Overview
Our partner faced significant challenges in scaling up vaccine production to meet global demand due to insufficient yields in both upstream fermentation and downstream processing.
Ginkgo Bioworks’s cell engineering platform streamlined our partner’s fermentation and processing, resulting in substantial increases in efficiency and yield. Within ten months, our partner saw improvements that ensured they could meet their aggressive commercialization timelines.
The challenge
Our partner, a vaccine developer, was looking to commercialize its vaccine supply for global distribution. Their initial vaccine development had been very successful. However, when scaling up for commercial production for the global market, they found that the upstream fermentation and downstream processing for a key component of their vaccine was not achieving their target yields. In order to meet their aggressive commercialization timeline, they needed to boost their production of this key component.
Our work
Ginkgo Bioworks focused on revamping our customer’s manufacturing process through a series of large-scale Design of Experiments (DoE). This approach allowed us to understand which parts of upstream and downstream processing had major effects on our partner’s final yield. Ginkgo collaborated with our partner to onboard and optimize their manufacturing process while keeping an eye towards the constraints on COGS for their commercialization.
The work was carried out in four stages:
Identifying Critical Process Parameters (CPPs)
This initial phase focused on understanding the key variables that influence the fermentation and downstream processes. Ginkgo leveraged the Ambr 250 fermentation vessels in our Foundry to provide data for the DoE we designed; we performed DSP optimization using material that was produced from these experiments.
Modeling Interactions Between CPPs
After identifying CPPs, our engineers developed models to predict how changes in these parameters could optimize the manufacturing process. Again, we leveraged our Foundry to test how these variables affected final yield.
Refinement and Validation of Predicted Optima
After developing base processes, we refined our work, using our extensive knowledge-base on fermentation and process optimization, to find other changes that could streamline the final process, which may not have been accounted for in our DoEs.
Robustness Testing and Further Validation
Although our development work gave improved results, we tested to make certain that our end-to-end process could be easily on-boarded at a wide variety of production facilities and was robust with respect to variations in temperatures, pH, or variable media at third-party manufacturing facilities.
Outcome
Increased fermentation efficiency
The optimized process that we developed demonstrated a >4-fold improvement in titers over our partner’s original process.
Batch yield improvement
Our revamped fermentation process, together with downstream process refinement, resulted in an overall 3-fold increase in batch yield.
Successful technology transfer
The optimized process was transferred to the customer’s Contract Manufacturing Organization (CMO), with validation runs confirming the anticipated 3-fold increase in performance at both Ginkgo and the CMO’s facilities. The three-way collaboration between Ginkgo, our partner and their CMO verified that our processes worked at the 1000L scale.
Rapid development cycle
Our work, from onboarding our partner’s process, to beginning to transfer our processes to our partner’s Contract Manufacturing Organization (CMO) was accomplished within 10 months of initiating the collaboration. We developed processes that resulted in a 3x increase in yield and ensured that our partner was able to scale-up and move on to commercialization on their intended timeline.
Work with us
Commercial manufacturing is often viewed through the lens of fixed costs of producing a product at scale. Yet in many cases, the key to maximizing the output of these fixed costs lies in optimizing the underlying biological processes. Ginkgo Bioworks’s cell engineering platform provides these biological solutions. Our Foundry brings together a collection of state-of-the-art technologies, tied together with automated workflows that are geared for efficient biological engineering and process development. Partnering with Ginkgo means gaining access to this technology without the costly investments in laboratory space and specialized equipment. Ginkgo engineers biology to transform your manufacturing challenges into competitive advantages.