Mathaes Roman, Mahler Hanns-Christian, Roggo Yves, Ovadia Robert, Lam Philippe, Stauch Oliver, Vogt Martin, Roehl Holger, Huwyler Joerg, Mohl Silke, Streubel Alexander
Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Current address: Drug Product Services, Lonza AG, Basel Switzerland
Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Current address: Drug Product Services, Lonza AG, Basel Switzerland.
PDA J Pharm Sci Technol. 2016 Jan-Feb;70(1):12-29. 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.
小瓶封盖过程是药品生产中的关键单元操作，因为它可能会产生外观缺陷，甚至影响容器密封完整性。然而，封盖设备和工艺存在显著差异，并且它们与潜在缺陷或容器密封完整性的关系尚未得到充分研究。在本研究中，我们应用了多种方法——残余密封力测试仪、自行开发的压电力传感器测量系统以及计算机断层扫描——来表征使用不同封盖工艺参数设置密封的不同容器密封系统组合。此外，使用氦气泄漏（物理容器密封完整性）测量这些样品的容器密封完整性，并将其与表征数据进行比较。不同的封盖设备设置导致残余密封力值在7至115 N之间。高封盖预压力和封盖板与柱塞之间的短距离可实现高残余密封力值。容器密封系统的选择影响了获得的残余密封力值。残余密封力测试仪和压电测量显示出相似的趋势。所有小瓶均通过了物理容器密封完整性测试，并且在所应用的任何设置下均未观察到塞子破裂，这表明在所研究的容器密封系统中，在所选择的封盖设置范围内，容器密封完整性是有保证的。
小瓶封盖过程是药品生产中的关键单元操作，因为它可能会产生外观缺陷，甚至影响容器密封完整性。然而，封盖设备和工艺存在显著差异，并且它们与潜在缺陷或容器密封完整性的关系尚未得到充分研究。在本研究中，我们应用了多种方法——残余密封力测试仪、自行开发的压电力传感器测量系统以及计算机断层扫描——来表征使用不同封盖工艺参数设置密封的不同容器密封系统组合。残余密封力测试仪可以独立于封盖设备分析各种不同的容器密封系统。使用残余密封力测试仪以及计算机断层扫描和泄漏测试等其他方法，可以为每个容器密封系统配置建立适当且安全的残余密封力范围。在所研究的残余密封力范围内，容器密封系统的物理容器密封完整性是有保证的。
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