FDA CRL - Takeda Pharmaceuticals U.S.A., Inc.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Takeda Pharmaceuticals, U.S.A., Inc. regarding its Biologics License Application (BLA) 761133 for MLNO0002 SC, originally submitted on March 7, 2019. The FDA determined that the application cannot be approved in its present form due to significant product quality deficiencies, primarily related to human factors (HF) validation of the Entyvio prefilled pen.

The main violations stemmed from a submitted human factors validation study that identified numerous use errors, close calls, and use difficulties with critical and non-critical tasks. Takeda had not implemented sufficient revisions to the product user interface to address these identified issues. The FDA provided detailed recommendations for improving the device design, device label/labeling, and the Instructions for Use (IFU). Specific IFU concerns included lack of clarity in figures, inaccurate depiction of injection sites, insufficient emphasis on critical warnings, unclear end-of-injection cues, and inadequate prominence for important information regarding storage, preparation, and device safety.

Required actions include implementing the FDA's recommended user interface revisions and conducting a new human factors validation study to demonstrate the effectiveness of these mitigations. Takeda must also submit updated Prescribing Information in structured product labeling (SPL) format and revise carton and container labeling, specifically by bolding storage statements and clarifying the expiration date format for improved user comprehension.