South Pacific Sera

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DSM-Firmenich

Email Daniel

Microbes that produce bioactive natural products and biologics have proven to be of high commercial and societal value as antimicrobial agents, crop protectants, immunomodulators, and fermented food and beverage producers, as well as antitumor, antiparasitic, and antiviral agents. Producing commercial titers of a compound or biologic can take years of development work to overcome limitations found in native strains. Side products, instability, genetic tractability, toxicity, and other issues are barriers to strain improvement. Advances in DNA and RNA sequencing and new genome mining and editing tools have provided valuable insights and capabilities for strain engineering. Nevertheless, over-producing valuable compounds is often limited by unknown genotypes and a lack of insights into metabolism and other unknown “dark matter” in microbes. In this session, some valuable lessons and new approaches to developing over-producing strains for commercial applications will be highlighted.

Matthew Bochman – Indiana University, USA
David Mead – Terra Bioforge, USA

Today, nearly 20 years after the FDA’s formal publication of a guidance document on process analytical technology (PAT), practitioners of biomanufacturing enjoy a powerful toolset for understanding and validating the relationship between process and product quality. Ann M. Thayer, reporting on the subject for Chemical and Engineering News in 2005, connected PAT to the wisdom of the Ancient Greeks in her title, “Know Thy Process”. With Industry 4.0 ambitions for “self-driving” automation, the original “Know Thyself” may now be more apropos: the process will know itself, correct itself, and call for help only when deviating beyond its design space. Many rewards await the successful implementor of PAT: process prediction, control, and understanding, increased yield, saved batches, and real-time release–quality assured by the process data alone. These rewards also extend beyond pharma into the industrial realm, where narrow margins often demand essentially perfect execution at massive scale with minimal staffing. In the most exciting applications, PAT offers a deviating process a path back into spec, yet the devil is in the details. As the instruments grow more complicated, so too grow the possibilities for failure or ambiguity. The presentations in this session explore recent advances in new sensor technologies, modern PAT tools for complexity reduction and process robustness, and PAT case studies that highlight the rewards realized and the technical hurdles overcome.

Tim Davies – Corteva AgriScience, USA
Gian Oddone – Biolucid LLC, USA

This session is an opportunity to share experiences – both positive and negative – found in the process of scaling up fermentations, down-scaling to address new concerns and then using those findings to scale up again. In today’s bioeconomy, companies are leveraging a diverse set of microbial chassis as hosts to produce a variety of products. Each microbial host may present its own unique set of scale up and scale down challenges. Whether scaling up a new production strain or simply an improved process, what unique set of challenges were identified and how were those addressed?

Mary Bosserman – Valent BioSciences, USA
Stefan de Kok – Geno, USA

Production of chemicals, pharmaceuticals, and other materials by fermentation is often significantly more sustainable than standard synthetic chemistry based manufacture. Nonetheless fermentation systems often require energy input, energy fossil based material and competitive feedstock that reduce their environmental and societal positive impact. This session will focus on showcasing recent advances in fermentation systems, alternative feedstocks, gas fermentation, process changes, and other novel technologies to improve the sustainability of fermentation systems and reduce the greenhouse gas emissions associated with bioproduction.

Craig Behnke – Lumen Bioscience, USA
Jimmy Roussel – Luxembourg Institute of Science and technology, Luxembourg
Ehsan Mahdinia – Mettler Toldeo, USA

Commercial fermentation success depends upon the ability to capture product with customer-desired attributes. Classical or unique challenges such as dilute product streams, large and diverse types of contaminants or specific project needs are significant barriers that oftentimes decide project success rate. Deliberate research strategies around the interplay between upstream and downstream processing can decrease risk and bring our products to market faster. This session will include presentations covering how scientists and engineers tie together upstream research initiatives with downstream solutions to create new or advanced, end to end approaches in fermentation.

Brad Cox – Corteva AgriScience, USA
Michael Japs – Geno, USA

With the growing amount of biotech products reaching the market and the increasing data types and quantity that can be collected and generated, there is a demand and opportunity to reduce the amount of learning loops with digital process development. Equally, there is a growing need to consider process control in the process development workflow. Thus, this session will focus on novel modeling approaches for effectively understanding and controlling industrially-relevant fermentation processes. The session can include mechanistic, data-driven and hybrid modeling approaches, as well as of the fluid dynamics of the bioreactor, among others. Consideration of model robustness is welcomed and is important when a model is used in commercial manufacturing to aid in decision making, or ultimately to automatically control bioreactor operation. Discussion will emphasize the actual applicability of modeling approaches in industry and be connected with case studies. Challenges and practical aspects that need to be considered for successful fermentation process modeling will also be considered.

Gisela Nadal Rey – Novozymes, Denmark
Keith Smith – Applied Materials, United Kingdom

Spurred by the increasingly alarming IPCC reports on global warming, more and more companies are committing to science-based targets for greenhouse gas emission reduction, often with important milestones in 2030 and 2040, and aiming for net-zero emissions by 2050. Net-zero commitments need to consider the entire value chain; for a fermentative production process not only scope 1 (own CO2 emissions) and scope 2 (CO2 emissions caused by purchased energy) emissions should be accounted for. For many products, scope 3 emissions are most significant. These are caused by production and transportation of fermentation feedstock and nutrients, as well as distribution and end-of-life use of the final products. Taking this perspective, electrification, energy reduction and switching to renewable electricity sources in the bioprocess itself are clearly insufficient to reach net-zero by 2050. Switching to alternative feedstocks with net-zero potential, CO2 capture and utilization, byproduct valorization (in other value chains), net-zero logistics and decreased consumption are all in scope. This session will aim to paint the bigger picture of future net-zero fermentation processes, and will discuss some of the identified challenges and opportunities in detail.

Wouter van Winden – DSM-Firmenich

Marty Muenzmaier – Cargill, USA

Poster presentations are an integral part of the RAFT technical program as they showcase cutting-edge developments, extend the technical scope of the program, and provide opportunities for in-depth one-on-one discussions. This year’s RAFT poster session will highlight new research and industrial applications in next-gen strain design, strain optimization, Process Analytical Techniques (including automation), process modeling, scaling (up & down), fermentation sustainability, and integrating upstream and downstream processing.

Nancy Dowe – National Renewable Energy Laboratory, USA
Ed Talideh – Lallemand Bio-Ingredients, Canada