Is the Rx Past OTC Prologue?

Rx-to-OTC switch questions that FDA asked advisory committees over the past 10 years can help guide future sponsors to success, says the lead researcher in an analysis of the agency's switch actions.

The journal SelfCare has published "an essential blueprint for designing and implementing any Rx-to-OTC drug development program," says lead author Bill Soller, professor and executive director of the Center for Consumer Self Care at the University of California, San Francisco, School of Pharmacy.  Well, maybe not essential -- but certainly intriguing.

Soller and his colleagues list questions - "OTC Considerations" - based on switch principles FDA set in 1990 and 1998 and questions to post-2002 advisory committees that evaluated first-in-class switches.

The analysis recommends 11 primary questions about the Rx fundamentals of a drug, its "OTCness" and overall risk vs. benefit.

1- Has the Rx product been on the market for a sufficient time and extent to enable full characterization of the drug's safety profile?

2- Can the condition be adequately self-diagnosed or is there a need for physician diagnosis?

3-vIs the minimally effective dose known?

4- Are there efficacy studies needed to support the intended OTC use of the switch candidate?

5- What are the patterns of diagnosing, prescribing and patient use in the Rx setting related to OTC intended use?

6- Are the studies supporting OTCness generalizable to the intended OTC target population?

7-Do consumers understand key communication objectives of the label, relating to directions for use, contraindications, in-use warnings and precautions?

8- Do consumers show they would be likely to be able to assess and take action on the treatment effect (e.g., take appropriate action if the drug is not working, serious side effects emerge, or self-monitoring is needed)?

9- Do consumers demonstrate successful self-selection and de-selection of the product under conditions (or simulated conditions) of actual use?

10- Does the pattern of actual use support that the label can be successfully used in practice?

11- Do the benefits of OTC availability outweigh the risks?

The list reflects materials FDA provided advisory committees and presented at meetings on first-in-class switches from 1992 to 2011. The latest was in 2007.

The authors say FDA "uses its discretion to select areas of concentration for advisory committee discussions on switch." Factors influencing the agency's questions for advisory committees include the novelty and uniqueness of a proposed OTC indication or Rx active ingredient; intrinsic and extrinsic toxicity of a switch candidate; and robustness of published and NDA-derived data and worldwide post-marketing surveillance evaluations, according to the article.

The analysis in SelfCare comes a month after FDA published a draft guidance on designing self-selection studies in support of OTC switches. The draft states FDA's interest in greater insight into consumers' thought processes and says study sponsors should follow up with medical history questions and additional open-ended queries.

What about the potential of Behind-the-Counter (BTC) arrangements?  Well, according to Eric Brass, a physician, director of Harbor-UCLA Center for Clinical Pharmacology and a professor at David Geffen School of Medicine at UCLA, "The statement that a company will voluntarily impose such a restriction cannot influence the regulatory decision, as the second company to market could not be held to the same restriction.” Good point. And, further, “If pharmacist assessment is required for safe and effective use by the consumer, I think that the drug would not be appropriate for OTC status today." Brass added that no public health benefit from expanding consumers' access to medicines through pharmacists has been established.

Maybe it’s time for the pharmacy community to step up to the plate and commence that conversation.