Product Monograph - Adacel-Polio
RECENT MAJOR LABEL CHANGES
| 1 INDICATIONS | 09/2020 |
|---|---|
| 4 DOSAGE AND ADMINISTRATION, 4.2 Recommended Dose and Dosage Adjustment | 09/2020 |
| 6 DOSAGE FORMS, STRENGTH, COMPOSITION AND PACKAGING | 06/2023 |
7 WARNINGS AND PRECAUTIONS
| 09/2020 |
TABLE OF CONTENTS
RECENT MAJOR LABEL CHANGES .............................................................................................. 2
TABLE OF CONTENTS ................................................................................................................ 2
PART I: HEALTH PROFESSIONAL INFORMATION ....................................................................... 4
1 INDICATIONS ................................................................................................................ 4
1.1 Pediatrics ................................................................................................................ 4
1.2 Geriatrics ................................................................................................................. 4
2 CONTRAINDICATIONS ................................................................................................... 4
4 DOSAGE AND ADMINISTRATION ................................................................................... 5
4.2 Recommended Dose and Dosage Adjustment ........................................................ 5
4.4 Administration ........................................................................................................ 6
5 OVERDOSAGE ............................................................................................................... 6
6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ................................... 6
7 WARNINGS AND PRECAUTIONS .................................................................................... 8
7.1 Special Populations ................................................................................................. 9
7.1.1 Pregnant Women .............................................................................................. 9
7.1.2 Breast-feeding ................................................................................................... 9
8 ADVERSE REACTIONS .................................................................................................. 10
8.2 Clinical Trial Adverse Reactions ............................................................................. 10
8.5 Post-Market Adverse Reactions ............................................................................ 12
9 DRUG INTERACTIONS .................................................................................................. 12
9.4 Vaccine-Drug Interactions ..................................................................................... 12
10 CLINICAL PHARMACOLOGY ......................................................................................... 13
10.1 Mechanism of Action ...................................................................................... 13
10.2 Pharmacodynamics ......................................................................................... 13
11 STORAGE, STABILITY AND DISPOSAL ........................................................................... 14
12 SPECIAL HANDLING INSTRUCTIONS ............................................................................. 14
PART II: SCIENTIFIC INFORMATION ......................................................................................... 15
13 PHARMACEUTICAL INFORMATION .............................................................................. 15
14 CLINICAL TRIALS .......................................................................................................... 16
14.1 Trial Design and Study Demographics ............................................................. 16
14.2 Study Results ................................................................................................... 17
14.4 Immunogenicity .............................................................................................. 31
15 MICROBIOLOGY .......................................................................................................... 31
16 NON-CLINICAL TOXICOLOGY ....................................................................................... 31
PATIENT MEDICATION INFORMATION ................................................................................... 32
PART I: HEALTH PROFESSIONAL INFORMATION
1 INDICATIONS
ADACEL®-POLIO is indicated for:
Active booster immunization for the prevention of tetanus, diphtheria, pertussis (whooping cough) and poliomyelitis in persons 4 years of age and above.
Vaccination during pregnancy for passive immunization against pertussis disease in young infants. (See 4 DOSAGE AND ADMINISTRATION, Pregnant Women, and Immunogenicity in Pregnancy.)
In children 4 to 6 years of age, ADACEL®-POLIO may be considered as an alternative for the fifth dose of diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis vaccine (DTaP-IPV).
Persons who have had tetanus, diphtheria or pertussis should still be immunized since these clinical infections do not always confer immunity. Human Immunodeficiency Virus (HIV)-infected persons, both asymptomatic and symptomatic, should be immunized against tetanus, diphtheria and pertussis according to standard schedules.
1.1 Pediatrics
ADACEL®-POLIO has been used in clinical studies in children as young as 3 years of age.
1.2 Geriatrics
ADACEL®-POLIO has been used in clinical studies in persons up to 91 years of age.
Tetanus Prophylaxis in Wound Management
The need for active immunization with a tetanus toxoid-containing preparation (such as Td Adsorbed vaccine, ADACEL® or ADACEL®-POLIO) with or without passive immunization with Tetanus Immune Globulin, depends on both the condition of the wound and the patient’s vaccination history. (See 4 DOSAGE AND ADMINISTRATION.)
