PT  - JOURNAL ARTICLE
AU  - Jakob Buecheler
AU  - Joerg Luemkemann
AU  - Henning Gieseler
AU  - Silke Mohl
AU  - Alexander Streubel
TI  - Residual Seal Force (RSF) Testing: A Suitable Method for Seal Quality Determination also for High Potent Parenterals
AID  - 10.5731/pdajpst.2018.008870
DP  - 2018 Jan 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - pdajpst.2018.008870
4099  - http://journal.pda.org/content/early/2018/10/23/pdajpst.2018.008870.short
4100  - http://journal.pda.org/content/early/2018/10/23/pdajpst.2018.008870.full
AB  - The capping of vials plays a critical role in drug product manufacturing process due to its complex interplay of several adjustable process steps. Seal quality, integrity and assurance of containment is essential for parenteral pharmaceuticals as the vial’s content may be contaminated, or in case of highly potent drugs (e.g. antibody drug conjugates) may bear a risk of contamination. The residual seal force (RSF) method can enable further insight in capping equipment settings independently of the container closure system (CCS) and their resulting seal quality. The present study investigates the accuracy of the RSF method focusing on different force settings, RSF development over time, distance between capping plates and vial neck (roller-axis), time point of flip-off button removal and internal and external vial pressure differences (flight simulation and vials closed under vacuum). Results show that the forces used on a RSF tester should be kept low to minimize deformation of the CCS and a period of stable RSF values after the initial decrease should be implemented between capping and RSF measurement to increase accuracy. Variations in the distance between the capping plates and vial neck (roller-axis) can result in incomplete crimps, or visual defects of the seals. Additionally, the time point of removal of the flip-off button as part of the sample preparation had no significant impact on RSF measurements. Finally, pressure differences between the vial interior and exterior had no significant impact on the RSF data.