SAFETY DATA SHEET

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1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE AND THE COMPANY/UNDERTAKING

Product Identifier
Material Name: ZIRABEV (Bevacizumab)
Trade Name: ZIRABEV
Compound Number: PF-06439535
Synonyms: Bevacizumab-Pfizer; Beva-PFE
Chemical Family: Recombinant protein

Relevant Identified Uses of the Substance or Mixture and Uses Advised Against
Intended Use: Pharmaceutical product

Details of the Supplier of the Safety Data Sheet

Pfizer Inc Pfizer Ltd
Pfizer Pharmaceuticals Group Ramsgate Road
235 East 42nd Street Sandwich, Kent
New York, New York 10017 CT13 9NJ
1-800-879-3477 United Kingdom
+00 44 (0)1304 616161
Emergency telephone number: Emergency telephone number:
CHEMTREC (24 hours): 1-800-424-9300 International CHEMTREC (24 hours): +1-703-527-3887
Contact E-Mail: pfizer-MSDS@pfizer.com

2. HAZARDS IDENTIFICATION

Classification of the Substance or Mixture

GHS - Classification
Reproductive Toxicity: Category 2

Label Elements
Signal Word: Warning
Hazard Statements: H361fd - Suspected of damaging fertility. Suspected of damaging the unborn child.

Precautionary Statements: P201 - Obtain special instructions before use

P202 - Do not handle until all safety precautions have been read and understood
P281 - Use personal protective equipment as required
P308 + P313 - IF exposed or concerned: Get medical attention/advice
P405 - Store locked up
P501 - Dispose of contents/container in accordance with all local and national regulations

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Other Hazards An Occupational Exposure Value has been established for one or more of the ingredients (see
Section 8).

Note: This document has been prepared in accordance with standards for workplace safety, which
requires the inclusion of all known hazards of the product or its ingredients regardless of the
potential risk. The precautionary statements and warning included may not apply in all cases.
Your needs may vary depending upon the potential for exposure in your workplace.

3. COMPOSITION / INFORMATION ON INGREDIENTS

Hazardous
Ingredient CAS Number EU GHS Classification %
EINECS/ELINCS
List
EDTA 60-00-4 200-449-4 Eye Irrit. 2A (H319) <1
SODIUM HYDROXIDE 1310-73-2 215-185-5 Skin Corr. 1A (H314) ###
Bevacizumab 216974-75-3 Not Listed Repr.2 (H361fd) 1-5

Ingredient CAS Number EU GHS Classification %

EINECS/ELINCS
List
Succinic acid 110-15-6 203-740-4 Not Listed *
Sucrose 57-50-1 200-334-9 Not Listed *
Polysorbate 80 9005-65-6 500-019-9 Not Listed *
Water for Injection 7732-18-5 231-791-2 Not Listed ###

Additional Information: * Proprietary

### as required
Ingredient(s) indicated as hazardous have been assessed under standards for workplace
safety. In accordance with 29 CFR 1910.1200, the exact percentage composition of this
mixture has been withheld as a trade secret.

For the full text of the CLP/GHS abbreviations mentioned in this Section, see Section 16

4. FIRST AID MEASURES

Description of First Aid Measures

Eye Contact: Flush with water while holding eyelids open for at least 15 minutes. Seek medical attention
immediately.

Skin Contact: Remove contaminated clothing. Flush area with large amounts of water. Use soap. Seek
medical attention.

Ingestion: Never give anything by mouth to an unconscious person. Wash out mouth with water. Do not
induce vomiting unless directed by medical personnel. Seek medical attention immediately.

Inhalation: Remove to fresh air and keep patient at rest. Seek medical attention immediately.
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Most Important Symptoms and Effects, Both Acute and Delayed

Symptoms and Effects of For information on potential signs and symptoms of exposure, See Section 2 - Hazards
Exposure: Identification and/or Section 11 - Toxicological Information.
Medical Conditions None known
Aggravated by Exposure:

Indication of the Immediate Medical Attention and Special Treatment Needed

Notes to Physician: None

5. FIRE FIGHTING MEASURES

Extinguishing Media: Extinguish fires with CO2, extinguishing powder, foam, or water.

Special Hazards Arising from the Substance or Mixture

Hazardous Combustion Formation of toxic gases is possible during heating or fire.
Products:

Fire / Explosion Hazards: Fine particles (such as mists) may fuel fires/explosions.

Advice for Fire-Fighters

During all firefighting activities, wear appropriate protective equipment, including self-contained breathing apparatus.

6. ACCIDENTAL RELEASE MEASURES

Personal Precautions, Protective Equipment and Emergency Procedures

Personnel involved in clean-up should wear appropriate personal protective equipment (see Section 8). Minimize exposure.

