title: Impact of Vial Capping on Residual Seal Force and Container Closure Integrity.
abstract: 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.
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Current address: Drug Product Services, Lonza AG, Basel Switzerland roman.mathaes@lonza.com.
authors.forename: Roman
authors.initials: R
authors.lastname: Mathaes
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, Switzerland; Current address: Drug Product Services, Lonza AG, Basel Switzerland.
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.affiliation: Complaints and Counterfeits, Quality Control for Commercial Bulk Products, F. Hoffmann-La Roche Ltd., Basel, Switzerland; and.
authors.forename: Yves
authors.initials: Y
authors.lastname: Roggo
authors.affiliation: Pharmaceutical Processing and Technical Development, Genentech Inc., USA;
authors.forename: Robert
authors.initials: R
authors.lastname: Ovadia
authors.affiliation: Pharmaceutical Processing and Technical Development, Genentech Inc., USA;
authors.forename: Philippe
authors.initials: P
authors.lastname: Lam
authors.affiliation: Pharmaceutical Processing and Technical Development, Genentech Inc., USA;
authors.forename: Oliver
authors.initials: O
authors.lastname: Stauch
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Martin
authors.initials: M
authors.lastname: Vogt
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Holger
authors.initials: H
authors.lastname: Roehl
authors.affiliation: Department of Pharmaceutical Technologies, University Basel, Switzerland;
authors.forename: Joerg
authors.initials: J
authors.lastname: Huwyler
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Silke
authors.initials: S
authors.lastname: Mohl
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Alexander
authors.initials: A
authors.lastname: Streubel
mesh_terms: D019245:Compressive Strength; D004345:Drug Industry / Q000295:instrumentation* / Q000379:methods / Q000592:standards; D004349:Drug Packaging / Q000295:instrumentation* / Q000379:methods / Q000592:standards; D004867:Equipment Design / Q000295:instrumentation* / Q000379:methods / Q000592:standards; D005898:Glass / Q000592:standards; D006801:Humans; D012408:Rubber / Q000592:standards; D054159:Torsion, Mechanical
chemical_list: D012408:Rubber
keywords: Cap; Capping; Container closure integrity; Container closure system; Helium leakage; Process control; Residual seal force; Seal; Stopper; Vial