title: The pharmaceutical vial capping process: Container closure systems, capping equipment, regulatory framework, and seal quality tests.
abstract: Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process. In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process.
authors.affiliation: Pharmaceutical Development & Supplies, Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland. Electronic address: 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: Pharmaceutical Development & Supplies, Technical Development Biologics Europe, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Buettiker
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 Processing and Technical Development, Genentech Inc., USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lam
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: Joerg
authors.initials: J
authors.lastname: Luemkemann
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 Technologies, University Basel, Switzerland.
authors.forename: Joerg
authors.initials: J
authors.lastname: Huwyler
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
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
mesh_terms: D004349:Drug Packaging / Q000295:instrumentation / Q000379:methods*; D008420:Manufactured Materials / Q000592:standards; D008422:Materials Testing / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D057947:Parenteral Nutrition Solutions / Q000737:chemistry / Q000592:standards
chemical_list: D057947:Parenteral Nutrition Solutions
keywords: Capping; Container closure integrity; Crimping; Process control; Residual seal force