FLUZONE- influenza a virus a/california/7/2009 x-179a (h1n1) antigen (formaldehyde inactivated), influenza a virus a/texas/50/2012 x-223a (h3n2) antigen (formaldehyde inactivated) and influenza b virus b/massachusetts/2/2012 bx-51b antigen (formaldehyde inactivated) injection, suspension
Sanofi Pasteur Inc.
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use Fluzone® safely and effectively. See full prescribing information for Fluzone.
Fluzone (Influenza Vaccine) Suspension for Intramuscular Injection 2014-2015 Formula Initial U.S. Approval 1980 INDICATIONS AND USAGEDOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHSSuspension for injection supplied in 2 presentations:; prefilled syringe (clear plunger rod), 0.5 mL; multi-dose vial, 5 mL. (3) CONTRAINDICATIONSSevere allergic reaction to any component of the vaccine, including egg protein, or after previous dose of any influenza vaccine. (4) WARNINGS AND PRECAUTIONS
ADVERSE REACTIONS
To report SUSPECTED ADVERSE REACTIONS, contact Sanofi Pasteur Inc., Discovery Drive, Swiftwater, PA 18370 at 1-800-822-2463 (1-800-VACCINE) or VAERS at 1-800-822-7967 or www.vaers.hhs.gov. USE IN SPECIFIC POPULATIONSSee 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: 6/2014 |
Fluzone® is a vaccine indicated for active immunization for the prevention of influenza disease caused by influenza A subtype viruses and type B virus contained in the vaccine.
Fluzone is approved for use in persons 6 months of age and older.
The dose and schedule for Fluzone are presented in Table 1.
Age | Dose | Schedule |
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"-" Indicates information is not applicable | ||
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6 months through 35 months | One or two doses*, 0.25 mL each | If 2 doses, administer at least 1 month apart |
36 months through 8 years | One or two doses*, 0.5 mL each | If 2 doses, administer at least 1 month apart |
9 years and older | One dose, 0.5 mL | - |
Inspect Fluzone visually for particulate matter and/or discoloration prior to administration. If either of these conditions exist, the vaccine should not be administered.
Before administering a dose of vaccine, shake the prefilled syringe or multi-dose vial. Withdraw a single dose of vaccine using a sterile needle and syringe. Use a separate sterile needle and syringe for each dose withdrawn from the multi-dose vial.
The preferred sites for intramuscular injection are the anterolateral aspect of the thigh in infants 6 months through 11 months of age, the anterolateral aspect of the thigh (or the deltoid muscle if muscle mass is adequate) in persons ≥12 months through 35 months of age, or the deltoid muscle in persons ≥36 months of age. The vaccine should not be injected into the gluteal area or areas where there may be a major nerve trunk.
Do not administer this product intravenously or subcutaneously.
Fluzone should not be combined through reconstitution or mixed with any other vaccine.
Fluzone is a suspension for injection.
Fluzone is supplied in 2 presentations:
1) Prefilled syringe (clear syringe plunger rod), 0.5 mL, for persons 36 months of age and older.
2) Multi-dose vial, 5 mL, for persons 6 months of age and older.
A severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine [see Description (11)], including egg protein, or to a previous dose of any influenza vaccine is a contraindication to administration of Fluzone.
The 1976 swine influenza vaccine was associated with an elevated risk of Guillain-Barré syndrome (GBS). Evidence for a causal relation of GBS with other influenza vaccines is inconclusive; if an excess risk exists, it is probably slightly more than 1 additional case per 1 million persons vaccinated. (1) If GBS has occurred within 6 weeks following previous influenza vaccination, the decision to give Fluzone should be based on careful consideration of the potential benefits and risks.
Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.
Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trial(s) of a vaccine cannot be directly compared to rates in the clinical trial(s) of another vaccine and may not reflect the rates observed in practice.
Children 6 Months through 8 Years of Age
In a multi-center study conducted in the US, children 6 months through 35 months of age received two 0.25 mL doses of Fluzone, and children 3 years through 8 years of age received two 0.5 mL doses of Fluzone, irrespective of previous influenza vaccination history. The two doses (2006-2007 formulation) were administered 26 to 30 days apart. The safety analysis set included 97 children 6 months through 35 months of age and 163 children 3 years through 8 years of age. Table 2 and Table 3 summarize solicited injection site reactions and systemic adverse events reported within 7 days post-vaccination via diary cards.