Environmental Precautions
Place waste in an appropriately labeled, sealed container for disposal. Care should be taken to avoid environmental release.

Methods and Material for Containment and Cleaning Up

Measures for Cleaning / Contain the source of spill if it is safe to do so. Collect spill with absorbent material. Clean spill
Collecting: area thoroughly.

Additional Consideration for Non-essential personnel should be evacuated from affected area. Report emergency
Large Spills: situations immediately. Cleanup operations should only be undertaken by trained personnel.

7. HANDLING AND STORAGE

Precautions for Safe Handling

Restrict access to work area. Avoid open handling. Minimize generating airborne mists and vapors. Use appropriate engineering
controls to maintain exposures below the B-OEB taking all applicable routes of exposure into consideration. A change area to
facilitate 'good laboratory/manufacturing' decontamination practices is recommended. Avoid inhalation and contact with skin, eye,
and clothing. When handling, use appropriate personal protective equipment (see Section 8). Wash hands and any exposed skin
after removal of PPE. Releases to the environment should be avoided. Review and implement appropriate technical and
procedural waste water and waste disposal measures to prevent occupational exposure or environmental releases. Potential
points of process emissions of this material to the atmosphere should be controlled with dust collectors, HEPA filtration systems
or other equivalent controls.

Conditions for Safe Storage, Including any Incompatibilities

Storage Conditions: Store as directed by product packaging.
Specific end use(s): Pharmaceutical drug product

8. EXPOSURE CONTROLS / PERSONAL PROTECTION

Control Parameters

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8. EXPOSURE CONTROLS / PERSONAL PROTECTION

Refer to available public information for specific member state Occupational Exposure Limits.

Sucrose
ACGIH Threshold Limit Value (TWA) 10 mg/m3
Australia TWA 10 mg/m3
Belgium OEL - TWA 10 mg/m3
Bulgaria OEL - TWA 10.0 mg/m3
Estonia OEL - TWA 10 mg/m3
France OEL - TWA 10 mg/m3
Ireland OEL - TWAs 10 mg/m3
Latvia OEL - TWA 5 mg/m3
Lithuania OEL - TWA 10 mg/m3
OSHA - Final PELS - TWAs: 15 mg/m3
Portugal OEL - TWA 10 mg/m3
Slovakia OEL - TWA 6 mg/m3
Spain OEL - TWA 10 mg/m3

SODIUM HYDROXIDE
ACGIH Ceiling Threshold Limit: 2 mg/m3
Australia PEAK 2 mg/m3
Austria OEL - MAKs 2 mg/m3
Bulgaria OEL - TWA 2.0 mg/m3
Czech Republic OEL - TWA 1 mg/m3
Estonia OEL - TWA 1 mg/m3
France OEL - TWA 2 mg/m3
Greece OEL - TWA 2 mg/m3
Hungary OEL - TWA 2 mg/m3
Japan - OELs - Ceilings 2 mg/m3
Latvia OEL - TWA 0.5 mg/m3
OSHA - Final PELS - TWAs: 2 mg/m3
Poland OEL - TWA 0.5 mg/m3
Slovakia OEL - TWA 2 mg/m3
Slovenia OEL - TWA 2 mg/m3
Sweden OEL - TWAs 1 mg/m3
Switzerland OEL -TWAs 2 mg/m3

The Biotherapeutic Occupational Exposure Band (B-OEB) is an acceptable daily intake (ADI) range, based on available hazard data
with appropriate safety factors applied. Engineering control measures should be utilized to bring exposures into the relevant B-OEB;
supplementary administrative controls and personal protective equipment are to be used to achieve exposure control to the bottom of
the band.

Bevacizumab
Pfizer Occupational Exposure B-OEB 4 (control exposure to the range of 10 µg/day to <100 µg/day)
Band (OEB):

Exposure Controls
Engineering Controls: Engineering controls should be used as the primary means to control exposures. Use process
containment, local exhaust ventilation, biosafety cabinet, or other engineering controls to
maintain airborne levels within the B-OEB range. It is recommended that all large scale
operations should be fully enclosed. Air recirculation is not recommended.

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8. EXPOSURE CONTROLS / PERSONAL PROTECTION

Personal Protective Refer to applicable national standards and regulations in the selection and use of personal
Equipment: protective equipment (PPE). Contact your safety and health professional or safety equipment
supplier for assistance in selecting the correct protective clothing/equipment based on an
assessment of the workplace conditions, other chemicals used or present in the workplace and
specific operational processes.

