Different Strategies to Make Biobetters: Physicochemical, Pharmacodynamics, and Pharmacokinetic Aspects Came Into Focus Publisher Pubmed



Pishgahzadeh E ; Bozorgchami N ; Talebi M ; Masoudifar R ; Ahmadi M ; Ghorbanibidkorpeh F
Source: International Journal of Pharmaceutics Published:2025

Abstract

Technological advancements in the discovery/development of biological products have led to significant improvements in both products and processes, resulting in more effective medications. Biological medications, or biopharmaceuticals, whose patents have expired, present a substantial opportunity for the development of biosimilars, biobetters, and subsequent iterations of biological drugs. Interest in biological drugs has surged, primarily because of their potential to address diseases that conventional synthetic drugs inadequately manage. These pathological conditions include cancer, diabetes, ophthalmic disorders, arthritis, Alzheimer's disease, hemophilia, and diseases related to the immune system. Biobetters represent a new category of biopharmaceutical molecules developed through modifications to their molecular profiles. These modifications can be achieved through molecular, chemical, or functional changes. As a result, these enhanced biologics can exhibit significant ameliorations, such as an extended half-life, reduced toxicity and adverse effects, mitigated immunogenic responses, and improved pharmacodynamic properties. The Quality by Design (QbD) approach plays a crucial role in developing biobetters and improved versions of existing protein-based therapeutics. By employing QbD principles, the design of biobetters can be optimized to enhance characteristics such as target epitope affinity, selectivity, and stability against degradation. Given the importance of this topic, this comprehensive review article aims to provide an in-depth examination of various approaches for developing biobetters, with a primary focus on pharmacodynamics and pharmacokinetics. The article begins by clarifying the concepts of biologics, biosimilars, and biobetters before delving into the diverse strategies used in creating biobetters. © 2025 Elsevier B.V., All rights reserved.