Complete Response Letter NDA 505b1 214315 (Jan 25, 2024)

Summary

This document is a deficiency letter from the U.S. Food and Drug Administration (FDA) regarding New Drug Application (NDA) 214315. It outlines several deficiencies related to human factors, prescribing information, carton and container labeling, proprietary name, and safety updates. The FDA found that the proposed product's user interface does not support safe and effective use due to identified use errors and close calls during human factors validation studies. The letter requests specific actions and data from the applicant to resolve these deficiencies before the application can be approved.

Key points

• Implement user interface revisions and design modifications to promote the safe and effective use of the proposed product.
• Provide data demonstrating that, with mitigations, the product user interface can be used safely and effectively to deliver the intended dose of drug substance.
• Consider the potential for a dose of the product to be provided within the existing mental model (e.g., 0.08 mg scopolamine nasal gel per single pump actuation in each nostril, totaling 0.16 mg over 2 actuations).
• Submit the Human Factors (HF) validation study protocol, along with the redesigned user interface, for FDA review and feedback prior to conducting an assessment of mitigation strategies.
• Review the labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPI).
• Use the SRPI checklist to ensure that the Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format in the response.
• Resubmit the proposed proprietary name when responding to all application deficiencies.

Cited reasons

• Inadequate Human Factors Design Leading to Use Errors and Potential for Patient Harm
• Incomplete Safety Update
• Proprietary Name Requires Resubmission
• Labeling Review Deferred Pending Application Adequacy
• The application received a Complete Response Letter primarily due to significant human factors deficiencies related to the user interface design, leading to use errors and potential for patient harm from incorrect dosing. Additional deficiencies include the need for a comprehensive safety update and the resubmission of the proprietary name. Labeling review is reserved until other issues are resolved.

Recommended actions

• Implement user interface revisions and design modifications to promote the safe and effective use of the proposed product.
• Provide data demonstrating that, with mitigations, the product user interface can be used safely and effectively to deliver the intended dose of drug substance.
• Consider the potential for a dose of the product to be provided within the existing mental model (e.g., 0.08 mg scopolamine nasal gel per single pump actuation in each nostril, totaling 0.16 mg over 2 actuations).
• Submit the Human Factors (HF) validation study protocol, along with the redesigned user interface, for FDA review and feedback prior to conducting an assessment of mitigation strategies.
• Review the labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPI).
• Use the SRPI checklist to ensure that the Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
• Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format in the response.
• Resubmit the proposed proprietary name when responding to all application deficiencies.

Deficiency summary

The application received a Complete Response Letter primarily due to significant human factors deficiencies related to the user interface design, leading to use errors and potential for patient harm from incorrect dosing. Additional deficiencies include the need for a comprehensive safety update and the resubmission of the proprietary name. Labeling review is reserved until other issues are resolved.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

NDA

Impact

Impact score

0.95

Estimated delay

545 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary theme is the critical inadequacy of the human factors design for the drug-device combination product, leading to significant use errors and potential patient harm. This necessitates substantial redesign and re-evaluation. Secondary themes include standard requirements for a comprehensive safety update and administrative tasks related to proprietary name and labeling.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%