Scaling up Plant Cell Pack technology to production scale

For the production of complex recombinant proteins, mammalian cells—particularly Chinese Hamster Ovary (CHO) cells—are typically used, as they are the gold standard in the industrial large-scale production of therapeutic antibodies.

However, when developing new product candidates, producing proteins for rare diseases, or creating therapeutic and/or diagnostic proteins needed on short notice, smaller-scale production systems are required. These systems must be able to rapidly and flexibly produce complex proteins on a gram scale.

The surge in demand for complex proteins during the COVID-19 pandemic—for both vaccines and diagnostics—demonstrated that mammalian cell production capacities are not designed for small- to medium-scale quantities required in product development. Furthermore, the pandemic revealed the risk of supply shortages in key cell culture media components, particularly fetal bovine serum, which further hampered production.

In addition, new innovative product candidates—such as certain growth hormones, metabolic enzymes, immunotoxins, and protein-based vaccines—are increasingly being developed, many of which cannot be produced efficiently in mammalian cells or can only be produced at very low yields.

To close this gap in medium-scale production capacity for the development and manufacture of complex proteins in a sustainable and crisis-resilient way, it is essential to establish alternative production platforms. Such medium-scale production capacities are especially crucial for small and medium-sized enterprises (SMEs) developing product candidates for niche applications. They enable the production of sufficient quantities for functionality, efficacy, or safety studies and help determine whether economic large-scale production is feasible and profitability can be achieved.

The overarching goal of this project is to transfer and scale up PCP technology for the transient production of recombinant proteins from the screening scale in microtiter plate (MTP) format (50-100 mg biomass per PCP for 1-2 μg of product) to medium production scale (approximately 5-20 kg biomass for 1 g of product).

To achieve a scale-up of recombinant protein production in PCPs by a factor of 1:1,000 to 1:10,000, two technical approaches (centrifugation and filtration) will be developed in combination with process control strategies (co-cultivation and incubation conditions) that can be directly and cost-effectively implemented in the existing infrastructure of industrial customers, particularly SMEs.