title: Bioanalytical strategy used in development of pharmacokinetic (PK) methods that support biosimilar programs.
abstract: The development of biosimilar products is expected to grow rapidly over the next five years as a large number of approved biologics reach patent expiry. The pathway to regulatory approval requires that similarity of the biosimilar to the reference product be demonstrated through physiochemical and structural characterization, as well as within in vivo studies that compare the safety and efficacy profiles of the products. To support nonclinical and clinical studies pharmacokinetic (PK) assays are required to measure the biosimilar and reference products with comparable precision and accuracy. The most optimal approach is to develop a single PK assay, using a single analytical standard, for quantitative measurement of the biosimilar and reference products in serum matrix. Use of a single PK assay for quantification of multiple products requires a scientifically sound testing strategy to evaluate bioanalytical comparability of the test products within the method, and provide a solid data package to support the conclusions. To meet these objectives, a comprehensive approach with scientific rigor was applied to the development and characterization of PK assays that are used in support of biosimilar programs. Herein we describe the bioanalytical strategy and testing paradigm that has been used across several programs to determine bioanalytical comparability of the biosimilar and reference products. Data from one program is presented, with statistical results demonstrating the biosimilar and reference products were bioanalytically equivalent within the method. The cumulative work has established a framework for future biosimilar PK assay development.
authors.affiliation: a Department of Pharmacokinetics and Drug Metabolism ; Amgen Inc. ; USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Colbert
authors.forename: Amber
authors.initials: A
authors.lastname: Umble-Romero
authors.forename: Samantha
authors.initials: S
authors.lastname: Prokop
authors.forename: Vincent Fung-Sing
authors.initials: VF
authors.lastname: Chow
authors.forename: Teresa
authors.initials: T
authors.lastname: Wong
authors.forename: Danielle
authors.initials: D
authors.lastname: DeSimone
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Susan
authors.initials: S
authors.lastname: Pederson
mesh_terms: D000818:Animals; D001688:Biological Products / Q000097:blood / Q000493:pharmacokinetics* / Q000592:standards; D059451:Biosimilar Pharmaceuticals / Q000097:blood / Q000493:pharmacokinetics* / Q000592:standards; D055808:Drug Discovery / Q000379:methods; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D011786:Quality Control; D012015:Reference Standards; D013678:Technology, Pharmaceutical / Q000379:methods*; D013810:Therapeutic Equivalency
chemical_list: D001688:Biological Products; D059451:Biosimilar Pharmaceuticals
keywords: ART, ambient room temperature; Avg, Average; BE, bioequivalence; BQL, Below the Quantification Limit; CV, Coefficient of Variation; ECL, Electrochemiluminescent; LLOQ, Lower Limit of Quantification; MRD, minimum required dilution; MSD, Meso Scale Discovery; PD, pharmacodynamics; PK, pharmacokinetic; TPA, Tripropylamine; ULOQ, Upper Limit of Quantification; bioanalytical; biosimilar; biotherapeutics; comparability; pharmacodynamics; pharmacokinetic; recombinant