2 CONTRAINDICATIONS
Hypersensitivity
Known systemic hypersensitivity reaction to any component of ADACEL®-POLIO or a life-threatening reaction after previous administration of the vaccine or a vaccine containing one or more of the same components are contraindications to vaccination. (See 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING). Because of uncertainty as to which component of the vaccine may be responsible, none of the components should be administered. Alternatively, such persons may be referred to an allergist for evaluation if further immunizations are considered.
Acute Neurological Disorders
Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures) within 7 days of a previous dose of a pertussis-containing vaccine that is not attributable to another identifiable cause is a contraindication to administration of any pertussis-containing vaccine, including ADACEL®-POLIO.
4 DOSAGE AND ADMINISTRATION
4.2 Recommended Dose and Dosage Adjustment
ADACEL®-POLIO should be administered as a single injection of 1 dose (0.5 mL) by the intramuscular route. The preferred site is the deltoid muscle.
Fractional doses (doses <0.5 mL) should not be given. The effect of fractional doses on safety and efficacy has not been determined.
If ADACEL®-POLIO is administered to a pregnant woman, it should ideally be done during the third trimester of pregnancy or according to recommendations from the National Advisory Committee on Immunization (NACI).
Health-care professionals should also refer to the National Advisory Committee on Immunization (NACI) recommendations for tetanus prophylaxis in routine wound management shown in Table 1 .
Table 1: NACI Recommended Use of Immunizing Agents in Wound Management
| History of Tetanus Immunization | Clean, Minor Wounds | All Other Wounds | ||
|---|---|---|---|---|
| Td* | TIG † (Human) | Td* | TIG† (Human) | |
| Uncertain or <3 doses of an immunization series‡ | Yes | No | Yes | Yes |
| ≥3 doses received in an immunization series‡ | No§ | No | No** | No†† |
* Adult-type tetanus and diphtheria toxoid.
† Tetanus immune globulin, given at a separate site from the Td.
‡ Primary immunization is at least 3 doses at age appropriate intervals.
§ Yes, if >10 years since last booster.
** Yes, if >5 years since last booster.
†† Yes, if persons are known to have a significant humoral immune deficiency state (e.g., HIV, agammaglobulinemia) since immune response to tetanus toxoid may be suboptimal.
A thorough attempt must be made to determine whether a patient has completed primary immunization. Persons who have completed primary immunization against tetanus and who sustain wounds that are minor and uncontaminated, should receive a booster dose of a tetanus toxoid-containing preparation if they have not received tetanus toxoid within the preceding 10 years. For tetanus-prone wounds (e.g., wounds contaminated with dirt, feces, soil and saliva, puncture wounds, avulsions and wounds resulting from missiles, crushing, burns or frostbite), a booster is appropriate if the patient has not received a tetanus toxoid-containing preparation within the preceding 5 years.
For adults who have not previously received a dose of acellular pertussis vaccine, a single tetanus-diphtheria (Td) booster dose should be replaced by a combined tetanus-diphtheria-acellular pertussis vaccine (Tdap).
4.4 Administration
Administration Route Related Precautions:
Do not administer ADACEL®-POLIO by intravascular injection: ensure that the needle does not penetrate a blood vessel.
Intradermal or subcutaneous routes of administration are not to be utilized.
ADACEL®-POLIO should not be administered into the buttocks.
Inspect for extraneous particulate matter and/or discolouration before use. (See 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING, Description). If these conditions exist, the product should be discarded.
Shake the syringe well until a uniform, cloudy, suspension results. Use a separate sterile needle and syringe, or a sterile disposable unit for each individual patient to prevent disease transmission. Needles should not be recapped but should be disposed of according to biohazard waste guidelines.
Before injection, the skin over the site to be injected should be cleansed with a suitable germicide. Administer the total volume of 0.5 mL intramuscularly (IM). The preferred site of injection is the deltoid muscle.
