When purifying MAbs from high-titer cell culture supernatants, economy was demonstrated to be even further improved by the use of MabSelect SuRe LX medium in the capture step of the downstream purification process (Fig 2). Between 20% and 46% higher binding capacity for various MAbs has been demonstrated (3).Ĭompared with a conventional protein A medium, process economy can be significantly improved by using MabSelect SuRe media in purification of MAbs (4). Compared to MabSelect SuRe medium, MabSelect SuRe LX offers an increased dynamic binding capacity (DBC) at a slightly longer residence time. To meet the needs associated with high-titer upstream processes, MabSelect SuRe LX was introduced (2). The highly cross-linked agarose matrix of MabSelect SuRe media enables the use of high flow velocities at production scale. The stability of the protein A ligand minimizes ligand leakage and allows for the use of rigorous and cost-effective cleaning procedures based on NaOH. MabSelect SuRe media consists of an alkaliand protease-stabilized, recombinant protein A ligand coupled to a rigid, high-flow agarose matrix. The high selectivity, resulting in excellent purity (often 99% or more) and high yields, makes protein A-based affinity chromatography media a suitable choice for the MAb capture step. To facilitate effective process development, our selection of chromatography media is available in bulk, as well as in a broad range of scalable formats for high-throughput process development. For the polishing steps, traditional ion exchangers such as Capto™ SP ImpRes and Capto Q media or multimodal chromatography media such as Capto adhere, Capto adhere ImpRes, or Capto MMC ImpRes are used (Table 1). The capture step of the purification process is most commonly performed using protein A media such as MabSelect SuRe™ or MabSelect SuRe LX media. GE Healthcare chromatography media for MAb purification are all based on high-flow agarose base matrices. New chromatography media are introduced with enhanced features, such as higher binding capacity or better selectivity. However, continuous improvements of these platforms are desirable as technologies are evolving. The use of platforms for MAb production is well-established. Downstream MAb purification platforms commonly include a protein A-based purification step followed by one or two polishing steps to remove remaining impurities (Fig 1). Technology platforms (i.e., standard sets of unit operations, conditions, and methods applied to a given class of molecules) allow for efficient processing from research and development, through clinical phase trials, to the manufacturing of the final product. MAbs, as a class of molecules, exhibit many shared properties, which make them well-suited for a platform approach to downstream processing. Improved productivity upstream has put greater demand on downstream processing to address the high titers of MAbs in harvested cell culture fluids.
As a consequence, the antibody titers in upstream cell culture processes have dramatically increased. Representing about 36% of the total biopharmaceutical market, with an annual sales growth rate of approximately 10%, MAbs are the single largest class of biological drugs today (1), The rapidly growing demand for MAbs has triggered a need for an elevated manufacturing capacity. An introduction to highthroughput process development (HTPD) is also given, together with specific case studies of purification step development. This paper is a guide to the development of MAb purification platforms and gives an overview of GE Healthcare Life Sciences offering of process chromatography media (resins) for MAb purification processes.
With increased MAb titers, the cell culture supernatant might contain an elevated number of impurities (e.g., aggregates) that need to be separated from the target molecule. Increasing product titers upstream can introduce challenges in downstream purification processes. As a result, more cost-effective, efficient, and flexible process purification solutions are of high priority for MAb manufacturers. The use of monoclonal antibodies (MAbs) and MAb conjugates as biopharmaceuticals have increased over the last decade.
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