Dose 1 (N*=90-92) Percentage | Dose 2 (N*=86-87) Percentage |
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Any | Moderate† | Severe‡ | Any | Moderate† | Severe‡ | |
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Injection-Site Tenderness | 47.3 | 8.8 | 0.0 | 56.3 | 3.4 | 1.1 |
Injection-Site Erythema | 29.3 | 0.0 | 0.0 | 32.2 | 1.1 | 0.0 |
Injection-Site Swelling | 16.7 | 0.0 | 0.0 | 14.9 | 0.0 | 0.0 |
Injection-Site Induration | 14.4 | 0.0 | 0.0 | 16.1 | 0.0 | 0.0 |
Injection-Site Ecchymosis | 14.4 | 1.1 | 0.0 | 14.9 | 2.3 | 0.0 |
Fever§ (≥100.4°F) | 11.0 | 4.4 | 0.0 | 10.3 | 3.4 | 1.1 |
Vomiting | 6.6 | 1.1 | 0.0 | 8.1 | 5.8 | 0.0 |
Crying Abnormal | 31.9 | 11.0 | 0.0 | 18.6 | 7.0 | 2.3 |
Drowsiness | 26.4 | 1.1 | 0.0 | 26.7 | 4.7 | 0.0 |
Appetite Lost | 23.1 | 8.8 | 0.0 | 19.8 | 5.8 | 1.2 |
Irritability | 42.9 | 19.8 | 1.1 | 34.9 | 17.4 | 4.7 |
Dose 1 (N*=150-151) Percentage | Dose 2 (N*=144-145) Percentage |
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Any | Moderate† | Severe‡ | Any | Moderate† | Severe‡ | |
"-" Indicates information was not collected | ||||||
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Injection-Site Pain | 59.3 | 8.0 | 0.0 | 62.1 | 9.7 | 0.7 |
Injection-Site Erythema | 27.8 | 3.3 | 0.7 | 27.6 | 2.1 | 0.7 |
Injection-Site Swelling | 19.9 | 5.3 | 0.0 | 14.5 | 2.8 | 0.0 |
Injection-Site Induration | 16.6 | 2.0 | 0.0 | 11.7 | 1.4 | 0.0 |
Injection-Site Ecchymosis | 12.6 | 0.7 | 0.7 | 15.2 | 0.7 | 0.0 |
Injection-Site Pruritus | 7.3 | - | - | 13.2 | - | - |
Fever§ (≥99.5°F) | 11.9 | 2.6 | 2.0 | 9.7 | 1.4 | 1.4 |
Headache | 16.7 | 2.0 | 0.7 | 11.8 | 1.4 | 1.4 |
Malaise | 20.0 | 2.7 | 1.3 | 14.6 | 4.2 | 0.7 |
Myalgia | 28.0 | 5.3 | 0.0 | 17.4 | 4.2 | 0.0 |
During the period from the first vaccination through 6 months following the second vaccination, there were no serious adverse events considered to be caused by vaccination and no deaths reported in this study.
Adults
Adults 18 through 64 years of age received Fluzone (2008-2009 formulation) in a multi-center trial conducted in the US. The safety analysis set included 1421 Fluzone recipients. Table 4 summarizes solicited injection-site reactions and systemic adverse events reported within 7 days post-vaccination via diary cards.
(N*=1392-1394) Percentage |
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Any | Grade 2† | Grade 3‡ | |
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Injection-Site Erythema | 13.2 | 2.1 | 0.9 |
Injection-Site Induration | 10.0 | 2.3 | 0.5 |
Injection-Site Swelling | 8.4 | 2.1 | 0.9 |
Injection-Site Pain | 53.7 | 5.8 | 0.8 |
Injection-Site Pruritus | 9.3 | 0.4 | 0.0 |
Injection-Site Ecchymosis | 6.2 | 1.1 | 0.4 |
Headache | 30.3 | 6.5 | 1.6 |
Myalgia | 30.8 | 5.5 | 1.4 |
Malaise | 22.2 | 5.5 | 1.8 |
Shivering | 6.2 | 1.1 | 0.6 |
Fever§ (≥99.5°F) | 2.6 | 0.4 | 0.2 |
Within 28 days and 6 months post-vaccination, a serious adverse event was reported by 5 (0.4%) and 20 (1.4%) Fluzone recipients, respectively. No serious adverse event was considered to be caused by vaccination. No deaths were reported during the 6 months post-vaccination.
Geriatric Adults
Adults 65 years of age and older received Fluzone (2006-2007 formulation) in a multi-center, double-blind trial conducted in the US. The safety analysis set included 1260 Fluzone recipients.
Table 5 summarizes solicited injection-site reactions and systemic adverse events reported within 7 days post-vaccination via diary cards. Onset was usually within the first 3 days after vaccination and a majority of the reactions resolved within 3 days.
