BioThrax® ( Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

Version 12.0, 01 Jun 2018

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS, LABELLING AND PACKAGE LEAFLET

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BioThrax® () 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

SUMMARY OF PRODUCT CHARACTERISTICS

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See Section 4.8 for how to report adverse reactions

1 NAME OF THE MEDICINAL PRODUCT BioThrax1 suspension for injection. Anthrax Vaccine Adsorbed (purified cell-free filtrate)

2 QUALITATIVE AND QUANTITATIVE COMPOSITION One dose (0.5 mL) contains: Anthrax filtrate: 50 micrograms (50 mcg) a, b For a full list of excipients, see Section 6.1. a Produced from cell-free filtrates of an avirulent strain of b Adsorbed on , hydrated (0.6 mg Al3+)

3 PHARMACEUTICAL FORM Suspension for injection. Sterile, milky-white liquid suspension, when mixed.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications BioThrax is indicated for the prevention of disease caused by Bacillus anthracis, in adults at risk of exposure. BioThrax should be used in accordance with official recommendations, where available.

4.2 Posology and method of administration Posology: Primary Immunisation: 3-doses each of 0.5 mL, given at 0, 1 and 6 months. Booster: 0.5 mL at three-year intervals OR as per official recommendations. Method of administration: The vaccine is given by deep intramuscular (IM) injection in the deltoid region.

1 To be known as “BaciThrax” in France

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

The vaccine may be given by the subcutaneous injection (SC) when medically indicated (for example, in persons with coagulation disorders) using the same posology. Separate injection sites must be used if more than one vaccine is administered at the same time. The vaccine must not be mixed with other in the same syringe. For instructions on handling of vaccine before administration, see Section 6.6.

4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients listed in Section 6.1.

4.4 Special warnings and precautions for use As with other vaccines, administration of BioThrax should be postponed in subjects suffering from an acute severe febrile illness. The presence of a minor , such as a cold, should not result in deferral of . Do not inject intravascularly. When administered subcutaneously there is a higher incidence of injection site adverse reaction compared to intramuscular administration. Before administration, the person’s medical immunisation history should be reviewed for possible vaccine sensitivities and/or previous vaccination-related adverse events, in order to determine the existence of any contraindications to immunisation. As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of a rare anaphylactic event following administration of the vaccine. Persons with impaired immune responsiveness due to congenital or acquired immunodeficiency, or immunosuppressive therapy may have reduced responses to active immunisation. Vaccination during chemotherapy, high dose corticosteroid therapy of greater than 2-week duration, or radiation therapy may result in a suboptimal response. Deferral of vaccination for 3 months after completion of such therapy may be considered. As with other vaccines, a protective immune response may not be elicited in all individuals. The safety and efficacy of BioThrax in children have not been established. The safety and efficacy of BioThrax in patients > 65 years have not been established. The vial stopper may contain natural rubber latex. Although the risk of developing allergic reactions is very small, healthcare professionals should consider the benefit-risk prior to administering this vaccine to subjects with known history of hypersensitivity to latex.

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

4.5 Interaction with other medicinal products and other forms of interaction Use with other vaccines: BioThrax can be given concurrently with any of the following monovalent or combination vaccines; cholera, diphtheria, hepatitis A and B, influenza, Japanese encephalitis, measles, meningitis, mumps, pertussis, plague, polio, rabies, rubella, smallpox, tetanus, varicella and yellow fever. There are no data on the effects of co-administration of BioThrax with other vaccines on the immune response. When given concomitantly with other vaccines, BioThrax must be administered at separate injection sites (see Section 6.2). Use with antibiotics: BioThrax may be administered simultaneously with ciprofloxacin. Other medicinal products: The immunological response may be diminished if the patient is undergoing immunosuppressant treatment (see Section 4.4).

