Container Closure Integrity is Integral
The Stopper Compression Analysis Service Provides Critical Information Necessary to
Insure Robust Seal Integrity and Repeatable Capper Setup
A stoppered vial is a universal parenteral drug container closure system. The system however should not be considered integral until the rubber stopper is crimped firmly in place with sufficient compression against the vial finish assuring all potential leakage is cut off at the seal interface. Analysis of this seal integrity should be a critical aspect of the packaging development, evaluation and qualification.
Stopper Compression Analysis Overview
A parenteral vial container closure system is made integral by compressing the flange of a rubber stopper against the sealing surface of a vial (finish crown) and securing it in place with a crimped aluminum ferrule or seal. The elastomeric properties of the rubber maintain a force that effectively seals the vial. Our experienced technicians analyze your specific container closure system and determine the optimal compression percentage to achieve leak rate cut off. This value is then correlated to Residual Seal Force (RSF) and verified by a standard leak testing method.
The RSF value is the measured stress the compressed rubber closure flange continues to exert on the vial-sealing surface after application (crimping) of an aluminum ferrule. By correlating RSF values for each set of vials to the compression calculation for those vials, RSF can then be used as an indirect test method to estimate closely the elastomeric closure compression.
RSF values may be used in effectively setting up vial cappers and for monitoring the crimping process. With an understanding of compression and leak rate cut-off RSF can be further used as a predictor of leakage risk.
The FDA recognizes the use of RSF as a predictor of seal integrity.
The FDA in its Guidance for Industry Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products recognizes the usefulness of properly validated seal force testing. Most importantly, RSF is useful in the establishment, validation and control of capping machine settings.
Genesis provides a complete report which includes all the test procedures used and data collected. This information can then be used to develop your vial sealing SOP’s.
The report includes:
- Stopper Flange Compression Analysis
- Levels of Compression Graphics
- Compression and Residual Seal Force Data
- Residual Seal Force Measurements
- Helium Leak Testing
- Discussion and Recommendations
- Stopper Compression Measurement Procedure
- Residual Seal Force Measurement Procedure
- Package Component Specifications
Impact of Vial Capping on Residual Seal Force and Container Closure Integrity | PDA Journal
The vial capping process is a critical unit operation during drug product manufacturing, as it could possibly generate cosmetic defects or even affect container closure integrity. Yet there is significant variability in capping equipment and processes, and their relation to potential defects or container closure integrity has not been thoroughly studied.
Roman Mathaes, Hanns-Christian Mahler, Yves Roggo, Robert Ovadia, Philippe Lam, Oliver Stauch, Martin Vogt, Holger Roehl, Joerg Huwyler, Silke Mohl and Alexander Streubel