Pneumocon 13

The Pneumococcal Polysaccharide Conjugate Vaccine, 13-Valent (Adsorbed) (PCV13-TT) is formulated by compounding the capsular polysaccharide antigen of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F, individually conjugated to tetanus toxoid carrier protein. The individual polysaccharides are extracted from the cultures of Streptococcus pneumoniae, and purified through centrifugation, precipitation, and ultrafiltration. The polysaccharides are chemically activated and derivatized, and then conjugated to tetanus toxoid carrier protein to form the glycoconjugate, with aluminum phosphate as the adjuvant. The vaccine should be shaken well to obtain a homogeneous milky white suspension. During storage, a white deposit and clear supernatant might be observed due to adjuvant precipitation.
Active substances: Capsular polysaccharides of Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F conjugated to tetanus toxoid carrier protein.
Excipients/Inactive Ingredients: Sodium chloride, sodium dihydrogen phosphate monohydrate, disodium hydrogen phosphate dodecahydrate, aluminum phosphate and water for injection.
Each dose (0.5 mL) of the vaccine contains: See Table 1.

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Pharmacology: Pharmacodynamic/Pharmacokinetics: Not applicable.
Clinical Trials: PCV13-TT Immunogenicity Clinical Trials in Healthy Subjects 2 through 71 Months of Age: In China, the pivotal phase III clinical trial of PCV13-TT was a randomized, blind and non-inferiority study comparing to Prevenar. This study evaluated the immunogenicity and safety of PCV13-TT and Prevenar in 2760 healthy subjects 2 through 71 months of age (at least 6 weeks of age). A total of 1040 infants aged 3 months were randomized in a 1:1 ratio as the PCV13-TT group and the Prevenar group, with PCV13-TT or Prevenar given at 3, 4, 5, and 12-15 months of age, respectively; for 520 infants aged 2 months (at least 6 weeks of age), PCV13-TT was vaccinated at 2, 4, 6 and 12-15 months of age. 1200 children of 7 through 71 months of age, including children 7 months through 11 months of age, 12 months through 23 months of age and 24 months through 5 years of age (prior to the 6^th birthday) who were naïve to the pneumococcal conjugate vaccine, were split into three age groups with each containing 400 subjects randomized in a 1:1 ratio given 3, 2 or 1 dose of PCV13-TT or Prevenar, respectively, according to the age-appropriate schedules in Table 8 to Table 10.
Immune responses elicited by PCV13-TT and Prevenar were measured by serotype-specific IgG antibody concentration and the geometric mean concentration (GMC) of serotype-specific IgG antibody one month post primary series as primary endpoints. The IgG and GMC of IgG post booster dose, as well as serotype-specific OPA titer and OPA geometric mean titer (GMT) one month post primary series and booster dose as secondary endpoints.
For the 7 serotypes in common to both vaccines, non-inferiority between vaccines was met if the lower limit of the 2-sided 97.5% confidence interval (CI) of the positive rate difference (PCV13-TT minus the Prevenar) was not less than -10%, or the lower limit of 2-sided 97.5% CI of the GMC ratio (PCV13-TT/Prevenar) was not less than 0.5.
The response to the 6 additional serotypes, which is contained in PCV13-TT but not in Prevenar, superiority between vaccines was met if the lower limit of 2-sided 95% CI of antibody positive rate was not less than 0, the lower limit of 2-sided 95% CI of the GMC ratio (PCV13-TT/Prevenar) was not less than 1, and the lower limit of 2-sided 95% CI of IgG antibody positive rate was not less than 70%.
A subset of sera randomly obtained from 100 subjects in each age group for PCV13-TT and Prevenar, totaling 900 subjects were tested by opsonophagocytic assay (OPA) to measure the ability of serotype-specific functional antibodies to eliminate corresponding pneumococci by promoting complement-mediated phagocytosis.
For immunogenicity assessment, the immunogenicity results of PCV13-TT (2 months of age) group, Prevenar (3 months of age) group and PCV13-TT (3 months of age) group were compared in sequence (please refer to Table 8 and Table 9 for dosing regimen for subjects in PCV13-TT (2 months of age) group and Prevenar (3 months of age group). The results are shown as follows: Main target population (3 months of age): Primary series: In PCV13-TT (3 months of age) group, after primary series, six out of seven common serotypes met the non-inferiority criteria with the exception of 6B; the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT group were non-inferior to the serotype with the lowest response among all the 7 common serotypes in the Prevenar group.
Booster dose: In PCV13-TT (3 months of age) group, after complete series, all 7 common serotypes met the non-inferiority criteria; the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT group were non-inferior to the serotype with the lowest response among all the 7 common serotypes in the Prevenar group.
For PCV13-TT (2 months of age) group vs Prevenar (3 months of age) group: Primary series: In PCV13-TT (2 months of age) group, after primary series, the IgG antibody was firstly compared between the PCV13-TT (2 months of age) group and the Prevenar (3 months of age) group, showing that all 7 common serotypes met the non-inferiority criteria and the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT (2 months of age) group were non-inferior to the serotype with the lowest IgG response among all 7 common serotypes in the Prevenar (3 months of age) group. The IgG antibody was then compared between the PCV13-TT (2 months of age) group and the PCV13-TT (3 months of age) group. IgG antibody of twelve out of the thirteen serotypes met the non-inferiority criteria with the exception of serotype 5.
Booster dose: In PCV13-TT (2 months of age) group, after complete series, the IgG antibody was firstly compared between the PCV13-TT (2 months of age) group and the Prevenar (3 months of age) group. All 7 common serotypes met the non-inferiority criteria and the 6 additional serotypes reached superiority threshold; besides, the 6 additional serotypes in the PCV13-TT (2 months of age) group were non-inferior to the serotype with the lowest IgG response among all 7 common serotypes in the Prevenar (3 months of age) group. The IgG antibody was then compared between the PCV13-TT (2 months of age) group and the PCV13-TT (3 months of age) group. IgG antibody of all the 13 serotypes met the non-inferiority criteria.
For PCV13-TT (7-11 months of age) group: Primary series: In PCV13-TT (7-11 months) group, after primary series, the proportions of subjects with IgG antibody concentration ≥0.35 μg/mL for common serotypes were all non-inferior to those in Prevenar group. The additional serotypes in PCV13-TT (7-11 months of age) group had reached superiority criteria after primary series.
Booster dose: In PCV13-TT (7-11 months of age) group, after complete series, all 7 common serotypes met the non-inferiority criteria and the 6 additional serotypes (except 19A) reached superiority threshold.
For PCV13-TT (12-23 months of age) group and PCV13-TT (24-71 months) group: Complete series: The proportions of subjects with IgG antibody concentration ≥0.35 μg/mL for common serotypes were all non-inferior to those in Prevenar group. The additional serotypes in PCV13-TT (12-23 months) group and PCV13-TT (24-71 months of age) group, superiority criteria were generally met after primary series, except for serotype 19A in PCV13-TT (12-23 months of age) group and serotypes 6A and 19A in PCV13-TT (24-71 months of age) group.
Please refer to Table 10 for dosing regimen for subjects in PCV13-TT (7-11 months of age) group, PCV13-TT (12-23 months of age) group and PCV13-TT (24-71 months of age) group.
The testing results of OPA antibody demonstrated that all 13 serotypes of PCV13-TT were capable of inducing anti-pneumococcal OPA antibodies in all age groups in the PCV13-TT group.
The immunogenicity data from subjects 2 months (at least 6 weeks of age) through 71 months of age are shown in Table 2 to Table 7. (See Tables 2 to 7.)

