NDC 49281-562 Quadracel

Diphtheria And Tetanus Toxoids And Acellular Pertussis Adsorbed And Inactivated Poliovirus Vaccine

NDC Product Code 49281-562

NDC CODE: 49281-562

Proprietary Name: Quadracel What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Diphtheria And Tetanus Toxoids And Acellular Pertussis Adsorbed And Inactivated Poliovirus Vaccine What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Product Characteristics

Color(s):
WHITE (C48325 - WHITE TO OFF-WHITE)

NDC Code Structure

  • 49281 - Sanofi Pasteur Inc.

NDC 49281-562-10

Package Description: 10 VIAL, SINGLE-USE in 1 PACKAGE > .5 mL in 1 VIAL, SINGLE-USE (49281-562-58)

NDC Product Information

Quadracel with NDC 49281-562 is a a vaccine lable product labeled by Sanofi Pasteur Inc.. The generic name of Quadracel is diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated poliovirus vaccine. The product's dosage form is injection, suspension and is administered via intramuscular form.

Labeler Name: Sanofi Pasteur Inc.

Dosage Form: Injection, Suspension - A liquid preparation, suitable for injection, which consists of solid particles dispersed throughout a liquid phase in which the particles are not soluble. It can also consist of an oil phase dispersed throughout an aqueous phase, or vice-versa.

Product Type: Vaccine What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Quadracel Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • CORYNEBACTERIUM DIPHTHERIAE TOXOID ANTIGEN (FORMALDEHYDE INACTIVATED) 15 [Lf]/.5mL
  • CLOSTRIDIUM TETANI TOXOID ANTIGEN (FORMALDEHYDE INACTIVATED) 5 [Lf]/.5mL
  • BORDETELLA PERTUSSIS TOXOID ANTIGEN (GLUTARALDEHYDE INACTIVATED) 20 ug/.5mL
  • BORDETELLA PERTUSSIS FILAMENTOUS HEMAGGLUTININ ANTIGEN (FORMALDEHYDE INACTIVATED) 20 ug/.5mL
  • BORDETELLA PERTUSSIS PERTACTIN ANTIGEN 3 ug/.5mL
  • BORDETELLA PERTUSSIS FIMBRIAE 2/3 ANTIGEN 5 ug/.5mL
  • POLIOVIRUS TYPE 1 ANTIGEN (FORMALDEHYDE INACTIVATED) 40 [D'ag'U]/.5mL
  • POLIOVIRUS TYPE 2 ANTIGEN (FORMALDEHYDE INACTIVATED) 8 [D'ag'U]/.5mL
  • POLIOVIRUS TYPE 3 ANTIGEN (FORMALDEHYDE INACTIVATED) 32 [D'ag'U]/.5mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • ALUMINUM PHOSPHATE (UNII: F92V3S521O)
  • PHENOXYETHANOL (UNII: HIE492ZZ3T)
  • POLYSORBATE 80 (UNII: 6OZP39ZG8H)
  • FORMALDEHYDE (UNII: 1HG84L3525)
  • GLUTARAL (UNII: T3C89M417N)
  • ALBUMIN BOVINE (UNII: 27432CM55Q)
  • NEOMYCIN (UNII: I16QD7X297)
  • POLYMYXIN B SULFATE (UNII: 19371312D4)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Intramuscular - Administration within a muscle.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Inactivated Corynebacterium Diphtheriae Vaccine - [EPC] (Established Pharmacologic Class)
  • Actively Acquired Immunity - [PE] (Physiologic Effect)
  • Vaccines -
  • Inactivated - [CS]
  • Diphtheria Toxoid - [CS]
  • Inactivated Clostridium Tetani Vaccine - [EPC] (Established Pharmacologic Class)
  • Actively Acquired Immunity - [PE] (Physiologic Effect)
  • Vaccines -
  • Inactivated - [CS]
  • Tetanus Toxoid - [CS]
  • Inactivated Bordetella Pertussis Vaccine - [EPC] (Established Pharmacologic Class)
  • Actively Acquired Immunity - [PE] (Physiologic Effect)
  • Pertussis Vaccine - [CS]
  • Vaccines -
  • Inactivated - [CS]
  • Pertussis Vaccine - [CS]
  • Inactivated Bordetella Pertussis Vaccine - [EPC] (Established Pharmacologic Class)
  • Actively Acquired Immunity - [PE] (Physiologic Effect)
  • Vaccines -
  • Inactivated - [CS]
  • Inactivated Bordetella Pertussis Vaccine - [EPC] (Established Pharmacologic Class)
  • Actively Acquired Immunity - [PE] (Physiologic Effect)
  • Vaccines -
  • Inactivated - [CS]
  • Pertussis Vaccine - [CS]
  • Inactivated Poliovirus Vaccine - [EPC] (Established Pharmacologic Class)
  • Actively Acquired Immunity - [PE] (Physiologic Effect)
  • Poliovirus Vaccines - [CS]
  • Vaccines -
  • Inactivated - [CS]
  • Inactivated Poliovirus Vaccine - [EPC] (Established Pharmacologic Class)
  • Actively Acquired Immunity - [PE] (Physiologic Effect)
  • Poliovirus Vaccines - [CS]
  • Vaccines -
  • Inactivated - [CS]
  • Inactivated Poliovirus Vaccine - [EPC] (Established Pharmacologic Class)
  • Actively Acquired Immunity - [PE] (Physiologic Effect)
  • Poliovirus Vaccines - [CS]
  • Vaccines -
  • Inactivated - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Sanofi Pasteur Inc.
Labeler Code: 49281
FDA Application Number: BLA125525 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: BLA - A product marketed under an approved Biologic License Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 03-24-2015 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Quadracel Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Quadracel™ is a vaccine indicated for active immunization against diphtheria, tetanus, pertussis and poliomyelitis. A single dose of Quadracel is approved for use in children 4 through 6 years of age as a fifth dose in the diphtheria, tetanus, pertussis vaccination (DTaP) series, and as a fourth or fifth dose in the inactivated poliovirus vaccination (IPV) series, in children who have received 4 doses of Pentacel® [Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, Inactivated Poliovirus and Haemophilus b conjugate (Tetanus Toxoid Conjugate) Vaccine] and/or DAPTACEL® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed).

