Abstract

Consumer behavior studies and thorough reviews of Rx drug safety and efficacy are expected components of Rx-to-OTC new drug applications in the U.S. Understanding the expectations of the Food and Drug Administration (FDA) for these studies and other data required for switch is vital for successful OTC drug development programs.

The core research questions were: (a) has the nature of the questions used by FDA to frame advisory committee deliberations of first-in-class switches changed in the period 1992-2011? (b) do FDA’s questions to advisory committees for first-in-class switches further inform 1990 and 1998 “switch principles” articulated by FDA representatives such that they can be consolidated into a modern comprehensive list of OTC Considerations?

Data collection derived principally from FDA advisory committee transcripts and background materials, FDA guidance, and the medical literature. Data synthesis resulted in the integration of published “switch principles” into a comprehensive list of Rx-to-OTC Considerations.

From 2002-2011 there has been a downward trend in the number of Rx-to-OTC switches in the U.S.  There were 50% fewer first-in-class switches in the U.S. than the prior 10-year period, a comparable number of line extensions and direct-to-OTC new drugs, and about 25% fewer follow-on switches.

A list of OTC Considerations with specific questions to explore for unique first-in-class switches encompasses evidence pertaining to safety, efficacy, OTC labeling, self-selection and effectiveness. This list is reflective of materials given to advisory committees and presented at public committee deliberations of first-in-class switches from the last ten years. Depending on novelty and uniqueness of the proposed OTC indication or Rx active ingredient, the intrinsic and extrinsic toxicity of the switch candidate, the robustness of the published and NDA-derived data and worldwide post-marketing surveillance evaluations, FDA uses its discretion to select areas of concentration for OTC drug development programs and advisory committee discussions
on switch.

In conclusion, an updated framework of OTC Considerations for Rx-to-OTC switch has been developed through an in-depth assessment of FDA advisory committee deliberations of first-in-class switches, and may serve not only as a milestone to document the progress that FDA and industry have made in developing the evidence base for switch, but also as a framework for OTC drug development and training of new OTC regulatory personnel.