guide healthcare professionals incase of temporary temperature excursion only.

0.5 mL suspension for injection in pre-filled syringe (Type I glass) with a tip cap (syntheticisoprene/bromobutyl blend rubber) and a plunger stopper (chlorobutyl rubber).

Pack sizes of 1, 10, and 50 pre-filled syringes, with or without needle.

Not all pack sizes may be marketed.

During storage, a white deposit and clear supernatant may be observed in the pre-filled syringecontaining the suspension. Pre-filled syringes should be stored horizontally to minimise theresuspension time.

Preparation for administration

Step 1. Vaccine resuspension

Hold the pre-filled syringe horizontally between the thumband the forefinger and shake vigorously until the contents ofthe syringe are a homogeneous white suspension. Do not usethe vaccine if it cannot be resuspended.

Step 2. Visual inspection

Visually inspect the vaccine for large particulate matter anddiscolouration prior to administration. Do not use if largeparticulate matter or discolouration is found. If the vaccine isnot a homogeneous white suspension, repeat steps 1 and 2.

Step 3. Remove syringe cap

Remove the syringe cap from the Luer lock adapter byslowly turning the cap counter clockwise while holding the

Luer lock adapter.

Note: Care should be taken to ensure that the extendedplunger rod is not depressed while removing the syringe cap.

Step 4. Attach a sterile needle

Attach a needle appropriate for intramuscular administration to the pre-filled syringe by holding the

Luer lock adapter and turning the needle clockwise.

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

Pfizer Europe MA EEIG

Boulevard de la Plaine 171050 Bruxelles

Belgium

EU/1/21/1612/001

EU/1/21/1612/002

EU/1/21/1612/003

EU/1/21/1612/004

EU/1/21/1612/005

EU/1/21/1612/006

Date of first authorisation: 14 February 2022

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu.