The Three Most Important Considerations for Rx-to-OTC Switches: Safety, Safety, and Safety

When considering a potential switch, the FDA is tasked with weighing the benefits of enhanced access against the incremental risks greater access will pose. In doing so, the FDA will generally consider the efficacy and safety profile of a drug based upon the studies conducted to gain Rx approval, as well as the clinical knowledge gained from first-hand experience of the product usage on the Rx marketplace. In addition, the FDA requires additional studies with consumers demonstrating that they can use the product safely in an OTC setting without third-party intervention.

In today’s switch environment, the FDA appears to place much of their emphasis in evaluating switch candidates on the safety aspects of a product. This is creating a unique challenge for sponsors as many of the products identified in this report as potential switch candidates are now about to face generic competition after being on the Rx market for over 10 years. This means their original safety and efficacy studies were conducted fifteen years ago, when measuring and evaluating safety issues were underdeveloped compared with today’s technology.

Without today’s technologies, many safety concerns were added to a product’s Rx label, which probably didn’t belong there in the first place. Now, years later, the FDA is asked to approve a product again, this time for OTC usage (which has an even higher bar for safety), and it’s easy to understand why they want a better, more current understanding of the key safety issues surrounding a drug. The sponsor is left to dispel the misconceptions contained in their Rx labels.

Let’s look at the last three first-in-classes switches: Galderma Laboratories’ Differin Gel (topical retinoid for acne), Merck’s Oxytrol for Women (anticholinergic for OAB), and Sanofi’s Nasacort Allergy 24HR (nasal steroid for allergy). In addition to demonstrating that consumers could use the products safely in an OTC environment, all three had to overcome unique safety concerns.

With Differin Gel, the potential for teratogenicity (birth defects) dominated the discussion at the FDA Advisory Committee meeting. In the end, Galderma Laboratories was able to present a convincing argument that demonstrated that the systemic absorption of this topical product was nominal and the threat of teratogenicity contained in their Rx label was overstated. While the company did not have to add any additional warning labels, the OTC Differin Gel label carries the standard warning, “If pregnant or breast feeding, ask a doctor before use.”

With Nasacort Allergy 24HR, the issue was steroid-induced growth suppression in children. Once again, the sponsor, Sanofi, was able to successfully argue that the systemic absorption from intranasal use was nominal and the potential for growth suppression outlined in their Rx label was overstated. Sanofi added, “When using this product, the growth rate of some children may be slower” to its Nasacort Allergy 24HR OTC Drug Facts label.

In the case of Oxytrol for Women, the concern was over the masking of prostate conditions, including BPH and prostate cancer in men. By naming the product Oxytrol for Women and putting “for use by women only” on the label, Merck was able to overcome this safety concern. However, the highly-restricted label was a detriment in the marketplace as it limited shelf placement and contributed to its commercial failure and eventual withdrawal from the market.

Having to go back and conduct new or reanalyze old safety studies is proving to be an additional risk factor, as well as a cost burden in today’s OTC switch environment. As a result, this is causing many companies to pause and reevaluate their switch portfolio, especially for products in categories where the market potential is not all that great to begin with.

Kline’s 12th edition in our venerable switch series, Rx-to-OTC Switch Forecasts U.S.A.: Next Frontier, will be published in Q3 2017 and analyzes safety and regulatory issues, market potential, and sales forecasts for switch candidates. This report takes an in-depth look at the safety issues associated with the leading switch candidates for OTC switch in the U.S. market, as shown below.

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