title: Evaluating imbalances of adverse events during biosimilar development.
abstract: Biosimilars are designed to be highly similar to approved or licensed (reference) biologics and are evaluated based on the totality of evidence from extensive analytical, nonclinical and clinical studies. As part of the stepwise approach recommended by regulatory agencies, the first step in the clinical evaluation of biosimilarity is to conduct a pharmacokinetics similarity study in which the potential biosimilar is compared with the reference product. In the context of biosimilar development, a pharmacokinetics similarity study is not necessarily designed for a comparative assessment of safety. Development of PF-05280014, a potential biosimilar to trastuzumab, illustrates how a numerical imbalance in an adverse event in a small pharmacokinetics study can raise questions on safety that may require additional clinical trials.
authors.affiliation: a Pfizer Inc , San Diego , CA , USA.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Vana
authors.affiliation: d Pfizer Inc , Cambridge , MA , USA.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Freyman
authors.affiliation: c Pfizer Inc., at the time of study conduct, Clinical Research and Development Consultant , Del Mar , CA , USA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Reich
authors.affiliation: a Pfizer Inc , San Diego , CA , USA.
authors.forename: Donghua
authors.initials: D
authors.lastname: Yin
authors.affiliation: d Pfizer Inc , Cambridge , MA , USA.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Li
authors.affiliation: a Pfizer Inc , San Diego , CA , USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Anderson
authors.affiliation: b Pfizer Inc , New York , NY , USA.
authors.forename: Ira A
authors.initials: IA
authors.lastname: Jacobs
authors.affiliation: d Pfizer Inc , Cambridge , MA , USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Zacharchuk
authors.affiliation: d Pfizer Inc , Cambridge , MA , USA.
authors.forename: Reginald
authors.initials: R
authors.lastname: Ewesuedo
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D059451:Biosimilar Pharmaceuticals / Q000009:adverse effects*; D017321:Clinical Trials, Phase I as Topic; D004311:Double-Blind Method; D017277:Drug Approval; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D059451:Biosimilar Pharmaceuticals; C000598430:PF-05280014
keywords: Biosimilar; HER2; breast cancer; safety; trastuzumab