FDA CRL - RB Health (US) LLC

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter on July 26, 2024, to RB Health (US) LLC regarding their New Drug Application (NDA 217338) for an extended-release tablet containing naproxen sodium, dextromethorphan hydrobromide, and guaifenesin. The primary issue identified was insufficient evidence to support the proposed 12-hour duration of action and dosing regimen for the combination product. While bioequivalence to approved components like Aleve was demonstrated, the FDA determined this was inadequate to justify a fixed 12-hour dosing interval, noting Aleve's 8-12 hour instructions. Additionally, supporting scientific literature was deemed insufficient due to varied formulations, and an indirect pharmacokinetic bridge relying on FDA reviews was considered an inappropriate regulatory source, as per 21 CFR 314.430(e)(2). The FDA expressed concerns about potential waning analgesic effects. To address these deficiencies, RB Health must either provide new clinical efficacy data for a 12-hour duration in a relevant patient population or conduct a relative bioavailability study to bridge to an existing product. Furthermore, a comprehensive safety update, as described in 21 CFR 314.50(d)(5)(vi)(b), is required upon resubmission. RB Health has one year to respond, and the submission must be clearly marked as a 'RESUBMISSION'.