Manufactured by Jetting - The Future in Protein A Affinity Matrix Design Part 2

In Part 1 of ‘Manufactured by Jetting - The Future in Protein A Affinity Matrix Design’, we identified the most important factors to consider during the evaluation of Protein A resins, including dynamic binding capacity, process economics and functional lifetime.

In Part 2, we discuss security of supply in mAb production, and managing risk by implementing a dual-sourcing strategy.  We also look at Purolite's patented ‘jetting’ process, and how it is being combined with a new alkaline-stable Protein A resin.

Security of Supply and Risk Management:

Commercial processes could be operated for more than 20 years. It is therefore important to evaluate the financial stability of a vendor and ensure procedures are established for disaster recovery and product discontinuation. Production capacity and lead time are also key considerations when selecting a vendor to ensure a consistent, stable supply of adequate volumes of resin.

With the continued growth and therapeutic commercial importance of mAb production, the availability of high-quality agarose resins is critical.  Furthermore, as the current commercial patents for therapeutic antibodies expire, the cost of manufacturing will be of increasing interest.  Approximately 90% of all biopharmaceuticals approved by the U.S. Food and Drug Administration utilise a single source of agarose resins from a single manufacturing site, presenting a security of supply risk to long-term clinical trial material production.

Currently, only one vendor on the market has the capacity to supply agarose-based resins in the volumes required by the industry.  Therefore, the ‘security of supply’ of Protein A affinity resins is a major concern.  This was until Purolite Life Sciences developed its range of batch emulsified Praesto® resins.  The goal being to design resins to deliver the same performance as the market leading resins, and ultimately enable dual sourcing. 

What is Jetting?
Jetting is a continuous emulsification technology for manufacturing chromatography beads. Unlike batch emulsification, jetting produces beads without the need for additional sieving.

Benefits of a Narrow Particle-Size Distribution:
Absence of both fine and course particles provides a number of benefits or potential advantages over the use of other technologies:

  • Improved flow properties
  • Decreased eddy diffusion (improved resolution and decreased buffer consumption)
  • Reproducible column packing
  • Decreased resin fouling
  • Improved virus clearance
  • Potential use of larger mesh-size column filters (less risk of clogging).

Combining Jetting with a new alkaline-stable Protein A Resin

One size does not fit all, but based on our experience, particle sizes of 45–90 µm are the most useful beads for the direct capture of mAbs from cell culture supernatant. Purolite decided to first launch a 50-µm bead to support the need of resins suitable for continuous chromatography, which typically involves high DBC at 1–2 minute residence times and 5–10 cm bed heights. Based on the jetting technology and high-flow agarose chemistry, the new resin still has sufficient pressure-flow properties to enable traditional large-scale column chromatography (Figure 2).

To support effective, alkaline-based, CIP (Figure 3) and sanitization protocols, a new ligand from Repligen was used. The new recombinant Protein A ligand - NGL-Impact™ A - was developed by Navigo by screening a large library of Protein A constructs for alkaline stability.

In the final part of ‘Manufactured by Jetting - The Future in Protein A Affinity Matrix Design’, we’ll look in more depth at how jetting and the NGL-Impact™ A ligand from Repligen work together to produce Purolite Life Science’s new Praesto® Jetted A50 resin.

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