4.6 Fertility, Pregnancy and Lactation Pregnancy: BioThrax should not be used during pregnancy unless the potential benefits of vaccination clearly outweigh the potential risks to the foetus. A retrospective controlled study reported congenital anomalies (e.g. foramen ovale) when mothers were inadvertently vaccinated during the first trimester of pregnancy. No effects on pregnancy, maternal behaviour, female fertility, or postnatal development were observed in animal (rabbit) studies (see Section 5.3). Breast-Feeding: The effect on breastfed infants of administration of BioThrax to their mothers has not been studied. It is unknown whether BioThrax is excreted in human milk. Fertility: There are limited data on fertility in humans. A retrospective controlled study of prior administration of BioThrax to the male partner at an in vitro fertilisation clinic demonstrated no effect on semen parameters, fertilisation rate, embryo quality, or clinical pregnancy rates. There were no vaccine-related reproductive effects in studies in rabbits (see Section 5.3)

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

4.7 Effects on ability to drive and use machines BioThrax has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned in Section 4.8 may temporarily affect the ability to drive or use machines.

4.8 Undesirable effects Summary of safety profile: The safety of BioThrax was evaluated in one controlled clinical study in 1,563 adults; 1,044 were assigned to treatment with between 1 and 8 intramuscular (IM) injections. The clinical study demonstrated that adverse reactions occurred less often after each successive IM dose administered. Further safety data was evaluated from post-market experience where over 14 million doses of BioThrax have been administered to over 3 million adults. The most common adverse reactions observed are injection site reactions, headache, muscle aches and fatigue. Tabulated list of adverse reactions: Adverse reactions (following primary immunisation or booster dose) considered as being at least possibly related to vaccination have been categorised by frequency. Frequencies are defined as follows: Very common: ≥1/10 Common: ≥1/100, <1/10 Uncommon: ≥1/1,000, <1/100 Rare: ≥1/10,000, <1/1,000 Very rare: <1/10,000, including isolated reports Not known: (cannot be estimated from the available data) Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. In addition to reports in clinical trials, worldwide voluntary reports of adverse reactions received for BioThrax are included in the list. Since these reactions are voluntarily reported from an unknown population size, it is difficult to reliably determine frequency of events, thus these will be classified as “Not known”.

Table 1 Adverse Reactions from Clinical Trials and Post-Marketing Experience (Adults) System Organ Class Frequency Adverse Reactions and infestations Common Rhinitis, sinusitis, respiratory tract infection Uncommon Herpes zoster Neoplasms benign, malignant and Rare Breast ductal carcinoma unspecified (including cysts and polyps)

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

System Organ Class Frequency Adverse Reactions Blood and lymphatic system Not known Enlarged axillary lymph node disorders disorders Rare Hypersensitivity (including difficulty breathing, weakness, hoarseness or wheezing, a fast heartbeat, hives, dizziness, paleness or swelling of the throat, lips or face.) Very rare Anaphylactic reaction Psychiatric disorders Common Insomnia Nervous system disorders Very common Headache Common Dizziness Uncommon Syncope Rare Pseudotumor cerebri with bilateral papilloedema, aqueductal stenosis with generalised seizures Not known Guillain-Barre syndrome, seizure, brachial radiculitis, somnolence Eye disorders Uncommon Eye allergy Cardiac disorders Uncommon Heart rate increase Not known Palpitations, heart rate decreased Respiratory, thoracic and Common Cough mediastinal disorders Uncommon Respiratory tract congestion, dyspnea, sneezing Not known Dysphonia Gastrointestinal disorders Common Nausea, dyspepsia Uncommon Upper abdominal pain, vomiting Not known Diarrhoea, dysphagia Skin and subcutaneous tissue Common Rash, pruritus disorders Rare Cold sweat Not known Angioedema, alopecia, eczema, dry skin Musculoskeletal and connective Very common Myalgia tissue disorders Common Arthralgia, back pain, neck pain Uncommon Joint stiffness, musculoskeletal stiffness Rare Rotator cuff syndrome Not known Rhabdomyolysis Reproductive system and breast Uncommon Dysmenorrhea disorders