Give the patient a permanent personal immunization record. In addition, it is essential that the physician or nurse record the immunization history in the permanent medical record of each patient. This permanent office record should contain the name of the vaccine, date given, dose, manufacturer and lot number.
5 OVERDOSAGE
| For management of a suspected drug overdose, contact your regional poison control centre. |
|---|
6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING
To help ensure the traceability of vaccines for patient immunization record-keeping as well as safety monitoring, health professionals should record the time and date of administration, quantity of administered dose (if applicable), anatomical site and route of administration, brand name and generic name of the vaccine, the product lot number and expiry date.
Table 2: Dosage Forms, Strengths, Composition and Packaging
| Route of Administration | Dosage Form / Strength/Composition | Non-medicinal Ingredients |
| Intramuscular injection | Suspension for injection. Active Ingredients: Each 0.5 mL dose is formulated to contain: Tetanus toxoid, reduced diphtheria toxoid, acellular pertussis antigens [pertussis toxoid (PT), filamentous haemagglutinin (FHA), pertactin (PRN), fimbriae types 2 and 3 (FIM)], and inactivated poliomyelitis vaccine [type 1 (Mahoney), type 2 (MEF-1) and type 3 (Saukett)]. | Excipients: Aluminum phosphate (adjuvant), 2-phenoxyethanol, ethanol, polysorbate 80. Manufacturing process residuals: Bovine serum albumin, formaldehyde, glutaraldehyde, streptomycin, neomycin and polymyxin B are present in trace amounts. |
Description
ADACEL®-POLIO is supplied as a sterile, uniform, cloudy, white suspension in a prefilled syringe.
Composition
Each dose (0.5 mL) is formulated to contain:
Active Ingredients
Tetanus Toxoid 5 Lf
Diphtheria Toxoid 2 Lf
Acellular Pertussis:
Pertussis Toxoid (PT) 2.5 µg
Filamentous Haemagglutinin (FHA) 5 µg
Pertactin (PRN) 3 µg
Fimbriae Types 2 and 3 (FIM) 5 µg
Inactivated Poliomyelitis Vaccine:
Type 1 (Mahoney)1 29 D-antigen units2
Type 2 (MEF-1)1 7 D-antigen units2
Type 3 (Saukett)1 26 D-antigen units2
1 Cultivated on Vero cells
2 These antigen quantities are strictly the same as those previously expressed as 40-8-32 D-antigen units, for virus type 1, 2 and 3 respectively, when measured by another similar / comparable/equivalent/ corresponding immunochemical method.
Other Ingredients
Excipients:
Aluminum Phosphate (adjuvant) 1.5 mg
2-phenoxyethanol 0.6% v/v
Ethanol 0.3% v/v
Polysorbate 80 <5 μg
Water for Injection q.s. 0.5 mL
Manufacturing Process Residuals:
Bovine serum albumin, formaldehyde, glutaraldehyde, streptomycin, neomycin and polymyxin B are present in trace amounts.
Packaging
ADACEL®-POLIO is supplied in prefilled syringes.
The syringes are made of USP Type 1 glass. The container closure system for all presentations of ADACEL®-POLIO is free of latex (natural rubber).
ADACEL®-POLIO may be available in packages of:
1 single dose syringe
10 single dose syringes
7 WARNINGS AND PRECAUTIONS
General
ADACEL®-POLIO is not to be used for the treatment of disease caused by Bordetella pertussis, Corynebacterium diphtheriae, Clostridium tetani or poliomyelitis infections.
Before administration of ADACEL®-POLIO, health-care providers should inform the recipient or parent or guardian of the recipient of the benefits and risks of immunization, inquire about the recent health status of the patient to be immunized, review the patient’s history concerning possible hypersensitivity to the vaccine or similar vaccine, previous immunization history, the presence of any contraindications to immunization and comply with any local requirements regarding information to be provided to the patient/guardian before immunization.
It is extremely important that the recipient, parent or guardian be questioned concerning any signs or symptoms of an adverse reaction after a previous dose of vaccine. (See 2 CONTRAINDICATIONS and 8 ADVERSE REACTIONS.)
The rates and severity of adverse events in recipients of tetanus toxoid are influenced by the number of prior doses and level of pre-existing antitoxins.
