Soller defines the roadmap for Rx-to-OTC switches

If you are a pharmaceutical company seeking to switch your prescription medication to one sold directly to consumers—as an over-the-counter or OTC drug—William Soller, PhD, has your road map.

In a recently published study, Soller and co-authors analyzed the questions framing U.S. Food and Drug Administration (FDA) advisory committee deliberations on prescription(Rx)-to-OTC switches since 2002—focusing on those addressing the first switches in a given drug class.

Analyzing committee transcripts, FDA guidance (including speeches by agency officials) and medical literature, the UCSF researchers combined the new material with switch principles established by the agency in the 1990s to generate an up-to-date and comprehensive synthesis of “OTC Considerations” for OTC new drug development.

The new study, “OTC considerations in expanding access to nonprescription medicines,” published in the September 2011 issue of SelfCare is the first full review of OTC switch criteria since a 2002 article by Soller, a faculty member in the UCSF School of Pharmacy, Department of Clinical Pharmacy, and executive director of the department-based Center for Self Care.

In response to invited public presentations on Rx-to-OTC switch, leading FDA officials articulated switch principles in 1990 and 1998. They initially emphasized a drug-centric approach (e.g. Does the drug have a large margin of safety?) and subsequently a more consumer-oriented perspective based on use patterns and label comprehension studies (e.g. Can the condition be adequately self-diagnosed? What is the consumer understanding of drug directions for safe use?).

With co-authors Philip Chan, PharmD, volunteer faculty member in the Department of Clinical Pharmacy, and UCSF student pharmacist Christopher Shaheen, Soller assessed materials given to advisory committees and presented at public deliberations over the last 10 years to both “document the progress that FDA and industry have made in developing the evidence base” for switches and to develop a modern framework for OTC new drug development.

Soller et al’s integrated list of modern “OTC Considerations” for Rx-to-OTC switches are derived from post-2002 first-in-class switch histories and the FDA’s 1990 and 1998 established switch principles. Source: SelfCare 2 (5): 117-138.

Table 2: OTC Considerations

Derived from Selected Post-2002 First-in-Class Switches and FDA 1990 and 1998 Switch Principles

Rx fundamentals

Safety

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? Including:
   1. Margin of safety;
   2. Safety across the drug’s therapeutic range and at high doses;
   3. Potential masking of serious disease by short or long term use;
   4. Potential for genotoxicity, tumorigenicity, and fetal and developmental toxicity;
   5. Any known special toxicity with discontinuation of therapy;
   6. Drug-drug interactions;
   7. Safety in special populations (e.g., women of child-bearing age, children, elderly);
   8. Other special conditions or toxicity in its class that may be associated with acute, chronic or chronic intermittent use.
2. Can the condition be adequately self-diagnosed, or is there a need for physician diagnosis?
   1. To what extent is misdiagnosis associated with current Rx practices relating to the intended OTC use of the product?

Efficacy

3. Is the minimally effective dose known?
4. Are there efficacy studies needed to support the intended OTC use of the switch candidate?

Rx use pattern

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

OTCness

General

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

Label comprehension: Can safety be handled entirely by the label?

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)?

Actual use

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? That is, does the pattern of use show that consumers will likely:
    1. Know when they should see a physician before using the product and once they have begun using the product;
    2. Not use the drug on an acute or chronic basis for conditions other than that intended by labeling;
    3. Use the correct dosage for the period of time specified in the label;
    4. Evaluate response(s) to treatment and successfully monitor progress with therapy, including identifying serious adverse events symptomatically or, for example, with periodic lab tests;
    5. Take other actions, as specific to the switch candidate.

Overall

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

The study notes that there has been a downward trend in U.S. Rx-to-OTC switches. There were one-half as many first-in-class switches from 2002 to 2011 versus the prior decade. In fact, among the 23 conversions of prescription drugs to over-the-counter availability since 2002, only four were first in class:

• Omeprazole (indication: frequent heartburn; brand name: Prilosec)
• Levonorgestrel (emergency contraceptive; Plan B)
• Loratadine (non-sedating antihistamine; Claritin®)
• Orlistat (weight loss; Alli)

While the study’s new synthesis can help guide drug companies working on Rx-to-OTC switch, it is hardly a simple prescription. The research authors note that based on a medication’s novelty, uniqueness of the proposed new indication, potential toxicity, and the quality/extent of reports about its safety worldwide (i.e. post-marketing surveillance), “FDA uses its discretion to select areas of concentration for OTC drug development programs and advisory committee discussions on switch.”

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OTC considerations in expanding access to nonprescription medicines