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US FDA•United StatesAL•Approval Letter

Approval Letter Other 210864 (Jan 1, 2021)

Issued January 1, 2021

Issued

January 1, 2021

Application

Other • 210864

Review center

Other

Stage

Final Decision

Letter type

Approval Letter

Response due January 1, 2022Product may be marketed.

Summary

This is a Complete Response letter from the FDA to Sedor Pharmaceuticals, LLC regarding their New Drug Application (NDA) 210864 for Sesquient (fosphenytoin sodium) injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to product quality (specifically, foreign particles), regulatory issues (reliance on reference listed drugs and Paragraph IV certifications), and requirements for prescribing information, carton/container labeling, proprietary name resubmission, and a comprehensive safety update. The letter outlines specific actions and information required for a complete response and resubmission.

Key points

  • Characterize the particles observed in the drug product and identify the root cause of their presence (e.g., container closure system, testing method/conditions, manufacturing equipment).
  • Provide a Risk Mitigation & Control Plan to mitigate the presence of particulates in your drug product.
  • Provide data demonstrating that the actions taken will prevent reoccurrence of particles in the drug product.
  • Submit an updated form FDA 356h to reflect reliance on only the Cerebyx (NDA 020450) and Carnexiv (NDA 206030) NDAs.
  • Send notice of Paragraph IV certification to Cydex Pharmaceuticals, the patent owner for patents 7,635,773, 8,410,077, 9,493,582, and 9,750,822.
  • Submit documentation of the date of receipt of such notice by Cydex Pharmaceuticals.
  • Submit documentation that clearly shows the delivery date of Paragraph IV notification to Lundbeck Pharmaceuticals.
  • Review the labeling review resources on the PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.

Cited reasons

  • Unresolved Particulate Matter in Drug Product
  • Inaccurate Reliance on Reference Listed Drugs (RLDs)
  • Incomplete Patent Certification Documentation
  • Pending Prescribing Information and Labeling Review
  • Requirement for Comprehensive Safety Update
  • The application received a Complete Response due to unresolved product quality issues concerning particulate matter, deficiencies in regulatory documentation regarding reliance on RLDs and patent certifications, and pending review of labeling information.

Recommended actions

  • Characterize the particles observed in the drug product and identify the root cause of their presence (e.g., container closure system, testing method/conditions, manufacturing equipment).
  • Provide a Risk Mitigation & Control Plan to mitigate the presence of particulates in your drug product.
  • Provide data demonstrating that the actions taken will prevent reoccurrence of particles in the drug product.
  • Submit an updated form FDA 356h to reflect reliance on only the Cerebyx (NDA 020450) and Carnexiv (NDA 206030) NDAs.
  • Send notice of Paragraph IV certification to Cydex Pharmaceuticals, the patent owner for patents 7,635,773, 8,410,077, 9,493,582, and 9,750,822.
  • Submit documentation of the date of receipt of such notice by Cydex Pharmaceuticals.
  • Submit documentation that clearly shows the delivery date of Paragraph IV notification to Lundbeck Pharmaceuticals.
  • Review the labeling review resources on the PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.

Deficiency summary

The application received a Complete Response due to unresolved product quality issues concerning particulate matter, deficiencies in regulatory documentation regarding reliance on RLDs and patent certifications, and pending review of labeling information.

Findings

Unresolved Particulate Matter in Drug Product

Severity: critical

The drug product contains foreign particles, and the applicant's explanation that initial findings were erroneous due to testing conditions is not sufficiently supported. The root cause of the particles has not been adequately identified, and a risk mitigation plan is lacking.

Recommended response: Characterize observed particles, identify root cause (e.g., container closure, testing, manufacturing equipment), provide a Risk Mitigation & Control Plan, and submit data demonstrating prevention of reoccurrence.

Inaccurate Reliance on Reference Listed Drugs (RLDs)

Severity: major

The application incorrectly listed multiple RLDs (Baxdela, Vfend, Zulresso) for Captisol safety data in the June 28, 2019 resubmission. Only Cerebyx and Carnexiv NDAs are deemed necessary for reliance.

Recommended response: Submit an updated FDA form 356h to reflect reliance only on Cerebyx and Carnexiv NDAs.

Incomplete Patent Certification Documentation

Severity: major

The applicant submitted Paragraph IV certifications for Carnexiv patents but failed to provide documentation of notice to the patent owner (Cydex Pharmaceuticals) as required. Additionally, documentation of delivery date to Lundbeck Pharmaceuticals for Paragraph IV notification was incomplete.

Recommended response: Send notice of Paragraph IV certification to Cydex Pharmaceuticals and submit documentation of receipt date. Submit documentation that clearly shows the delivery date of Paragraph IV notification to Lundbeck Pharmaceuticals.

Cited: 21 CFR 314.52(a), 21 CFR 314.52(e)

Pending Prescribing Information and Labeling Review

Severity: major

The FDA reserves comment on the proposed labeling until other application deficiencies are resolved. The applicant is encouraged to review labeling resources and use the SRPI checklist. Draft carton and container labeling also needs revision.

Recommended response: Review labeling resources, use SRPI checklist, revise labeling to conform with regulations and guidances, and submit updated content of labeling in SPL format. Resubmit revised draft carton and container labeling.

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

Requirement for Comprehensive Safety Update

Severity: major

A comprehensive safety update is required upon resubmission, including data from all nonclinical and clinical studies, detailed description of significant changes in safety profile, retabulation of adverse events, case report forms for deaths/serious adverse events, updated exposure information, and worldwide safety experience.

Recommended response: Provide a complete safety update as per 21 CFR 314.50(d)(5)(vi)(b), including all specified data and analyses.

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

Regulatory context

Submission stage
final decision
Regulatory pathway
505(b)(2)

Impact

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

Comparative intelligence

Peer companies: Parke Davis, Lundbeck Pharmaceuticals, Cydex Pharmaceuticals

Historical frequency: 0 similar letters

Strategic insights

Key issues include critical product quality concerns with particulates requiring root cause analysis and mitigation, along with administrative and regulatory compliance gaps related to RLD reliance and patent notifications, all of which necessitate a comprehensive resubmission.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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