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US FDA•United StatesAL•Approval Letter

Approval Letter Other (Nov 13, 2025)

Issued November 13, 2025

Issued

November 13, 2025

Application

Other

Review center

Other

Stage

Final Decision

Letter type

Approval Letter

Response due November 13, 2026Product may be marketed.

Summary

This FDA letter communicates deficiencies and requirements for the approval of New Drug Application (NDA) 212782. It addresses issues related to prescribing information, carton and container labeling, manufacturing facility inspections, product quality, and safety updates, requiring the applicant to submit a comprehensive response within one year.

Key points

  • Review labeling review resources, including regulations, guidance documents, and the Selected Requirements for Prescribing Information (SRPI) checklist.
  • Use the SRPI checklist to ensure 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.
  • Achieve satisfactory resolution of deficiencies conveyed during surveillance inspection of the manufacturing facility.
  • Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
  • Describe in detail any significant changes or findings in the safety profile within the safety update.
  • Incorporate new safety data when assembling sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.
  • Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.

Cited reasons

  • Unresolved Manufacturing Facility Deficiencies
  • Inadequate Clinical Safety Data Update and Presentation
  • Missing English Translations of Foreign Labeling
  • Discrepancy in Osmolality Data
  • Inadequate Degradation Products Specification
  • Insufficient Updated Stability Data
  • Pending Labeling Review
  • The application received a Complete Response Letter due to unresolved manufacturing facility observations, significant deficiencies in clinical safety data presentation and completeness (including adverse event reporting, exposure information, worldwide experience, and foreign labeling translations), and pending comments on prescribing information and carton/container labeling until other issues are resolved. Several product quality (CMC) issues related to analytical data and specifications also require resolution.

Recommended actions

  • Review labeling review resources, including regulations, guidance documents, and the Selected Requirements for Prescribing Information (SRPI) checklist.
  • Use the SRPI checklist to ensure 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.
  • Achieve satisfactory resolution of deficiencies conveyed during surveillance inspection of the manufacturing facility.
  • Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.
  • Describe in detail any significant changes or findings in the safety profile within the safety update.
  • Incorporate new safety data when assembling sections describing discontinuations due to adverse events, serious adverse events, and common adverse events.
  • Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.

Deficiency summary

The application received a Complete Response Letter due to unresolved manufacturing facility observations, significant deficiencies in clinical safety data presentation and completeness (including adverse event reporting, exposure information, worldwide experience, and foreign labeling translations), and pending comments on prescribing information and carton/container labeling until other issues are resolved. Several product quality (CMC) issues related to analytical data and specifications also require resolution.

Findings

Unresolved Manufacturing Facility Deficiencies

Severity: critical

Satisfactory resolution of observations from the manufacturing facility inspection is required before this NDA may be approved.

Recommended response: Address all outstanding observations from the manufacturing facility inspection and provide evidence of satisfactory resolution to the agency.

Inadequate Clinical Safety Data Update and Presentation

Severity: major

The safety update should include data from all nonclinical and clinical studies/trials. Specific issues include: significant changes or findings in the safety profile, new safety data presentation (separate tables for other indications, combined tabulations, comparison tables), retabulation of premature trial discontinuations, case report forms and narrative summaries for deaths/serious adverse events, information on changes in common adverse events, updated exposure information, and a summary of worldwide safety experience.

Recommended response: Provide a comprehensive safety update incorporating all new clinical and nonclinical data. Ensure all required tabulations, comparisons, case reports, and worldwide experience summaries are complete and accurately presented as per regulatory guidance.

Cited: 21 CFR 314.50(d)(5)(vi)(b)

Missing English Translations of Foreign Labeling

Severity: minor

Provide English translations of current approved foreign labeling not previously submitted.

Recommended response: Submit complete English translations for all approved foreign labeling that has not yet been provided to the agency.

Discrepancy in Osmolality Data

Severity: major

Explain the significant difference in Osmolality reported for developmental drug product batch BORP1068 with that reported at release for NDA exhibit batches 7Q10042A, 7Q10043A and 7Q10044A. Also, provide stability data which establishes that the values observed at release for the NDA exhibit batches does not change over time.

Recommended response: Investigate and provide a detailed explanation for the osmolality discrepancy. Submit supporting stability data to demonstrate consistency over time for the exhibit batches.

Inadequate Degradation Products Specification

Severity: major

Revise the release and stability specification for Degradation Products to report all known and unknown impurities, and degradants observed at or above the method limit of quantitation, and to report total impurities as the sum of all observed known and unknown impurities, or degradants. This will permit trend analysis for degradants and establish mass balance.

Recommended response: Update the degradation product specifications to include all impurities and degradants above the limit of quantitation, ensuring proper trend analysis and mass balance calculations.

Insufficient Updated Stability Data

Severity: major

Provide updated stability data from the on-going stability studies on the NDA exhibit batches to justify the proposed criteria in the release specification.

Recommended response: Submit the most recent stability data from ongoing studies for the exhibit batches to support the proposed release specifications.

Pending Labeling Review

Severity: info

Comments on proposed labeling (Prescribing Information, Carton and Container Labeling) are reserved until the application is otherwise adequate. However, an updated content of labeling in SPL format is required upon resubmission.

Recommended response: Prepare updated content of labeling in SPL format, ensuring compliance with SRPI checklist, for submission with the complete response. Be prepared for further labeling comments once other deficiencies are resolved.

Cited: 21 CFR 314.50(l)(1)(i)

Regulatory context

Submission stage
final decision
Regulatory pathway
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 primarily due to critical manufacturing facility issues and significant deficiencies in the clinical safety data package, including incomplete reporting, inadequate data presentation, and missing worldwide safety information. Several product quality (CMC) issues related to analytical data and specifications also require resolution. Labeling review is pending resolution of these core issues.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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