Approval Letter Other 212097 (Nov 13, 2025)

Summary

This letter from the FDA identifies deficiencies in NDA 212097/S-012, specifically regarding dose accuracy testing, chemistry, manufacturing, and controls (CMC) for IV administration, prescribing information, proprietary name resubmission, and a comprehensive safety update. The applicant is required to address these deficiencies within one year to avoid withdrawal of the application.

Key points

• Provide information and data of comparative dose accuracy testing between the proposed product and the relied-upon listed drug, supporting complete dose delivered of glucagon without submicron particle formation events prior to administration as provided in the labeling.
• Conduct dose accuracy testing by glucagon content assay in a diluted solution collected after delivery via syringes with needles.
• Use dynamic light scattering analysis to determine submicron particles in a diluted glucagon solution after delivery.
• Provide admixture studies using the proposed Gvoke vial formulation to inform drug product compatibility and stability for the proposed dosing and administration technique (i.e., as provided in the labeling Section 2.4).
• Include comparative gelling and agglomeration studies using the Gvoke vial formulation with the relied-upon listed drug.
• Review 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.

Cited reasons

• Insufficient Comparative Dose Accuracy Data
• Inadequate IV Administration Compatibility and Stability Data
• Comprehensive Safety Update Required
• Proprietary Name Resubmission Pending Approval
• The application for Gvoke is not approvable due to significant deficiencies in Chemistry, Manufacturing, and Controls (CMC) data, specifically regarding comparative dose accuracy and IV administration compatibility/stability. A comprehensive safety update is also required, and the proprietary name needs to be resubmitted upon addressing all deficiencies.

Recommended actions

• Provide information and data of comparative dose accuracy testing between the proposed product and the relied-upon listed drug, supporting complete dose delivered of glucagon without submicron particle formation events prior to administration as provided in the labeling.
• Conduct dose accuracy testing by glucagon content assay in a diluted solution collected after delivery via syringes with needles.
• Use dynamic light scattering analysis to determine submicron particles in a diluted glucagon solution after delivery.
• Provide admixture studies using the proposed Gvoke vial formulation to inform drug product compatibility and stability for the proposed dosing and administration technique (i.e., as provided in the labeling Section 2.4).
• Include comparative gelling and agglomeration studies using the Gvoke vial formulation with the relied-upon listed drug.
• Review 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.

Deficiency summary

The application for Gvoke is not approvable due to significant deficiencies in Chemistry, Manufacturing, and Controls (CMC) data, specifically regarding comparative dose accuracy and IV administration compatibility/stability. A comprehensive safety update is also required, and the proprietary name needs to be resubmitted upon addressing all deficiencies.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

NDA

Impact

Impact score

0.75

Estimated delay

545 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application received a Complete Response Letter due to critical gaps in CMC data related to product performance and stability, and an incomplete safety profile. An administrative issue with the proprietary name also needs to be resolved upon resubmission.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%