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The vaccine is indicated for use in infants and children 6 weeks through 5 years of age (before the 6^th birthday).
Immune responses in recipients could be elicited by immunization of PCV13-TT, and this vaccine is indicated for the prevention of invasive diseases caused by 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) of Streptococcus pneumoniae.
The vaccine does not protect against diseases caused by Streptococcus pneumoniae serotypes that are not contained in the vaccine.

Since this product is a suspension containing an adjuvant, shake vigorously immediately prior to use to obtain a homogenous, white suspension in the vaccine container. This product is for intramuscular injection only. The preferred sites for injection are the anterolateral aspect of the thigh in infants and the deltoid muscle of the upper arm in toddlers and children. The injection volume is 0.5 mL for each single human dose. The vaccine should not be injected in and/or near the areas where nerve trunks and/or blood vessels may locate.
Vaccination schedules for infants and toddlers: The product is to be administered as a four-dose series at 2, 4, 6, and 12-15 months of age or 3, 4, 5, and 12-15 months of age, respectively, as described in Table 8 and Table 9. (See Tables 8 and 9.)

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For children 7 months through 5 years of age who have not received the product, the catch-up schedule in Table 10 applies: See Table 10.

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Overdose with PCV13-TT is unlikely due to its presentation as a single-dose vial or a single-dose pre-filled syringe. No overdose data are available for the product in recipients.

Hypersensitivity to any component of the product, including active substances, excipients, or tetanus toxoid, etc.

