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Product Approval Information

Last Updated: 3/20/2003

Public Health Service
Food and Drug Administration
1401 Rockville Pike
Rockville, MD 20852-1448
March 14, 2003

Our STN: BL 103471/1039

Donald Gay
Chiron Corporation
4560 Horton Street
Emeryville, CA 94608-2916

Dear Mr. Gay:

Your request to supplement your biologics license application for Interferon beta-1b (Betaseron®) to revise the Clinical Studies section to include data from two studies conducted in patients with secondary progressive multiple sclerosis (MS), to update the Adverse Reactions and Warnings sections to include new safety information, and to provide a Medication Guide, has been approved.

We acknowledge your written agreements to provide additional information as described in your letters of May 10, 2002 and March 14, 2003, as outlined below:

  1. To provide reports and analyses of adverse events cited in the package insert that were observed in the post-marketing experience with Interferon-beta-1b, as well as other adverse events of interest. A final report will be submitted to FDA by July 12, 2003.

  3. To conduct a pregnancy registry study to prospectively record and analyze pregnancy outcomes in 300 pregnant women with MS exposed to Interferon beta-1b at the time of conception or during the first trimester of pregnancy. This information will be used to assess the potential risk to the mother, fetus and/or live born infant. The final protocol will be submitted to FDA by September 15, 2003. Patient accrual will be completed by March 31, 2008, the study will be completed by March 31, 2009, and a final study report submitted to FDA by October 31, 2009.

  5. To provide validation information for the MxA neutralization assay for antibodies to Interferon beta-1b, including validation information regarding cutoff, intra-assay, inter-assay, and inter-operator precision, sensitivity (limit of detection and limit of quantification), specificity, and robustness. The revised validation information, excluding serum stability studies, will be submitted to FDA by May 15, 2003.

  7. To validate the stability of serum samples. In accordance with the International Conference on Harmonisation (ICH), Q2A, “Text on Validation of Analytical Procedures,” and Q2B, “Validation of Analytical Procedures: Methodology,” the serum samples will be placed on stability for eighteen months. The interim analysis data will be submitted to FDA by December 31, 2003, and the validation information will be submitted to FDA by May 15, 2004.
Pursuant to 21 CFR Part 208, FDA has determined that this product poses a serious and significant public health concern requiring the distribution of a Medication Guide. Distribution of a Medication Guide is necessary for safe and effective use of this product. FDA has determined that Interferon beta-1b is a product for which patient labeling could help prevent serious adverse effects and inform the patient of serious risks relative to benefit that could affect their decisions to use, or continue to use, the product. See 21 CFR 208.1. FDA hereby approves the Medication Guide you submitted March 14, 2003. Please note that the Medication Guide must be printed in a minimum of ten point high text, as described in 21 CFR 208.20. In accordance with 21 CFR 208, you are responsible for ensuring that this Medication Guide is available for every patient who is dispensed a prescription for this product. In addition, you are responsible for ensuring that the label of each container or package includes a prominent and conspicuous instruction to authorized dispensers to provide a Medication Guide to each patient to whom the drug is dispensed, and states how the Medication Guide is provided.

Please submit all final printed labeling at the time of use and include implementation information on FDA Form 356h. Please provide a PDF-format electronic copy as well as original paper copies (ten for circulars and five for other labels). In addition, you may wish to submit draft copies of the proposed introductory advertising and promotional labeling with an FDA Form 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448. Final printed advertising and promotional labeling should be submitted at the time of initial dissemination, accompanied by an FDA form 2253.

All promotional claims must by consistent with and not contrary to approved labeling. No comparative promotional claim or claim of superiority over other products should be made unless data to support such claims are submitted to and approved by the Center for Biologics Evaluation and Research.

This information will be included in your biologics license application file.

Sincerely yours,

--- signature ---

Karen D. Weiss, M.D.
Division of Clinical Trial Design and Analysis
Office of Therapeutics Research and Review
Center for Biologics Evaluation and Research

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