**MATERIAL SAFETY DATA SHEET**

Transcription

1 Date Issued: August 19, 2009 Version: 5.0 Supersedes: August 8, 2006 Page 1 of 5 Section 1 Product and Company Identification Product Name: Herceptin Chemical Name: Anti-p185 HER2 Chemical Family: High molecular weight protein therapeutic (humanized IgG1 monoclonal antibody) Company Name: Genentech, Inc. Company Address: 1 DNA Way, South San Francisco, CA Company Phone: (650) Emergency Phone: (800) Section 2 Hazards Identification Emergency Overview Herceptin derives its therapeutic benefit from a monoclonal antibody (trastuzumab) that is not well absorbed by inhalation or by contact with eyes, skin, or mucous membranes. Adverse health effects have been observed in patients following intravenous (IV) infusion of therapeutic doses for the treatment of metastatic breast cancer. Although the health effects of occupational exposure to this product are not fully known or characterized, no adverse effects are anticipated as a result of occupational or incidental exposure. This product is a white to pale yellow, odorless, lyophilized powder. For more product information see Section 11 or visit Routes of Exposure Direct contact with eyes, skin, or mucous membranes is the possible primary route of occupational exposure. No adverse health effects through these routes are expected to occur in occupational exposure conditions due to the large size of trastuzumab (a full length monoclonal antibody with a molecular weight of ~140,000 daltons) and its poor potential for absorption. Page 1 of 6

2 Section 3 Composition/Information on Ingredients Component(s) CAS Number Trastuzumab L-Histidine HCL L-Histidine Polysorbate 20, USP Trehalose dihydrate Sterile Water for injection (Contains 1.1% benzyl alcohol as a preservative) Formula (drug substance): Antibody framework region derived from human immunoglobulin G 1 (IgG 1 ) Synonyms (drug substance): Trastuzumab Eye/Skin Contact Section 4 First Aid Measures Immediately flush eyes thoroughly with water or wash skin for at least 5 minutes as a prudent chemical hygiene practice. Report exposure to supervisor. Section 5 Fire Fighting Measures Flammability/Explosivity Not considered flammable or explosive. Note: High airborne concentrations of finely divided organic particulates can explode spontaneously in air or if ignited. Section 6 Accidental Release Measures Wet down spilled material to minimize airborne dispersion. Soak up material with absorbent, e.g., paper towels, and wash spill area thoroughly with soap and water. Dispose of collected material in accordance with applicable waste disposal regulations. Section 7 Handling and Storage Avoid contact with skin, eyes and clothing. Wash hands thoroughly after handling. Protect from light and store with desiccant. Store in a well ventilated area. Page 2 of 6

3 Skin Protection Section 8 Exposure Control and Personal Protective Equipment As a prudent chemical hygiene practice, wear protective equipment that minimizes the potential for skin contact, such as latex gloves and lab coat. Wash hands and other potentially exposed areas immediately after handling material. Eye Protection As a prudent chemical hygiene practice, use safety glasses with side shields. Other Clean all protective equipment after use. Section 9 Physical and Chemical Properties Molecular Weight ~140,000 Daltons ph: ~6.0 Boiling Point (degrees C): Not applicable Melting Point No data available Vapor Pressure: ~17 mmhg (for reconstituted solution) Solubility in Water: Soluble Evaporation Rate: Negligible (for reconstituted solution) Appearance: White to pale yellow, odorless, lyophilized powder Specific Gravity: ~1 Vapor Density: Not applicable Percent Volatile: Not applicable Section 10 Stability and Reactivity Stability: Hazardous Polymerization: Hazardous Decomposition Products: No data available Will not occur None expected Page 3 of 6

4 Section 11 Toxicological Information Eye/Skin No data available Systemic SIngle-dose Acute intravenous (IV) injections of trastuzumab at doses up to 94 mg/kg in mice and 47 mg/kg in monkeys were very well tolerated. There were no test material-related clinical signs of toxicity, effects on body weight, food consumption, clinical pathology parameters evaluated in monkeys only), or macroscopic or microscopic pathologic findings. Repeat-dose Trastuzumab at a dose of 1.5 mg/kg was administered by IV bolus injection to monkeys, followed by a 43-day observation period. On Day 44, a second injection of trastuzumab was administered. There were no trastuzumabrelated effects on clinical observations, body weight, food consumption, body temperature, respiration or heart rates, hematology, or serum chemistry parameters, and there was no evidence of antibody formation. The same observation was made in 4-, 12- and 26-week studies in monkeys. Reproductive and Developmental Toxicity Reproduction studies have been conducted in cynomolgus monkeys at IV doses up to 25 times the weekly human maintenance dose of 2 mg/kg Herceptin and have revealed no evidence of impaired fertility or harm to the fetus. However, HER2 protein expression is high in many embryonic tissues including cardiac and neural tissues; in mutant mice lacking HER2, embryos died in early gestation. Placental transfer of Herceptin during the early (Days of gestation) and late (Days of gestation) fetal development period was observed in monkeys. There are no adequate and well-controlled studies in pregnant women. Carcinogenicity and Mutagenicity Herceptin has not been tested for its carcinogenic potential. No evidence of mutagenic activity was observed in Ames tests using six different test strains of bacteria, with and without metabolic activation, at concentrations of up to 5,000 µg/ml trastuzumab. Human peripheral blood lymphocytes treated in vitro at concentrations of up to 5000 µg/plate Trastuzumab, with and without metabolic activation, revealed no evidence of mutagenic potential. In an in vivo mutagenic assay (the micronucleus assay), no evidence of chromosomal damage to mouse bone marrow cells was observed following bolus I doses of up to 118 mg/kg trastuzumab. Page 4 of 6

5 Medical Conditions Aggravated by Exposure None known or reported Clinical Studies Adverse health effects that have been observed in patients following IV infusion of therapeutic doses (4 mg/kg, then 2 mg/kg) for treatment of metastatic breast cancer in HER2 overexpressed tumors include cardiomyopathy (cardiac failure), and hypersensitivity reactions including anaphylaxis, infusion reactions, and pulmonary events. For the complete description of warnings, precautions, and adverse reactions please refer to the Genentech web site at Occupational Exposure Limit None currently established by OSHA, NIOSH, ACGIH, or Genentech. Section 12 Ecological Information Persistence and Degradability This product is protein based and will rapidly degrade in the environment. Aquatic Toxicity No data available, but not expected to elicit aquatic toxicity Section 13 Disposal Considerations Dispose of waste residues according to prescribed federal, state, and local guidelines. Section 14 Transportation Information Hazard Class This biotherapeutic is non-hazardous under U.S. Department of Transportation (DOT) Hazardous Materials Regulations (49 CFR) and the International Air Transport Association (IATA). Packing Group Not applicable United Nations (UN) Number Not applicable Page 5 of 6

6 Section 15 Regulatory Information European Union (EU) Risk and Safety Phrases Not assigned Other Regulatory Not listed by IARC, NTP, OSHA or California Proposition 65 as a carcinogen. Not listed by California s Proposition 65 as a reproductive or developmental toxin. Section 16 Other Information No additional information. The above information is offered in good faith and with the belief that it is accurate. While efforts are made to provide useful information relating to handling, in the event of an adverse incident associated with this product, this Material Safety Data Sheet is not, and is not intended to be, a substitute for consultation with appropriately trained personnel. Page 6 of 6