N*=1258-1260 Percentage |
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Any | Moderate† | Severe‡ | |
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Injection-Site Pain | 24.3 | 1.7 | 0.2 |
Injection-Site Erythema | 10.8 | 0.8 | 0.6 |
Injection-Site Swelling | 5.8 | 1.3 | 0.6 |
Myalgia | 18.3 | 3.2 | 0.2 |
Malaise | 14.0 | 3.7 | 0.6 |
Headache | 14.4 | 2.5 | 0.3 |
Fever§ (≥99.5°F) | 2.3 | 0.2 | 0.1 |
Within 6 months post-vaccination, 93 (7.4%) Fluzone recipients experienced a serious adverse event (N=1260). No deaths were reported within 28 days post-vaccination. A total of 7 deaths were reported during the period Day 29-180 post-vaccination: 7 (0.6%) among Fluzone recipients (N=1260). The majority of these participants had a medical history of cardiac, hepatic, neoplastic, renal, and/or respiratory diseases. No deaths were considered to be caused by vaccination.
The following events have been spontaneously reported during the post-approval use of Fluzone. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. Adverse events were included based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to Fluzone.
Data evaluating the concomitant administration of Fluzone with other vaccines are not available.
Pregnancy Category C: Animal reproduction studies have not been conducted with Fluzone. It is also not known whether Fluzone can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Fluzone should be given to a pregnant woman only if clearly needed.
It is not known whether Fluzone is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Fluzone is administered to a nursing woman.
Safety and effectiveness of Fluzone in children below the age of 6 months have not been established. Safety and immunogenicity of Fluzone were evaluated in children 6 months through 8 years of age. [See Adverse Reactions (6.1) and Clinical Studies (14.1).]
Safety and immunogenicity of Fluzone were evaluated in adults 65 years of age and older. [See Adverse Reactions (6.1) and Clinical Studies (14.3).] Antibody responses to Fluzone are lower in persons ≥65 years of age than in younger adults.
Fluzone (Influenza Vaccine) for intramuscular injection is an inactivated influenza vaccine, prepared from influenza viruses propagated in embryonated chicken eggs. The virus-containing allantoic fluid is harvested and inactivated with formaldehyde. Influenza virus is concentrated and purified in a linear sucrose density gradient solution using a continuous flow centrifuge. The virus is then chemically disrupted using a non-ionic surfactant, octylphenol ethoxylate (Triton® X-100), producing a "split virus". The split virus is further purified and then suspended in sodium phosphate-buffered isotonic sodium chloride solution.
Fluzone suspension for injection is clear and slightly opalescent in color.
Antibiotics are not used in the manufacture of Fluzone.
No presentation of Fluzone is made with natural rubber latex.
Fluzone is standardized according to United States Public Health Service requirements and is formulated to contain HA of each of the following three influenza strains recommended for the 2014-2015 influenza season: A/California/07/2009 X-179A (H1N1), A/Texas/50/2012 X-223A (H3N2), and B/Massachusetts/02/2012 (B Yamagata lineage). The amounts of HA and other ingredients per dose of vaccine are listed in Table 6. The 0.5 mL single-dose, pre-filled syringe presentation is manufactured and formulated without thimerosal or any other preservative. The 5mL multi-dose vial presentation contains thimerosal, a mercury derivative, added as a preservative. Each 0.5 mL dose from the multi-dose vial contains 25 mcg mercury. Each 0.25 mL dose from the multi-dose vial contains 12.5 mcg mercury.
Ingredient | Quantity (per dose) |
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Fluzone 0.25 mL Dose | Fluzone 0.5 mL Dose |
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"-" Indicates information is not applicable | ||
Active Substance: Split influenza virus, inactivated strains*: | 22.5 mcg HA total | 45 mcg HA total |
A (H1N1) | 7.5 mcg HA | 15 mcg HA |
A (H3N2) | 7.5 mcg HA | 15 mcg HA |
B | 7.5 mcg HA | 15 mcg HA |
Other: | ||
Sodium phosphate-buffered isotonic sodium chloride solution | QS† to appropriate volume | QS† to appropriate volume |
Formaldehyde | ≤50 mcg | ≤100 mcg |
Octylphenol ethoxylate | ≤75 mcg | ≤150 mcg |
Gelatin | 0.05% | 0.05% |
Preservative | ||
Single-dose presentations | - | - |
Multi-dose presentation (thimerosal) | 12.5 mcg mercury | 25 mcg mercury |
Influenza illness and its complications follow infection with influenza viruses. Global surveillance of influenza identifies yearly antigenic variants. For example, since 1977, antigenic variants of influenza A (H1N1 and H3N2) viruses and influenza B viruses have been in global circulation. Specific levels of hemagglutination inhibition (HI) antibody titer post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza virus infection. In some human studies, antibody titers ≥1:40 have been associated with protection from influenza illness in up to 50% of subjects. (2) (3)
Antibodies against one influenza virus type or subtype confer limited or no protection against another. Furthermore, antibodies to one antigenic variant of influenza virus might not protect against a new antigenic variant of the same type or subtype. Frequent development of antigenic variants through antigenic drift is the virologic basis for seasonal epidemics and the reason for the usual change of one or more new strains in each year's influenza vaccine. Therefore, influenza vaccines are standardized to contain the hemagglutinins of influenza virus strains representing the influenza viruses likely to be circulating in the US during the influenza season.
