Human Factors Validation Study Deficiencies and Lack of User Interface Revisions
Severity: criticalThe human factors (HF) validation study for the Entyvio prefilled pen identified several use errors, close calls, and use difficulties with critical and non-critical tasks. The sponsor did not implement revisions to the product user interface to address these issues. The agency recommends implementing revisions and conducting a new HF validation study.
Recommended response: Revise the product user interface based on identified use errors and conduct a new human factors validation study to demonstrate effectiveness of mitigations and ensure safety.
Deficiencies in Prefilled Pen Instructions for Use (IFU)
Severity: majorMultiple recommendations for revising the IFU based on HF study results and heuristic analysis, including labeling figures, clarifying injection site selection, emphasizing 'Do not' statements for recapping, clarifying end-of-injection cues, improving clarity for window check, increasing prominence of important information (children, storage, preparation), and emphasizing device safety.
Recommended response: Implement all recommended revisions to the Prefilled Pen IFU to improve clarity, reduce use errors, and enhance patient understanding and safety.
Deficiencies in Prefilled Pen Device Design and Labeling
Severity: majorRecommendations to label the needle end on the device body and revise the design of the cap (remove ridges) to minimize needle stick injury and underdose risk, based on observed errors and subjective feedback.
Recommended response: Revise the prefilled pen device design (cap) and device labeling (needle end) to mitigate identified risks of needle stick injury and underdosing.
Prescribing Information (PI) Review Reserved
Severity: infoThe agency reserves comment on the proposed labeling until the application is otherwise adequate. The sponsor is encouraged to review PLR Requirements and SRPI checklist.
Recommended response: Review and update the Prescribing Information according to PLR requirements and SRPI checklist once other deficiencies are addressed.
Carton and Container Labeling Deficiencies
Severity: majorMultiple issues including: bolding storage statement, revising expiration date format (YYYY-MM-DD), consistency of 'Manufactured by' statement, inclusion of linear bar codes, 'Do not shake' statement, 'No Preservative' wording, inactive ingredient formatting, and dosage statement revision.
Recommended response: Implement all recommended revisions to carton and container labeling, ensuring compliance with specific CFR sections and FDA guidance on format and content.
Cited: 21 CFR 201.25, 21 CFR 610.67, 21 CFR 610.61(e)
Medication Guide Statement Requirement
Severity: minorAdd the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide' or appropriate alternative to carton and container labels.
Recommended response: Add the required Medication Guide statement to carton and container labels as per 21 CFR 208.24(d).
Cited: 21 CFR 208.24(d)
Proprietary Name Review Terminated
Severity: infoReview of the proposed proprietary name has been terminated due to application deficiencies. The sponsor is advised to resubmit the proposed proprietary name when responding to application deficiencies.
Recommended response: Resubmit the proposed proprietary name with the complete response to all application deficiencies.
Non-Proprietary Name (Suffix) Decision
Severity: infoFDA previously intended to assign a four-letter suffix but has now determined that a suffix will not be designated. Vedolizumab will be the proper name if the BLA is approved.
Recommended response: Acknowledge the FDA's decision regarding the non-proprietary name and plan for 'vedolizumab' as the proper name.
Unresolved Manufacturing Facility Inspection Findings
Severity: criticalDeficiencies were conveyed to the representative of the manufacturing facility during a recent inspection. Satisfactory resolution of these deficiencies is required before approval.
Recommended response: Address and satisfactorily resolve all deficiencies identified during the manufacturing facility inspection.
