Implementation of machine learning tool for continued process verification of process chromatography unit operation.

Recent advancements in technology, such as the emergence of artificial intelligence (AI) and machine learning (ML), have facilitated the progression of the biopharmaceutical industry toward the implementation of Industry 4.0. As per the guidelines set by the USFDA, process validation for biopharmaceutical production consists of three stages: process design, process qualification, and continuous process verification (CPV).

Development of a novel capture step for purification of antigen binding fragments (Fabs).

Antigen binding fragments (Fabs) are an emerging class of biotherapeutics, widely accepted as an alternative to the traditional monoclonal antibodies (mAbs). The small size of the Fabs offers better tissue penetrability and lack of Fc region, thereby resulting in reduced side effects. However, since Fab molecules lack Fc region, Protein A chromatography (the ubiquitous capture step in mAb platforms) cannot be employed.

Development of continuous processing platform utilizing aqueous two-phase extraction for purification of monoclonal antibodies.

Monoclonal antibody downstream processing typically entails chromatography-based purification processes beginning with Protein A chromatography, accounting for 50 % of the total manufacturing expense. Alternatives to protein A chromatography have been explored by several researchers. In this paper, aqueous two-phase extraction (ATPE) has been proposed for continuous processing of monoclonal antibodies (mAbs) as an alternative to the traditional protein A chromatography.

A novel method for continuous chromatographic separation of monoclonal antibody charge variants by combining displacement mode chromatography and step elution.

Charge heterogeneity of monoclonal antibodies is considered a critical quality attribute and hence needs to be monitored and controlled by the manufacturer. Typically, this is accomplished via separation of charge variants on cation exchange chromatography (CEX) using a pH or conductivity based linear gradient elution. Although an effective approach, this is challenging particularly during continuous processing as creation of linear gradient during continuous processing adds to process complexity and can lead to deviations in product quality upon slightest changes in gradient formation.

Refolding of Proteins Expressed as Inclusion Bodies in E. coli.

Microbial-based biotherapeutics that are produced in Escherichia coli (E. coli) can be generated intracellularly in the form of inclusion bodies (IBs) or in soluble active form in periplasmic space or extracellularly. Overexpression of these biotherapeutics in E.