FDA CRL - CMP DEVELOPMENT LLC

CMP Development LLC received a Complete Response Letter (CRL) from the FDA for its New Drug Application (NDA) 213260, concerning atorvastatin calcium oral suspension, submitted under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The FDA determined the application could not be approved due to significant deficiencies.

Key issues included product quality concerns, specifically lacking detail in commercial batch records, which require revision. Additionally, objectionable conditions were observed at two distinct manufacturing facilities during a records review and a recent inspection. Satisfactory resolution of these facility issues is mandatory.

The most critical problems were in clinical pharmacology. Relative bioavailability studies showed the proposed product did not meet conventional 80-125% criteria compared to the listed drug. Under fasting conditions, exposure to atorvastatin and its metabolites was significantly higher, raising safety concerns. Conversely, the product exhibited a substantially greater reduction in drug exposure when administered with food, potentially leading to a loss of efficacy. These substantial differences in bioavailability, food effect, and wide fluctuations in drug levels mean the listed drug's efficacy and safety data cannot be relied upon.

Required actions include reformulating the product and conducting new relative bioavailability studies to demonstrate bioequivalence, or performing full clinical studies to establish safety and effectiveness. Resolution of facility observations and a comprehensive safety update are also necessary.