2 Dosage And Administration

For intramuscular use only.Just before use, shake the vial well, until a uniform, white, cloudy suspension results. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If either of these conditions exist, the product should not be administered.Using a sterile needle and syringe and aseptic technique, withdraw and administer a 0.5 mL dose of Quadracel vaccine intramuscularly into the deltoid muscle of the upper arm.Quadracel should not be combined through reconstitution or mixed with any other vaccine.

3 Dosage Forms And Strengths

Quadracel is a suspension for injection in 0.5 mL single dose vials.

4.1 Hypersensitivity

Severe allergic reaction (e.g., anaphylaxis) to any ingredient of Quadracel [see Description (11)] or following any diphtheria toxoid, tetanus toxoid, pertussis-containing vaccine, or inactivated poliovirus vaccine, is a contraindication to administration of Quadracel.

4.2 Encephalopathy

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 Quadracel.

4.3 Progressive Neurologic Disorder

Progressive neurologic disorder, including infantile spasms, uncontrolled epilepsy, or progressive encephalopathy is a contraindication to administration of any pertussis-containing vaccine including Quadracel. Pertussis vaccine should not be administered to individuals with such conditions until a treatment regimen has been established and the condition has stabilized.

5.1 Management Of Acute Allergic Reactions

Epinephrine hydrochloride solution (1:1,000) and other appropriate agents and equipment must be available for immediate use in case an anaphylactic or acute hypersensitivity reaction occurs.

5.2 Adverse Reactions Following Prior Pertussis Vaccination

  • If any of the following events have occurred within the specified period after administration of a pertussis vaccine, the decision to administer Quadracel should be based on careful consideration of benefits and risks.Temperature of ≥40.5°C (≥105°F) within 48 hours, not attributable to another identifiable cause.Collapse or shock-like state (hypotonic-hyporesponsive episode [HHE]) within 48 hours.Persistent, inconsolable crying lasting ≥3 hours within 48 hours.Seizures with or without fever within 3 days.

5.3 Guillain-Barré Syndrome

If Guillain-Barré syndrome occurred within 6 weeks of receipt of a prior vaccine containing tetanus toxoid, the decision to give any tetanus toxoid-containing vaccine, including Quadracel, should be based on careful consideration of the potential benefits and possible risks.

5.4 Limitations Of Vaccine Effectiveness

Vaccination with Quadracel may not protect all individuals.

