End-to-End continuous processes enabling the implementation of lean, flexible and portable biomanufacturing

Veena Warikoo, Ph.D.
Genzyme Sanofi

  • Historically, conversion from batch to continuous processing has resulted in lean, fully automated and agile manufacturing regardless of the nature of an industry. This conversion has enabled these industries to overcome key business continuity challenges by reducing manufacturing OPEX, CAPEX, and in many cases, enhancing portability. The Biologics industry is facing similar challenges due to the emergence of competition from biosimilars, cost pressures due to declining industry growth, and the desire to gain access to emerging markets through standardization and portability. To leverage the lessons learned from other industries, there has been significant interest in the implementation of continuous bioprocessing. At present, the confluence of downstream emerging technologies and the business need to innovate is catalyzing the development of continuous bioprocessing
  • This talk will show that continuous bioprocessing is a means for realizing our vision of a lean manufacturing facility with a “ballroom” design floor plan that utilizes multiple parallel and independent production lines designed as functionally closed “end-to-end” systems
  • We will provide a case study which demonstrates the feasibility of end-to-end continuous bioprocessing using a mAb as a model protein
    • Through the use of both well-established and new technologies this case study will show integration of upstream and downstream unit operations to meet our operational design goals of a) process train simplification, b) uninterrupted and fully automated purification to the DS over an extended period of time, and c) steady state operation with respect to process flows and product quality
    • We will also provide an update on the development and integration of continuous viral filtration and ultrafiltration/diafiltration unit operations, which are critical to the universal application of end-to-end bioprocessing
    • Examples will be presented to show real time process monitoring using continuous and cyclic data from SMB
  • Scale up to manufacturing scale
    • Data will be presented to show functionally closed operation at manufacturing scale for prolonged durations, thus demonstrating the feasibility of controlled but non-classified (CNC) biomanufacturing facilities. The solution includes the use of a proprietary waste disposable technology to prevent the facility from getting contaminated
    • A key design goal for process intensification will be demonstrated, at scale, through the achievement of a maximum viable cell density of >150MCell/mL at a volumetric productivity of >2.5g/L/day
  • Next, the presentation will highlight ongoing work on at/in-line monitoring of the product quality using Process Analytical Technology and data management solutions
  • Finally, the presentation will conclude with a brief discussion of the generic input from regulatory authorities in response to Sanofi’s continuous biomanufacturing program