(T1030-06-33) Real World Application of Deterministic, Non-destructive CCI Testing on the Entire Batch (100%) - Not a Concept Anymore!

Purpose: The most common container closure systems (CCS) used by the pharmaceutical industry for parenteral products include vials and pre-filled syringes. These CCS are not required to be subjected to 100% Container Closure Integrity Testing (CCIT) in alignment with current compendial and regulatory guidance. While this does allow the sterile injectable industry to maintain its standard mode of operation one may challenge the status quo by raising a ‘what if’ scenario where implementation of 100% CCIT is a requirement, not a choice. Are we as pharmaceutical scientists ready for that? Do we have a non-destructive deterministic CCIT method that can be reproducibly applied to a large batch of manufactured drug product? Can that method be applicable to both liquid and lyophilized presentation?

Methods: The work presented in this poster will demonstrate that non-destructive, deterministic laser-based headspace CCIT methods can readily be employed when testing various batch sizes of either lyophilized or liquid filled products. Key insights will be provided on the development of CO₂ and O₂ headspace analysis method for lyophilized and liquid presentation respectively, establishment of appropriate acceptance criteria, method validation and implementation of 100% testing on the entire batch.

Results: Acceptance criteria for O₂ based headspace analysis was established to be 8 mbar and an entire batch of lyophilized DP (~12000 vials) stoppered under N₂ was subject to the CCI testing utilizing the O₂ based headspace analysis method and one vial was identified to have CCIT breach and was rejected. For liquid DP, CO₂ based head space analysis was developed with acceptance criteria of 13 mbar and an entire lot of liquid drug vial (~35000 vials) was subject to CCI testing. Every single vial of this DP lot passed the acceptance criteria.

Conclusion: What can be claimed is today, the sterile injectable industry is capable of developing product specific non-destructive deterministic 100% CCIT method that can be reliably applied to both liquid and lyophilized presentation in vial

References: 21 CFR 211.94(b)
21 CFR 600.11(h); EU Annex 1: Manufacture of Sterile Products