How to Bridge the Gap Between New Discoveries and Useful Bioproducts
Deborah Pascoe, PhD, Culture’s VP of Operations, shared technical and non-technical learnings from her career as a leader and entrepreneur in biomanufacturing. See what her varied experience has taught her about how biotech companies can turn new discoveries into useful products sooner.
Mattie: In your years of experience as a leader in both biopharma and industrial biomanufacturing, what are some of the critical elements of success for companies in this space?
Deborah: On the technical side, performing comprehensive, consistently executed experiments that translate into your manufacturing facility is essential. The data should be stored and tracked in a way that you can perform broader analyses well into the future. On the people side, having a wide range of subject matter expertise and diverse perspectives helps uncover blind spots and create new insights.
Mattie: How does Culture fit into that picture?
Deborah: Even when companies have substantial in-house bioreactor infrastructure, it can be hard to secure capacity to generate large datasets, such as DOE studies - if they already have that infrastructure, it’s likely they have many programs they're working on, which doesn’t leave much flexibility to perform large experiments. There’s a lot of reshuffling and reprioritizing to use capacity effectively. Culture alleviates this problem by providing access to bioreactors with much shorter lead times than buying in-house bioreactors. Working with Culture also eliminates the time and investment required to expand your lab and staff. Instead of focusing on infrastructure expansion and running bioreactors, scientists can focus on experiment design and leave the execution of experiments to us.
In terms of data management, for the most part, people are still downloading files and reviewing and plotting fermentation trends in Excel or JMP. Culture’s online dashboard allows collaborators to see trends and data in real time - not just current process values, but also measurement trends, controller outputs, and calculated values. Storing these data in the cloud with online access facilitates team collaboration, especially right now when so many people are working remotely.
Culture's online tools also mean that, unlike traditional CROs, Culture offers clients unparalleled transparency into our lab and gives scientists real-time control over their experiments.
Mattie: When did you first realize how important thorough and consistent experiments are for biotech companies?
Deborah: It goes back to the start of my career in pharma. I moved to the U.S. from Australia to pursue a PhD in the pharmaceutical industry. I worked at Merck in New Jersey before going to Northwestern University to join a research team growing human stem cells from blood. After a few years there, I took a non-traditional path and completed the remainder of my PhD at Genentech, where I switched to research on CHO cells, the workhorse of manufacturing for biologics today.
I finished my thesis work at Genentech, studying the metabolic behavior of CHO cells in the company’s cell culture processes at lab and manufacturing scales. I later led teams in Process Development and in Manufacturing Sciences. Manufacturing Sciences is essentially the technical support for manufacturing - engineers and scientists who work on bringing new products into manufacturing, troubleshooting issues on the production floor, and helping to keep operations within quality and regulatory requirements.
I was fortunate to spend the first decade of my career at Genentech, where there is a strong commitment to science and doing experiments well. The top priority was ensuring products were safe and effective for patients - no shortcuts. This is where I learned to appreciate the importance of designing and structuring logical experiments, executing them consistently, having a strong understanding of your process, and thoroughly documenting execution.
As my career progressed, I moved from cell culture to drug product, which involves filling and packaging for pharmaceuticals. It was very different from what I had been doing in cell culture; it was much more mechanical, closer to the patient, and centered around sterility, quality, and regulatory compliance. That move showed that my skills were transferable and that I could lead in other areas while maintaining this commitment to high-quality science and execution. It gave me the confidence to later work in new fields including genetic testing and industrial biomanufacturing, and to found a company, paths I hadn't considered when I first started in biotechnology.
Mattie: So, after those experiences, what made you excited to join Culture?
Deborah: I was excited to join Culture because Culture solves a specific need for reproducible execution of high-quality experiments along with data visualization and analysis for those experiments. This need to accelerate bioprocess development spans across companies in this space. Whether it’s in synthetic biology, food tech, agricultural products, or biopharma, scientists need to run many bioreactor experiments and wrangle reams of data to enable new discoveries and create useful products. I was so impressed by how many customers Culture already has at this stage - it shows how much of a demand there is for bioreactor capacity and how we’re filling this gap in the biotech ecosystem.
Mattie: In the other parts of your career that you mentioned - industrial biomanufacturing and starting a company - did the need for reproducible experiments and data management consistently apply?
Deborah: Absolutely, perhaps even more so. In industrial biotech, being able to iterate quickly by incorporating the results of one experiment into the design of the next is critical. For example, at Zymergen the work centered on rapidly screening and evolving strains. We needed to quantify how different strains perform in bioreactors and leverage those insights to inform strain engineering work. Fermentation is always the bottleneck because it’s expensive and equipment constrained - we had to be very selective in deciding which strains would move from high-throughput screening to fermentation with our limited bioreactor capacity at the time. Tight reproducibility in execution and results was more important at Zymergen than anywhere I had worked before.
As I gained more exposure to synthetic biology and agtech companies, I recognized that many of them have expertise in genetic engineering but not in fermentation. These companies have to navigate a transition from molecular biology to growing strains to make a real product. Molecular biology is a very different skill set from fermentation, which requires knowledge of cellular metabolism to develop optimized processes and manufacture the product at a reasonable cost.
