FDA CRL - Dow Pharmaceutical Sciences Inc.

The FDA issued a Complete Response Letter (CRL) on June 15, 2018, to Dow Pharmaceutical Sciences, Inc. (c/o Valeant Pharmaceuticals North America, LLC) regarding its New Drug Application (NDA 209354) for halobetasol propionate and tazarotene lotion, 0.01%/0.045%. The application, initially submitted on August 18, 2017, was deemed unapprovable primarily due to insufficient nonclinical toxicology data, as specified under 21 CFR 314.125(b)(4) of the Federal Food, Drug, and Cosmetic Act. The main issue was an inadequate scientific bridge to the listed drugs, Ultravate and Tazorac, with the proposed combination product exhibiting higher bioavailability for its individual components. To resolve these deficiencies, the FDA requires comprehensive nonclinical studies for both active ingredients. This includes genetic toxicology, systemic embryofetal development, fertility/reproductive function, pre- and postnatal development, and carcinogenicity studies in two species (systemic and dermal routes). The company must also submit protocols for carcinogenicity studies, revise the Prescribing Information, and resubmit the proprietary name, Duobrii. A critical action involves providing a detailed safety update (21 CFR 314.50(d)(5)(vi)(b)), incorporating new safety data, adverse event retabulations, case reports for serious events, updated exposure, and worldwide safety experience. Dow Pharmaceutical Sciences has one year to submit a complete response to these requirements, per 21 CFR 314.110, or the application may be considered withdrawn.