Hands: Wear impervious disposable gloves (e.g. Nitrile, etc.) as minimum protection (double
recommended). (Protective gloves must meet the standards in accordance with EN374,
ASTM F1001 or international equivalent.)
Eyes: Wear safety glasses as minimum protection. (Safety glasses must meet the standards in
accordance with EN166, ANSI Z87.1 or international equivalent.)
Skin: Wear impervious disposable protective clothing when handling this compound. Full body
protection is recommended (scale dependent). (Protective clothing must meet the standards in
accordance with EN13982, ANSI 103 or international equivalent.)
Respiratory protection: If airborne exposures are within or exceed the Biotherapeutic Occupational Exposure Band (B-
OEB) range, wear an appropriate respirator with a protection factor sufficient to control
exposures to the bottom of the B-OEB range. Under normal conditions of use, if the applicable
Biotherapeutic Occupational Exposure Band (B-OEB) is exceeded, wear an appropriate
respirator with a protection factor sufficient to control exposures to below the B-OEB (e.g.
particulate respirator with a full mask, P3 filter). (Respirators must meet the standards in
accordance with EN136, EN143, ASTM F2704-10 or international equivalent.)

9. PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Liquid Color: Clear, colorless

Odor: No data available. Odor Threshold: No data available.
Molecular Formula: Mixture Molecular Weight: Mixture

Solvent Solubility: No data available

Water Solubility: No data available
pH: No data available.
Melting/Freezing Point (°C): No data available
Boiling Point (°C): No data available.
Partition Coefficient: (Method, pH, Endpoint, Value)
EDTA
No data available
Succinic acid
No data available
Sucrose
No data available
Polysorbate 80
No data available
SODIUM HYDROXIDE
No data available
Water for Injection
No data available
Bevacizumab
No data available
Decomposition Temperature (°C): No data available.

Evaporation Rate (Gram/s): No data available

Vapor Pressure (kPa): No data available
Vapor Density (g/ml): No data available
Relative Density: No data available
Viscosity: No data available
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Flammablity:
Autoignition Temperature (Solid) (°C): No data available
Flammability (Solids): No data available
Flash Point (Liquid) (°C): No data available
Upper Explosive Limits (Liquid) (% by Vol.): No data available
Lower Explosive Limits (Liquid) (% by Vol.): No data available

10. STABILITY AND REACTIVITY

Reactivity: No data available

Chemical Stability: Stable under normal conditions of use.
Possibility of Hazardous Reactions
Oxidizing Properties: No data available
Conditions to Avoid: Fine particles (such as mists) may fuel fires/explosions. As a precautionary measure, keep
away from heat sources and electrostatic discharge.
Incompatible Materials: As a precautionary measure, keep away from strong oxidizers
Hazardous Decomposition No data available
Products:

11. TOXICOLOGICAL INFORMATION

Information on Toxicological Effects

General Information: The following information is from a related compound and is presumed to be predictive of the
effects produced by this material.
Short Term: Not determined, however, there may be potential for adverse reactions associated with
administration of antibodies to humans, including potential systemic allergic reactions. This
substance, based on the composition, may also cause eye irritation, skin irritation, and may
produce allergic reactions following direct contact. This material is a novel research
formulation intended to be pharmacologically active, and is assumed to be harmful if injected.
Known Clinical Effects: The following effects are based on a chemically-related material: headache, increase in blood
pressure (hypertension), nose bleed, back pain, gastrointestinal perforation, hemorrhage, red,
itchy, scaly skin (exfoliative dermatitis).

Acute Toxicity: (Species, Route, End Point, Dose)

EDTA
Rat Oral LD50 > 2000 mg/kg
Rat Oral LD50 4500 mg/kg

Sucrose
Rat Oral LD 50 29,700 mg/kg

Polysorbate 80
Rat Intravenous LD 50 1790 mg/kg
Mouse Oral LD 50 25 g/kg

Acute Toxicity Comments: A greater than symbol (>) indicates that the toxicity endpoint being tested was not achievable
at the highest dose used in the test.

Repeated Dose Toxicity: (Duration, Species, Route, Dose, End Point, Target Organ)

Bevacizumab

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11. TOXICOLOGICAL INFORMATION

26 Week(s) Monkey Intravenous <=2 mg/kg NOAEL Female reproductive system, Bone
1 Month(s) Monkey Intravenous 10 mg/kg/day * NOAEL None identified
1 Month(s) Monkey Intravenous 2 mg/kg/day (9 doses) LOEL Bone
Repeated Dose Toxicity Comments: * Note: Doses were administerd twice weekly.

Reproduction & Development Toxicity: (Duration, Species, Route, Dose, End Point, Effect(s))

Bevacizumab
Embryo / Fetal Development Rabbit Intravenous <10 mg/kg NOAEL Developmental toxicity

Carcinogen Status: None of the components of this formulation are listed as a carcinogen by IARC, NTP or OSHA.

12. ECOLOGICAL INFORMATION

Environmental Overview: Releases to the environment should be avoided. Environmental properties of the formulation
have not been thoroughly investigated.