Syncope (fainting) has been reported following vaccination with ADACEL®-POLIO. Procedures should be in place to prevent falling injury and manage syncopal reactions.
As with any vaccine, ADACEL®-POLIO may not protect 100% of vaccinated persons.
Febrile and Acute Disease: Vaccination should be postponed in cases of an acute or febrile disease. However, a disease with low-grade fever should not usually be a reason to postpone vaccination.
Hematologic
Because any intramuscular injection can cause an injection site hematoma in persons with any bleeding disorders, such as haemophilia or thrombocytopenia, or in persons on anticoagulant therapy, intramuscular injections with ADACEL®-POLIO should not be administered to such persons unless the potential benefits outweigh the risk of administration. If the decision is made to administer any product by intramuscular injection to such persons, it should be given with caution, with steps taken to avoid the risk of hematoma formation following injection.
Immune
The possibility of allergic reactions in persons sensitive to components of the vaccine should be evaluated. Hypersensitivity reactions may occur following the use of ADACEL®-POLIO even in persons with no prior history of hypersensitivity to the product components.
As with all other products, epinephrine hydrochloride solution (1:1,000) and other appropriate agents should be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs. Health-care providers should be familiar with current recommendations for the initial management of anaphylaxis in non-hospital settings, including proper airway management.
Immunocompromised persons (whether from disease or treatment) may not achieve the expected immune response. If possible, consideration should be given to delaying vaccination until after the completion of any immunosuppressive treatment. Nevertheless, vaccination of persons with chronic immunodeficiency, such as HIV infection, is recommended even if the immune response might be limited.
Neurologic
ADACEL®-POLIO should not be administered to individuals with progressive neurological disorder, uncontrolled epilepsy, or progressive encephalopathy until a treatment regimen has been established and the condition has stabilized.
If Guillain-Barré syndrome has occurred within 6 weeks of receipt of prior vaccine containing tetanus toxoid, the decision to give ADACEL®-POLIO or any vaccine containing tetanus toxoid should be based on careful consideration of the potential benefits and possible risks.
7.1 Special Populations
7.1.1 Pregnant Women
ADACEL®-POLIO and ADACEL® vaccination during pregnancy for passive immunization against pertussis in early infancy has been evaluated in published studies. Safety data from 4 randomized controlled trials (outcomes for 310 pregnancies) and 6 observational studies (outcomes for 125,356 pregnancies) of women who received ADACEL®-POLIO or ADACEL® during pregnancy (the majority in the 3rd trimester) have shown no vaccine-related adverse effect on pregnancy or on the health of the fetus/newborn child. These studies support the administration of ADACEL®-POLIO during pregnancy. (See 14 CLINICAL TRIALS: Immunogenicity in Pregnancy).
7.1.2 Breast-feeding
The effect of administration of ADACEL®-POLIO during lactation has not been assessed. As ADACEL®-POLIO is inactivated, any risk to the mother or the infant is improbable. However, the effect on breast-fed infants of the administration of ADACEL®-POLIO to their mothers has not been studied. The risks and benefits of vaccination should be assessed before making the decision to immunize a nursing woman.
8 ADVERSE REACTIONS
8.2 Clinical Trial Adverse Reactions
Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.
The safety of ADACEL®-POLIO has been evaluated in a total of 1,636 participants who received a single dose of ADACEL®-POLIO in 7 clinical trials (644 children 3 to 7 years of age, 992 adolescents and adults 11 to 60 years of age). Pain was the most common injection site reaction in all age groups. Most injection site reactions occurred within 3 days following vaccination. The most frequent systemic reaction was headache in adolescents and adults and tiredness in children. These reactions were usually transient and of mild to moderate intensity.
Table 3 presents the frequencies of the solicited injection site and systemic adverse events reported in 3 UK clinical trials in which children previously primed with 3 doses of PEDIACEL® [Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine and Haemophilus b Conjugate Vaccine (Tetanus Protein – Conjugate)] or a whole-cell pertussis combination vaccine, received a pre-school booster dose of ADACEL®-POLIO at 3 to 5 years of age. In addition, adverse events of irritability (7.3%), injection site bruising (3.3%), injection site pruritus (2.7%) and dermatitis (1.3%) were reported within 7 days of vaccination in two of these studies.
