ECA revises Container-/Closure-Integrity Testing (CCIT) Position Paper

The Position Paper, issued by the ECA Visual Inspection Working Group, provides best practice recommendations for Container Closure Integrity (CCI) Testing of parenteral drug products. It is intended as a complement to pharmacopoeial monographs and reflects current GMP practice. It defines a lifecycle CCI control strategy, integrating qualification/validation, routine controls, supplier management, and stability studies.

In addition to editorial improvements, the new version 3.0 contains the following changes.

Supplementary interpretations of Annex 1 CCI(T) requirements

The new version provides expanded and practical interpretations of Annex 1 clauses 8.22 to 8.28. It differentiates clearly between fusion-sealed containers (e.g. ampoules, BFS/FFS units), which require 100 % integrity testing, and mechanically closed systems (e.g. vials and prefilled syringes), where integrity assurance is achieved through validated process controls and risk-based CCIT sampling.

In line with clause 8.23, the paper now emphasizes that sampling frequency and sample size should be scientifically justified, typically applying statistical sampling plans such as ISO 2859 (S3/S4) for destructive CCIT methods.

Further clarifications address the verification of vacuum for lyophilized products (8.24), the inclusion of CCI testing in transport validation (8.25), and the qualification of stopper-height detection systems (8.28) as critical in-process controls supporting overall container-closure integrity.

Inclusion of prefilled syringes

Prefilled syringes are now explicitly integrated into the CCI concept and validation framework. Chapter 4 and 4.1 describe requirements for stopper and tip-cap setting validation, PPQ sampling for CCI, and corresponding process controls-aligning syringe systems with vial-based CCI principles.

Addition of CCI Verification within stability testing

A new section (Chapter 4.5) defines CCI verification as part of the product's lifecycle control strategy. It clarifies that, for non-fusion-sealed containers such as vials and prefilled syringes, validated CCIT methods should be applied within the stability program to confirm integrity over shelf life, while 100 % testing at batch release remains unnecessary if a robust control strategy is in place.

Completion, approval, and publication are planned for the end of November 2025.

The new document will be made available to all members of the ECA Visual Inspection group on the group's website.