NEWS

An industry first – a holistic approach to container closure integrity

17 January 2024
Fill Finish
Jane Worthington
Global Change Facilitator

Container closure systems (CCS) for parenteral products must maintain sterility and product quality throughout their shelf life until final use. Traditionally, there is a tendency to demonstrate appropriate control of the integrity of a CCS through testing, e.g., by sterility and/or container closure integrity testing (CCIT) of drug products.

A holistic approach to CCI is recommended and, in line with current regulations, a science- and risk-based approach in (bio)pharmaceutical product development and manufacture.

A holistic approach is more robust and aims to build quality into the design and processes rather than testing or inspecting the finished product, and this is why we have published BioPhorum’s holistic approach to container closure integrity.

It provides an industry perspective on ensuring CCI throughout the product lifecycle and includes discussions on development, validation, routine manufacturing, shipping and stability, and the ongoing monitoring of holistic CCI strategy. It also includes appendices on qualification activities, a process performance qualification readiness checklist, CCS assembly steps (and associated preventions and detections), and analytical considerations.

“Our industry needs to move the needle from CCIT to CCI,” said Henri Hebting, Sr Director TS/MS at Eli Lilly. “Testing has never been the sole way to assure parenteral drug products are safe to inject. It all relies on the robustness of what we do every day, whether in development, designing good CCS, or in manufacturing to execute reliable processes. This paper is an unprecedented summary of best-in-class practices our industry experts have been applying to assure we deliver safe medicines to patients.”

This paper is intended to trigger technical and scientific discussions. Key topics include:

  • Building CCI of a parenteral drug product into the overall process and assuming CCI through a holistic approach, rather than relying solely on final release/stability testing of the product
  • Taking a robust ‘quality by design’ approach with formalized risk assessments to de-risk CCI by the tailored design of critical component interfaces and confirming the robustness of design with characterization data
  • Ensuring close collaboration with primary packaging component suppliers and robust change management processes to guarantee consistent quality of parts between batches and supplier manufacturing sites over long periods.

To our knowledge, it is the first publication of an industry-wide view of a holistic approach to CCI for a parenteral product.

“This paper provides a roadmap for industry on how to assure CCI, which is long overdue,” said Michael Edey, Senior Principal Engineer at Pfizer. “Building quality into parenteral products to assure patient safety, rather than attempting to test quality in, is the basis of the paper. While regulations continue to evolve, a roadmap for biopharmaceutical companies on how to fulfill them in this complex and often misunderstood field is most welcome. This paper represents an opportunity to build knowledge across industry and provide further stimulus for engagement with all partners.”

Specific considerations and studies around a holistic approach to CCI are exemplified at different stages in the product lifecycle. The use of ‘quality by design’ principles and scientific and risk-based justifications are emphasized at each stage for a ‘new’ drug product, i.e., CCS design and development, validation, routine manufacture, stability, and shipment.

Where a high level of assurance is created by a holistic approach throughout the lifetime of a product, final testing may be reduced or even eliminated at a batch level or during routine stability testing. Nonetheless, some analytical CCIT method considerations are provided.

Industry should stop considering CCIT as a compliance endpoint and see the value of managing CCI as a risk to the safety and efficacy of drug product, which must be managed during the whole lifecycle. Our paper is a crucial part of making that happen. For more information, download the paper here and contact Jane Worthington, Global Change Facilitator, at jane.worthington@biophorum.com

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