Material Safety Data Sheet

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Section 1. Identification

Product Name: Interferon beta-1a (bulk intermediate) Chemical Name: Interferon beta-1a (bulk intermediate) CAS Number: 145258-61-3 Substance: Interferon beta-1a is produced by recombinant DNA technology. Interferon beta-1a is a 166 amino acid glycoprotein with a predicted molecular weight of approximately 22,500 daltons. It is produced by mammalian cells (Chinese Hamster Ovary cells) into which human interferon beta gene has been introduced. The amino acid sequence of AVONEX®, is identical to that of natural human interferon beta. Other Names or Code Numbers: AVONEX®, BG9418, recombinant human interferon beta, r-HuIFN-b.AVONEX®, BG9418, BG9317, BG9216, BG9015, recombinant human interferon beta, r-HuIFN-b, Betaferon, recombinant human fibroblast interferon.

Section 2. Composition / Information on Ingredients

Components % Optional OSHA PEL ACGIH TLV OTHER STANDARDS Interferon beta-1a None None None Finished Drug Product Human Serum Albumin, USP 15.0 mg Excipient Materials: Sodium Chloride, USP 5.8 mg Dibasic Sodium Phosphate, USP 5.7 mg Monobasic Sodium Phosphate, USP 1.2 mg

Section 3. Hazards Identification

General Statement: Interferon beta-1a is a recombinant form of a naturally occuring protein. The final product is sold as a prescription injectable drug. Carcinogen Status: OSHA: No NTP: No IARC: No Carcinogen Statement: No carcinogenicity data for interferon beta-1a are available in animals or humans. Mutagenic Effects: Interferon beta-1a was not mutagenic when tested in the Ames bacterial mutagenicity test and in an in vitro cytogenetic assay in human lymphocytes in the presence and absence of metabolic activation. Teratogenic Effects: No information. Reproductive Effects: The reproductive toxicity of interferon beta-1a has not been been studied in humans. In pregnant monkeys given interferon beta at 100 times the recommended weekly human dose, no teratogenic or other adverse effects on fetal development were observed. Abortifacient activity was evident following 3 to 5 doses at this level. No abortifacient effects were observed in monkeys treated at 2 times the recommended weekly human dose. Menstrual irregularities were observed in monkeys administered a dose 100 times the recommended weekly human dose. Treatment of monkeys with interferon beta at 2 times the recommended weekly human dose had no effects on cycle duration or ovulation. Neurotoxic Effects: No specific studies have been performed to evaluate neurotoxicity. However, in repeat dose toxicity studies in rhesus monkeys, no signs of neurotoxicity were evident at doses up to 50 mcg/kg (10 MU/kg). The most common adverse events associated with exposure of humans to interferon beta-1a by intravenous, subcutaneous or intramuscular injection are flu-like symptoms, muscle ache, fever, chills and asthenia. Doses of up to 90 mcg (18 MU) have been administered subcutaneously in clinical trials. Single doses of 200 mcg/kg (40 MU/kg) in rats and mice and 90 mcg/kg (18 MU/kg) in guinea pigs have been administered with no observed toxicity. Recombinant human interferon beta-1a was well tolerated in rhesus monkeys following repeat subcutaneous administration up to 50 mcg/kg (10 MU/kg), excluding expected fever and antibody production to both human serum albumin and recombinant human interferon beta. Slight, but reversible decreases in platelets were observed in monkeys at the 50 mcg/kg dose level. Human Serum Albumin, USP used in the formulation of Biogen's finished drug product, is derived from human plasma. Final product has been heated for 10 hours at 60 °C. The Human Serum Albumin meets the requirements of the USP, EP and 21 CFR Part 640.81(e).

Section 4. First Aid Measures

If Inhaled: Remove to fresh air. Get medical attention. If breathing has stopped, give artificial respiration. Treat symptomatically and supportively. If Swallowed: Wash out with water. In Case of Skin or Eye Contact: No data available. May cause irritation; flush with copious amounts of freely flowing running water. If irritation persists, seek medical care. Skin Absorption: Limited available data indicates that interferon beta-1a is not absorbed across intact skin. If Injected: No data available Medical Conditions Aggravated by Exposure: No data available.

Section 5. Fire Fighting Measures

Flash Point: No data available Flammable Limits: n/a Extinguishing Media: Use water spray, CO2, ABC dry chemical or foam. Special Fire Fighting Materials: No special procedures. Unusual Fire and Explosion Hazards: No data available.

Section 6. Accidental Release Measures

Interferon beta-1a is not a hazardous material as defined by the U.S. EPA. No data available. Wear gloves to clean up a spill. No other special procedures should be necessary.

Section 7. Handling and Storage

No special safety precautions are required. For final product quality assurance, vials must be stored in a 2 - 8 °C (36 - 46 °F) refrigerator. Should refrigeration be unavailable, AVONEX® can be stored at 25 °C (77 °F) for a period of up to 30 days. DO NOT EXPOSE TO HIGH TEMPERATURES. DO NOT FREEZE. Following reconstitution, it is recommended the product be used as soon as possible within 6 hours stored at 2 - 8 °C (36 - 46 °F).

Section 8. Exposure Control / Personal Protection

Wear gloves, lab coat, and safety glasses to prevent skin and eye contact.

Section 9. Physical and Chemical Properties

Molecular Formula: 166 amino acid glycoprotein Molecular Weight: approximately 22,500 daltons Appearance/Odor: White to off-white lyophilized powder/odorless Solubilities: Water, phospate buffered saline Boiling Point: Approximately 100 °C Melting Point: Approximately 0 °C Vapor Pressure (mm HG): N/A Vapor Density (Air = 1): N/A Specific Gravity (H(2)0 = 1): N/A pH:

Section 10. Stability and Reactivity

Interferon beta-1a is Stable Hazardous Polymerization: Will Not Occur Incompatible Materials: No data available Conditions to Avoid: No special safety precautions required. See above statement. Hazard Decomposition Products: No data available.

Section 11. Toxicology Information

THE CHEMICAL, PHYSICAL AND TOXICOLOGICAL PROPERTIES OF INTERFERON BETA-1a HAVE NOT BEEN THOROUGHLY INVESTIGATED. Refer to Section 3.

Section 12. Ecological Information

No data available. Interferon beta-1a (bulk intermediate) is not a regulated hazardous material.

Section 13. Disposal Considerations

Interferon beta-1a (bulk intermediate) is not a regulated hazardous material. Follow federal, state and local environmental regulations for disposal.

Section 14. Transport Information

DOT Proper Shipping Name: n/a Hazard Class: n/a ID #: n/a

Section 15. Regulatory Information

No data available.

Section 16. Other Information

MSDS Created: 2-May-96 Revised: 24-Apr-97 Prepared By: Susan B. Lee, CIH Manager, Environmental Health and Safety DISCLAIMER: The above mentioned data are based on Biogen's best present knowledge of this product. Biogen cannot guarantee completeness or accuracy of the information contained herein, and disclaims all liability for incompleteness or inaccuracy of the information and for any claims of damages arising from handling or use of this product.