The power of the 505(b)(2) process is realized when the sponsor has to conduct few, if any, studies to get their drug product approved. For many drugs there is wealth of data available in the public domain. The challenge is locating the data and then preparing it for the FDA in such a way that the reviewers will understand how it applies to your product formulation. Let’s look at an example.
Alcon received approval in November 2007 for Triamcinolone Acetonide Injectable Suspension via 505(b)(2) for use in Sympathetic Ophthalmia, Temporal Arteritis, Uveitis, Ocular Inflammatory Conditions Unresponsive to Topical Corticosteroids and Visualization during Vitrectomy. The drug has been used systemically for many years. The solution intended for systemic use, BMS’ KENALOG was approved in 1965 under DESI. Despite having benzyl alcohol as a preservative and known to cause sterile endophthalmitis when injected into the vitreous, it has been used off-label for many years in ophthalmic settings. There exists a large body of information on such uses. Alcon took advantage of this data. Alcon reformulated the solution to remove benzyl alcohol (single-use vial). Alcon conducted no Phase 1 or Phase 2 studies. They could have received approval for all but the last of the aforementioned indications without any clinical studies. The safety and efficacy of the product was based on 299 publications, a meta-analysis and a single clinical trial to demonstrate safety and efficacy in Visualization during Vitrectomy (interestingly, this is a device indication, but is considered a drug indication when coupled with the other drug indications).
What can we learn from this Alcon approval? Look for off-label uses that are backed by solid pharmacokinetic and/or clinical studies and make sure you have sufficient product changes (formulation, package, etc.) that distinguish your product from the generics.