Downstream process development strategies for effective bioprocesses: Trends, progress, and combinatorial approaches

Abstract

The biopharmaceutical industry is at a turning point moving toward a more customized and patient-oriented medicine (precision medicine). Straightforward routines such as the antibody platform process are extended to production processes for a new portfolio of molecules. As a consequence, individual and tailored productions require generic approaches for a fast and dedicated purification process development. In this article, different effective strategies in biopharmaceutical purification process development are reviewed that can analogously be used for the new generation of antibodies. Conventional approaches based on heuristics and high-throughput process development are discussed and compared to modern technologies such as multivariate calibration and mechanistic modeling tools. Such approaches constitute a good foundation for fast and effective process development for new products and processes, but their full potential becomes obvious in a correlated combination. Thus, different combinatorial approaches are presented, which might become future directions in the biopharmaceutical industry.

Microbioreactor Systems for Accelerated Bioprocess Development

“…This is certainly due to the much higher complexity of such holistic approaches. For further information on recent developments in high‐throughput downstream processing the reader is referred to the following reviews …”

Model‐based monitoring of industrial reversed phase chromatography to predict insulin variants

“…Mechanistic models can be excellent tools for comparing process conditions, such as buffer compositions, salt concentrations or column resins, simulating and screening sequential process units against alternative options and for supporting process decisions, such as pooling decisions . In addition to the capability of mechanistic models in downstream process development, they have also been used for monitoring of biopharmaceuticals and their impurities. For example, monoclonal antibodies and their variants have been modeled in size exclusion chromatography, cation exchange chromatography, and hydrophobic interaction chromatography .…”

“…Mechanistic models can be excellent tools for comparing process conditions, such as buffer compositions, salt concentrations or column resins, [9][10][11] simulating and screening sequential process units against alternative options [12][13][14] and for supporting process decisions, such as pooling decisions. [15][16][17] In addition to the capability of mechanistic models in downstream process development, 18,19 they have also been used for monitoring of biopharmaceuticals and their impurities.…”

A generalized purification step for viral particles using mannitol flocculation

“…While there have been substantial improvements in virus particle purification methods, there still lacks a purification method that is applicable to many different virus particle types and could possibly be adapted into a platform process for multiple viral products. There is a need for a viral particle platform technology that mirrors the antibody revolution of the antibody platform …”