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

System Organ Class Frequency Adverse Reactions General disorders and Very common Injection site pain (burning sensation immediately administration site conditions after the shot is given; pain causing decreased mobility of injected arm), injection site swelling, injection site induration, injection site erythema, injection site bruising, injection site pruritus, injection site warmth, fatigue Common Fever, chills, axillary pain Uncommon Influenza-like illness, malaise, Injection site numbness/tingling Not known Injection site urticaria Infants and children (up to 10 years of age) The safety and efficacy of BioThrax in children have not been established. Adolescents (from 11 years of age) The safety and efficacy of BioThrax in adolescents have not been established. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V

4.9 Overdose Experience of overdose is limited. In the event of overdose, monitoring of vital functions and possible symptomatic treatment is recommended.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties Pharmacotherapeutic group: , ATC code: J07AC Mechanism of action: Bacillus anthracis includes three proteins known as protective antigen (PA), lethal factor (LF) and edema factor (EF). Individually these proteins are not cytotoxic but the combination of PA with LF or EF results in the formation of toxins. BioThrax works by stimulating the immune system to produce protective against PA. When PA is blocked, LF and EF are not able to interact with PA and the toxins are thereby neutralised Clinical efficacy and safety:

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

The efficacy of BioThrax has not been evaluated through clinical trials. Vaccine efficacy has been inferred from immunogenicity data including anti-PA IgG and toxin neutralisation titres. An earlier version of anthrax vaccine adsorbed (administered SC at 0, 2, 4 weeks, 6, 12, 18 months) was evaluated for clinical efficacy in an exposed, susceptible, supervised population of 1,249 mill workers between 1955-1959. Twenty-six cases occurred, 4 in individuals who had incomplete , 21 in uninoculated employees, and one in a vaccinated employee. The data indicated a vaccine effectiveness of 92.5 percent (95% lower CI = 65%). Surveillance data collected by the U.S Centers for Disease Control and Prevention (CDC) between 1962 and 1974 identified 27 cases of anthrax disease, 24 in unvaccinated individuals and 3 where vaccine schedule was incomplete. No documented cases of anthrax were reported for individuals who had received at least three of the recommended six doses of anthrax vaccine (either predecessor or BioThrax). Immunogenicity: The immunogenicity of BioThrax has been evaluated in immunised subjects and animals through quantification of anti-protective antigen (PA) IgG immune response and through the ability of those antibodies to neutralise anthrax lethal toxin. Anti-PA IgG antibodies have been found to be highly correlated to toxin neutralisation antibody (TNA) levels. Anti- PA IgG and TNA antibodies correlate with survival and protection from anthrax disease. Non-human primates (NHP) studies demonstrate that vaccination against anthrax disease protects against an otherwise lethal challenge of anthrax spores, and is associated with a protective immune response as measured by anti-PA IgG or TNA titres. It is not ethically possible to conduct similar studies in healthy volunteers, so the efficacy of BioThrax is based on extrapolation from survival rates and protective antibody levels in NHP studies. Thus, the NHP studies are used to estimate the putative protective antibody levels in humans. Antibody levels in humans were measured during the vaccine priming schedule and followed over time to include the response to a booster dose of vaccine. Data obtained from NHP studies, allows for extrapolation to estimate human survival for immunised subjects at different time points during the vaccination schedules. Subjects receiving the 6-month priming immunisation are estimated to have an 86.8% probability of survival if exposed to anthrax spores up to 3 years later, increasing to a 99.7% probability of survival if exposed one month (i.e. at 43-months) after a single booster dose given at 3 years post-priming (i.e. booster at 42-months). Table 2 below summarises antibody response in humans before and after completion of the primary vaccination regimen (0, 1, 6 months) using different dosing schedules and the predicted survival rates in humans based on NHP studies. Table 3 summarises antibody response in humans before and after booster vaccination (at 3 years post primary immunisation) using different dosing schedules and the predicted survival rates in humans based on NHP studies.

