Dinesh Palanivelu,
Biocon Research Centre, Bangalore, India
Title: Evolution of Structure-Function paradigm in Biopharmaceutics based on Global Regulatory Needs
Biography
Biography: Dinesh Palanivelu,
Abstract
Protein biopharmaceuticals become a major focus in biotechnology industry for treating various life-threatening diseases. Unraveling their structural complexity represents an biggest analytical challenge. In past decade, the state-of-the-art analytical tools have been developed to dissect primary and higher order structures, PTM modifications, purity and impurity profiles and pharmacokinetic properties to provide Structure-Activity Relationship (SAR), specifically in the field of biosimilars1. Biosimilars are defined as follow-on-biologics that have been shown to have comparable quality, safety, and efficacy to the innovator products. Regulatory approval for a biosimilar version is provided on the basis of its comparability to an innovator product2. The complexity of the manufacturing process, analytical methods, structural heterogenity and the possibility of severe immunogenicity reactions makes evaluation of similarity between an innovator and the biosimilar version a great challenge for the scientific community and regulatory agencies3.
Biosimilar development involves an iterative target-directed approach, driven by thorough understanding of the structure and its biological function of a target molecule. This includes understanding batch-to-batch consistency, stability, and whether variants or aggregates can be linked to safety and efficacy4. The role of Higher-Order-Structure (HOS) has become a major investigation tool for establishing Structure-Function relationship. Differences in HOS provides potential clues to any observed biological and/or immunological differences between proteins and variant forms. What is required to integrate HOS into existing biopharmaceutical processes? Will doing so prove worth the cost, time, and effort?
Here, we present the pleothera of HOS tools designed for biosimilar programs to understand the purity and impurity profiles to establish its SAR across several orthogonal analytical methods. Extensive HOS characterization datasets adds value to the totalilty of evidence which helps the regulatory agencies in the decision making process. In summary, the paradigm shift in structure-function relationship is the current requirement for global regulatory approvals for biosimilars.