Approval Letter Other 209510 (Jan 1, 2020)

Summary

The FDA issued a Complete Response letter for New Drug Application (NDA) 209510 for Barhemsys (amisulpride) injection, indicating that the application cannot be approved in its current form. Deficiencies were identified in product quality/facility inspections, prescribing information, proprietary name, and safety update requirements. The letter outlines specific actions and data submissions required for potential approval, including resolving manufacturing issues, providing comprehensive safety data updates, and addressing labeling concerns.

Key points

• Satisfactorily resolve deficiencies identified during the manufacturing facility inspection.
• Review labeling review resources including PLR Requirements for Prescribing Information, Pregnancy and Lactation Labeling Final Rule websites, regulations, guidance documents, and the Selected Requirements for Prescribing Information (SRPI).
• If revising labeling, use the SRPI checklist to ensure conformity with format items in regulations and guidances.
• Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format.
• Resubmit the proposed proprietary name, Barhemsys, when responding to application deficiencies.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b).
• Describe in detail any significant changes or findings in the safety profile.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events by presenting new safety data from studies/clinical trials for the proposed indication using the same format as the original submission, presenting tabulations of the new safety data combined with the original application data, including tables that compare frequencies of adverse events in the original application with the retabulated frequencies, and providing separate tables for the frequencies of adverse events occurring in clinical trials for indications other than the proposed indication.

Cited reasons

• Manufacturing Facility Deficiencies
• Prescribing Information (Labeling) Inadequacies
• Proprietary Name Resubmission Required
• Inadequate Safety Update and Data Presentation
• Insufficient Pharmacokinetic Data in Severe Renal Impairment
• The application cannot be approved in its present form due to unresolved manufacturing facility deficiencies, inadequate prescribing information, and insufficient safety data, particularly regarding the safety update requirements and pharmacokinetic characterization in severe renal impairment. The proprietary name also needs to be resubmitted.

Recommended actions

• Satisfactorily resolve deficiencies identified during the manufacturing facility inspection.
• Review labeling review resources including PLR Requirements for Prescribing Information, Pregnancy and Lactation Labeling Final Rule websites, regulations, guidance documents, and the Selected Requirements for Prescribing Information (SRPI).
• If revising labeling, use the SRPI checklist to ensure conformity with format items in regulations and guidances.
• Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format.
• Resubmit the proposed proprietary name, Barhemsys, when responding to application deficiencies.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b).
• Describe in detail any significant changes or findings in the safety profile.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events by presenting new safety data from studies/clinical trials for the proposed indication using the same format as the original submission, presenting tabulations of the new safety data combined with the original application data, including tables that compare frequencies of adverse events in the original application with the retabulated frequencies, and providing separate tables for the frequencies of adverse events occurring in clinical trials for indications other than the proposed indication.

Deficiency summary

The application cannot be approved in its present form due to unresolved manufacturing facility deficiencies, inadequate prescribing information, and insufficient safety data, particularly regarding the safety update requirements and pharmacokinetic characterization in severe renal impairment. The proprietary name also needs to be resubmitted.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2) New Drug Application (NDA)

Impact

Impact score

0.95

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application received a Complete Response due to critical manufacturing deficiencies, significant gaps in safety data presentation and analysis, and inadequate clinical pharmacology characterization for a vulnerable patient population, alongside required labeling updates.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%