Celltrion Inc. – FDA CRL

The Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to CELLTRION, Inc. regarding their Biologics License Application (BLA 761091) for CT-P6, submitted under section 351(k) of the Public Health Service Act. The FDA determined the application cannot be approved in its present form due to several outstanding deficiencies.

Key issues include unresolved deficiencies identified during a recent inspection of Celltrion's manufacturing facility. Product quality concerns were also raised, specifically regarding the Drug Product (DP) release specification for protein content, which needs adjustment to consistently meet the 420 mg label claim. The application lacked sufficient data to support the derivation of overfill volume and fill weight limits, requiring additional information on the filling machine capabilities and process development results. Furthermore, the proposed specifications for a critical quality attribute known to adversely affect potency were deemed inadequate, necessitating revised manufacturing processes or tightened drug substance (DS) release and stability specifications. An existing acceptance criterion for another DS attribute was considered unacceptably broad and requires tightening.

To address these, Celltrion must resolve the facility deficiencies, adjust DP specifications, provide comprehensive data for fill volume/weight controls, and tighten specifications for critical quality attributes. Additionally, the company is required to resubmit updated prescribing information, carton and container labeling, and re-propose the proprietary name, Herzuma. A comprehensive safety update, incorporating new and combined clinical study data, is also mandated.