Impact of Vial Capping on Residual Seal Force and Container Closure Integrity

• Published in: PDA journal of pharmaceutical science and technology Vol. 70; no. 1; p. 12
• Main Authors: Mathaes, Roman, Mahler, Hanns-Christian, Roggo, Yves, Ovadia, Robert, Lam, Philippe, Stauch, Oliver, Vogt, Martin, Roehl, Holger, Huwyler, Joerg, Mohl, Silke, Streubel, Alexander
• Format: Journal Article
• Language: English
• Published: United States 01.01.2016
• Subjects: Compressive Strength; Drug Industry - instrumentation; Drug Industry - methods; Drug Industry - standards; Drug Packaging - instrumentation; Drug Packaging - methods; Drug Packaging - standards; Equipment Design - instrumentation; Equipment Design - methods; Equipment Design - standards; Glass - standards; Humans; Rubber - standards; Torsion, Mechanical; Helium leakage; Capping; Residual seal force; Cap; Stopper; Process control; Vial; Container closure integrity; Seal; Container closure system
• ISSN: 1948-2124
• DOI: 10.5731/pdajpst.2015.005876

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. In this study we applied several methods-residual seal force tester, a self-developed system of a piezo force sensor measurement, and computed tomography-to characterize different container closure system combinations that had been sealed using different capping process parameter settings. Additionally, container closure integrity of these samples was measured using helium leakage (physical container closure integrity) and compared to characterization data. The different capping equipment settings lead to residual seal force values from 7 to 115 N. High residual seal force values were achieved with high capping pre-compression force and a short distance between the capping plate and plunge. The choice of container closure system influenced the obtained residual seal force values. The residual seal force tester and piezoelectric measurements showed similar trends. All vials passed physical container closure integrity testing, and no stopper rupture was seen with any of the settings applied, suggesting that container closure integrity was warranted for the studied container closure system with the chosen capping setting ranges. 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. In this study we applied several methods-residual seal force tester, a self-developed system of a piezo force sensor measurement, and computed tomography-to characterize different container closure system combinations that had been sealed using different capping process parameter settings. The residual seal force tester can analyze a variety of different container closure systems independent of the capping equipment. An adequate and safe residual seal force range for each container closure system configuration can be established with the residual seal force tester and additional methods like computed tomography scans and leak testing. In the residual seal force range studied, the physical container closure integrity of the container closure system was warranted.