Physicochemical and Biological Characterization of a Biosimilar Trastuzumab

Abstract

According to the World Health Organization, the incidence of malignant neoplasms and endocrine, blood, and immune disorders will increase in the upcoming decades along with the demand of affordable treatments. In response to this need, the development of biosimilar drugs is increasing worldwide. The approval of biosimilars relies on the compliance with international guidelines, starting with the demonstration of similarity in their physicochemical and functional properties against the reference product. Subsequent clinical studies are performed to demonstrate similar pharmacological behavior and to diminish the uncertainty related to their safety and efficacy. Herein we present a comparability exercise between a biosimilar trastuzumab and its reference product, by using a hierarchical strategy with an orthogonal approach, to assess the physicochemical and biological attributes with potential impact on its pharmacokinetics, pharmacodynamics, and immunogenicity. Our results showed that the high degree of similarity in the physicochemical attributes of the biosimilar trastuzumab with respect to the reference product resulted in comparable biological activity, demonstrating that a controlled process is able to provide consistently the expected product. These results also constitute the basis for the design of subsequent delimited pharmacological studies, as they diminish the uncertainty of exhibiting different profiles.

Conformational characterization of a novel anti-HER2 candidate antibody

“…The intensity of the Trp absorption signal for this mAb was comparable to Herceptin, although small differences for the Tyr and Phe residues were observed. These results are in correspondence with obtained by other authors for Herceptin [9].…”

“…In fact, the national health system of Cuba acquires this product at a high price in the international market (US $ 30,000 the treatment of one patient per year), which means that the number of patients who can obtain this benefit is limited [8]. The approval of biosimilar molecules has been recognized not only as an alternative, but also as a necessity to increase health coverage and improve the quality of life of cancer patients [9].…”

A phase I dose-escalation study of a biosimilar trastuzumab in Chinese metastasis breast cancer patients

“…More and more accumulative data from the different clinical trials demonstrate the efficacy of trastuzumab among the patients with HER2 overexpression. Since the patent exclusivity rights for trastuzumab has expired in Europe and will lose in the United Stated in 2019, a number of biosimilars trastuzumab are undergoing the preclinical and clinical trials in different countries (Yin et al 2014 ; Lopez-Morales et al 2015 ; Wisman et al 2014 ; Akbarzadeh-Sharbaf et al 2012 ), and their pharmacokinetic features, efficacy and pharmacovigilance issues are arousing greater attention (Thill 2015 ; Cortes et al 2014 ). We demonstrated the phase I data which finished over the past 10 years since the phase III data have just been achieved and the manufacturer approved to release the study data.…”

Scientific and Regulatory Perspective on Monoclonal Antibody Biosimilars

“…For the development of analytical methods, the information of the analytical limitations, like specificity in each analytical technique should be known by the manufactures. The characteristics including physicochemical, biological, and other related properties (e.g., impurities, finished products, and specification) are analyzed by the head-to-head comparative studies [27][28][29][30]. For mAb analysis, the common characteristics and analytical methods to ensure product quality are provided in Table 1, and these analytical items could also be applied to the comparative study of biosimilar mAbs and reference mAbs [5].…”