Approval Letter Other 214581 (Jan 1, 2022)

Summary

This is a Complete Response Letter from the FDA to Novitium Pharma LLC regarding their New Drug Application (NDA) 214581 for Hydroxychloroquine Sulfate Tablets. The FDA has determined that the application cannot be approved in its present form and outlines specific deficiencies and recommendations.

Key points

• Address Biopharmaceutics Deficiencies.
• Incorporate new safety data from studies/clinical trials for the proposed indication, presenting it 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.
• Provide separate tables for frequencies of adverse events occurring in clinical trials for indications other than the proposed indication.
• Present a retabulation of reasons for premature trial discontinuation, incorporating drop-outs from newly completed trials, and describe any new trends or patterns.
• Provide case report forms and narrative summaries for each patient who died during a clinical trial or who did not complete a trial due to an adverse event.
• Provide narrative summaries for serious adverse events.

Cited reasons

• Biopharmaceutics Deficiencies
• Incomplete Safety Data Presentation for Adverse Events
• Missing Case Report Forms and Narrative Summaries
• Outdated Clinical Study Exposure Information
• Incomplete Summary of Worldwide Safety Experience
• Missing English Translations of Approved Foreign Labeling
• The application cannot be approved in its present form due to significant deficiencies primarily related to the comprehensive presentation and completeness of safety data from clinical trials, including adverse event reporting, case report forms, exposure information, and worldwide safety experience. Additionally, there is an undisclosed biopharmaceutics deficiency and a requirement for English translations of foreign labeling.

Recommended actions

• Address Biopharmaceutics Deficiencies.
• Incorporate new safety data from studies/clinical trials for the proposed indication, presenting it 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.
• Provide separate tables for frequencies of adverse events occurring in clinical trials for indications other than the proposed indication.
• Present a retabulation of reasons for premature trial discontinuation, incorporating drop-outs from newly completed trials, and describe any new trends or patterns.
• Provide case report forms and narrative summaries for each patient who died during a clinical trial or who did not complete a trial due to an adverse event.
• Provide narrative summaries for serious adverse events.

Deficiency summary

The application cannot be approved in its present form due to significant deficiencies primarily related to the comprehensive presentation and completeness of safety data from clinical trials, including adverse event reporting, case report forms, exposure information, and worldwide safety experience. Additionally, there is an undisclosed biopharmaceutics deficiency and a requirement for English translations of foreign labeling.

Findings

Regulatory context

Submission stage

late cycle

Regulatory pathway

505(b)(2)

Impact

Impact score

0.75

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary theme of the Complete Response Letter is the inadequacy and lack of comprehensive organization of clinical safety data, alongside an undisclosed biopharmaceutics issue. The agency requires a more thorough and well-structured presentation of adverse event data, complete patient narratives, updated exposure information, and a global safety overview to ensure the safety profile of the drug is fully understood.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%