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Evaluating Biomanufacturing Possibilities to Meet Patient Needs

By Nick Hutchinson, Business Steering Group Leader for Mammalian Cell Culture

Drug sponsors must find the biomanufacturing strategy that can best accommodate uncertain and evolving demand forecasts in order to deliver innovative biologics that address blockbuster indications, rare diseases, or global pandemic threats. There are three major biologic manufacturing strategies, each with specific advantages: scale up, scale out, and continuous. Though sponsors may initially feel tied to the offering of a specific contract development and manufacturing organization (CDMO), opting to partner with a manufacturer that provides all three allows you to seamlessly pivot as demand evolves throughout different clinical phases, affording a dynamic, cost-effective plan for the life cycle of your drug. As you consider the strategy that pairs best with your needs, examine each approach and the scenarios in which they excel.

The High-Volume Approach: Scale Up

Scale up, or traditional large-scale manufacturing, is the tried-and-true, fed-batch strategy for producing large volumes of biologic medicines. It is an ideal solution for customers in late-stage clinical development planning to begin commercial manufacturing. Though scale up is widely considered the most conventional strategy for meeting high demand, it requires up-front investments in time and money. When looking for a CDMO to accommodate your production ramp up, seek partners that have significant experience scaling and validating processes at your intended scale. At FUJIFILM Diosynth Biotechnologies (FDB), a world-leading CDMO with manufacturing capabilities for all three strategies, our large-scale, stainless-steel manufacturing platform leverages multiple 20,000-L bioreactors that offer high efficiency and a lower cost of goods. We have invested in network capacity localized in Europe and North America with sustainable modular-designed facilities that enable process transfers with unprecedented speed for maximum agility.

The Flexible Approach: Scale Out

Scale out is used to increase capacity while staying within the 2,000-L range often used for clinical batches. It is ideal for manufacturing targeted therapeutics for niche indications, where the patient population and overall need are much smaller. Scale out allows you to rapidly increase and ramp up output without having to perform additional studies required for large-scale manufacturing. Furthermore, it offers greater flexibility, lower upfront costs, and shorter lead times thanks to smaller, modular, single-use facilities. On the downside, it does not allow the efficiency of scale provided by a scale-up approach.

At FDB, our scale-out approach is conducted in high-throughput ballroom facilities with multiple 2,000-L bioreactors. By remaining at the same scale throughout, you have the advantage of collecting more data about your manufacturing process. If demand shifts, our clients can move to scale up rapidly and easily due to the alignment between our fed-batch manufacturing platforms.

The High Productivity Approach: Continuous Manufacturing

Continuous is an innovative manufacturing solution that leverages small, agile facilities that adapt easily to forecast fluctuations while providing the cost efficiency of large-scale systems. According to the FDA, continuous manufacturing has, “the potential to improve product quality and reliability, lower manufacturing costs, reduce waste, decrease inventory, and increase manufacturing flexibility in response to product demand.”1 The industry is still adopting this strategy and sponsors are less familiar with the regulatory considerations of continuous operations. Despite caution within the sector, continuous is emerging as a beneficial strategy that is suitable during any phase of a drug manufacturing life cycle.

This potential is reflected at FDB. Our MaruX™ continuous platform uses 500-L bioreactors and offers the ability to deliver large volumes while leveraging smaller, more flexible single-use facilities that require less capital investment and lower consumable costs. Due to its intensive nature, continuous allows for greater output in a smaller manufacturing footprint, resulting in a more sustainable process. For clients who prefer to start at a scale-up or scale-out fed-batch approach, FDB can accommodate an eventual move to continuous manufacturing to take advantage of this agility. To ramp up output from a continuous manufacturing platform, the process runs longer, and if further increases in production are required, additional bioreactors can be added with the same downstream process. In the future, we will deploy the MaruX platform at the 2,000-L scale

What Strategy Meets Your Needs?

To determine what best suits your product, work with a CDMO that provides both expert insight and a variety of manufacturing techniques in-house. At FDB, we partner with clients to determine their needs. If you’re bringing an existing process to our team, we assess the titers and recoveries across purification to determine how best to fulfill your required quantity. If a process has high yields and titers, that allows us to meet a small demand from a small facility. Alternately, if a process has lower yields and titers but high demand, we are more likely to use a large-scale approach.

We also examine a customer’s approach to risk, including the amount of data on demand they need to comfortably scale up. When working with customers dealing with uncertainty or constrained by investments, we stay adaptable and communicate regularly. In certain scenarios, we recommend extending production with a continuous or scale-out strategy. If high demand is forecasted later, subsequent scale up is easy thanks to our network of large-scale capacity. Throughout a manufacturing partnership, we strive to meet clients where they are, including accommodating the strategy they are inclined towards while sharing guidance from previous experience. Ultimately, it is a collaborative effort that seeks to accommodate a customer’s comfort levels and the product’s demand profile.

Proceed With Curiosity

It is critical to start thinking about your manufacturing strategy from the outset of your biologics program and throughout its life cycle. When navigating uncertain forecasts or limited budgets, consider partnering with a CDMO that can accommodate multiple manufacturing strategies and the diverse scenarios faced by biologic sponsors. This efficiency can save you time and money on your path to patients.

References

  1. Center for Drug Evaluation and Research. (2022, June 28). An FDA self-audit of continuous manufacturing for Drug Products. U.S. Food and Drug Administration. https://www.fda.gov/drugs/cder-small-business-industry-assistance-sbia/fda-self-audit-continuous-manufacturing-drug-products

About the Author

Nick Hutchinson is the Business Steering Group Leader for Mammalian Cell Culture at FDB. He has global responsibility for leading the design of new mammalian cell culture services and evaluating investments in new manufacturing capacity. Prior to this role, he led FDB’s streamlined monoclonal antibody development and manufacturing services, which included process development and process transfer to FDB’s GMP manufacturing site for early-phase clients. Before joining FDB, he worked for other contract manufacturing organizations and for suppliers to the bioprocessing industry. Nick received a Biochemical Engineering Doctorate from University College London and an MBA from Durham University.

About FDB

FDB is a global CDMO operating in Europe and North America with integrated platforms to meet client demands and deliver medicines to patients faster. FDB has capabilities not only with drug substance manufacturing but also with finished goods manufacturing on both sides of the Atlantic, allowing a customer to work with a single provider for their end-to-end manufacturing needs.

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