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

Table 2 Serum Anti-PA IgG GMC Antibody and TNA ED50 Results by Vaccination Regimen Primary Schedule with 95% Confidence Interval

Schedule Month 1 Month 2 Month 6 1 month after primary series completed (Month 7) Anti-PA TNA Anti-PA TNA Anti-PA TNA Anti-PA TNA % Predicted (µg/mL) (µg/mL) (µg/mL) (µg/mL) Survival 7-5-4 IM 2.6 20.2 46.4 165.5 3.9 22.2 206.9 1423.9 99.4% (n=782) (2.4, 2.9) (19.2, 21.3) (42.2, (146.2, (3.6, 4.3) (20.8, (187.1, (1253.1, (98.0, 51.0) 187.4 23.6) 227.0) 1617.9) 99.9%) Anti-PA IgG = anti-protective antigen (geometric mean concentration)

TNA ED50 = toxin neutralisation antibody (geometric mean titre)

Table 3 Serum Anti-PA IgG GMC Antibody and TNA ED50 Results by Vaccination Regimen Booster with 95% Confidence Interval Schedule Month 42 (Before booster) Month 43 (1 month after booster) Anti-PA TNA % Predicted Anti-PA TNA % Predicted (µg/mL) Survival (µg/mL) Survival 4-IM1 6.0 42.7 86.8% 433.2 2825.9 99.7% (5.3, 6.9) (33.8, 54.0) (80.8, 92.1) (379.6, 494.4) (2175.2, 3671.3) (98.7, 100.0) (n=161) (n=70) (n=157) (n=66) 5-IM 21.6 174.1 95.8% 310.0 1876.2 99.7% (18.9, 24.7) (139.3, 217.6) (91.6, 98.5) (270.5, 355.3) (1603.1, 2195.9) (98.5, 100.0) (n=145) (n=72) (n=141) (n=67) 7-IM 35.7 215.2 98.1% 254.8 1451.0 99.7% (31.2, 40.9) (166.4, 278.4) (94.9, 99.5) (222.0, 292.4) (1139.5,1847.7) (98.5, 100.0) (n=147) (n=67) (n=139) (n=56) 1 - This is the licensed posology for BioThrax as shown in Section 4.2 Anti-PA IgG = anti-protective antigen immunoglobulin G (geometric mean concentration) TNA ED50 = toxin neutralisation antibody (geometric mean titre)

Figure 1 shows the anti-PA IgG antibody concentration and Figure 2 the TNA titre over time, for the different vaccine schedules. The 0, 1 and 6-month timepoints correspond to the primary immunisation schedule and a booster is given at 42 months (3-years post-priming). The 7-month timepoint corresponds to one month post-primary immunisation completion and 43-months to one month post-booster dose.

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

Figure 1 Anti-PA IgG Antibody Concentration Over Time

Note: Lower limit of quantification (LLOQ) for the assay is 1.8 mcg/mL

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

Figure 2 TNA ED50 Titre Over Time

Note: Lower limit of quantification (LLOQ) for the assay is TNA ED50 = 18

5.2 Pharmacokinetic properties Not applicable.

5.3 Preclinical safety data Non-clinical data reveal no special hazard for humans based on conventional studies of pharmacology, single and repeated dose toxicity. No effects on female fertility, reproductive or postnatal development were observed in animal (rabbit) studies at doses relevant to the clinical dose (see Section 4.6).

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients Sodium chloride Water for injections For adsorbant, see Section 2.

6.2 Incompatibilities In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products, see Section 4.5.

6.3 Shelf life 4 years After first opening, the vial is to be used within 28 days, and stored as per Section 6.4.

6.4 Special precautions for storage Store in a refrigerator (2 ºC – 8 ºC). Do not freeze. Store in the original package in order to protect from light.

