Issued January 1, 2019
Issued
January 1, 2019
Application
Other • 208193
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
The FDA issued a Complete Response Letter for New Drug Application (NDA) 208193 for Ozobax (baclofen) oral solution, indicating that the application cannot be approved in its current form. The letter outlines deficiencies related to product quality, including the need for additional stability studies and addressing gaps in the control strategy. It also details requirements for updating prescribing information and container labels to conform with regulatory standards, including using the SRPI checklist and submitting content in Structured Product Labeling (SPL) format. Furthermore, the applicant is required to submit a revised Initial Pediatric Study Plan (iPSP) and resubmit the proposed proprietary name. The letter provides recommendations for addressing these issues and specifies the process for resubmission or requesting a meeting.
The application cannot be approved in its present form due to an inadequate manufacturing and control strategy, insufficient drug product stability data, various deficiencies in prescribing information and container labels, the need to resubmit the proprietary name, and unfulfilled Pediatric Research Equity Act (PREA) requirements.
The proposed manufacturing and control strategy is insufficient to assure the identity, purity, strength, and quality of the commercial drug product, lacking controls over critical quality attributes at release and over shelf life.
Recommended response: Address gaps in the control strategy to ensure product quality throughout its lifecycle.
Current stability data is unreliable; if no samples are available for retesting, stability studies need to be repeated. Additional batches must be placed on stability to support the proposed shelf life, following ICH Q1A (R2) guidelines.
Recommended response: Repeat stability studies, place two additional batches on stability, and submit sufficient long-term data to support the proposed shelf life.
Cited: ICH Q1A (R2)
Labeling comments are reserved until the application is otherwise adequate. The sponsor is encouraged to review PLR, P&L, and SRPI guidelines and submit updated content in SPL format. Specific issues include inappropriate information in the dosage form/strength section, blurry drug substance structure, and missing details in the how supplied section.
Recommended response: Review labeling resources, use the SRPI checklist, revise specific sections (dosage form/strength, drug substance structure, how supplied), and submit updated content in SPL format.
Cited: 21 CFR 314.50(l)(1)(i)
The proposed proprietary name, Ozobax, was found acceptable pending approval but must be resubmitted with the response to application deficiencies.
Recommended response: Resubmit the proposed proprietary name along with the complete response to all application deficiencies.
Specific requests include performing a risk assessment screening, providing batch analysis data for batch C0412, and providing reference standard source information.
Recommended response: Provide the requested risk assessment, batch analysis data for batch C0412, and detailed reference standard source information.
Issues with container labels include an undefined expiration date format, missing temperature scale designations (e.g., '°C' or '°F') after numerical values, and a misleading cautionary statement that needs to be removed.
Recommended response: Define a clear expiration date format, add temperature scale designations to all numerical values, and remove the misleading cautionary statement from the container label.
The application is not exempt from Pediatric Research Equity Act (PREA) requirements, and a revised Initial Pediatric Study Plan (iPSP) must be submitted as part of the response.
Recommended response: Submit a revised Initial Pediatric Study Plan (iPSP) to address the PREA requirements.
The application received a Complete Response due to significant deficiencies spanning product quality (manufacturing, controls, stability), comprehensive labeling issues (prescribing information, container labels, proprietary name), and unfulfilled pediatric study requirements, indicating a need for substantial data and documentation updates.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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