Upstream Processing

Synthetic Biology and Genome Engineering

Monday 3/18/2024, 8:00-11:00 AM

Synthetic biology and genome engineering have transformed biotechnology. Next generation techniques in sequencing/synthesis have accelerated cellular prototyping, decreased development timelines, and enabled the collection of large, previously unimaginable biochemical datasets. Talks within this session will highlight rapid advances within the fields of synthetic biology and genome engineering with a particular focus on de novo genome design, multiplex genome editing, genetic engineering in non-model organisms and industrial hosts, transcriptional reprogramming, genetic circuit design, biosensors, tool development, metabolic engineering, and pathway engineering. Talks will also aim to address how advances in synthetic biology and genome engineering have created new opportunities for therapeutic development, disease diagnostics, biomaterials and biofuels synthesis, and environmental remediation.

Engineering Microbes and Microbial Communities

Tuesday 3/19/2024, 8:00-11:00 AM

Advances in synthetic biology and metabolic engineering have enabled the design and engineering of genes and pathways to produce chemicals and other biological products important to humans in various microbial hosts. This session aims to bring together all aspects of this engineering process, from the design of metabolically engineered pathways and strains, to their construction, optimization and use in whole-cell microbial biocatalysts. We welcome presentations on biocatalytic pathway design, building, and testing; the development of metabolic modeling tools and methodologies for whole cell factory optimization; the creation of genetic tools for engineering microbes or microbial communities; and the incorporation of novel substrates, biochemical reactions, or regulatory mechanisms within biological systems. Additionally, we encourage submission of talks that engineer microbial communities for the production of molecules, therapeutic applications, or other biotechnological objectives.

Mammalian Cell Line Development, Media and Metabolism

Monday 3/18/2024, 2:00 – 5:00 PM

Mammalian cell culture has become an essential means for production of an ever-increasing number of viral vaccines, recombinant proteins, monoclonal antibodies and other biopharmaceuticals. The advent of cell-based therapy and gene therapy, where the desired products are the cells (e.g., t-cells and stem cells) or viral capsids encoding the gene of interest, further expand the need for optimal cell culture conditions. The growth of mammalian cells in nutrient-enhanced media is profoundly intertwined with the cell’s metabolism and its response to the physicochemical environment. Over time, the field has matured into a multidisciplinary activity including genetic manipulation of cell lines to obtain highly productive clones, medium and feed development, bioreactor characterization, and process control to optimize conditions for desired productivity and product quality. This session will encompass multiple aspects of mammalian cell culture development, including advances in the development of improved production vectors, novel clone selection strategies, engineering of host cell lines, cell expansion strategies, metabolic pathway analysis and engineering, media development, multivariate analysis of processes and, innovative cell line and cell culture process development. Papers relevant to these topics are highly encouraged, but not limited to those focusing on cell line development, vector engineering, cell culture medium optimization, medium preparation and storage, medium chemistry understanding, medium impact on cell function and metabolism, effects of media in controlled environments, metabolic engineering, metabolic modeling, ‘omics analyses of mammalian cells in varying culture conditions, and management of raw material changes in medium components.

Integrated, Intensified, and Continuous Processes

Sunday 3/17/2024, 8:00-11:00 AM

In the last decade, technical advances in both upstream and downstream have led to the advent of innovative technologies and exploration of integrated continuous biomanufacturing (ICB). Continuous manufacturing is becoming an attractive choice for process intensification of relatively stable products such as monoclonal antibodies and vaccines, in addition to the labile products for which continuous manufacturing (e.g., perfusion) has historically been used. Current ICB technologies and platforms promise to reduce manufacturing footprint, capital investment, and operational costs enabling flexible facility designs while increasing productivity and ensuring product quality consistency. This session will encompass advances in upstream perfusion and continuous processing, including advances in process development, process characterization, bioreactor engineering and cell retention devices, scale-up/scale-down model development, and cell line engineering/adaptation. Papers relevant to these topics are highly encouraged, including those focusing on process control and handling operational complexity, cell retention, ICB platform development, media development, bioreactor design, and process/facility economics.

Applications of Innovative Technologies

Wednesday 3/20/2024, 8:00-11:00 AM

The development and commercialization of biotherapeutics depends on successful upstream process development to identify the ideal protein candidates and its final cell line for commercial production, as well as cell culture media, bioreactor process conditions, and process control/monitoring. Enhancements in laboratory automation, DNA synthesis, and synthetic biology have led to rapid advances in the throughput and approaches taken in upstream process development. The application of technologies such as cell-free expression, microfluidics, and automated bioreactors has enabled the rapid design and testing of increasingly large numbers of protein candidates and production conditions in reasonable timelines. Advances in machine learning and other computational methods are being implemented on the multidimensional data sets generated during high-throughput upstream process development to drive process decision-making and generate cross-program learnings. This session will focus on developing and applying experimental and computational tools, workflows, and processes that increase our ability to perform therapeutic candidate development in a high-throughput, automated fashion. This session will explore advances in functional artificial intelligence-based algorithms for accurate sampling of property landscape, analytical characterization, and the rational design of biological materials and functions. Finally, this session will foster discussion on the use of community standards and initiatives to improve these processes as new ways to distribute and share data across the community.

Case Studies: Challenges in Upstream Processing During Manufacturing

Sunday 3/17/2024, 2:00 – 5:00 PM

This session will focus on case studies describing challenges in upstream processing during manufacturing. Invited topics include but are not limited to: Examples of troubleshooting and resolving unexpected challenges in upstream process development, technology transfer, and/or manufacturing; strategies to control charge variant and glycosylation profiles; development, qualification, and use of bioreactor scale-down models; the use of computational modeling and digital tools in upstream process development (e.g. computational fluid dynamics); applications of upstream process analytical technology for bioreactor control; strategies to decrease upstream cost of goods, and novel approaches to bioreactor harvest to ensure cell or product purity. Case studies that incorporate multiple of these examples are of special interest.