Industrial Biotech: What Does it Really Mean to “Begin with The End In Mind?”

by H. Brett Schreyer (Lee Enterprises Consulting, Inc./Biofuels Digest) ... The short answer is the sooner you start planning for your final process, the better. As a bio-product progresses through strain screening, bench-scale process development, piloting, and to large scale production, changes to the process become progressively more expensive. You don’t want to be making significant changes to a plant you just built when production is about to begin. Such a change could cost on the order of millions to tens of millions of dollars in change orders, equipment, installation, and lost production time. Let’s dig a little deeper into what it means to “start with the end in mind.”

Start with Techno-Economic Analysis
The most important example of beginning with the end in mind is the work required even before the first stain is made. This is the techno-economic analysis (TEA) that builds up the business model and justifies the business case to develop a fermentation-based product.

What will be discussed in this article is what beginning with the end in mind means at the R&D level. This will be discussed through three examples: strain selection, media development, and integration of upstream and downstream processes.

Early stage entrepreneurs in industrial biotech may not even be thinking about the final process when selecting a host strain to engineer as the immediate priority may just be getting proof of concept to secure funding, or the initial stages of strain development may have been completed by an academic institution not focused on commercialization.So if the host strain has already been locked in, then you’ll need to be ready to deal with the typical traits of that strain at scale because the host strain, such as commonly used Escherichia coli or Saccharomyces cerevisiae, can influence process robustness, repeatability, strain stability, performance metrics (production rate, titer, yield), and operating costs at large scale.

If one truly starts with the end in mind, then one needs to think about the targeted attributes of the large-scale fermentation process when selecting an organism for production.

Media Preparation at Large-Scale can Present Challenges
What about media formulation? If you start with the end in mind, what does that look like? Let’s start at the end, large-scale media preparation, and work backwards towards early stage media development.

It’s All One Process
The final example of beginning with the end in mind is integration of upstream and downstream processes. Although upstream and downstream process development are usually separate groups in a company, they should not be siloed. From the beginning of development, it is important to envision the entire process of converting raw materials to finished product as a single process, and that fermentation and purification (along with all supportive processes such as logistics, utilities, waste treatment, packaging, etc.) are intricately connected. For example, as previously mentioned in media development, not reducing the media recipe to the bare minimum means downstream will have to specify filtration or chromatography operations to remove the excess media components, adding to both capital and operating expenses.

Envision the Final Process
“Beginning with the end in mind” is a methodology when developing a process for large scale production. At each step of the process, scientists and engineers developing the strain, the fermentation process, and the purification process need to continuously be asking themselves, “What does this look like at production scale?” By planning ahead and anticipating problems, a company that “begins with the end in mind” will have a more successful, less expensive, and quicker scale-up to production. READ MORE