N-1 perfusion refers to the intensification of cell growth in the step prior to the production bioreactor. This occurs when a cell retention device is attached to the N-1 bioreactor to attain high cell density and viability.
Brandon Downey, associate director, R&D Biologics, at Lonza recently spoke to us about the advantages of this approach:
“N-1 perfusion is a form of seed train intensification which offers several benefits. It intensifies the fed-batch process, thus increasing facility throughput while still maintaining some of the benefits of fed-batch processes along with fed-batch production slot scheduling for the downstream process."
The CDMO, he continued, has also demonstrated that the process leads to around 70% higher titer, thereby helping to reduce costs for customers.
However, one potential challenge for all intensified cell culture processes, including N-1 perfusion, is the need to balance feeds to accommodate diversity in cell growth or metabolic characteristics from product to product, explained Downey.
“Lonza has overcome this challenge by incorporating automated feeds in the N-1 and production bioreactor steps – this automatically adjusts to variations in nutrient consumption and growth rate between cell lines by utilizing process analytical technologies to detect cell growth and nutrient concentration during the process and then automatically adjusts feed rates to maintain optimal growth and productivity.”
Increased process titers
The Swiss CDMO invested CHF 850m (US$839m) in May 2021 in the construction of two new commercial mammalian facilities that are set to incorporate Lonza’s next-generation intensified manufacturing process, which produces harvest titers in the 8-10 g/L range, a significant increase over legacy processes, said Downey.
The new sites will be located in Visp in Switzerland - that is set to be completed in 2024 – and in Portsmouth in the US – the company anticipates that plant will go live next year.
“As part of this investment, the new facilities include N-1 perfusion capability, which enables increased process titers. The downstream capabilities are also designed to support such high-titer processes and accommodate the next generation of mammalian biologics. In addition, the facilities will include state-of-the-art technologies in automation and will feature a largely automated cell culture process allowing the platform to accommodate a diversity of products and cell lines.”
The sites, he said, offer customers an optimized path through BLA to market as well as the flexibility to meet challenges in product forecasting during the initial years of product launch.