Astex Pharmaceuticals, Inc – FDA CRL

Scilex Pharmaceuticals, Inc. received a Complete Response Letter (CRL) from the FDA regarding its New Drug Application (NDA 207962) for ZTlido (lidocaine patch 1.8%). The FDA determined that the application, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, cannot be approved in its current form due to several deficiencies spanning regulatory, clinical, clinical pharmacology, and nonclinical aspects. Key issues include the absence of required patent certifications or statements for patents associated with a referenced listed drug. The application also lacked sufficient scientific justification or a "bridge" to support reliance on the FDA's previous safety and effectiveness findings for a listed drug and published literature. Clinically, the FDA found the adhesion data for ZTlido insufficient, as the provided 48-hour assessment did not align with the product's intended 12-hour use period. The comparative bioavailability study was also flawed because surgical tape was inappropriately used to secure the reference drug, invalidating the demonstration of equivalent systemic exposure. Furthermore, nonclinical concerns were raised regarding drug product degradants: the proposed specification for 2,6-xylidine exceeded acceptable daily intake limits, and specifications for other impurities exceeded qualification thresholds, requiring either reduction or additional safety qualification. To address these issues, Scilex must either remove references to the listed drug or provide proper patent certifications, justify reliance on reference data, submit new or revised adhesion data relevant to the 12-hour use, conduct a new comparative bioavailability study without using tape, and revise degradant specifications or provide compelling safety data in accordance with regulatory guidelines.