title: Pharmacokinetic Comparability of a Biosimilar Trastuzumab Anticipated from Its Physicochemical and Biological Characterization.
abstract: Comparability between a biosimilar and its reference product requires the evaluation of critical quality attributes that may impact on its pharmacological response. Herein we present a physicochemical characterization of a biosimilar trastuzumab focused on the attributes related to the pharmacokinetic response. Capillary isoelectrofocusing (cIEF) and cation exchange chromatography (CEX) were used to evaluate charge heterogeneity; glycosylation profiles were assessed through hydrophilic interaction liquid chromatography (HILIC); aggregates content was evaluated through size exclusion chromatography (SEC) while binding affinity to FcRn was evaluated using isothermal titration calorimetry (ITC). The biosimilar trastuzumab and its reference product exhibited a high degree of similarity for the evaluated attributes. In regard to the pharmacokinetic parameters, randomized, double blind, and two-arm parallel and prospective study was employed after the administration of a single intravenous dose in healthy volunteers. No significant differences were found between the pharmacokinetic profiles of both products. Our results confirm that similarity of the critical quality attributes between a biosimilar product, obtained from a different manufacturing process, and the reference product resulted in comparable pharmacokinetic profiles, diminishing the uncertainty related to the biosimilar's safety and efficacy.
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Mariana P
authors.initials: MP
authors.lastname: Miranda-Hernández
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: López-Morales
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Nelly
authors.initials: N
authors.lastname: Piña-Lara
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Francisco C
authors.initials: FC
authors.lastname: Perdomo-Abúndez
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Néstor O
authors.initials: NO
authors.lastname: Pérez
authors.affiliation: Dirección Médica, Probiomed S.A. de C.V., Avenue Ejército Nacional No. 499, Colonia Granada, Delegación Miguel Hidalgo, 11520 México, D.F., Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Revilla-Beltri
authors.affiliation: Dirección Médica, Probiomed S.A. de C.V., Avenue Ejército Nacional No. 499, Colonia Granada, Delegación Miguel Hidalgo, 11520 México, D.F., Mexico.
authors.forename: Aarón
authors.initials: A
authors.lastname: Molina-Pérez
authors.affiliation: Laboratorios Clínicos, Puebla de Bioequivalencia, S.A. de C.V., Boulevard Díaz Ordaz No. 808, 72530 Puebla, PUE, Mexico.
authors.forename: Larisa
authors.initials: L
authors.lastname: Estrada-Marín
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Flores-Ortiz
authors.affiliation: Laboratorios Clínicos, Puebla de Bioequivalencia, S.A. de C.V., Boulevard Díaz Ordaz No. 808, 72530 Puebla, PUE, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Ruiz-Argüelles
authors.affiliation: Unidad de Investigación y Desarrollo, Probiomed S.A. de C.V. Cruce de carreteras Acatzingo-Zumpahuacán, 52400 Tenancingo, MEX, Mexico.
authors.forename: Emilio
authors.initials: E
authors.lastname: Medina-Rivero
mesh_terms: D000293:Adolescent; D000328:Adult; D059451:Biosimilar Pharmaceuticals / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068878:Trastuzumab / Q000502:physiology*; D055815:Young Adult
chemical_list: D059451:Biosimilar Pharmaceuticals; D000068878:Trastuzumab