Annual vaccination with the current vaccine is recommended because immunity during the year after vaccination declines and because circulating strains of influenza virus change from year to year.
In a multi-center study conducted in the US, 68 children 6 months through 35 months of age given two 0.25 mL doses of Fluzone and 120 children 3 years through 8 years of age given two 0.5 mL doses of Fluzone were included in the per-protocol analysis set. The two doses (2006-2007 formulation) were administered 26 to 30 days apart. Females accounted for 42.6% of the participants in the 6 months through 35 months age group and 53.3% of the participants in the 3 years through 8 years age group. Most participants in the 6 months through 35 months and 3 years through 8 years age groups, respectively, were Caucasian (70.6% and 79.2%), followed by Hispanic (19.1% and 13.3%), and Black (7.4% and 4.2%).
The percentage of participants who received influenza vaccination during the previous influenza season was 54.4% for the 6 months through 35 months age group and 27.5% for the 3 years through 8 years age group. Table 7 shows seroconversion rates and the percentage of participants with an HI titer ≥1:40 pre-vaccination and one month following the second dose of Fluzone.
Antigen | Age Group | Pre-Vaccination Titer ≥1:40 % (95% CI) | Post-Vaccination† Titer ≥1:40 % (95% CI) | Seroconversion‡
% (95% CI) |
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N=68 (6 to 35 months); N=120 (3 through 8 years) | ||||
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A (H1N1) | 6 through 35 months | 11.8 (5.2; 21.9) | 92.6 (83.7; 97.6) | 88.2 (78.1; 94.8) |
3 through 8 years | 40.0 (31.2; 49.3) | 99.2 (95.4; 100.0) | 78.3 (69.9; 85.3) | |
A (H3N2) | 6 through 35 months | 29.4 (19.0; 41.7) | 100.0 (94.7; 100.0) | 91.2 (81.8; 96.7) |
3 through 8 years | 80.0 (71.7; 86.7) | 100.0 (97.0; 100.0) | 61.7 (52.4; 70.4) | |
B | 6 through 35 months | 1.5 (0.0; 7.9) | 20.6 (11.7; 32.1) | 20.6 (11.7; 32.1) |
3 through 8 years | 3.3 (0.9; 8.3) | 58.3 (49.0; 67.3) | 53.3 (44.0; 62.5) |
Adults 18 through 64 years of age received Fluzone (2008-2009 formulation) in a multi-center trial conducted in the US. For immunogenicity analyses, there were 1287 participants who received Fluzone in the per-protocol analysis set. There were fewer males (35.8%) than females. The mean age was 42.6 years (ranged from 18.2 through 65.0 years). Most participants were Caucasian (80.0%), followed by Hispanic (11.0%), and Black (6.3%). Table 8 shows seroconversion rates at 28 days following vaccination and the percentage of participants with an HI titer ≥1:40 prior to vaccination and 28 days following vaccination.
Antigen | Pre-Vaccination Titer ≥1:40 | Post-Vaccination* Titer ≥1:40 | Seroconversion† |
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% (95% CI) N‡=1285-1286 | % (95% CI) N‡=1283-1285 | % (95% CI) N‡=1283-1285 |
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A (H1N1) | 39.1 (36.4; 41.8) | 91.7 (90.0; 93.1) | 60.5 (57.7; 63.2) |
A (H3N2) | 33.6 (31.0; 36.2) | 91.4 (89.8; 92.9) | 74.8 (72.3; 77.1) |
B | 41.2 (38.5; 44.0) | 89.3 (87.4; 90.9) | 54.2 (51.4; 56.9) |
Adults 65 years of age and older received Fluzone (2006-2007 formulation) in a multi-center trial conducted in the US. For immunogenicity analyses, there were 1275 participants who received Fluzone in the immunogenicity analysis set. Females accounted for 54.7% of participants. The mean age was 72.9 years (ranged from 65 through 94 years of age); 36% of participants were 75 years of age or older. Most participants were Caucasian (92.9%), followed by Hispanic (3.7%), and Black (2.7%). Table 9 shows seroconversion rates at 28 days following vaccination and the percentage of participants with an HI titer ≥1:40 prior to vaccination and 28 days following vaccination.
