Approval Letter Other 210821 (Jan 1, 2019)

Summary

This is a Complete Response letter from the FDA to Valeant Pharmaceuticals Ireland regarding their New Drug Application (NDA) for tetracaine hydrochloride ophthalmic solution, 0.5%. The FDA has determined that the application cannot be approved in its present form due to non-compliance with current good manufacturing practice (cGMP) regulations at the manufacturing facility and issues with proposed labeling.

Key points

• The methods, facilities, and controls used for the manufacture, processing, packing, or holding of the drug substance or drug product must comply with current good manufacturing practice regulations (21 CFR 210 and 211).
• The applicant must address observations made during the inspection of the Bausch & Lomb Inc. manufacturing facility that were not consistent with cGMP regulations.
• The applicant must submit a revised package insert, draft carton, and container labeling that is consistent with the attached draft labeling and FDA's labeling review resources.
• When responding to the deficiencies, the applicant must include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b).
• Within one year, the applicant must resubmit the application or take other actions available under 21 CFR 314.110.
• A resubmission must fully address all listed deficiencies and be clearly marked as 'RESUBMISSION' in the cover letter.
• Observations during a recent inspection of the Bausch & Lomb Inc. manufacturing facility (FEI 1000113778) were not consistent with current good manufacturing practice regulations (21 CFR 210 and 211). Compliance with cGMP is required before approval.
• The proposed package insert, draft carton, and container labeling are not consistent with agency requirements. The agency reserves comment until the application is otherwise adequate but encourages review of attached draft labeling and resources.

Cited reasons

• Manufacturing Facility Non-Compliance with cGMP
• Inadequate Proposed Labeling
• Safety Update Required for Resubmission
• The application received a Complete Response due to significant manufacturing facility non-compliance with current Good Manufacturing Practice (cGMP) regulations and inadequate proposed labeling. A safety update is also required for resubmission.

Recommended actions

• The methods, facilities, and controls used for the manufacture, processing, packing, or holding of the drug substance or drug product must comply with current good manufacturing practice regulations (21 CFR 210 and 211).
• The applicant must address observations made during the inspection of the Bausch & Lomb Inc. manufacturing facility that were not consistent with cGMP regulations.
• The applicant must submit a revised package insert, draft carton, and container labeling that is consistent with the attached draft labeling and FDA's labeling review resources.
• When responding to the deficiencies, the applicant must include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b).
• Within one year, the applicant must resubmit the application or take other actions available under 21 CFR 314.110.
• A resubmission must fully address all listed deficiencies and be clearly marked as 'RESUBMISSION' in the cover letter.

Deficiency summary

The application received a Complete Response due to significant manufacturing facility non-compliance with current Good Manufacturing Practice (cGMP) regulations and inadequate proposed labeling. A safety update is also required for resubmission.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2) New Drug Application (NDA)

Impact

Impact score

0.95

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The primary themes for the Complete Response are critical manufacturing quality system deficiencies and non-compliant labeling, necessitating a comprehensive resubmission addressing both cGMP and labeling requirements, along with a safety update.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%