Manufactured by Jetting - The Future in Protein A Affinity Matrix Design Part 3

In Part 2 of ‘Manufactured by Jetting - The Future in Protein A Affinity Matrix Design’, we discussed security of supply in mAb production, and managing risk by implementing a dual-sourcing strategy.  We also looked at Purolite Life Science’s patented ‘jetting’ process, and how it is being combined with a new alkaline-stable Protein A resin.

In the final part, we look at the new Praesto® Jetted A50 Protein A resin from Purolite Life Sciences

Characteristics of the New Praesto® Jetted A50 Protein A Resin

Praesto® Jetted A50 resin is the first product designed by combining the new technology for continuous manufacturing of agarose beads with a novel alkaline-stable Protein A ligand - NGL Impact A from Repligen Corporation. Process economy calculations based on characteristics of the new resin show the potential reduction of resin cost by >75% in clinical manufacturing. Figures 4 and 5 show the narrower particle-size distribution and dynamic binding capacities of the Praesto® Jetted A50 resin compared with three different resins.

Productivity and Process-Economy Simulations

Another important factor to consider when selecting a resin is
process economy, which is driven by resin price and resin lifetime, facility constraints, hardware requirements, and buffer consumption. Column dimensions vary widely from the standard 15–25-cm bed height typically used in traditional batch chromatography to 5–10-cm bed height columns that are used often in different continuous strategies. We determined DBC using a purified biosimilar of Avastin, bevacizumab. Table 1 shows four agarose-based protein A resins based on a common case, as follows:

  • Capture of a mAb from cell culture supernatant at 2000-L scale
  • Feed titer of 5.0 g/L
  • Capture of 10 kg MAb.
  • Load to 80% of the initially determined DBC at 10% breakthrough
  • Limit process time (purification only) to 10 hours
  • Residence time of two or six minutes
  • Bed heights of 10 and 20 cm and diameters of 45 and 60 cm
  • Buffer volume/purification cycle estimated to 17CV
  • Elution pool volume of 3 CV/cycle.

Figure 4. Particle-size distribution of the novel Protein A resin based on jetting technology vs traditional batch emulsified agarose resin, results determined by static imaging analysis.

 

Process Modeling

Our calculations provide an estimate of the effect of resin price and performance (Table 1). Factors related to risk, time, and cost of implementation, and
fulfilment of regulatory requirement also must be considered. However, it is clear that the use of new, high-capacity resins can lower cost of goods (CoGs) significantly. Even for conventional batch chromatography, applied savings of >75 % can be achieved.

Select Customer Results

The Praesto® Jetted A50 resin was introduced to the market in April 2018. Table 2 summarizes feedback from initial trials by several different pharmaceutical companies.

 

The Future: Jetting Technology

The industry is rapidly advancing mAb technology. Fc-fusion proteins, bispecific antibodies, IgG fragments, and drug-conjugated mAbs now make up most biologics in clinical pipelines. We believe that with the evolution of new classes of IgG-related biologics and novel expression systems, the industry also will have a constant need for new types of chromatography resins.

Successful implementation of jetting technology for continuous emulsification of agarose beads enables the design of a new platform of Protein A resins. We now can jet beads with 25–200-µm mean particle sizes.

 

Jetting is a robust and quantitative process that allows
a fast design of new agarose beads, matching requirements from both new chromatography ligands and novel pharmaceutical molecules and process technologies. The box on the next page shows data on a 25-µm bead with an open pore structure designed for counter-current tangential chromatography.

 

This article first appeared in Manufactured by Jetting - The Future in Protein A Affinity Matrix Design | Hans J. Johansson, Patrick Gilbert, Mark Hicks, and Oleg Shinkazh

* MabSelect is a trademark of GE Healthcare.  Amsphere is a trademark of JSR Life Sciences