The Critical Role of CCI in Drug Development and Manufacturing

This whitepaper provides a detailed examination of Lonza’s holistic, data-driven approach to CCI, developed in collaboration with industry experts and applied across our global network for parenteral combination products.

For Contract Development and Manufacturing Organizations (CDMOs), a reputation for uncompromising quality is central to success. However, sterility assurance continues to represent a leading cause of drug recalls, with FDA enforcement reports regularly citing container closure integrity (CCI) deficiencies. In parallel, the revised EU GMP Annex 1 has reinforced global expectations, emphasizing contamination control strategies and validated CCI testing methods across sterile product development.

The implication is clear: CCI compliance must evolve from a release- and stability-focused exercise to a comprehensive, lifecycle-spanning strategy.

Current industry challenges:

The pharmaceutical sector is navigating an increasingly complex landscape characterized by:

• Development of novel and complex therapeutic modalities (e.g., mRNA, lipid nanoparticles)
• Supply chain vulnerabilities impacting material consistency and availability
• Escalating costs that demand efficient, resource-conscious development pathways
• Expanding regulatory requirements mandating science- and risk-based quality strategies

These dynamics necessitate robust, proactive quality control measures capable of ensuring sterility, product integrity, and compliance from early development through commercial distribution.

This whitepaper provides a detailed examination of Lonza’s holistic, data-driven approach to CCI, developed in collaboration with industry experts and applied across our global network for parenteral combination products.

Key topics include:

• Integration of risk-based CCI strategies into container closure system development, material qualification, manufacturing, and distribution/storage.
• Comparative analysis of probabilistic vs. deterministic CCI testing methods, with emphasis on helium leak detection as the most sensitive and regulatory-preferred deterministic technique.
• Application of proprietary testing technologies, enabling CCI assessment under challenging conditions, including cryogenic storage at -80°C for sensitive modalities.
• Use of early, platform-based data generation to minimize reliance on scarce drug substance, shorten development timelines, and mitigate regulatory/technical risks.

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