5.5 Altered Immunocompetence

If Quadracel is administered to immunocompromised persons, including persons receiving immunosuppressive therapy, the expected immune response may not be obtained. [See Drug Interactions (7.2).]

6 Adverse Reactions

In a clinical study, the most common solicited injection site reactions were pain (>75%), increase in arm circumference (>65%), erythema (>55%), and swelling (>40%). Common solicited systemic reactions were myalgia (>50%), malaise (>35%), and headache (>15%).

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to vaccine use and for approximating rates of those events.In a randomized, controlled, multicenter study conducted in the US and Puerto Rico (Study M5I02; ClinicalTrials.gov Identifier: NCT01346293), 3372 children, 4 to 6 years of age, who had received 4 doses of DAPTACEL and/or Pentacel vaccine(s) received Quadracel, or DAPTACEL + IPOL (Poliovirus Vaccine Inactivated) vaccines administered concomitantly but at separate sites. Subjects also received Measles, Mumps, and Rubella Virus Vaccine Live (MMR) (Merck & Co., Inc.) and Varicella Virus Vaccine Live (Varicella vaccine) (Merck & Co., Inc.) administered concomitantly at separate sites. Safety was evaluated in 2733 subjects who received Quadracel and 621 subjects who received DAPTACEL + IPOL vaccines.Among these subjects, 51.5% were male, 48.5% were female, 75.7% were Caucasian, 8.6% were Black, 7.9% were Hispanic, 0.9% were Asian, and 7.8% were of other racial/ethnic groups. The mean age for both groups was 4.4 years and the ratio of male to female subjects and ethnicity were balanced between both groups.Solicited injection site reactions and systemic reactions were collected daily for 7 days following vaccination, via diary cards. Participants were monitored for unsolicited adverse events for 28 days and serious adverse events (SAEs) for 6 months after vaccination.

Other

Solicited Adverse ReactionsThe incidence and severity of solicited injection site and systemic adverse reactions that occurred within 7 days after vaccination in each study group are shown in Table 1.Table 1: Percentage of Children 4 through 6 years of Age with Solicited Adverse Reactions by Intensity Within 7 Days of Vaccination with Quadracel or Concomitant but Separate DAPTACEL and IPOL vaccines Co-Administered with MMR and Varicella VaccinesClinicalTrials.gov Identifier: NCT01346293.Quadracel(NN = The number of subjects with available data.= 2500-2689)DAPTACEL + IPOL(N= 598-603)Injection Site ReactionsQuadracel siteDAPTACEL or IPOL sitePainGrade 1: Easily tolerated, Grade 2: Sufficiently discomforting to interfere with normal behavior or activities, Grade 3: Incapacitating, unable to perform usual activities.Any77.476.5Grade 156.454.9Grade 219.018.6Grade 32.03.0Change in limb circumferenceGrade 1: > 0 to < 25 mm increase over pre-vaccination measurement, Grade 2: ≥ 25 to ≤ 50 mm increase over pre-vaccination measurement, Grade 3: > 50 mm increase over pre-vaccination measurement. Any68.165.1Grade 159.858.6Grade 28.26.5Grade 30.20.0ErythemaAny59.153.4> 0 to < 25 mm31.631.8≥ 25 to < 50 mm9.59.6≥ 50 mm18.011.9SwellingAny40.236.4> 0 to < 25 mm23.523.1≥ 25 to < 50 mm8.16.1≥ 50 mm8.67.1Extensive limb swellingSwelling of the injected limb including the adjacent joint (i.e., elbow and/or shoulder) as compared to baseline.Any1.51.3Systemic ReactionsMyalgiaGrade 1: No interference with activity, Grade 2: Some interference with activity, Grade 3: Significant; prevents daily activity.Any53.852.6Grade 136.033.5Grade 215.816.3Grade 31.92.8MalaiseAny35.033.2Grade 121.718.7Grade 210.611.1Grade 32.63.3HeadacheAny15.616.6Grade 111.911.9Grade 23.14.0Grade 30.60.7FeverAny6.06.9≥ 38.0°C to ≤ 38.4°C2.63.0≥ 38.5°C to ≤ 38.9°C2.11.8≥ 39.0°C1.32.0

Serious Adverse EventsIn Study M5I02, within 28 days following vaccination with Quadracel, or DAPTACEL + IPOL vaccines, and concomitant MMR and varicella vaccines, 0.1% of subjects (3/2733) in the Quadracel group experienced a serious adverse event. During the same time period, 0.2% subjects (1/621) in the DAPTACEL + IPOL group experienced a SAE. Within the 6-month follow-up period after vaccination, SAEs were reported in 0.8% of subjects (21/2733) who received Quadracel and 0.5% of subjects (3/621) who received DAPTACEL + IPOL vaccines, none of which were assessed as related to vaccination.

