Automated and Rapid Methods to Assess Quality & Stability of Biologies: Recent Developments and Practical Ways to Implement Them in Formulation Development

摘要

Therapeutic proteins are challenging to develop and manufacture because their marginal stability makes them prone to denaturation and aggregation during purification, storage, distribution, and administration. While there is an absence of a definitive strategy that can prevent these instabilities against all forms of stress, we are at the dawn of a new era with the emergence of new analytical tools that can enable both prediction and real-time monitoring of protein stability. These tools not only have low sample requirements but also generate highly precise and reproducible data that can be effectively implemented in an advanced Design of Experiments (DOE) approach employing a multivariate response-surface design space. In this article, the author uses a real case study using an IgG 1 antibody to illustrate how to properly combine some of these new high-throughput tools with a novel approach to formulation development that considers the key factors/forces that impact physical stability of proteins in solution. Emphasis will be placed on high-throughput, low sample requirement strategies that are useful for industrial application.