title: Consistent manufacturing and quality control of a highly complex recombinant polyclonal antibody product for human therapeutic use.
abstract: The beneficial effect of antibody therapy in human disease has become well established mainly for the treatment of cancer and immunological disorders. The inherent monospecificity of mAbs present limitations to mAb therapy which have become apparent notably in addressing complex entities like infectious agents or heterogenic endogenous targets. For such indications mixtures of antibodies comprising a combination of specificities would convey more potent biological effect which could translate into therapeutic efficacy. Recombinant polyclonal antibodies (rpAb) consisting of a defined number of well-characterized mAbs constitute a new class of target specific antibody therapy. We have developed a cost-efficient cell banking and single-batch manufacturing concept for the production of such products and demonstrate that a complex pAb composition, rozrolimupab, comprising 25 individual antibodies can be manufactured in a highly consistent manner in a scaled-up manufacturing process. We present a strategy for the release and characterization of antibody mixtures which constitute a complete series of chemistry, manufacturing, and control (CMC) analytical methods to address identity, purity, quantity, potency, and general characteristics. Finally we document selected quality attributes of rozrolimupab based on a battery of assays at the genetic-, protein-, and functional level and demonstrate that the manufactured rozrolimupab batches are highly pure and very uniform in their composition.
authors.affiliation: Symphogen A/S, Elektrovej Building 375, 2800 Lyngby, Denmark.
authors.forename: Torben P
authors.initials: TP
authors.lastname: Frandsen
authors.forename: Henrik
authors.initials: H
authors.lastname: Naested
authors.forename: Søren K
authors.initials: SK
authors.lastname: Rasmussen
authors.forename: Peter
authors.initials: P
authors.lastname: Hauptig
authors.forename: Finn C
authors.initials: FC
authors.lastname: Wiberg
authors.forename: Lone Kjaer
authors.initials: LK
authors.lastname: Rasmussen
authors.forename: Anne Marie Valentin
authors.initials: AM
authors.lastname: Jensen
authors.forename: Pia
authors.initials: P
authors.lastname: Persson
authors.forename: Margareta
authors.initials: M
authors.lastname: Wikén
authors.forename: Anders
authors.initials: A
authors.lastname: Engström
authors.forename: Yun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Thorpe
authors.forename: Cecilia
authors.initials: C
authors.lastname: Förberg
authors.forename: Anne B
authors.initials: AB
authors.lastname: Tolstrup
mesh_terms: D001709:Biotechnology / Q000379:methods / Q000592:standards*; D002460:Cell Line; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000737:chemistry / Q000627:therapeutic use; D011786:Quality Control; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000627:therapeutic use; D015203:Reproducibility of Results
chemical_list: D007074:Immunoglobulin G; D011994:Recombinant Proteins; C558236:rozrolimupab