6.5 Nature and contents of container 5 mL (10 x 0.5 mL doses) suspension in a multi-dose vial (Type I glass) with stopper (chlorobutyl rubber), in a pack size of 1.

6.6 Special precautions for disposal and other handling Before use the vial should be shaken well to form a homogeneous suspension. The vaccine should be visually inspected before use. If the product appears discoloured or has visible particulate matter, discard the vial. Mark the vial with date and time of opening. Use a separate sterile needle and syringe for each person to avoid transmission of viral hepatitis and other infectious agents.

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

Place the multidose vial into storage away from the immediate patient environment following the storage conditions outlined in Section 6.4. Never pool or combine leftover contents for later use. Any unused product or waste material should be disposed of in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER Emergent Sales and Marketing Germany GmbH Vichystraße 14 76646 Bruchsal Germany Tel: 0049 7251 32197031 Fax: 0049 7251 32197010

8 MARKETING AUTHORISATION NUMBER(S) PEI.H.04350.01.1

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION Date of first authorisation: 24/06/2013

10 DATE OF REVISION OF THE TEXT

06/2018

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

LABELLING

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

PARTICULARS TO APPEAR ON

{NATURE/TYPE}

1. NAME OF THE MEDICINAL PRODUCT BioThrax® Suspension for injection Anthrax Vaccine Adsorbed (purified cell-mfree filtrate) m2. STATEMENT OF ACTIVE SUBSTANCE(S) One dose (0.5 mL) contains: 50 micrograms Anthrax antigen adsorbed on aluminium- hydroxide, hydrated (0.6 mg Al3+). 3. LIST OF EXCIPIENTS Benzethonium chloride, formaldehyde, sodium chloride and water for injections.

4. PHARMACEUTICAL FORM AND CONTENTS 1 multidose vial containing 5 mL (0.5 mL/dose) 5. METHOD AND ROUTE(S) OF ADMINISTRATION Read the package leaflet before use. Intramuscular use 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE REACH AND SIGHT OF CHILDREN Keep out of the reach and sight of children. 7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE EXP: 9. SPECIAL STORAGE CONDITIONS Store in a refrigerator (2-8 ºC). Do not freeze. Store in the original package in order to protect from light. 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER Emergent Sales and Marketing Germany GmbH Vichystraße 14 76646 Bruchsal Germany

12. MARKETING AUTHORISATION NUMBER(S) PEI.H.04350.01.1

13. BATCH NUMBER LOT:

14. GENERAL CLASSIFICATION FOR SUPPLY Medicinal product subject to medical prescription. 15. INSTRUCTIONS ON USE Shake well before use. 16. INFORMATION IN BRAILLE

17. UNIQUE IDENTIFIER – 2D BARCODE

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

LABEL FOR 10-DOSE VIAL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION BioThrax® Suspension for injection Anthrax Vaccine Adsorbed (purified cell-free filtrate) 2. METHOD OF ADMINISTRATION IM

3. EXPIRY DATE EXP:

4. BATCH NUMBER LOT:

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 1 multidose vial containing 5 mL (0.5 mL/dose) 6. OTHER Emergent Sales and Marketing Germany GmbH Vichystraße 14 76646 Bruchsal Germany

Medicinal product subject to medical prescription. Store in a refrigerator (2-8 ºC). Do not freeze. Store in the original package in order to protect from light. Shake well before use.

