title: Investigating factors leading to fogging of glass vials in lyophilized drug products.
abstract: Vial "Fogging" is a phenomenon observed after lyophilization due to drug product creeping upwards along the inner vial surface. After the freeze-drying process, a haze of dried powder is visible inside the drug product vial, making it barely acceptable for commercial distribution from a cosmetic point of view. Development studies were performed to identify the root cause for fogging during manufacturing of a lyophilized monoclonal antibody drug product. The results of the studies indicate that drug product creeping occurs during the filling process, leading to vial fogging after lyophilization. Glass quality/inner surface, glass conversion/vial processing (vial "history") and formulation excipients, e.g., surfactants (three different surfactants were tested), all affect glass fogging to a certain degree. Results showed that the main factor to control fogging is primarily the inner vial surface hydrophilicity/hydrophobicity. While Duran vials were not capable of reliably improving the level of fogging, hydrophobic containers provided reliable means to improve the cosmetic appearance due to reduction in fogging. Varying vial depyrogenation treatment conditions did not lead to satisfying results in removal of the fogging effect. Processing conditions of the vial after filling with drug product had a strong impact on reducing but not eliminating fogging.
authors.affiliation: Pharmaceutical Development & Supplies, Pharma Technical Development Biologics EU, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Ahmad M
authors.initials: AM
authors.lastname: Abdul-Fattah
authors.forename: Richard
authors.initials: R
authors.lastname: Oeschger
authors.forename: Holger
authors.initials: H
authors.lastname: Roehl
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bauer Dauphin
authors.forename: Martin
authors.initials: M
authors.lastname: Worgull
authors.forename: Georg
authors.initials: G
authors.lastname: Kallmeyer
authors.forename: Hanns-Christian
authors.initials: HC
authors.lastname: Mahler
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004349:Drug Packaging / Q000379:methods*; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods; D005898:Glass / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal
keywords: Cosmetic defect; Fogging of glass vials; Lyophilization; Marangoni effect; Monoclonal antibodies; Solid state characterization; Vial depyrogenation; Vial washing; Visual inspection