520 was designed to restrict. This is made clear by the examples the FDA offered of “several other FDA-approved drugs that are distributed under restricting marketing plans pursuant to 21 C.F.R. § 314.520.” Defs.’

13. As stated in FDA’s Guidance regarding Content and Format of Labeling: A boxed warning is ordinarily used to highlight for prescribers one of the following situations:  There is an adverse reaction so serious in proportion to the potential benefit from the drug (e.g., a fatal, life-threatening or permanently disabling adverse reaction) that it is essential that it be considered in assessing the risks and benefits of using the drug OR  There is a serious adverse reaction that can be prevented or reduced in frequency or severity by appropriate use of the drug (e.g., patient selection, careful monitoring, avoiding certain concomitant therapy, addition of another drug or managing patients in a specific manner, avoiding use in a specific clinical situation) OR  FDA approved the drug with restrictions to ensure safe use because FDA concluded that the drug can be safely used only if distribution or use is restricted (e.g., under 21 CFR 314.520 and 601.42 “Approval with restrictions to assure safe use” or under 505-1(f)(3) of the Federal Food, Drug, and Cosmetic Act (FDCA) “Risk Evaluation and Mitigation Strategies” Elements to assure safe use).

Subpart H of the Act gives the Agency the authority to approve a product with restrictions to assure safe use "if the FDA concludes that a drug product shown to be effective can be safely used only if distribution or use is restricted." [Footnote 6: 21 CFR 314.520] The restrictions can include distribution restricted to certain facilities or physicians with special training or experience; distribution conditioned on the performance of specified medical procedures; or limitations imposed that are commensurate with the specific safety concerns presented. [Footnote 7: Ibid.] The Agency can place these postmarketing restrictions on both prescription and OTC products.

Nothing in the FDCA prohibits a sponsor from voluntarily limiting distribution of a product it Case 1:07-cv-00668-JDB Document 12 Filed 06/29/2007 Page 39 of 46 FDA regulations provide "If FDA concludes that a drug product shown to be effective can be12/ safely used only if distribution or use is restricted, FDA will require such postmarketing restrictions as are needed to assure safe use of the drug product." 21 C.F.R. § 314.520(a). Although not explicitly relied on here, there are several other FDA-approved drugs that are distributed under restricted marketing plans that address a variety of safety concerns.