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

PACKAGE LEAFLET

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

PACKAGE LEAFLET: INFORMATION FOR THE USER BioThrax Suspension for Injection Anthrax Vaccine Adsorbed (purified cell-free filtrate) This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of Section 4 for how to report side effects. Read this leaflet carefully and completely before your first injection of this medicine. - Keep this leaflet. You may need to read it again. - If you have further questions, ask your doctor or healthcare provider. - If any of the side effects gets serious, or if you notice any side effects not listed in Section 4 of this leaflet, please tell your doctor or healthcare provider. In this leaflet: - 1. What BioThrax is and what it is used for - 2. Before you are injected with BioThrax - 3. How to use BioThrax - 4. Possible side effects - 5. How to store BioThrax - 6. Contents of the pack and other information

1 WHAT BIOTHRAX IS AND WHAT IT IS USED FOR What is BioThrax? BioThrax is a vaccine used to prevent infection due to Bacillus anthracis. What is it used for? It is used in adults to prevent anthrax disease. Anthrax disease is a bacterial infection caused by exposure to Bacillus anthracis and your body’s response to this infection. Vaccination with BioThrax prepares your body to fight off the infection by blocking the toxin that is produced by infection.

2 BEFORE YOU ARE INJECTED WITH BIOTHRAX Do NOT use BioThrax: - If you are allergic to the active substance or any of the other ingredients in this vaccine (listed in Section 6).

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

Take special care with BioThrax Please inform your doctor if you: - have an impaired immune responsiveness due to congenital or acquired immunodeficiency or - are receiving immunosuppressive therapy; - have had an allergic reaction following a previous dose of BioThrax or any of the vaccine components; - have a latex allergy or hypersensitivity, because the vial stopper contains dry natural rubber blend which may contain trace amounts of latex proteins. Children The safety and effectiveness of BioThrax in children has not been established. Geriatrics The safety and effectiveness of BioThrax in subjects over 65 years of age has not been established. Taking Other medicines Please tell your doctor or healthcare provider if you are being treated with immunosuppresive therapy, or high-dose corticosteroid therapy, or cytotoxic medicine (e.g. chemotherapy). Using BioThrax with food and drink No special restrictions or precautions are indicated when receiving BioThrax . Pregnancy and breast-feeding If you are pregnant, think you may be pregnant or are trying to get pregnant or breast- feeding, ask your doctor or healthcare provider to advise before receiving any vaccination or medication. As a precaution, pregnant women should not be routinely vaccinated with anthrax vaccine. Driving and using machines BioThrax has no or negligible influence on the ability to drive or use machinery. However, some of the side-effects listed under Section 4, may temporarily affect ability to drive or use machines.

3 HOW TO USE BIOTHRAX This vaccine has been prescribed for you and will be administered by your doctor or healthcare provider. To administer, a small sterile needle and syringe will be used to withdraw a 0.5 mL dose of BioThrax from the multi-dose vial. The dose will be administered through an intramuscular (IM) injection in your upper arm. Recommended injection schedule

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

For reliable protection, an initial vaccination regimen of 0.5 mL intramuscular (IM) at 0, 1 and 6 months, then booster doses every 3 years are recommended. If you miss an injection Notify your doctor or healthcare provider to determine the best course of action. In most instances, continuation of the schedule with adjustment to the times of injection is all that is needed to maintain your immunity. If you stop receiving the injections If you have any further questions on the use of this product, ask your doctor or healthcare provider.

4 POSSIBLE SIDE EFFECTS Like all medicines, BioThrax may cause side effects, although not everybody gets them. If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or healthcare provider. Provide them with information regarding your symptoms, time and date of side effect and when you received the vaccination. They can then use this information to treat you and report the incident as required by law. Very Common (more than 1 per 10)  Soreness, pain, redness, bruising, itching, swelling, or warmth at injection site  Motion limitation in the injected arm  A lump where the shot was given  A burning sensation may occur immediately after the shot is given and can last about a minute  Muscle aches, fatigue or headaches Common (less than 1 per 10, but equal or more than 1 per 100)  Discomfort in the armpit area (axillary lymph node).  Chills, fever, dizziness, insomnia, nausea, or indigestion (dyspepsia).  Cough, nasal/sinus ,or other respiratory tract infection  Rash, itching.  Joint, back or neck aches Uncommon (less than 1 per 100, but equal or more than 1 per 1000)  Injection site numbness/tingling  Influenza-like illness, respiratory tract congestion, shortness of breath, sneezing, shingles (herpes zoster).

