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US FDA•United StatesAL•Approval Letter

Approval Letter Other 761164 (Jan 1, 2022)

Issued January 1, 2022

Issued

January 1, 2022

Application

Other • 761164

Review center

Other

Stage

Final Decision

Letter type

Approval Letter

Response due January 1, 2023Product may be marketed.

Summary

This is a Complete Response letter from the FDA to Bioverativ USA, Inc. regarding their Biologics License Application (BLA) for sutimlimab. The FDA has determined that the application cannot be approved in its present form and outlines specific deficiencies and recommendations that must be addressed for approval.

Key points

  • Review labeling review resources on PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
  • Use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
  • Include updated content of labeling in structured product labeling (SPL) format.
  • Submit draft carton and container labeling based on FDA's proposed revisions dated August 13, 2020.
  • Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide' or an appropriate alternative to the carton and container labels per 21 CFR 208.24(d).
  • Resubmit the proposed proprietary name, Enjaymo, when responding to the application deficiencies.
  • Ensure satisfactory resolution of observations from the facility inspection.
  • Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.

Cited reasons

  • Prescribing Information Adequacy
  • Carton and Container Labeling Revisions
  • Medication Guide Statement Requirement
  • Proprietary Name Resubmission
  • Unresolved Facility Inspection Observations
  • Comprehensive Safety Update Required
  • The application cannot be approved in its present form due to outstanding issues related to prescribing information, carton and container labeling, medication guide requirements, proprietary name resubmission, unresolved facility inspection observations, and the need for a comprehensive safety update including detailed clinical data, adverse event reporting, and worldwide experience.

Recommended actions

  • Review labeling review resources on PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
  • Use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure Prescribing Information conforms with format items in regulations and guidances if labeling is revised.
  • Include updated content of labeling in structured product labeling (SPL) format.
  • Submit draft carton and container labeling based on FDA's proposed revisions dated August 13, 2020.
  • Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide' or an appropriate alternative to the carton and container labels per 21 CFR 208.24(d).
  • Resubmit the proposed proprietary name, Enjaymo, when responding to the application deficiencies.
  • Ensure satisfactory resolution of observations from the facility inspection.
  • Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.

Deficiency summary

The application cannot be approved in its present form due to outstanding issues related to prescribing information, carton and container labeling, medication guide requirements, proprietary name resubmission, unresolved facility inspection observations, and the need for a comprehensive safety update including detailed clinical data, adverse event reporting, and worldwide experience.

Findings

Prescribing Information Adequacy

Severity: major

The agency reserves comment on proposed labeling until the application is otherwise adequate. The sponsor is encouraged to review PLR requirements, Pregnancy and Lactation Labeling Final Rule, and SRPI checklist. Updated content of labeling [21 CFR 601.14(b)] in structured product labeling (SPL) format is required.

Recommended response: Review and revise prescribing information according to PLR requirements, Pregnancy and Lactation Labeling Final Rule, and SRPI checklist. Ensure submission in SPL format.

Cited: updated content of labeling [21 CFR 601.14(b)]

Carton and Container Labeling Revisions

Severity: major

Submit draft carton and container labeling based on the agency's proposed revisions dated August 13, 2020.

Recommended response: Incorporate FDA's proposed revisions for carton and container labeling and resubmit.

Medication Guide Statement Requirement

Severity: major

Add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.' or an appropriate alternative to the carton and container labels per 21 CFR 208.24(d).

Recommended response: Ensure the required Medication Guide statement is prominently displayed on carton and container labels as per 21 CFR 208.24(d).

Cited: per 21 CFR 208.24(d)

Proprietary Name Resubmission

Severity: minor

Resubmit the proposed proprietary name, Enjaymo, when responding to the application deficiencies. The name was found acceptable pending approval of the application in the current review cycle.

Recommended response: Include the proprietary name resubmission as part of the complete response package.

Unresolved Facility Inspection Observations

Severity: critical

During a recent inspection of the manufacturing facility, field investigators conveyed deficiencies. Satisfactory resolution of these observations is required before this application may be approved.

Recommended response: Address and resolve all outstanding observations from the facility inspection and provide documentation of satisfactory resolution.

Comprehensive Safety Update Required

Severity: critical

A comprehensive safety update is required as described at 21 CFR 314.50(d)(5)(vi)(b). This includes: detailed description of significant changes/findings in safety profile; incorporation of new safety data from studies/trials for proposed indication (same format, combined with original data, comparative tables); separate tables for adverse event frequencies for other indications; retabulation of reasons for premature trial discontinuation; case report forms and narrative summaries for patient deaths or discontinuations due to adverse events, and for serious adverse events; information suggesting substantial change in incidence of common, less serious adverse events; updated exposure information for clinical studies/trials; summary of worldwide experience and updated estimate of use for product marketed in other countries; and English translations of current approved foreign labeling.

Recommended response: Conduct a thorough safety data review, compile all requested information, and submit a comprehensive safety update addressing all specified points, ensuring data consistency and completeness.

Cited: as described at 21 CFR 314.50(d)(5)(vi)(b)

Regulatory context

Submission stage
final decision
Regulatory pathway
BLA (Biologics License Application) under section 351(a) of the Public Health Service Act

Impact

Impact score
0.95
Estimated delay
365 days
Estimated rework cost
$0
Subsequent action
resubmission

Strategic insights

The application requires substantial additional information and resolution of identified issues across labeling, manufacturing quality systems, and a comprehensive safety data update before approval can be considered. Key deficiencies include unresolved facility inspection findings and significant gaps in safety data presentation and analysis.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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