This aligns with the reason I had earlier founded Flora Therapeutics - to help solve this problem for microbiome companies. The mission of Flora Therapeutics was to isolate and grow microbes under GMP standards to use them in clinical trials. I had the idea after seeing the gap that existed between the in silico identification of potentially relevant microbes and the stage at which they’re actually useful to patients. Efficient execution of fermentation experiments with improved data management would get products like these to market faster.
Mattie: How does solving the problems of experiment execution and data management help get products to market faster?
Deborah: Going from a strain to a commercial product requires hundreds of bioreactor experiments. There’s a constant need to reprioritize programs and make cuts when you have a limited number of in-house bioreactors. Having cost-effective and flexible capacity, like Culture provides, means you can do the experiments you want to do without sacrificing the quality of your experiment designs due to capacity limitations. It also saves time on the negotiations and bureaucracy around making those tradeoffs and allows the programs to keep moving.
Mattie: We’ve talked a lot about the technical challenges that biotech companies need to solve. What are some of the most important non-technical lessons you’ve learned?
Deborah: It’s crucial to work collaboratively and communicate effectively across teams. The more complex the work, the more you need to collaborate across disciplines and blend skills and approaches. Over the years, my work has become increasingly interdisciplinary; for example, at Zymergen, we were integrating biology, software, and automation. Culture is especially interdisciplinary, combining innovations in hardware, automation, biology, software, and analysis, so we can build novel bioreactor technology and run it in the cloud.
Along with communication, it’s important to build teams of people with diverse backgrounds and skill sets. I began to focus on this when I worked in manufacturing sciences, leading a team where some people had a process development background and others started their careers with hands-on work in manufacturing operations. My team would not have been successful without the perspective each individual brought to the table. At Culture, the partnership between our new client success team and our bioprocessing team will be key to ensuring we understand and communicate the needs of our customers and the real-time work in the lab.
Mattie: How do you plan to apply your learnings to your work at Culture?
Deborah: I’ve been impressed by how many products we're working on, our team’s work ethic, and the systems already in place considering the early stage of the company. Because our business is growing and we’re hiring more people, each team member is doing fewer but more specific things. This can be disorienting for early hires, who go from doing almost everything to focusing on a subset of what they were doing before. It’s somewhat counterintuitive that success can mean taking on less scope.
As we grow, it’ll be important for us to focus on how we organize and structure our work. One key lesson for me has been to put work in the hands of the right people to get it done. In that vein, we are expanding our hardware operations and R&D teams, we’ve created a client success team, and we’ll be looking to fill more roles in logistics, business operations, procurement, and quality.
Another priority of mine is to continue to expand training for the team, including cross-training for different systems so that our work is highly reproducible and efficient. Process documentation will be an important part of that too. It all comes back to running high-quality, consistent and reproducible experiments, and doing so in a way that we can scale our operations.
Mattie: What goals or plans do you have for Culture that will best help our clients run experiments and get the data they need to accelerate their bioprocess development?
Deborah: My focus over the next year will be on efficiently onboarding customers. I want to increase structure and have clear communication when onboarding new clients, helping to successfully complete this quickly and get to the real value-add of running novel experiments. Another goal is to ensure we have the highest possible success rates so customers can keep making progress rapidly. My goal for Culture is to be the leader in the industry for bioreactor capacity and the go-to partner for companies looking to do large numbers of experiments in a short time frame. Ultimately, our clients care about having reliable results so they can make data-driven decisions on tight timelines, and we can provide those data quickly.
In the longer term, there are so many directions Culture could go. Working in close partnership with our customers, we continue to learn and to expand our capabilities. For example, we recently added analytical chemistry capabilities, including HPLC, so we can measure product titers and enable faster cycle times between experiments. We have also begun work in mammalian cell cultures. I look forward to seeing how we continue to grow with our customers, and how we adapt and evolve based on their needs.
Mattie: Finally, you talked about what drew you to Culture, but why did you decide to join Culture at this particular juncture in your career?
Deborah: A big draw was to join the executive team in focusing on how to grow, put effective systems in place, and make the company a great place to work - a place where our employees can grow along with the company and thrive in their careers. At the same time, I also get to manage the bioprocess aspects of our work. It’s especially good timing as Culture expands into mammalian cell culture work, which is my original technical background. Fre Tachea, our Director of Bioprocessing, leads a dedicated and innovative team who consistently goes above and beyond to get the work done.
This job is the perfect combination of process development and operations. I get a lot of satisfaction in seeing that we do things robustly, efficiently, and on time. I really enjoy figuring out how to do things well at a large scale. We’re at an exciting time for the business. After raising a Series A in 2020, we’re building new technical and business systems, expanding our capacity and team, and bringing on more customers every month. It’s fulfilling to be able to build on what this team has already done and support a talented group of people.
Besides that, it’s important to me to have an impact on a company that is itself impactful - a company that’s driving progress and providing something useful to humanity. Culture enables products that are making the world better to move forward.