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

 Malaise  Rapid heart rate  Joint or muscle stiffness, extremity (arm) pain  Eye allergy  Skin redness (including skin flushing)  Fainting  Upper abdominal pain, vomiting, menstrual-like cramps (dysmenorrhea). Rare (more than 1 per 1000 but equal to or more than 1 per 10,000)  Serious allergic reaction. Signs of a serious allergic reaction include difficulty breathing, weakness, hoarseness or wheezing, a fast heartbeat, hives, dizziness, paleness or swelling of the throat, lips or face.  Breast ductal carcinoma  Increased pressure inside the skull (pseudotumor cerebri)  Narrowing of duct leading to increased fluid in brain (aqueductal stenosis)  Rotator cuff (shoulder tendon) tear  Cold sweat Very rare (less than 1 per 10,000)  Severe, potentially life threatening allergic reaction (anaphylactic reactions) Side effects that have been reported during marketed use include:  Guillain-Barre syndrome (disorder in which immune system attacks nerves), seizure, brachial neuritis, somnolence  Rhabdomyolysis (condition in which muscle cells break down)  Swelling of deep layers of skin (angioedema), hair loss (alopecia), eczema, dry skin  Slow heart rate, palpitations  Difficulty in speaking (dysphonia)  Diarrhoea, feeling of lump in throat (dysphagia)  Enlarged axillary lymph node  Hives at the injection site If you experience any unusual condition, such as difficulty breathing, weakness, hoarseness or wheezing, a fast heartbeat, hives, dizziness, paleness or swelling of the throat, lips or face within a few minutes after the shot or within a few minutes to an hour after the shot, notify your doctor or healthcare provider immediately as this could be a sign of a severe reaction.

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix 5 By reporting side effects you can help provide more information on the safety of this medicine.

5 HOW TO STORE BIOTHRAX  Keep out of the reach and sight of children.  Do not use BioThrax after the expiry data which is stated on the label.  Do not use more than 28 days after first opening.  Store in refrigerator (2-8 °C).  Do not freeze.  Store in the original package in order to protect from light.

6 CONTENTS OF THE PACK AND OTHER INFORMATION What BioThrax contains One dose (0.5 mL) contains:  Anthrax antigen filtrate: 50 micrograms  Adsorbed on aluminium hydroxide (0.6 mg aluminium per dose)  Benzethonium chloride  Formaldehyde  Sodium chloride  Water for injections The product is sterile and does not contain any living or dead bacteria. The container of this medicinal product contains latex rubber. May cause severe allergic reactions. What BioThrax looks like and vial contents BioThrax is a milky-white suspension (when mixed) contained in a clear glass vial. The vial is closed with a stopper (chlorobutyl) and sealed with an aluminium cap. The product is supplied sterile and one vial contains enough vaccine for 10 injections of 0.5 mL. Marketing Authorisation Holder Emergent Sales and Marketing Germany GmbH Vichystraße 14

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BioThrax® (Anthrax Vaccine Adsorbed) 1.3.1 Summary of Product Characteristics, Labelling and Package Leaflet

76646 Bruchsal, Germany Telephone: 0049 7251 32197031 Facsimile: 0049 7251 32197010 e-mail: [email protected] Manufacturer Emergent Sales and Marketing Germany GmbH Vichystr. 14 76646 Bruchsal, Germany Telephone: 0049 7251 32197031 Facsimile: 0049 7251 32197010 e-mail: [email protected] For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder. For product quality or safety concerns, please contact: Emergent BioSolutions, Inc Telephone: 0049 7251 32197031 Facsimile: 0049 7251 32197010 E-Mail: [email protected] This leaflet was last revised in June 2018.

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