title: Comparability assessments of process and product changes made during development of two different monoclonal antibodies.
abstract: To assess the impact of manufacturing changes on antibody structure and function during the course of product development, three comparability studies were performed for each of two different IgG1 monoclonal antibody product candidates. Comparability study #1 evaluated the effect of changing the cell line and bulk drug substance manufacturing process for cell culture and purification. Results indicated that these process changes led to differences in sialylation of N-glycans and/or C-terminal lysine levels. Comparability study #2 results confirmed that scale-up of the bulk process and transfer to the commercial site, combined with changing from a lyophilized to a liquid dosage form, did not impact the structural or functional integrity of the antibodies. Comparability study #3 examined possible differences arising when the liquid formulation filled into pre-filled syringes and vials. Results indicated nearly identical molecular structure, biological activity, and degradation profiles except for a small yet statistically significant increase in the levels of subvisible particles in pre-filled syringes. These results from comparability studies with two different monoclonal antibodies are discussed with respect to the timing of the manufacturing changes and overall comparability strategies to assure safety and efficacy during development.
authors.affiliation: Pharmaceutical Development and Manufacturing Sciences, Janssen Pharmaceutical Companies of Johnson & Johnson, 145 King of Prussia Road, Radnor, PA 19087, USA. tlubinie@its.jnj.com
authors.forename: Anthony
authors.initials: A
authors.lastname: Lubiniecki
authors.forename: David B
authors.initials: DB
authors.lastname: Volkin
authors.forename: Marcia
authors.initials: M
authors.lastname: Federici
authors.forename: Michael D
authors.initials: MD
authors.lastname: Bond
authors.forename: Michael L
authors.initials: ML
authors.lastname: Nedved
authors.forename: Linda
authors.initials: L
authors.lastname: Hendricks
authors.forename: Promod
authors.initials: P
authors.lastname: Mehndiratta
authors.forename: Mark
authors.initials: M
authors.lastname: Bruner
authors.forename: Sudhir
authors.initials: S
authors.lastname: Burman
authors.forename: Paul
authors.initials: P
authors.lastname: Dalmonte
authors.forename: Jane
authors.initials: J
authors.lastname: Kline
authors.forename: Alex
authors.initials: A
authors.lastname: Ni
authors.forename: Mark E
authors.initials: ME
authors.lastname: Panek
authors.forename: Bill
authors.initials: B
authors.lastname: Pikounis
authors.forename: Gordon
authors.initials: G
authors.lastname: Powers
authors.forename: Omid
authors.initials: O
authors.lastname: Vafa
authors.forename: Rich
authors.initials: R
authors.lastname: Siegel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004345:Drug Industry / Q000379:methods / Q000592:standards*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D020014:K562 Cells; D011485:Protein Binding; D017452:Receptors, IgG / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods / Q000592:standards*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D017452:Receptors, IgG