Pregnancy Category CAnimal reproduction studies have not been conducted with Quadracel. It is also not known whether Quadracel can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.

Diphtheria Diphtheria is an acute toxin-mediated disease caused by toxigenic strains of C. diphtheriae. Protection against disease is due to the development of neutralizing antibodies to diphtheria toxin. 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. (6) Levels of 1.0 IU/mL have been associated with long-term protection. (7)

TetanusTetanus is an acute disease caused by an extremely potent neurotoxin produced by C. tetani. Protection against disease is due to the development of neutralizing antibodies to tetanus toxin. A serum tetanus antitoxin level of at least 0.01 IU/mL, measured by neutralization assay, is considered the minimum protective level. (6) (8). A tetanus antitoxoid level ≥0.1 IU/mL as measured by the ELISA used in clinical studies of Quadracel is considered protective.

PertussisPertussis (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. There is no well-established serological correlate of protection for pertussis. Because DAPTACEL contains the same pertussis antigens manufactured by the same process as those in Quadracel, the effectiveness of Quadracel against pertussis was based on a comparison of pertussis immune responses following Quadracel to those following DAPTACEL (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed). [See Clinical Studies (14)]. The efficacy of the pertussis component of DAPTACEL was determined in clinical trials of DAPTACEL administered to infants (see DAPTACEL prescribing information). Quadracel contains twice as much detoxified PT and four times as much FHA as DAPTACEL.

PoliomyelitisPolioviruses, of which there are three serotypes (Types 1, 2, and 3), are enteroviruses. The presence of poliovirus type-specific neutralizing antibodies has been correlated with protection against poliomyelitis. (9)

Manufactured by:Sanofi Pasteur LimitedToronto Ontario CanadaDistributed by:Sanofi Pasteur Inc.Swiftwater PA 18370 USAQuadracel™ is a trademark of Sanofi Pasteur Limited.R0-0315 USA

6.2 Postmarketing Experience

  • The following adverse events have been spontaneously reported, during the post-marketing use of Quadracel outside the US, in infants and children from 2 months through 6 years of age. Because these events are reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency reliably or establish a causal relationship to vaccine exposure. This list includes adverse events based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to Quadracel.Immune system disorders  Anaphylactic reaction, hypersensitivity and allergic reactions (such as rash, urticaria, dyspnea)Psychiatric disorders ScreamingNervous system disorders Somnolence, convulsion, febrile convulsion, HHE, hypotoniaCardiac disorders Cyanosis Vascular disorders PallorGeneral disorders and administration site conditions Listlessness Injection site reactions (including inflammation, mass, sterile abscess, and edema) Large injection site reactions (>50 mm), including limb swelling which may extend from the injection site beyond one or both jointsInfections and InfestationsInjection site cellulitis, injection site abscess

7.1 Concomitant Administration With Other Vaccines

In the US clinical trial, Study M5I02, Quadracel was administered concomitantly with one or more of the following US-licensed vaccines: MMR vaccine and varicella vaccine. [See Adverse Reactions (6.1).]When Quadracel is given at the same time as another injectable vaccine(s), the vaccines should be administered with different syringes and at different injection sites.

7.2 Immunosuppressive Treatments

Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to Quadracel. [See Warnings and Precautions (5.5).]

8.4 Pediatric Use

The safety and effectiveness of Quadracel has not been established in children less than 4 years of age or children 7 through 16 years of age and is not approved for use in these age groups.

