title: Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels.
abstract: Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product.
authors.affiliation: Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.
authors.forename: Craig
authors.initials: C
authors.lastname: Zupke
authors.affiliation: Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.
authors.forename: Lowell J
authors.initials: LJ
authors.lastname: Brady
authors.affiliation: Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Slade
authors.affiliation: Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.
authors.forename: Philip
authors.initials: P
authors.lastname: Clark
authors.affiliation: Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.
authors.forename: R Guy
authors.initials: RG
authors.lastname: Caspary
authors.affiliation: Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.
authors.forename: Brittney
authors.initials: B
authors.lastname: Livingston
authors.affiliation: Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.
authors.forename: Lisa
authors.initials: L
authors.lastname: Taylor
authors.affiliation: Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.
authors.forename: Kyle
authors.initials: K
authors.lastname: Bigham
authors.affiliation: Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.
authors.forename: Arvia E
authors.initials: AE
authors.lastname: Morris
authors.affiliation: Product and Process Development, Amgen Inc., 1201 Amgen Court West, Seattle, WA, 98119.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Bailey
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D016466:CHO Cells; D003412:Cricetulus; D006801:Humans; D008956:Models, Chemical; D017711:Nonlinear Dynamics; D010865:Pilot Projects; D011134:Polysaccharides / Q000737:chemistry*; D011786:Quality Control
chemical_list: D000906:Antibodies; D011134:Polysaccharides
keywords: % high mannose; control lever; critical quality attributes (CQA); glycosylation; mannose; quality by design (QbD)