Approval Letter Other 212501 (Jan 1, 2021)

Summary

This is a Complete Response letter from the FDA to Ingenus Pharmaceuticals, LLC regarding their New Drug Application (NDA) for Cyclophosphamide Injection. The FDA has determined that the application cannot be approved in its current form due to deficiencies related to facility inspections, prescribing information, carton and container labeling, and the need for a safety update.

Key points

• Satisfactorily resolve objectionable conditions observed during the manufacturing facility inspection.
• Provide a statement from the manufacturing facility confirming that all issues have been resolved.
• Submit draft Prescribing Information (PI) that conforms to the content and format regulations at 21 CFR 201.56(a) and (d) and 201.57.
• Review labeling review resources on the PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
• Use the Selected Requirements for Prescribing Information (SRPI) checklist to correct any formatting errors in the PI.
• Submit updated content of labeling in structured product labeling (SPL) format as described at FDA.gov, pursuant to 21 CFR 314.50(l)(1)(i).
• Provide a highlighted or marked-up copy showing all changes to the labeling, as well as a clean Word version, with annotations supporting proposed changes.
• Submit draft carton and container labeling revised based on FDA's proposed revisions.

Cited reasons

• Unresolved Manufacturing Facility Observations
• Non-conforming Prescribing Information (PI)
• Required Revisions to Carton and Container Labeling
• Inadequate Safety Update
• The application cannot be approved in its present form due to unresolved manufacturing facility observations, non-conforming prescribing information and carton/container labeling, and an inadequate safety update. Comprehensive revisions and resolution of facility issues are required.

Recommended actions

• Satisfactorily resolve objectionable conditions observed during the manufacturing facility inspection.
• Provide a statement from the manufacturing facility confirming that all issues have been resolved.
• Submit draft Prescribing Information (PI) that conforms to the content and format regulations at 21 CFR 201.56(a) and (d) and 201.57.
• Review labeling review resources on the PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
• Use the Selected Requirements for Prescribing Information (SRPI) checklist to correct any formatting errors in the PI.
• Submit updated content of labeling in structured product labeling (SPL) format as described at FDA.gov, pursuant to 21 CFR 314.50(l)(1)(i).
• Provide a highlighted or marked-up copy showing all changes to the labeling, as well as a clean Word version, with annotations supporting proposed changes.
• Submit draft carton and container labeling revised based on FDA's proposed revisions.

Deficiency summary

The application cannot be approved in its present form due to unresolved manufacturing facility observations, non-conforming prescribing information and carton/container labeling, and an inadequate safety update. Comprehensive revisions and resolution of facility issues are required.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2)

Impact

Impact score

0.95

Estimated delay

545 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application received a Complete Response due to critical manufacturing quality issues, significant deficiencies in both prescribing and carton/container labeling, and an incomplete safety update. Resolution of these issues is mandatory for approval.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%