New FDA Guidance for COVID-19 Packaging Changes: Glass Vials and Stoppers

Recommendation

5/6 June 2024

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COVID-19 injectable products may need some changes to the primary packaging components (e.g., glass vials and stoppers) due to supply chain issues affecting their availability. Therefore, the U.S. FDA has issued a new guidance with recommendations for the appropriate reporting category and the content of post approval change submissions for some common changes to container closure systems (CCS) consisting of glass vials and stoppers used for parenteral drug products (e.g. vaccines).

Examples for common changes related to glass vials and stoppers

According to the agency, applicants must validate the effects of the change prior to distribution of the drug, and, as appropriate, conduct additional qualification tests or submit information to address product-specific risks as part of that assessment. For example, this additional information to be submitted to FDA could include studies to assess:

• Formulation attributes (such as high pH),
• Glass delamination,
• Particulate matter,
• Extractables & Leachables,
• The effect of the lyophilization process on product quality.

Applicable tests and studies are, for example, provided in the United States Pharmacopeia (e.g. USP general chapters <660>, <1660>, <381>) and in the European Pharmacopoeia (e.g. Ph. Eur. chapters 3.2.1 / 3.2.9).

Appendix A of the guidance includes recommended information to support the change together with the recommended reporting category (i.e. prior approval supplement, CBE-30, annual report) for common changes to glass vials and stoppers (used for drugs and biologics). For example changes to

• the properties: E.g. change in stopper rubber / elastomer material, stopper dimensions, change to different composition or type of glass, change from glass to a new material (e.g., plastic), 
• the manufacturing or processing: E.g. changes in vial sterilization or depyrogenation method (e.g., changing from moist to dry heat), stopper washing / siliconization process, method of stopper sterilization (e.g., from moist heat to irradiation),
• the source or site of manufacture: E.g. change of site of vial or stopper manufacture or processing, sterilization, testing. 

Tools to facilitate CCS changes

For CCS changes that are the subject of this guidance, the agency considers the following risk-based approaches and existing tools:

• A lower supplement reporting category. Applicants should provide their rationale, supporting information, and risk-mitigation approaches.
• A comparability protocol (CP), which is a comprehensive, prospectively written plan for assessing the effect of proposed post approval CMC changes.

For more information please see FDA´s new Guidance COVID-19 Container Closure System and Component Changes: Glass Vials and Stoppers.