title: Development of a quantitative mass spectrometry multi-attribute method for characterization, quality control testing and disposition of biologics.
abstract: Regulatory agencies have recently recommended a Quality by Design (QbD) approach for the manufacturing of therapeutic molecules. A QbD strategy requires deep understanding at the molecular level of the attributes that are crucial for safety and efficacy and for insuring that the desired quality of the purified protein drug product is met at the end of the manufacturing process. A mass spectrometry (MS)-based approach to simultaneously monitor the extensive array of product quality attributes (PQAs) present on therapeutic molecules has been developed. This multi-attribute method (MAM) uses a combination of high mass accuracy / high resolution MS data generated by Orbitrap technology and automated identification and relative quantification of PQAs with dedicated software (Pinpoint). The MAM has the potential to replace several conventional electrophoretic and chromatographic methods currently used in Quality Control to release therapeutic molecules. The MAM represents an optimized analytical solution to focus on the attributes of the therapeutic molecule essential for function and implement QbD principles across process development, manufacturing and drug disposition.
authors.affiliation: a Analytical Sciences; Amgen Inc. ; Seattle , WA USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Rogers
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Nightlinger
authors.forename: Brittney
authors.initials: B
authors.lastname: Livingston
authors.forename: Phil
authors.initials: P
authors.lastname: Campbell
authors.forename: Robert
authors.initials: R
authors.lastname: Bailey
authors.forename: Alain
authors.initials: A
authors.lastname: Balland
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D001688:Biological Products / Q000592:standards*; D002846:Chromatography, Affinity; D002853:Chromatography, Liquid; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010449:Peptide Mapping / Q000379:methods*; D011499:Protein Processing, Post-Translational; D011786:Quality Control; D012984:Software; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D001688:Biological Products
keywords: monoclonal antibody; multi-attribute method (MAM); peptide map; product quality attributes; quality by design