Antigen | Pre-Vaccination HI Titer ≥1:40 | Post-Vaccination* Titer ≥1:40 | Seroconversion† |
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% (95% CI) N‡=1267-1268 | % (95% CI) N‡=1252 | % (95% CI) N‡=1248-1249 |
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A (H1N1) | 45.9 (43.2; 48.7) | 76.8 (74.3; 79.1) | 23.1 (20.8; 25.6) |
A (H3N2) | 68.6 (66.0; 71.2) | 96.5 (95.3; 97.4) | 50.7 (47.9; 53.5) |
B | 27.3 (24.9; 29.9) | 67.6 (64.9; 70.2) | 29.9 (27.4; 32.6) |
Single-dose, prefilled syringe, without needle, 0.5 mL (NDC 49281-014-88) (not made with natural rubber latex). Supplied as package of 10 (NDC 49281-014-50).
Multi-dose vial, 5 mL (NDC 49281-394-78) (not made with natural rubber latex). Supplied as package of one (NDC 49281-394-15). A maximum of ten doses can be withdrawn from the multi-dose vial.
Store all Fluzone presentations refrigerated at 2° to 8°C (35° to 46°F). DO NOT FREEZE. Discard if vaccine has been frozen.
Between uses, return the multi-dose vial to the recommended storage conditions at 2° to 8°C (35° to 46°F).
Do not use after the expiration date shown on the label.
See FDA-approved patient labeling (Patient Information).
Fluzone is a registered trademark of Sanofi Pasteur Inc.
Manufactured by:
Sanofi Pasteur Inc.
Swiftwater PA 18370 USA
6592, 6596
Patient Information Sheet
Fluzone®
Influenza Vaccine
Please read this information sheet before getting Fluzone vaccine. This summary is not intended to take the place of talking with your healthcare provider. If you have questions or would like more information, please talk with your healthcare provider.
What is Fluzone vaccine?
Fluzone is a vaccine that helps protect against influenza illness (flu).
Fluzone vaccine is for people who are 6 months of age and older.
Vaccination with Fluzone vaccine may not protect all people who receive the vaccine.
Who should not get Fluzone vaccine?
You should not get Fluzone vaccine if you:
Tell your healthcare provider if you or your child have or have had:
How is the Fluzone vaccine given?
Fluzone vaccine is a shot given into the muscle of the arm.
For infants, Fluzone vaccine is a shot given into the muscle of the thigh.
What are the possible side effects of Fluzone vaccine?
The most common side effects of Fluzone vaccine are:
These are not all of the possible side effects of Fluzone vaccine. You can ask your healthcare provider for a list of other side effects that is available to healthcare professionals.
Call your healthcare provider for advice about any side effects that concern you. You may report side effects to the Vaccine Adverse Event Reporting System (VAERS) at 1-800-822-7967 or http://vaers.hhs.gov.
What are the ingredients in Fluzone vaccine?
Fluzone vaccine contains 3 killed flu virus strains.
Inactive ingredients include formaldehyde, octylphenol ethoxylate, and gelatin. The preservative thimerosal is only in the multi-dose vial of Fluzone vaccine.
NDC 49281-394-78
Flu
5 mL
Influenza
Vaccine
Fluzone®
Rx only
Contains Preservative
NDC 49281-394-15
2014-2015 Formula
Influenza Vaccine
Fluzone®
5 mL
Rx only
For 6 months of age and older
For intramuscular
injection only
SANOFI PASTEUR
FLUZONE
influenza a virus a/california/7/2009 x-179a (h1n1) antigen (formaldehyde inactivated), influenza a virus a/texas/50/2012 x-223a (h3n2) antigen (formaldehyde inactivated), and influenza b virus b/massachusetts/2/2012 bx-51b antigen (formaldehyde inactivated) injection, suspension |
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FLUZONE
influenza a virus a/california/7/2009 x-179a (h1n1) antigen (formaldehyde inactivated), influenza a virus a/texas/50/2012 x-223a (h3n2) antigen (formaldehyde inactivated), and influenza b virus b/massachusetts/2/2012 bx-51b antigen (formaldehyde inactivated) injection, suspension |
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Labeler - Sanofi Pasteur Inc. (086723285) |
Establishment | |||
Name | Address | ID/FEI | Business Operations |
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Sanofi Pasteur Inc. | 086723285 | MANUFACTURE |