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The latest papers on monoclonal antibody production | BioQuality.biz

The 30 monoclonal antibodies authorized for marketing as human drugs represent, in terms of market share, the most important biotherapeutics. Two recent papers in Biotechnology Progress address GMP production of monoclonal antibodies. One deals with the important topic of process robustness, introducing a simulation tool to assess process robustness–current and future–in a mAb production facility. The second article presents a review of design and validation of downstream processing.

1) Decisional tool to assess current and future process robustness in an antibody purification facility, Stonier A, Simaria AS, Smith M, Farid SS, University College London, Department of Biochemical Engineering, Torrington Place, London, WC1E 7JE. UK; Lonza Biologics plc, MS&T, 228 Bath Road, Slough, SL1 4DX, UK, Biotechnol Prog. 2012 May 29. doi: 10.1002/btpr.1569 [Epub ahead of print]


  • Increases in cell culture titers in existing facilities have prompted efforts to identify strategies that alleviate purification bottlenecks whilst controlling costs
  • This paper describes the application of a database-driven dynamic simulation tool to identify optimal purification sizing strategies and visualise their robustness to future titer increases
  • The tool harnessed the benefits of MySQL to capture the process, business and risk features of multiple purification options and better manage the large datasets required for uncertainty analysis and optimization
  • The database was linked to a discrete-event simulation engine so as to model the dynamic features of biopharmaceutical manufacture and impact of resource constraints
  • For a given titer, the tool performed brute force optimisation so as to identify optimal purification sizing strategies that minimised the batch material cost whilst maintaining the schedule
  • The tool was applied to industrial case studies based on a platform monoclonal antibody purification process in a multisuite clinical scale manufacturing facility
    • The case studies assessed the robustness of optimal strategies to batch-to-batch titer variability and extended this to assess the long-term fit of the platform process as titers increase from 1 to 10 g/L, given a range of equipment sizes available to enable scale intensification efforts
  • Novel visualisation plots consisting of multiple Pareto frontiers with tie-lines connecting the position of optimal configurations over a given titer range were constructed
    • These enabled rapid identification of robust purification configurations given titer fluctuations, and the facility limit that the purification suites could handle in terms of the maximum titer and hence harvest load

To see the Abstract, and a link to obtain this paper: http://www.ncbi.nlm.nih.gov/pubmed/22641562

2) State of the art in downstream processing of monoclonal antibodies: Process trends in design and validation, Pa MG, Mm A, Centro de Biotecnología-FEMSA, Tecnológico de Monterrey at Monterrey, Av. Eugenio Garza Sada 2501, 64849 Monterrey, N.L., México, Biotechnol Prog. 2012 May 29. doi: 10.1002/btpr.1567. [Epub ahead of print]


  • Monoclonal antibodies are the most important family of biopharmaceutical compounds in terms of market share
  • At present, 30 monoclonal antibodies have been approved and are now commercialized for therapeutic purposes
  • Monoclonal antibodies are typically produced in widely-varying scale by mammalian cell culture in bioreactors
  • Regardless of scale, from laboratory to commercial settings, the recovery and purification of monoclonal antibodies presents important challenges
  • Depending on the scale, the particular product, and the type of production process (bioreactor operation, process time, complexity of the culture media, cell density, etc.), many possible downstream configurations are possible and have been used
  • The paper reviews each type of unit operation that forms a downstream train for monoclonal antibody production
  • The article also provides information regarding typical operation settings and critical variables for centrifugation, ultrafiltration, affinity chromatography, ion exchange chromatography, and viral removal operations
  • In addition, some important considerations required for the formulation of drugs based on monoclonal antibodies are discussed

To see the Abstract, and a link to obtain this paper: http://www.ncbi.nlm.nih.gov/pubmed/22641473

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