In clinical trials in children ADACEL®-POLIO showed a comparable safety profile to that of ADACEL® [Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed]. Therefore, the safety of ADACEL®-POLIO, in particular for use as a 4 to 6 years-old booster dose is further supported by a study conducted with ADACEL® in 298 children.
The frequency of the solicited injection site and systemic adverse events reported in a Canadian clinical trial in adolescents and adults are also presented in Table 3.
Table 3: Frequency (%) of Solicited Reactions Observed in Clinical Trials in Children, Adolescents and Adults, Following a Single Booster Dose of ADACEL®-POLIO
| Solicited Reactions | Children 3 to 5 Years of Age* (N = 307) | Adolescents 12 to 18 Years of Age┼ (N = 350) | Adults 19 to 60 Years of Age┼ (N = 366) | ||||||||
| Injection Site Reactions | |||||||||||
| Pain | 46.5 – 71.3 | 88.3 | 86.3 | ||||||||
| Swelling | 20.4 – 34.0 | 21.2 | 16.7 | ||||||||
| Redness | 35.7 – 48.7 | 17.5 | 23.0 | ||||||||
| Systemic Reactions | |||||||||||
| Fever¥ | 7.0 – 12.7 | 14.2 | 2.7 | ||||||||
| Headache | N.S. | 41.3 | 37.7 | ||||||||
| Nausea | N.S. | 17.5 | 14.5 | ||||||||
| Diarrhea | 7.6 – 10.0 | 5.4 | 15.8 | ||||||||
| Vomiting | 2.5 – 6.7 | 3.2 | 2.5 | ||||||||
| Body Ache | N.S. | 26.1 | 24.0 | ||||||||
| Sore or Swollen Joints | 1.3 | 11.2 | 11.2 | ||||||||
| Tiredness | 35.7 – 52.7 | 37.2 | 29.8 | ||||||||
| Chills | N.S. | 17.5 | 11.2 | ||||||||
| Rash | 7.0 – 8.7 | N.S. | N.S. | ||||||||
*Adverse reactions reported within 7 days of vaccination. Range of frequencies across 3 UK studies. ┼ Adverse reactions reported within 14 days of vaccination. ¥ Fever was defined as temperature ≥37.5°C in children, ≥38.0°C in adolescents and adults. Fever was solicited up to 7 days post-vaccination in children, up to 72 hours in adolescents and adults. N.S.: Not solicited. | |||||||||||
8.5 Post-Market Adverse Reactions
The following additional adverse events have been spontaneously reported during the post-marketing use of ADACEL®-POLIO. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.
Blood and Lymphatic Disorders
Lymphadenopathy
Immune System Disorders
Anaphylactic reactions, such as urticaria, face edema and dyspnea
Nervous System Disorders
Convulsions, vasovagal syncope, Guillain-Barré syndrome, facial palsy, myelitis, brachial neuritis, transient paresthesia/hypoesthesia of vaccinated limb, dizziness
Musculoskeletal and Connective Tissue Disorders
Pain in vaccinated limb
Gastro intestinal disorders
Abdominal pain
General Disorders and Administration Site Conditions
Extensive limb swelling, which may extend from the injection site beyond one or both joints and is frequently associated with erythema, and sometimes with blisters, has been reported following administration of ADACEL®-POLIO. The majority of these reactions appeared within 48 hours of vaccination and spontaneously resolved over an average of 4 days without sequelae. The risk appears to be dependent on the number of prior doses of d/DTaP vaccine, with a greater risk following the 4th and 5th doses.
Malaise, pallor, injection site induration
9 DRUG INTERACTIONS
9.4 Vaccine-Drug Interactions
Immunosuppressive treatments may interfere with the development of the expected immune response. (See 7 WARNINGS AND PRECAUTIONS.)
