Bioprocess Intensification: Aspirations and Achievements

Abstract

There are many drivers to intensify the manufacturing of a biological product. Advances are occurring throughout the biomanufacturing arena, from process development techniques to improved manufacturing platforms, equipment and facilities. Many employ the term 'bioprocess intensification' to refer to systems for producing more product per cell, time, volume, footprint or cost. This need is being driven by two emerging priorities: cost control and process efficiency. We are seeing great interest in the power of such disciplines as synthetic biology, process simplification, continuous bioprocessing and digital techniques in the optimization of bioprocess development and manufacturing. Other powerful disciplines here include process automation, improved monitoring and prefabricated facility modularity and podularity. Bioprocess intensificationDefining bioprocess intensification (BI) is difficult, for at least four reasons. First, the number of new biological products, from exosomes to DNA vaccines, makes even cataloging new initiatives difficult. Second are the many biomanufacturing advances, including new process development techniques and new manufacturing platforms, equipment and facilities. Third, intensification efforts include many advances in science and technology as they support diverse analytic, diagnostic and therapeutic product applications [1].The fourth difficulty relates to just what improvements in a process should be regarded as BI. Some have applied the term to most any process improvement, but many use it only when referring to getting more product from a process by producing more product per cell, time, volume, footprint or cost [2]. Used this way, BI refers to any activity that increases such common metrics as the cell-specific, volumetric or facility productivity. BI can be accomplished by such improvements as producing more product per time period upstream or retaining more quality product downstream. Defined this way, BI is a subordinate or supporting technology to the so-called nextgeneration or 'factory of the future' initiatives. BI can be enabled by such corollary technologies as continuous or digital biomanufacturing (Figure 1).Many process improvements affect values and metrics not in the original purview of BI. For example, a development initiative intended to improve product quality can also reduce failed batches and thereby increase a plant's annual productivity. Limiting the categorization of an activity to its primary, intended goals can increase clarity. We herein define BI as an activity intended to increase productivity by any metric.

Modeling the Downstream Processing of Monoclonal Antibodies Reveals Cost Advantages for Continuous Methods for a Broad Range of Manufacturing Scales

“…Batch bioprocessing using SS equipment has proven to be safe and reliable for decades and most of the recent, top‐selling mAbs have been manufactured this way . SU technologies are not particularly novel, but they have typically been implemented in the small to medium scales of manufacturing for a variety reasons . Lately, SU technologies have become more widely used at larger manufacturing scales, with the Amgen facility in Singapore as a prime example .…”

“…SU technology, both upstream and downstream, has been consistently shown to reduce mAb manufacturing costs at many stages and scales . Utilization of SU technology in mAb processes, especially at small to medium scales, is also not particularly unfeasible or controversial . Continuous bioprocessing has been shown to reduce costs, but more practical challenges remain and adoption is still in its infancy …”

Integrating Biocatalysis with Viscous Deep Eutectic Solvents in Lab‐On‐A‐Chip Microreactors

“…[1,2] Herein, process intensification is an outstanding tool to develop safer, more efficient, and cost-effective processes using small devices. [3][4][5][6][7] To reach these goals, an interdisciplinary approach is needed, comprising (bio)catalysis, reactor engineering, reaction media, mass and heat transfer assessment, process integration, and so on. In this area, microreactors are gaining increasing relevance in different chemical segments, from synthesis to analytic chemistry or for ultrahigh-throughput screening purposes.…”

“…Driven by environmental concerns, the development of sustainable production means for the chemical industry is one of the main current challenges of process engineering [1,2] . Herein, process intensification is an outstanding tool to develop safer, more efficient, and cost‐effective processes using small devices [3–7] . To reach these goals, an interdisciplinary approach is needed, comprising (bio)catalysis, reactor engineering, reaction media, mass and heat transfer assessment, process integration, and so on.…”

Integrated autolysis, DNA hydrolysis and precipitation enables an improved bioprocess for Q-Griffithsin, a broad-spectrum antiviral and clinical-stage anti-COVID-19 candidate

“…This has been recognized through regulatory initiatives such as the Advanced Technology Team within FDA [3] and the formation of government-academic-industrial partnerships such as the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL) [4] . At the level of process design, the key trends are intensification and flexibility, where intensification refers to increasing efficiency on the basis of cost, space, and/or time [5] , and flexibility refers to processes that are modular, portable from facility to facility, and amenable to changes in production rates [4] . At the level of technology, some approaches are especially interesting because of their potential to deliver both flexibility and intensification simultaneously.…”