Approval Letter Other 206185 (Jan 1, 2018)

Summary

This document is a Complete Response letter from the FDA to Sun Pharma Advanced Research Company Limited regarding their New Drug Application (NDA) for Xelpros (latanoprost ophthalmic emulsion), 0.005%. The FDA has determined that the application cannot be approved in its present form due to unresolved deficiencies related to manufacturing facilities and requires a comprehensive safety update.

Key points

• Satisfactorily resolve deficiencies identified during the inspection of the Sun Pharmaceutical Industries, Ltd. manufacturing facility (FEI# 3002809586).
• Resubmit the proposed proprietary name, Xelpros, when responding to the application deficiencies.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b), which must detail any significant changes or findings in the safety profile.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, presenting new data from studies/clinical trials for the proposed indication in the same format as the original submission.
• Present tabulations of the new safety data combined with the original NDA data and include tables comparing frequencies of adverse events.
• For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in clinical trials.
• Present a retabulation of the reasons for premature trial discontinuation, incorporating drop-outs from newly completed trials, and describe any new trends or patterns identified.
• Provide case report forms and narrative summaries for each patient who died during a clinical trial or who did not complete a trial because of an adverse event, and for serious adverse events.

Cited reasons

• Manufacturing Facility Deficiencies
• Proprietary Name Resubmission
• Comprehensive Safety Update Required
• The FDA issued a Complete Response Letter due to unresolved manufacturing facility deficiencies, the need for resubmission of the proprietary name, and extensive requirements for a comprehensive safety update, including clinical, nonclinical, and worldwide safety data, as well as foreign labeling translations.

Recommended actions

• Satisfactorily resolve deficiencies identified during the inspection of the Sun Pharmaceutical Industries, Ltd. manufacturing facility (FEI# 3002809586).
• Resubmit the proposed proprietary name, Xelpros, when responding to the application deficiencies.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b), which must detail any significant changes or findings in the safety profile.
• Incorporate new safety data into sections describing discontinuations due to adverse events, serious adverse events, and common adverse events, presenting new data from studies/clinical trials for the proposed indication in the same format as the original submission.
• Present tabulations of the new safety data combined with the original NDA data and include tables comparing frequencies of adverse events.
• For indications other than the proposed indication, provide separate tables for the frequencies of adverse events occurring in clinical trials.
• Present a retabulation of the reasons for premature trial discontinuation, incorporating drop-outs from newly completed trials, and describe any new trends or patterns identified.
• Provide case report forms and narrative summaries for each patient who died during a clinical trial or who did not complete a trial because of an adverse event, and for serious adverse events.

Deficiency summary

The FDA issued a Complete Response Letter due to unresolved manufacturing facility deficiencies, the need for resubmission of the proprietary name, and extensive requirements for a comprehensive safety update, including clinical, nonclinical, and worldwide safety data, as well as foreign labeling translations.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2) NDA

Impact

Impact score

0.95

Estimated delay

545 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary themes are critical manufacturing quality control issues and significant data gaps in the safety profile, requiring a thorough re-evaluation and presentation of clinical and nonclinical safety data, which are fundamental for product approval.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%