Abstract
A production system based on airlift reactors has been developed for the manufacture of monoclonal antibodies. The production vessels have a working volume of 1000 litres and computer control provides a high degree of process automation. We have observed antibody production levels between 40 and 500 mg / litre, with an overall average for all cell lines of 109 mg / litre. A serum free medium is in routine use at production scale. More than half the antibody generated in batch culture is produced during the decline phase of growth. For product recovery, the culture supernatant is first clarified by continuous centrifugation and then concentrated by tangential flow ultrafiltration. The antibody is subsequently purified by high resolution separation techniques, in particular chromatography on immobilised Protein A. For therapeutic antibodies, the emphasis is increasingly on analytical techniques (e.g.DNA assays) required to validate process consistency and product quality.
The current batch fermentation process is capable of producing 100 g batches of antibody for an average cell line. A 10,000 litre fermenter, capable of producing kilogram batches, has been designed.
