TY - JOUR
T1 - Pharmacokinetic Comparability of a Biosimilar Trastuzumab Anticipated from Its Physicochemical and Biological Characterization
AU - Miranda-Hernández, Mariana P.
AU - López-Morales, Carlos A.
AU - Piña-Lara, Nelly
AU - Perdomo-Abúndez, Francisco C.
AU - Pérez, Néstor O.
AU - Revilla-Beltri, Jorge
AU - Molina-Pérez, Aarón
AU - Estrada-Marín, Larisa
AU - Flores-Ortiz, Luis F.
AU - Ruiz-Argüelles, Alejandro
AU - Medina-Rivero, Emilio
N1 - Publisher Copyright:
© 2015 Mariana P. Miranda-Hernández et al.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84948780993&partnerID=8YFLogxK
U2 - 10.1155/2015/874916
DO - 10.1155/2015/874916
M3 - Artículo
SN - 2314-6133
VL - 2015
JO - BioMed Research International
JF - BioMed Research International
M1 - 874916
ER -