Manufacturing of Recombinant Proteins Using Quality by Design (QbD) Methodology: Current Trend and Challenges

Since the introduction in 2009, the Quality by Design (QbD) is a methodology widely used in the development of therapeutic proteins. The fundamental concept of QbD is that the development of a therapeutic protein starts with the comprehensive understanding of the target product profile in terms of identity, strength, quality, purity, and potency. The manufacturing is then designed to ensure the product produced from the designed process meet the target product profile consistently and reproducible matter. Presently, all marketing application for therapeutic proteins submitted to FDA or EU regulatory agencies require the QbD methodology implemented during their product development and manufacturing stages. Despite of its effectiveness and regulatory requirements, the implementation of QbD concept in its entirety has been limited due to (1) insufficient time to fully characterize the target protein profile in the beginning of development process, (2) complexity of input and output parameters prohibiting the full design of experiments, and (3) challenges in collecting and analyzing the end-to-end product and manufacturing data. In order to overcome those challenges, many efforts are on-going with the most noticeable progress made in the advanced data analytics and machine learning perspective.