title: The Pharmaceutical Capping Process-Correlation between Residual Seal Force, Torque Moment, and Flip-off Removal Force.
abstract: The majority of parenteral drug products are manufactured in glass vials with an elastomeric rubber stopper and a crimp cap. The vial sealing process is a critical process step during fill-and-finish operations, as it defines the seal quality of the final product. Different critical capping process parameters can affect rubber stopper defects, rubber stopper compression, container closure integrity, and also crimp cap quality. A sufficiently high force to remove the flip-off button prior to usage is required to ensure quality of the drug product unit by the flip-off button during storage, transportation, and until opening and use. Therefore, the final product is 100% visually inspected for lose or defective crimp caps, which is subjective as well as time- and labor-intensive. In this study, we sealed several container closure system configurations with different capping equipment settings (with corresponding residual seal force values) to investigate the torque moment required to turn the crimp cap. A correlation between torque moment and residual seal force has been established. The torque moment was found to be influenced by several parameters, including diameter of the vial head, type of rubber stopper (serum or lyophilized) and type of crimp cap (West(®) or Datwyler(®)). In addition, we measured the force required to remove the flip-off button of a sealed container closure system. The capping process had no influence on measured forces; however, it was possible to detect partially crimped vials. In conclusion, a controlled capping process with a defined target residual seal force range leads to a tight crimp cap on a sealed container closure system and can ensure product quality.
  The majority of parenteral drug products are manufactured in a glass vials with an elastomeric rubber stopper and a crimp cap. The vial sealing process is a critical process step during fill-and-finish operations, as it defines the seal quality of the final product. An adequate force to remove the flip-off button prior to usage is required to ensure product quality during storage and transportation until use. In addition, the complete crimp cap needs to be fixed in a tight position on the vial. In this study, we investigated the torque moment required to turn the crimp cap and the force required to remove the flip-off button of container closure system sealed with different capping equipment process parameters (having different residual seal force values).
authors.affiliation: Pharmaceutical Development & Supplies, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland; roman.mathaes@lonza.com.
authors.forename: Roman
authors.initials: R
authors.lastname: Mathaes
authors.affiliation: Pharmaceutical Development & Supplies, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
authors.affiliation: Device Development, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Lothar
authors.initials: L
authors.lastname: Vorgrimler
authors.affiliation: Device Development, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Henrik
authors.initials: H
authors.lastname: Steinberg
authors.affiliation: Device Development, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Sascha
authors.initials: S
authors.lastname: Dreher
authors.affiliation: Complaints and Counterfeits, Quality Control for Commercial Bulk Products, F.Hoffmann-La Roche Ltd., Kaiseraugst, Switzerland;
authors.forename: Yves
authors.initials: Y
authors.lastname: Roggo
authors.affiliation: Pharmaceutical Development & Supplies, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Alejandra
authors.initials: A
authors.lastname: Nieto
authors.affiliation: Pharmaceutical Development & Supplies, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Helen
authors.initials: H
authors.lastname: Brown
authors.affiliation: Pharmaceutical Development & Supplies, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Holger
authors.initials: H
authors.lastname: Roehl
authors.affiliation: Pharmaceutical Development & Supplies, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Michael
authors.initials: M
authors.lastname: Adler
authors.affiliation: Pharmaceutical Development & Supplies, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Joerg
authors.initials: J
authors.lastname: Luemkemann
authors.affiliation: Department of Pharmaceutical Technologies, University Basel, Switzerland; and.
authors.forename: Joerg
authors.initials: J
authors.lastname: Huwyler
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, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Silke
authors.initials: S
authors.lastname: Mohl
authors.affiliation: Pharmaceutical Development & Supplies, Technical Development Biologics Europe, F.Hoffmann-La Roche Ltd., Basel, Switzerland;
authors.forename: Alexander
authors.initials: A
authors.lastname: Streubel
mesh_terms: D004349:Drug Packaging / Q000295:instrumentation / Q000379:methods*; D005898:Glass / Q000592:standards*; D057947:Parenteral Nutrition Solutions / Q000592:standards; D012408:Rubber / Q000592:standards*; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D019415:Torque
chemical_list: D057947:Parenteral Nutrition Solutions; D012408:Rubber
keywords: Capping; Container closure system (CCS); Crimp cap; Crimping; Flip-off removal; Process control; Residual seal force (RSF); Torque moment