11 Description

Quadracel (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine) is a sterile suspension for intramuscular injection.Each 0.5 mL dose is formulated to contain 15 Lf diphtheria toxoid, 5 Lf tetanus toxoid, acellular pertussis antigens [20 mcg detoxified pertussis toxin (PT), 20 mcg filamentous hemagglutinin (FHA), 3 mcg pertactin (PRN), 5 mcg fimbriae types 2 and 3 (FIM)], and inactivated polioviruses [40 D-antigen units (DU) Type 1 (Mahoney), 8 DU Type 2 (MEF-1), 32 DU Type 3 (Saukett)].Corynebacterium diphtheriae is grown in modified Mueller's growth medium. (1) After purification by ammonium sulfate fractionation, the diphtheria toxin is detoxified with formaldehyde and diafiltered.Clostridium tetani is grown in modified Mueller-Miller casamino acid medium without beef heart infusion. (2) Tetanus toxin is detoxified with formaldehyde and purified by ammonium sulfate fractionation and diafiltration. Diphtheria and tetanus toxoids are individually adsorbed onto aluminum phosphate.The acellular pertussis vaccine antigens are produced from Bordetella pertussis cultures grown in Stainer-Scholte medium (3) modified by the addition of casamino acids and dimethyl-beta-cyclodextrin. PT, FHA and PRN are isolated separately from the supernatant culture medium. FIM are extracted and copurified from the bacterial cells. The pertussis antigens are purified by sequential filtration, salt-precipitation, ultrafiltration and chromatography. PT is detoxified with glutaraldehyde. FHA is treated with formaldehyde and the residual aldehydes are removed by ultrafiltration. The individual antigens are adsorbed separately onto aluminum phosphate.Poliovirus Type 1, Type 2 and Type 3 are each grown in separate cultures of MRC-5 cells, a line of normal human diploid cells, by the microcarrier method. (4) (5) The cells are grown in CMRL (Connaught Medical Research Laboratories) 1969 medium, supplemented with calf serum. For viral growth, the culture medium is replaced by Medium 199, without calf serum. After clarification and filtration, the viral suspensions are concentrated by ultrafiltration, and purified by liquid chromatography steps. The monovalent viral suspensions are inactivated with formaldehyde. Monovalent concentrates of each inactivated poliovirus are combined to produce a trivalent poliovirus concentrate.The adsorbed diphtheria, tetanus and acellular pertussis antigens are combined with aluminum phosphate , 2-phenoxyethanol (not as a preservative) and water for injection, into an intermediate concentrate. The trivalent poliovirus concentrate is added and the vaccine is diluted to its final concentration.Each 0.5 mL dose contains 1.5 mg aluminum phosphate (0.33 mg aluminum) as the adjuvant, polysorbate 80 (approximately 10 ppm by calculation), ≤5 mcg residual formaldehyde, <50 ng residual glutaraldehyde, ≤50 ng residual bovine serum albumin, 3.3 mg (0.6% v/v) 2-phenoxyethanol (not as a preservative), <4 pg of neomycin and <4 pg polymyxin B sulfate.Quadracel does not contain a preservative.Both diphtheria and tetanus toxoids induce at least 2 neutralizing units per mL in the guinea pig potency test. The potency of the acellular pertussis antigens is evaluated by the antibody response of immunized mice to detoxified PT, FHA, PRN and FIM as measured by enzyme-linked immunosorbent assay (ELISA). The potency of the inactivated poliovirus antigens is determined by measuring antibody-mediated neutralization of poliovirus in sera from immunized rats.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Quadracel has not been evaluated for carcinogenic or mutagenic potential or impairment of fertility.