Do not vaccinate via intravenous route or by gluteal intramuscular injection, and ensure the syringe needle is not puncturing blood vessels during injection.
Check if the package, container, label, appearance and expiration date of the vaccine are in compliance with corresponding requirements before administration. Do not use the vaccine in case that any crack is observed in the container, loosened stopper, detached label, foreign particle(s) or discoloring inside the container, etc. Do not use the vaccine after the expiration date.
During storage, a white deposit and clear supernatant can be observed. This does not constitute a sign of deterioration. The vaccine should be shaken well to obtain a homogeneous white suspension prior to expelling air from the syringe, and should be inspected visually for any particulate matter and/or variation of physical aspect prior to administration. Do not use if the content appears otherwise.
Use immediately after unsealing. A single human dose shall be used up each time according to prescribing information.
The vaccination should be postponed in case of fever, acute diseases, and acute attack of chronic diseases.
Appropriate monitoring and medical care and rescue measures should be readily available in case of occurrence of rare hypersensitivity reactions during vaccination. If allergic reactions occur after vaccination, please go to the vaccination site or hospital in time.
Cautions should be taken for vaccination in recipients with thrombocytopenia, any coagulopathy or those who are receiving anticoagulant treatment.
Preterm infants should be monitored for the potential risk of apnea during primary series. For preterm infants under hospitalization (gestational age ≤30 weeks at birth) vaccinated with PCV13-TT according to the recommended immunization schedule, at least 48 hours of monitoring should be considered. Given the benefit of vaccination in preterm infants, discontinued or deferred vaccination of the product is not recommended.
Given that no safety and immunogenicity data are available for PCV13-TT in immuno-compromised individuals (e.g., malignancy or nephrotic syndrome), vaccination in this special group should be considered on an individual basis.
The use of PCV13-TT does not replace the use of 23-valent Pneumococcal Polysaccharide Vaccine in children ≥24 months of age with conditions such as sickle cell disease, asplenia, HIV infection, chronic illness, or those who are immuno-compromised.
Under no circumstances shall the tetanus toxoid contained in the vaccine replace the routine immunization of tetanus vaccine or tetanus-containing vaccine.
This product cannot guarantee all recipients can be protected from any diseases caused by Streptococcus pneumoniae.

Pregnancy: No data are available for using the product in pregnant women.
Lactation: Whether this product is excreted into human milk remains unknown.

Clinical Trials for PCV13-TT: Two clinical trials (phase I and III) of PCV13-TT were conducted in China, including 120 and 2760 subjects, respectively; among all subjects (N=2880), 1754 had been vaccinated with at least one dose of PCV13-TT. The adverse events were observed through safety follow-up for all subjects, starting from the first dose through 7 days and 30 days post each dose for solicited and unsolicited adverse events, with long-term safety monitoring conducted until around 6 months after the last vaccination for serious adverse events (SAES).
Summary: The incidence rates of adverse reactions reported in clinical trials, according to the guidance on classifications of adverse reactions recommended by The Council for International Organizations of Medical Sciences (CIOMS), are classified as: very common (≥10%), common (≥1% to <10%), uncommon (≥0.1% to <1%), rare (≥0.01% to <0.1%), and very rare (<0.01%). The safety data for the primary series of PCV13-TT collected from both phase I and phase III clinical trials of all subjects are summarized as follows: See Table 11.

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Adverse Reactions in Phase III Clinical Trial: Serious Adverse Events: SAEs were collected from Dose 1 till 180 days post complete series. In phase III, 1 case of SAE was reported during the primary series in the PCV13-TT (3 months of age) group (please refer to Table 9 for dosing regimen for subjects aged 3 months in PCV13-TT group). This SAE was reported to be fever and considered to be possibly related to PCV13-TT. Other SAEs were adjudicated to be irrelevant to PCV13-TT.
The Incidence Rates and Severity of Solicited Adverse Reactions: The incidence rates and severity of solicited adverse reactions post primary series and booster dose in phase III clinical trial of PCV13-TT comparing to the comparator vaccine (Pneumococcal 7-valent Conjugate Vaccine [Diphtheria CRM197 Protein], referred to as Prevenar) are summarized in Table 12 and Table 13. (See Tables 12 and 13.)

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Incidence Rates and Severity of Unsolicited Adverse Reactions: The incidence rates of unsolicited adverse reactions for PCV13-TT were 0.06%-0.73% with most episodes being grade 1 in severity. The documented symptoms include: nasal obstruction, rhinorrhea, nasopharyngitis, upper respiratory tract infection, oral ulcer, abdominal pain, abdominal distension, decreased appetite, hyperhidrosis, increased tearing and eye discharge and red eyelids.

No concomitant immunization data are available either inside or outside of China for the product.
During the phase III clinical trial of the product, the interval between vaccination of the product and any other diphtheria, tetanus, and acellular pertussis (DTaP)-containing vaccine was ≥10 days. No adverse impact of DTaP-containing vaccine was observed on the immunogenicity of PCV13-TT under the indicated immunization interval.

Incompatibilities: This vaccine should not be mixed with other medicinal products considering that no compatibility studies have been conducted.

Transport and store refrigerated at 2°C to 8°C, protect from light.
DO NOT FREEZE. Discard if the vaccine is frozen.
Shelf Life: The shelf life of the vaccine is 24 months.

Vaccines, Antisera & Immunologicals

J07AL02 - pneumococcus, purified polysaccharides antigen conjugated ; Belongs to the class of pneumococcal bacterial vaccines.

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