Toxicity:
Aquatic Toxicity: (Species, Method, End Point, Duration, Result)

Bevacizumab
Scenedesmus subspicatus (Green Alga) OECD ErC50 72 Hours > 100 mg/L
Daphnia magna (Water Flea) OECD EC50 48 Hours > 100 mg/L

Persistence and Degradability:

Biodegradation: (Method, Inoculum, Biodeg Study, Result, Endpoint, Duration, Classification)
Bevacizumab
OECD Activated sludge Ready 96% After 28 Day(s) Ready

Bio-accumulative Potential: No data available

Mobility in Soil: No data available

13. DISPOSAL CONSIDERATIONS

Waste Treatment Methods: Dispose of waste in accordance with all applicable laws and regulations. Member State
specific and Community specific provisions must be considered. Considering the relevant
known environmental and human health hazards of the material, review and implement
appropriate technical and procedural waste water and waste disposal measures to prevent
occupational exposure and environmental release. It is recommended that waste minimization
be practiced. The best available technology should be utilized to prevent environmental
releases. This may include destructive techniques for waste and wastewater.

14. TRANSPORT INFORMATION

The following refers to all modes of transportation unless specified below.

Not regulated for transport under USDOT, EUADR, IATA, or IMDG regulations.

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Transportation classification is based on data and/or procedures that may not be reflected on this document. The classification was
conducted as per defining criteria in the international transportation regulations and the shipper's knowledge of the material.

15. REGULATORY INFORMATION

Safety, Health and Environmental Regulations/Legislation Specific for the Substance or Mixture
Caution - Substance not fully tested (VIIA)

Succinic acid
CERCLA/SARA 313 Emission reporting Not Listed
California Proposition 65 Not Listed
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
EU EINECS/ELINCS List 203-740-4

Sucrose
CERCLA/SARA 313 Emission reporting Not Listed
California Proposition 65 Not Listed
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
REACH - Annex IV - Exemptions from the Present
obligations of Register:
EU EINECS/ELINCS List 200-334-9

EDTA
CERCLA/SARA 313 Emission reporting Not Listed
CERCLA/SARA Hazardous Substances 5000 lb
and their Reportable Quantities: 2270 kg
California Proposition 65 Not Listed
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
Standard for the Uniform Scheduling Schedule 4
for Drugs and Poisons:
EU EINECS/ELINCS List 200-449-4

Polysorbate 80
CERCLA/SARA 313 Emission reporting Not Listed
California Proposition 65 Not Listed
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
EU EINECS/ELINCS List 500-019-9

SODIUM HYDROXIDE

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15. REGULATORY INFORMATION

CERCLA/SARA 313 Emission reporting Not Listed
CERCLA/SARA Hazardous Substances 1000 lb
and their Reportable Quantities: 454 kg
California Proposition 65 Not Listed
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
Standard for the Uniform Scheduling Schedule 5
for Drugs and Poisons: Schedule 6
EU EINECS/ELINCS List 215-185-5

Water for Injection

CERCLA/SARA 313 Emission reporting Not Listed
California Proposition 65 Not Listed
Inventory - United States TSCA - Sect. 8(b) Present
Australia (AICS): Present
REACH - Annex IV - Exemptions from the Present
obligations of Register:
EU EINECS/ELINCS List 231-791-2

Bevacizumab
CERCLA/SARA 313 Emission reporting Not Listed
California Proposition 65 Not Listed
Standard for the Uniform Scheduling Schedule 4
for Drugs and Poisons:
EU EINECS/ELINCS List Not Listed

16. OTHER INFORMATION

Text of CLP/GHS Classification abbreviations mentioned in Section 3

Reproductive toxicity-Cat.2; H361fd - Suspected of damaging fertility. Suspected of damaging the unborn child.
Serious eye damage/eye irritation-Cat.2A; Skin corrosion/irritation-Cat.1A; H314 - Causes severe skin burns and eye damage

Data Sources: Pfizer proprietary drug development information. Publicly available toxicity information.

Reasons for Revision: Updated Section 3 - Composition / Information on Ingredients. Updated Section 1 -
Identification of the Substance/Preparation and the Company/Undertaking. Updated Section 2 -
Hazard Identification. Updated Section 7 - Handling and Storage. Updated Section 11 -
Toxicology Information.

Revision date: 19-Feb-2019

Product Stewardship Hazard Communication
Prepared by: Pfizer Global Environment, Health, and Safety Operations

Pfizer Inc believes that the information contained in this Safety Data Sheet is accurate, and while it is provided in good faith, it is without
warranty of any kind, expressed or implied. If data for a hazard are not included in this document there is no known information at this
time.

End of Safety Data Sheet

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