Dawn Ecker, managing director, bioTRAK database services, BDO USA

For nearly two decades, Ecker’s team has leveraged its bioTRAK database to monitor business trends in recombinant-protein manufacturing. On the supply side, the database tracks bioproduction capacity across

240 facilities and 140 companies for products that will reach US and EU markets. It contains information about all available bioreactors, including appropriate expression technologies, scales, applications (clinical or commercial production), equipment formats, production locations, and operational statuses. The database also tracks capacity demand, gathering information about active drug programs and their modalities, development phases, production hosts, volumetric demand per year, manufacturing locations, and drug-product requirements.

Ecker highlighted several use cases for the database. Its supply-related data facilitate competitor analyses, evaluations of potential site acquisitions, and selection of contract manufacturers. The demand data can help manufacturers and industry suppliers to understand capacity needs for different applications. That enables forecasting of requirements for equipment and raw materials. “And when we look at supply and demand in parallel,” she said, the resulting forecast “can help the industry to understand where it is and where it is heading.”

Ecker began with supply trends for protein expression by mammalian cells. When her group began collecting data in 2007, biomanufacturers had installed about 2.2 million L of bioreactor capacity. Today, that value is ~6.7 million L, representing a compound annual growth rate (CAGR) of 6.6% and a total increase of >200%. Between 2020 and 2024 alone, capacity increased by 27% (with a CAGR of 6.3%), and biomanufacturers are projected to add another 2.2 million L by 2028, which would bring total capacity to 8.9 million L at a four-year CAGR of 7.1%.

Noting that “capacity is not always equally available,” Ecker analyzed supply data by company type, with categories for drug developers with internal capabilities, contract manufacturers, and “hybrid companies” with capacity for internal and external programs. Over time, contract partners have amassed a considerable share of the industry’s total capacity. Such companies owned 8% (200,000 L) in 2007 but accounted for 20% (1.1 million L) in 2020 and 28% (1.9 million L) in 2024. That share is expected to increase to 38% (3.4 million L) in 2028. Although developers own 57% (3.9 million L) of production capacity in 2024, their share of the total continues to decline — especially as manufacturing platforms solidify for antibodies.

By total volume, installation of stainless-steel (SS) bioreactors continues to outpace that for single-use (SU) systems. That result is unsurprising considering current scale limitations for SU technologies (<6000 L) and high demand for popular biologics. But SU options prevail at more modest scales. In 2007, only 8% of installed 2000-L bioreactors were in such formats; today, that figure is nearly 90%. Drivers for SU adoption include such systems’ minimal equipment-cleaning requirements, operational flexibility, relative ease of installation, and reduced cost barriers to entry.

Shifting to demand trends, Ecker showed that products from mammalian expression systems continue to dominate pipelines, accounting for 70% of marketed biologics, 86% of candidates at the biologics license application (BLA) stage, 85% of those in phase 3 trials, 85% in phase 2 studies, and 90% in phase 1 trials. By contrast, microbially expressed products represent 30% of marketed biologics and 14%, 14%, 15%, and 9% of candidates at BLA, phase 3, phase 2, and phase 1 stages, respectively. Antibodies and derivatives represent the dominant product type for mammalian-cell processes.

Based on such information, BDO can generate risk-adjusted forecasts of capacity demand in kilograms of protein per year and batch-adjusted liters per year. Currently, demand runs close to 47,500 kg/year (~2.5 million L). By 2028, however, total and volumetric demand both are expected to double. In turn, demand for outsourced production is likely to increase as well.

BDO also can break down capacity demand by bioreactor scale. For instance, bioTRAK data indicate that a 2000-L bioreactor could generate enough protein over a year to satisfy demand for ~50% of currently marketed biologics; two reactors working in parallel could address production requirements for 62% of marketed products. About 20% of commercial biologics would require a bioreactor of >10,000 L, and only 10% of products would benefit from manufacturing with two >10,000-L bioreactors operated in parallel. Trends are similar for biologics in clinical development, with slightly higher demand at the 2000-L scale. Ecker confirmed, however, that demand remains for >10,000-L production. “Titers are improving, which is going to decrease the amount of material that you need to make, but I don’t think that stainless steel is going away anytime soon.”

Watch Online

See full presentations online at https://bioprocessintl.com/category/bpi-theater/bpi-theater-bio-2024.