Recent Advances and Future Directions in Downstream Processing of Therapeutic Antibodies

Abstract

Despite the advent of many new therapies, therapeutic monoclonal antibodies remain a prominent biologics product, with a market value of billions of dollars annually. A variety of downstream processing technological advances have led to a paradigm shift in how therapeutic antibodies are developed and manufactured. A key driver of change has been the increased adoption of single-use technologies for process development and manufacturing. An early-stage developability assessment of potential lead antibodies, using both in silico and high-throughput experimental approaches, is critical to de-risk development and identify molecules amenable to manufacturing. Both statistical and mechanistic modelling approaches are being increasingly applied to downstream process development, allowing for deeper process understanding of chromatographic unit operations. Given the greater adoption of perfusion processes for antibody production, continuous and semi-continuous downstream processes are being increasingly explored as alternatives to batch processes. As part of the Quality by Design (QbD) paradigm, ever more sophisticated process analytical technologies play a key role in understanding antibody product quality in real-time. We should expect that computational prediction and modelling approaches will continue to be advanced and exploited, given the increasing sophistication and robustness of predictive methods compared to the costs, time, and resources required for experimental studies.

Science and claims of the arena of food bioactives: comparison of drugs, nutrients, supplements, and nutraceuticals

“…11 Again, the latter are highly specific (and often inhibitors in nature). 12 Often, traditional and modern drugs directly or indirectly evolve from the vegetable realm. 13 This is a consequence of the evolutionary interaction between animals, plants, and plant foods (see below).…”

Modeling Chromatography Binding through Molecular Dynamics Simulations with Resin Fragments

“…Growing titers of upstream manufacturing increase the amount of material to be processed, requiring higher binding capacity resins. Such intensification also increases the amount of process-associated impurities, with host cell proteins (HCP) 1 being particularly challenging. Moreover, the structural complexity of manufactured biologics is steadily growing in the form of a variety of fusion proteins, multispecific mAbs, and vaccine products.…”

“…3 Multiple in silico approaches are being explored in the field to improve the speed, decrease costs, and increase the robustness of chromatography process development. 1 principles of chromatography, Quantitative Structure−Activity Relationship (QSAR) based on structural properties of purified proteins, and physics-based molecular simulations.…”

Robust method for chromatogram shape analysis to improve early detection of performance drifts and adverse changes in process parameters during purification column operations

“…Several recent examples for the implementation of PAT have demonstrated the feasibility and benefits of investing in such approach. [2][3][4][5] While some of these examples have focused on implementing new in-line/at-line instruments and sensors, [6][7][8][9][10][11][12][13][14][15] others have focused on how to best utilize the available data to make predictions and real-time decisions using multivariate analysis. [8,[16][17][18][19][20][21][22][23][24] Biotechnology processes often consist of several unit operations fed by multiple input parameters.…”