On June 12, 2103 the Food and Drug Administration (FDA) published a final rule amending the orphan drug regulations (21 CFR Part 316). The amendments are intended to clarify regulatory provisions and make minor improvements to address issues regarding orphan drug designation and orphan drug exclusivity.

The final rule largely finalizes the amendments as proposed in October 2011. Reed Smith previously prepared a client alert summarizing the proposed rule and discussing the potential impact of the proposal on the drug, biological product, and biotechnology industries. In the final rule, the FDA has revised the proposed rule by, among other things:

  1. Adding a definition of "orphan subset" that is consistent with the explanation of orphan subset in the proposed rule;
  2. Clarifying the existing regulation in accordance with FDA’s long-standing practice that a designated drug is eligible for orphan exclusive approval only if the same drug has not already been approved for the same use or indication;
  3. Removing language stating that to demonstrate clinical superiority in terms of "major contribution to patient care," the drug must provide safety and effectiveness "comparable to the approved drug," because the language incorrectly implied that FDA would require direct proof of comparability (e.g., through non-inferiority trials);
  4. Updating the contact information required in requests for designation and for permanent-resident agents;
  5. Clarifying that a designation request need only include "relevant" in vitro laboratory data and data from "clinical experience" with the drug;
  6. Clarifying that FDA will notify the sponsor in writing whenever FDA considers a designation request voluntarily withdrawn;
  7. Codifying FDA’s longstanding interpretation that FDA can refuse to grant a designation request if the request is otherwise ineligible for designation under Part 316;
  8. Stating that that FDA’s publicly-available posting of designated drugs will include whether a drug is no longer designated if the drug loses designation after the effective date of the final rule;
  9. Making explicit an option that has always existed for sponsors – that sponsors may voluntarily withdraw a designation request, or an actual designation, at any time by submitting a written request to FDA;
  10. Clarifying that the scope of orphan drug exclusivity is limited to the indications or uses for which the designated drug is approved;
  11. Clarifying that that a designated drug that is otherwise the same as a previously approved drug receives 7-years market exclusivity ("orphan drug exclusivity") upon approval only if the sponsor of the second-in-time drug demonstrates upon approval that its drug is clinically superior to the previously approved drug; and
  12. Updating the FDA address listed in the regulations and adding an online address for the Orange Book.

The final rule is effective on August 12, 2013.