Concomitant Vaccine Administration
ADACEL®-POLIO may be administered concurrently with a dose of hepatitis B vaccine. Supportive data from a study conducted with ADACEL® suggests that ADACEL®-POLIO may be used concomitantly with trivalent influenza vaccine. ADACEL®-POLIO has been safely administered concomitantly with measles-mumps-rubella vaccine in non-controlled clinical studies in children 3 to 5 years of age. Data are not available on concomitant use of ADACEL®-POLIO and varicella vaccine.
Administering the most widely used live and inactivated vaccines during the same patient visit has produced seroconversion rates and rates of adverse reactions similar to those observed when the vaccines are administered separately. Vaccines administered concomitantly should be given using separate syringes at separate sites. Simultaneous administration is suggested, particularly when there is concern that a person may not return for subsequent vaccination.
ADACEL®-POLIO should not be mixed in the same syringe with other parenterals.
10 CLINICAL PHARMACOLOGY
10.1 Mechanism of Action
Tetanus and Diphtheria: Protection against disease attributable to C. tetani is due to the development of neutralizing antibodies to tetanus toxin.
Protection against disease attributable to C. diphtheriae is due to the development of neutralizing antibodies to diphtheria toxin.
Pertussis: Pertussis (whooping cough) is a respiratory disease caused by B. pertussis. This Gram-negative coccobacillus produces a variety of biologically active components, though their role in either the pathogenesis of, or immunity to, pertussis has not been clearly defined. The mechanism of protection from B. pertussis disease is not well understood.
Poliomyelitis: Inactivated poliomyelitis vaccine induces the production of detectable levels of neutralizing antibodies against each type of poliovirus. The detection of type-specific neutralizing antibodies has been correlated with protection.
10.2 Pharmacodynamics
Tetanus and Diphtheria: A serum tetanus antitoxin level of at least 0.01 IU/mL, measured by neutralization assay, is considered the minimum protective level. One month after a single booster dose of ADACEL®-POLIO, seroprotective tetanus antitoxin levels were achieved in 100% of adults and adolescents, and 100% of children 3.5 to 4.1 years of age.
A serum diphtheria antitoxin level of 0.01 IU/mL is the lowest level giving some degree of protection. Antitoxin levels of at least 0.1 IU/mL are generally regarded as protective for diphtheria. 83.8% of adults, 97.1% of adolescents and at least 97.6% of children 3.5 to 4.1 years of age achieved a seroprotective antitoxin level of 0.1 IU/mL against diphtheria.
Pertussis: In a clinical trial in Sweden (Sweden I Efficacy Trial) using TRIPACEL® [Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed], the same pertussis components as present in ADACEL®-POLIO (i.e., PT, FHA, PRN and FIM) have been shown to prevent pertussis in infants with a protective efficacy of 85.2% using the World Health Organization (WHO) case definition (≥21 consecutive days of paroxysmal cough with culture or serologic confirmation or epidemiological link to a confirmed case). In the same study, the protective efficacy against mild disease was 77.9%.
Minimum serum antibody levels to specific pertussis vaccine components that confer protection against the development of clinical pertussis have not been established. Nevertheless, a number of studies have demonstrated a correlation between the presence of serum antibody responses to pertussis vaccine components and protection against clinical disease. The acellular pertussis formulations of ADACEL®-POLIO and ADACEL® compared to TRIPACEL® differ only in the amount of PT (2.5 μg in ADACEL®-POLIO and ADACEL® versus 10 μg in TRIPACEL®) and the amount of diphtheria toxoid (2 Lf in ADACEL®-POLIO and ADACEL® versus 15 Lf in TRIPACEL®). Furthermore, the IPV antigens present in ADACEL®- POLIO are not included in the formulation of TRIPACEL®.
The efficacy of ADACEL®-POLIO is based on a comparison of pertussis antibody levels achieved in ADACEL®-POLIO recipients with those measured with TRIPACEL® in the Sweden I Efficacy Trial. In particular, ADACEL®-POLIO was demonstrated, both in children and in adolescents and adults, to elicit antibody levels against pertussis antigens, which were consistently higher than those found to be protective in the Sweden I Efficacy Trial. In addition, in a clinical study with ADACEL® among Canadian 4 to 6 year-olds, it was demonstrated that, in the context of the Canadian immunization schedule, the pertussis antigens formulation of ADACEL®-POLIO also elicited serum antibody levels that were consistently higher than those measured in the Sweden I Efficacy Trial.