14.1 Immunogenicity

In Study M5I02, children 4 through 6 years of age received Quadracel or DAPTACEL + IPOL as the fifth dose in the diphtheria, tetanus, and pertussis vaccination series and the fourth or fifth dose in the inactivated poliovirus vaccination series. Subjects also received their second dose of MMR and Varicella vaccines, concomitantly. The immunogenicity subset comprised 263 subjects in the Quadracel group and 253 subjects in the DAPTACEL + IPOL vaccines group. [See study description in Adverse Reactions (6.1)].Antibody levels to diphtheria, tetanus, pertussis (PT, FHA, PRN and FIM) and poliovirus antigens were measured in sera obtained immediately prior to vaccination and 28 days after vaccination. The co-primary endpoints were booster response rates and antibody geometric mean concentrations/titers (GMCs/GMTs) to diphtheria, tetanus, pertussis and poliovirus antigens elicited after vaccination. Booster response rates and antibody GMCs/GMTs following Quadracel vaccination were compared to those after DAPTACEL + IPOL vaccination.Quadracel was non-inferior to DAPTACEL + IPOL vaccines administered concomitantly at separate sites, as demonstrated by comparison of the post-vaccination antibody booster response rates and GMCs/GMTs to diphtheria and tetanus (Table 2), to all pertussis antigens (Table 3) and to poliovirus 1, 2 and 3 (Table 4).Table 2: Booster Response Rates, Pre- and Post-Vaccination Seroprotection Rates and Post-Vaccination Antibody Levels to Diphtheria and Tetanus Antigens Following Quadracel or Concomitant but Separate DAPTACEL and IPOL Vaccines Co-Administered with MMR and Varicella VaccinesClinicalTrials.gov Identifier: NCT01346293.Quadracel(NN = The number of subjects with available data. =253-262)DAPTACEL + IPOL(N =248-253)Anti-Diphtheria% Booster ResponseBooster response: In subjects with pre-vaccination antibody concentrations < 0.1 IU/mL, a post-vaccination level ≥ 0.4 IU/mL; in subjects with pre-vaccination antibody concentrations ≥ 0.1 IU/mL but < 2.0 IU/mL, a 4-fold rise in post-vaccination level; in subjects with pre-vaccination antibody level ≥ 2.0 IU/mL, a 2-fold rise in post-vaccination level.97.3Quadracel was non-inferior to DAPTACEL + IPOL based on the post-vaccination booster response rates for diphtheria and tetanus (lower limits of the 2-sided 95% CIs of the difference [Quadracel minus DAPTACEL + IPOL] were >-10%).99.2Pre-vaccination % ≥0.1 IU/mLSeroprotection: anti-diphtheria and anti-tetanus antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL.90.783.1Post-vaccination % ≥0.1 IU/mL100.099.6Post-vaccination % ≥1.0 IU/mL99.699.6Post-vaccination GMC (IU/mL)18.6Quadracel was non-inferior to DAPTACEL + IPOL based on the post-vaccination GMCs for diphtheria and tetanus (lower limits of the 2-sided 95% CIs of the ratio [Quadracel / DAPTACEL + IPOL] were > 2/3).15.5Anti-Tetanus% Booster Response84.284.3Pre-vaccination % ≥0.1 IU/mL91.789.1Post-vaccination % ≥0.1 IU/mL100.099.2Post-vaccination % ≥1.0 IU/mL98.996.8Post-vaccination GMC (IU/mL)6.45.5Table 3: Booster Response Rates and Post-vaccination Antibody Levels to Pertussis Antigens Following Quadracel or Concomitant but Separate DAPTACEL and IPOL Vaccines Co-Administered with MMR and Varicella VaccinesClinicalTrials.gov Identifier: NCT01346293.Quadracel(NN = The number of subjects with available data. =250-255)DAPTACEL + IPOL(N =247-249)Anti-PT% Booster ResponseBooster response: In subjects with pre-vaccination antibody concentrations < LLOQ, a post-vaccination level ≥ 4×LLOQ; in subjects with pre-vaccination antibody concentrations ≥ LLOQ but < 4×LLOQ, a 4-fold rise in post-vaccination level; in subjects with pre-vaccination antibody level ≥ 4×LLOQ, a 2-fold rise in post-vaccination level.95.2Quadracel was non-inferior to DAPTACEL + IPOL based on the post-vaccination booster response rates for all pertussis antigens (lower limits of the 2-sided 95% CIs of the difference [Quadracel minus DAPTACEL + IPOL] were > -10%).89.9Post-vaccination GMC (EU/mL)120.7Quadracel was non-inferior to DAPTACEL + IPOL based on the post-vaccination GMCs for all pertussis antigens (lower limits of the 2-sided 95% CIs of the ratio [DTaP-IPV / DAPTACEL + IPOL] were > 2/3).61.3Anti-FHA% Booster Response94.987.5Post-vaccination GMC (EU/mL)123.579.0Anti-PRN% Booster Response96.993.1Post-vaccination GMC (EU/mL)282.6187.5Anti-FIM% Booster Response97.292.4Post-vaccination GMC (EU/mL)505.8378.9Table 4: Booster Response Rates, Pre- and Post-Vaccination Seroprotection Rates and Post-vaccination Antibody Levels to Poliovirus Antigens Following Quadracel or Concomitant but Separate DAPTACEL and IPOL Vaccines Co-Administered with MMR and Varicella VaccinesClinicalTrials.gov Identifier: NCT01346293.Quadracel(NN = The number of subjects with available data. =247-258)DAPTACEL + IPOL(N =248-253)Anti-Poliovirus 1% Booster ResponseBooster response: In subjects with pre-vaccination antibody concentrations < 1:8 dilution, post-vaccination levels ≥ 1:8 dil; in subjects with pre-vaccination antibody concentrations ≥ 1:8 dilution, a 4-fold rise in post-vaccination antibody levels.85.9Quadracel was non-inferior to DAPTACEL + IPOL based on the post-vaccination booster response rates for polio types 1, 2 and 3 (lower limits of the 2-sided 95% CIs of the difference [Quadracel minus DAPTACEL + IPOL] were > -10%).82.3Pre-vaccination % ≥1:8 dilution98.498.8Post-vaccination % ≥1:8 dilution100.099.6Post-vaccination GMT3477Quadracel was non-inferior to DAPTACEL + IPOL based on the post-vaccination GMTs for polio types 1, 2 and 3 (lower limits of the 2-sided 95% CIs of the ratio [Quadracel / DAPTACEL + IPOL] were > 2/3).2731Anti-Poliovirus 2% Booster Response78.379.0Pre-vaccination % ≥1:8 dilution99.699.6Post-vaccination % ≥1:8 dilution100.0100.0Post-vaccination GMT34913894Anti-Poliovirus 3% Booster Response85.084.7Pre-vaccination % ≥1:8 dilution96.893.1Post-vaccination % ≥1:8 dilution100.0100.0Post-vaccination GMT45913419

