US FDA•United StatesAL•Approval Letter

Approval Letter Other 761148 (Jan 1, 2022)

Issued January 1, 2022

Issued

January 1, 2022

Application

Other • 761148

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 Spectrum Pharmaceuticals, Inc. regarding their Biologics License Application (BLA) for SPI-2012. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to product quality (manufacturing facility inspections), prescribing information, carton and container labeling, proprietary name resubmission, and the need for a comprehensive safety update.

Key points

Satisfactorily resolve deficiencies identified during manufacturing facility inspections.
Review labeling review resources and revise labeling, ensuring conformity with format items in regulations and guidances using the SRPI checklist.
Include updated content of labeling in structured product labeling (SPL) format.
Resubmit the proposed proprietary name (Rolontis) when responding to application deficiencies.
Include a comprehensive safety update with the resubmission, detailing significant changes or findings in the safety profile.
Present new safety data from studies/clinical trials for the proposed indication in the same format as the original submission.
Present tabulations of new safety data combined with original application data.
Include tables comparing frequencies of adverse events in the original application with retabulated frequencies.

Cited reasons

Unresolved Manufacturing Facility Deficiencies
Comprehensive Safety Update Required
Prescribing Information Adequacy Pending
Carton and Container Labeling Adequacy Pending
Proprietary Name Resubmission Required
The application cannot be approved in its present form due to unresolved manufacturing facility deficiencies, the need for a comprehensive safety update, and pending issues related to proprietary name, prescribing information, and carton/container labeling. Satisfactory resolution of all deficiencies is required for approval.

Recommended actions

Satisfactorily resolve deficiencies identified during manufacturing facility inspections.
Review labeling review resources and revise labeling, ensuring conformity with format items in regulations and guidances using the SRPI checklist.
Include updated content of labeling in structured product labeling (SPL) format.
Resubmit the proposed proprietary name (Rolontis) when responding to application deficiencies.
Include a comprehensive safety update with the resubmission, detailing significant changes or findings in the safety profile.
Present new safety data from studies/clinical trials for the proposed indication in the same format as the original submission.
Present tabulations of new safety data combined with original application data.
Include tables comparing frequencies of adverse events in the original application with retabulated frequencies.

Deficiency summary

The application cannot be approved in its present form due to unresolved manufacturing facility deficiencies, the need for a comprehensive safety update, and pending issues related to proprietary name, prescribing information, and carton/container labeling. Satisfactory resolution of all deficiencies is required for approval.

Findings

Unresolved Manufacturing Facility Deficiencies

Severity: critical

During recent inspections of two manufacturing facilities, field investigators conveyed deficiencies to facility representatives. Satisfactory resolution of these deficiencies is required before this application may be approved.

Recommended response: Address all identified deficiencies at the manufacturing facilities and provide evidence of satisfactory resolution to the agency, including any necessary corrective and preventive actions (CAPA).

Comprehensive Safety Update Required

Severity: major

A comprehensive safety update is required, including data from all nonclinical and clinical studies/trials. This update must detail significant changes in the safety profile, present new safety data combined with original data, compare adverse event frequencies, provide case report forms and narrative summaries for deaths/serious adverse events, update exposure information, summarize worldwide safety experience, and provide English translations of foreign labeling.

Recommended response: Compile and submit a comprehensive safety update, ensuring all new nonclinical and clinical data are included, detailed adverse event analyses are performed, and all required documentation (e.g., case report forms, worldwide experience, translations) is provided.

Prescribing Information Adequacy Pending

Severity: major

The agency reserves comment on the proposed prescribing information until the application is otherwise adequate. The sponsor is encouraged to review labeling resources and use the SRPI checklist to ensure conformity with format items in regulations and guidances. An updated content of labeling in SPL format is required.

Recommended response: Revise prescribing information to conform with FDA regulations and guidance, utilizing the SRPI checklist, and submit the updated content in Structured Product Labeling (SPL) format once other deficiencies are resolved.

Cited: 21 CFR 601.14(b)

Carton and Container Labeling Adequacy Pending

Severity: major

The agency reserves comment on the proposed container label and carton labeling until the application is otherwise adequate.

Recommended response: Update and resubmit carton and container labeling once the application's core deficiencies are resolved and the prescribing information is finalized.

Proprietary Name Resubmission Required

Severity: minor

The proposed proprietary name, Rolontis, was found acceptable pending approval of the application. The sponsor is required to resubmit the proposed proprietary name when responding to the application deficiencies.

Recommended response: Resubmit the proposed proprietary name 'Rolontis' as part of the complete response to the application deficiencies.

Regulatory context

Submission stage: final decision
Regulatory pathway: BLA 351(a)

Impact

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

Strategic insights

The primary obstacles to approval are critical manufacturing facility compliance issues and the need for a comprehensive update of safety data. Labeling and proprietary name issues are pending resolution of these core deficiencies.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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