Lotte Biologics taps virtual simulation to cut scale-up risk, advances dual-site tech transfer

Lotte Biologics is deploying virtual simulation technology to reduce uncertainty in biopharmaceutical scale-up — widely regarded as one of the hardest challenges in commercialization — while accelerating an integrated technology transfer strategy across its global production sites.

The company presented its scale-up strategy and process simulation capabilities using computational fluid dynamics (CFD) at the 2026 BIO International Convention in San Diego on Tuesday (local time).

Scale-up — replicating at a large commercial facility the same quality and productivity achieved at laboratory scale — is a notoriously difficult task in biopharmaceutical development. When bioreactor volumes expand by hundreds or even thousands of times, oxygen supply patterns, fluid flow and the physical stress on cells all change, raising the risk of reduced productivity or outright process failure.

To minimize those process risks, Lotte Biologics has been applying CFD technology to precisely analyze fluid dynamics inside bioreactors — along with oxygen transfer and mixing efficiency — in a virtual environment. "CFD allows us to quantify and pre-analyze fluid behavior inside a bioreactor in a virtual setting," said Han Jae-jun, the company's chief technology officer. "By minimizing uncertainty during scale-up and analyzing internal flow and conditions in advance, we can identify optimal production parameters and improve both process stability and production efficiency."

Lotte Biologics is now applying its CFD capabilities to technology transfer between global production sites and to pilot bioreactor design, advancing what it calls a "dual-site" strategy linking the United States and South Korea. A key example is the transfer of the 5kL bioreactor process from its Syracuse, New York factory — where a substantial number of commercial production batches have been completed — to the 15kL production bioreactors at its Songdo Bio Campus.

"We are using CFD simulation to precisely analyze critical data that are difficult to obtain through experiments alone, including shear stress, oxygen transfer rate and energy dissipation rate," Han said. "By predicting in advance how mixing efficiency and energy transfer characteristics change as bioreactor scale increases, we are improving the stability of the technology transfer process and proactively managing risk."

In addition, Lotte Biologics incorporated CFD technology into the design of a 500L pilot bioreactor — a scaled-down version of the 15kL commercial unit. Rather than simply reducing the size, the company aligned oxygen transfer rates and energy dissipation rates to replicate the process environment of commercial production equipment, and optimized the design of key components including the impeller and sparger. The result is a pilot bioreactor that closely mirrors actual production conditions, providing a foundation for accurately bridging process development outcomes to the commercial production stage.

"CFD technology goes beyond simple simulation — it is a core tool for improving the likelihood of success across process development, scale-up and technology transfer," Han said. "We plan to continue strengthening our differentiated CFD-based process development and technology transfer capabilities to firmly establish a technological competitive edge in the global contract development and manufacturing organization market."