15 References

  • 1Stainer DW. Production of diphtheria toxin. In: Manclark CR, editor. Proceedings of an informal consultation on the World Health Organization requirements for diphtheria, tetanus, pertussis and combined vaccines. United States Public Health Service, Bethesda, MD. DHHS 91-1174. 1991:7-11.2Mueller JH, Miller PA. Variable factors influencing the production of tetanus toxin. J Bacteriol 1954;67(3):271-7.3Stainer DW, Scholte MJ. A simple chemically defined medium for the production of phase I Bordetella pertussis. J Gen Microbiol 1970;63:211-20.4van Wezel AL, et al. Inactivated poliovirus vaccine: current production methods and new developments. Rev Infect Dis 1984;6 (Suppl 2):S335-40.5Montagnon BJ et al. Industrial scale production of inactivated poliovirus vaccine prepared by culture of vero cells on microcarrier. Rev Infect Dis 1984;6 (Suppl 2):S341-4.6Department of Health and Human Services, Food and Drug Administration. Biological products; bacterial vaccines and toxoids; implementation of efficacy review; proposed rule. Federal Register 1985;50(240):51002-117.7Tiwari TSP, Wharton M. Diphtheria toxoid. In: Plotkin SA, Orenstein WA, and Offit PA, editors. Vaccines. 6th ed. Philadelphia, PA: WB Saunders; 2012:153-66.8Roper M, Wassilak SGF, Tiwari TSP, Orenstein WA. Tetanus toxoid. In: Plotkin SA, Orenstein WA, and Offit PA, editors. Vaccines. 6th ed. Philadelphia, PA: WB Saunders; 2012:746-72.9Sutter RW, et al. Defining surrogate serologic tests with respect to predicting protective vaccine efficacy: Poliovirus vaccination. In: Williams JC, et al. eds. Combined vaccines and simultaneous administration. Current issues and perspectives. New York, NY: The New York Academy of Sciences. 1995:289-99.

16.1 How Supplied

The vial stopper for this product is not made with natural latex rubber.Quadracel is supplied in a single dose vial (NDC No. 49281-562-58) in packages of 10 vials (NDC No. 49281-562-10).

16.2 Storage And Handling

Quadracel should be stored at 2° to 8°C (35° to 46°F). Do not freeze. Product which has been exposed to freezing should not be used. Do not use after expiration date shown on the label.

17 Patient Counseling Information

  • Inform the parent or guardian of the following:The potential benefits and risks of immunization with Quadracel.The common adverse reactions that have occurred following administration of Quadracel or other vaccines containing similar components.Other adverse reactions can occur. Call healthcare provider with any adverse reactions of concern.Provide the Vaccine Information Statements (VIS), which are required by the National Childhood Vaccine Injury Act of 1986.

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