The U.S. Food and Drug Administration (FDA) Center for Drug Evaluation and Research, and Center for Biologics Evaluation and Research have issued final guidance (24 July 2024) on "Container Closure System and Component Changes: Glass Vials and Stoppers." that provides important information for industry stakeholders regarding the regulatory expectations for changes to container closure systems, specifically focusing on glass vials and stoppers.
Container Closure System (CCS) is a combination of packaging components that together contain and protect the drug product, including vials and stoppers.
Risk-Based Approach is a method of assessing and categorizing changes based on their potential impact on product quality and patient safety.
As part of this guidance, new drug applications (NDAs), biologic license applications (BLAs), and abbreviated new drug applications (ANDAs) holders are informed about reporting and implementing common changes to container closure system components (CCS), such as glass vials and stoppers, for parenterally administered sterile drug products, including biological products.
Additionally, this guidance discusses the path available to application holders for obtaining Agency feedback. Furthermore, it discusses risk-based tools that can be used to facilitate the implementation of changes to glass vials and stoppers CCSs. This guidance does not apply to other types of CCS.
The FDA outlines different regulatory approaches for Chemistry, Manufacturing, and Controls (CMC) changes related to glass vials and stoppers. These approaches depend on the nature and significance of the changes, as well as their potential impact on the drug product. Key aspects include:
Submission Types: Depending on the changes, manufacturers may need to submit a Prior Approval Supplement (PAS), Changes Being Effected in 30 Days (CBE-30), or document the changes in an annual report.
Communication with FDA: The guidance encourages early and proactive communication with the FDA to clarify regulatory expectations and ensure a smooth approval process.
The guidance also details typical changes that may occur with glass vials and stoppers, including:
Material Changes: Alterations in the composition of glass or elastomeric materials.
Design Modifications: Changes in the physical dimensions or shape of the vials and stoppers.
Manufacturing Process Adjustments: Updates in manufacturing processes or supplier changes that could affect product quality.
The FDA advocates for a risk-based approach in determining the appropriate reporting category for changes. This approach involves assessing the potential impact on product quality and patient safety, and categorizing the changes accordingly. Comparability protocols are pre-approved, detailed plans that outline specific tests and acceptance criteria for demonstrating that a change does not adversely affect the quality of the drug product.
The guidance includes a comprehensive list of references and regulatory documents that provide additional context and detailed information on regulatory requirements and best practices for managing changes to glass vials and stoppers.
Also there is an An appendix provides tables categorizing different types of CCS changes and the corresponding regulatory requirements for products with approved Abbreviated New Drug Applications (ANDAs), New Drug Applications (NDAs), or Biologics License Applications (BLAs).
For more detailed information, refer to the full guidance document.
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