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.
Highlights
Biopharmaceutical products containing chimeric, humanized, or fully human monoclonal antibodies are among the most successful and demanded therapies due to their highly specific mechanisms of action that result in an improvement of the patients’ conditions and an increase in the survival rate, while minimizing the adverse side-effects when compared to other treatments [1]
Higher order structure was evaluated by differential scanning calorimetry (DSC), circular dichroism (CD), and fluorescence lifetime using the time correlated single photon counting technique (TCSPC)
critical quality attributes (CQAs) were identified using a risk analysis, considering each of the physicochemical and functional properties that may have an impact on efficacy and safety of trastuzumab (Table 1) [9,10,11,12,13,14,15,16,17]
Summary
Biopharmaceutical products containing chimeric, humanized, or fully human monoclonal antibodies (mAbs) are among the most successful and demanded therapies due to their highly specific mechanisms of action that result in an improvement of the patients’ conditions and an increase in the survival rate, while minimizing the adverse side-effects when compared to other treatments [1]. New manufacturing sites, process scale-ups as well as process improvements contribute to the well-known heterogeneity, naturally present in biotherapeutic products. For this purpose, the ICH Q5 E guideline provides the principles for assessing comparability of licensed biotechnological products subject to process changes throughout their life cycle [2]. The ICH Q5 E guideline provides the principles for assessing comparability of licensed biotechnological products subject to process changes throughout their life cycle [2] In this sense, the approval of biosimilar products, which have been recognized as an alternative but as a necessity to increase health coverage and improve the quality of life of patients, follows a similar comparability scheme. International guidelines on biosimilarity [3,4,5] outline that the approval of biosimilars must rely on the demonstration of comparability towards the reference product, starting with an exhaustive physicochemical and biological characterization whose results will provide evidence to support the extent of additional clinical evaluation [6,7,8].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