Poliomyelitis: In all clinical trials, 99.0% to 100% of vaccinees in all age groups achieved seroprotective levels (≥1:8 dilution) of anti-poliovirus antibodies for all three types.
11 STORAGE, STABILITY AND DISPOSAL
Store at 2° to 8°C (35° to 46°F). Do not freeze. Discard product if exposed to freezing (≤ 0°C). ADACEL®-POLIO has been shown to remain stable at temperatures above 8°C and up to 25°C, for a maximum of 3 days (72 hours). These data are not recommendations for shipping or storage but may guide decision for use in case of temporary temperature excursions.
12 SPECIAL HANDLING INSTRUCTIONS
Do not use after expiration date.
PART II: SCIENTIFIC INFORMATION
13 PHARMACEUTICAL INFORMATION
Drug Substance
Proper name: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed Combined with Inactivated Poliomyelitis Vaccine (Tdap-IPV)
Product Characteristics:
ADACEL®-POLIO is a sterile, uniform, cloudy, white suspension of tetanus and diphtheria toxoids and acellular pertussis vaccine adsorbed separately on aluminum phosphate and combined with inactivated poliomyelitis vaccine (vero cell origin) types 1, 2 and 3, and suspended in water for injection. Acellular pertussis vaccine is composed of five purified pertussis antigens (PT, FHA, PRN and FIM).
C. diphtheriae is grown in modified Mueller’s growth medium. After purification by ammonium sulphate fractionation, diphtheria toxin is detoxified with formaldehyde and diafiltered. C. tetani is grown in modified Mueller-Miller casamino acid medium without beef heart infusion. Tetanus toxin is detoxified with formaldehyde and purified by ammonium sulphate fractionation and diafiltration. Diphtheria and tetanus toxoids are individually adsorbed onto aluminum phosphate.
The 5 acellular pertussis vaccine components are obtained from B. pertussis cultures grown in Stainer-Scholte medium modified by the addition of casamino acids and dimethyl-beta-cyclodextrin. Pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) are isolated separately from the supernatant culture medium. Fimbriae types 2 and 3 (FIM) are extracted from the bacterial cells. These antigens are purified by sequential filtration, salt-precipitation, ultrafiltration and chromatography. PT is detoxified with glutaraldehyde and FHA is treated with formaldehyde and the residual aldehydes are removed by diafiltration. The individual antigens are adsorbed onto aluminum phosphate.
The adsorbed diphtheria, tetanus and acellular pertussis components are combined with aluminum phosphate (as adjuvant), 2-phenoxyethanol and water for injection, to formulate the Tdap concentrate.
Inactivated poliomyelitis vaccine (IPV) is a highly purified, inactivated poliovirus vaccine including three types of poliovirus: Type 1 (Mahoney), Type 2 (MEF-1) and Type 3 (Saukett). Each of the three strains of poliovirus is individually grown in vero cells, which are cultivated on microcarriers. The single virus harvest is concentrated and purified, then inactivated with formaldehyde to produce the type 1, 2 or 3 monovalent. Monovalents of each type are then combined in appropriate quantities to produce a trivalent concentrate.
The Tdap concentrate is combined with IPV, aluminum phosphate (as adjuvant), 2-phenoxyethanol, ethanol and water for injection containing polysorbate 80.
The potency of tetanus and diphtheria toxoids are measured by in vitro antigenicity enzyme-linked immunosorbent assays (ELISA), which detects immunologically relevant epitopes. Alternatively, the potency can be assessed in guinea pigs, with the tetanus toxoid inducing at least 20 IU and the diphtheria toxoid inducing at least 2 IU per single dose. The potency of the acellular pertussis vaccine components is verified by the antibody response of immunized mice to PT, FHA, PRN and FIM as measured by enzyme-linked immunosorbent assay. The content in IPV components is verified by ELISA determination of D antigen content for each of the 3 types of IPV.