Approval Letter Other 208042 (Jan 1, 2018)

Summary

This is a Complete Response letter from the FDA to Teva Pharmaceuticals USA regarding their New Drug Application (NDA) 208042 for buprenorphine and naloxone sublingual film. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facility inspection, prescribing information, Medication Guide, Risk Evaluation and Mitigation Strategy (REMS), and safety update requirements.

Key points

• The applicant must notify the FDA in writing when the Lohmann Therapy Systems manufacturing facility is ready for a satisfactory inspection.
• The applicant must review labeling resources and revise prescribing information to conform with format items in regulations and guidances, including updated content of labeling in SPL format.
• The applicant must use the active base only for the product name throughout the package insert, labeling pouches, and cartons, and express strengths as the base with a corresponding equivalency statement to the salt form of the APIs.
• The applicant must add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.' or an appropriate alternative to the carton and container labels per 21 CFR 208.24(d).
• The applicant must include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies, incorporating new safety data from all nonclinical and clinical studies/trials.
• The applicant must resubmit or take other actions available under 21 CFR 314.110 within one year after the date of this letter.
• A resubmission must fully address all listed deficiencies and be clearly marked 'RESUBMISSION' in large, bolded type at the beginning of the cover letter, stating it is a complete response.
• The field investigator could not complete the inspection of the Lohmann Therapy Systems manufacturing facility (FEI 1000121692) because the facility was not ready for inspection. A satisfactory inspection is required before approval.

Cited reasons

• Incomplete Manufacturing Facility Inspection
• Non-compliance with USP Salt Policy for Product Naming
• Missing or Inadequate Medication Guide Statement on Labels
• Unsatisfactory Risk Evaluation and Mitigation Strategy (REMS)
• Inadequate Safety Update and Clinical Data Presentation
• The application cannot be approved in its present form due to an incomplete manufacturing facility inspection, non-compliance with USP salt policy for product naming, an inadequate Medication Guide statement, an unsatisfactory Risk Evaluation and Mitigation Strategy (REMS), and the need for a comprehensive safety update with updated clinical data and narratives.

Recommended actions

• The applicant must notify the FDA in writing when the Lohmann Therapy Systems manufacturing facility is ready for a satisfactory inspection.
• The applicant must review labeling resources and revise prescribing information to conform with format items in regulations and guidances, including updated content of labeling in SPL format.
• The applicant must use the active base only for the product name throughout the package insert, labeling pouches, and cartons, and express strengths as the base with a corresponding equivalency statement to the salt form of the APIs.
• The applicant must add the bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.' or an appropriate alternative to the carton and container labels per 21 CFR 208.24(d).
• The applicant must include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies, incorporating new safety data from all nonclinical and clinical studies/trials.
• The applicant must resubmit or take other actions available under 21 CFR 314.110 within one year after the date of this letter.
• A resubmission must fully address all listed deficiencies and be clearly marked 'RESUBMISSION' in large, bolded type at the beginning of the cover letter, stating it is a complete response.

Deficiency summary

The application cannot be approved in its present form due to an incomplete manufacturing facility inspection, non-compliance with USP salt policy for product naming, an inadequate Medication Guide statement, an unsatisfactory Risk Evaluation and Mitigation Strategy (REMS), and the need for a comprehensive safety update with updated clinical data and narratives.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2) NDA

Impact

Impact score

0.95

Estimated delay

450 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application received a Complete Response due to critical manufacturing site readiness issues, multiple labeling deficiencies related to product naming and medication guide, an unapproved REMS, and the need for a thorough and updated safety data submission, indicating significant gaps across CMC, clinical, and regulatory compliance aspects.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%