title: Lyophilization cycle development for a high-concentration monoclonal antibody formulation lacking a crystalline bulking agent.
abstract: An efficient freeze-dry cycle was developed for a high concentration monoclonal antibody formulation lacking a crystalline bulking agent. The formulation, at multiple protein concentrations, was characterized using differential scanning calorimetry (DSC) and freeze-dry microscopy. At low protein concentrations the glass transition temperature of the maximally freeze-concentrated solution (T(g)') determined by DSC was similar to the collapse temperature determined by freeze-dry microscopy. However, at higher protein concentrations, the difference between collapse temperature and T(g)' became progressively larger. The difference between the onset temperature for collapse and the complete collapse temperature also became progressively larger as protein concentration increased. JMP Design of Experiment studies were used to assess the effect of freezing rate, primary drying shelf temperature, and chamber pressure on primary drying product temperature, length of primary drying, and product quality attributes. Primary drying was shortened significantly by adjusting to conditions where the product temperature substantially exceeded T(g)' without any apparent detrimental effect to the product.
authors.affiliation: Human Genome Sciences, Inc., Department of Pharmaceutical Sciences, 14200 Shady Grove Road, Rockville, Maryland 20850, USA. james_colandene@hgsi.com
authors.forename: James D
authors.initials: JD
authors.lastname: Colandene
authors.forename: Linda M
authors.initials: LM
authors.lastname: Maldonado
authors.forename: Alma T
authors.initials: AT
authors.lastname: Creagh
authors.forename: John S
authors.initials: JS
authors.lastname: Vrettos
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Goad
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Spitznagel
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D005612:Freeze Drying; D008853:Microscopy; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000911:Antibodies, Monoclonal