The way to a design space for an animal cell culture process according to Quality by Design (QbD)

Application of a Quality by Design Approach to the Cell Culture Process of Monoclonal Antibody Production, Resulting in the Establishment of a Design Space

“…Another description of a design space can be achieved by applying constraints to the prediction models, as has been shown in other case studies . In such a case, the area within the criteria with values that predict high‐mannose can be defined as the design space.…”

“…FMEA is a common and useful risk analysis tool to find process parameters that require further process characterization . Process characterization experiments are typically conducted using DoE to evaluate not only the main effects of parameters but also their interactions . The potential CPPs that were identified by this risk assessment of the production culture step in the cell culture process were experimentally evaluated on a scaled down model by a multivariate study using DoE.…”

“…9,10 Interpretations of the application of QbD described in the guidelines differ within the industry, and concrete case studies of QbD as applied to biopharmaceutical drug substances are still limited. Some reports show original QbD approaches that focus on risk assessment and process characterization using design of experiments (DoE) for the processes of cell culture [11][12][13][14][15][16][17][18][19][20] and purification, 13,15,21,22 and the CMC Biotech Working Group published a mock case study covering all of the QbD elements for an antibody drug substance and drug product. 23 Interpre-tation of these initiatives by industry has been an ongoing process, with some notable industry and regulatory collaborations for biopharmaceuticals, and each pharmaceutical company should take on the challenge of this approach and find its own way.…”

“…12,13,16 Process characterization experiments are typically conducted using DoE to evaluate not only the main effects of parameters but also their interactions. [11][12][13][14][15][16][17][18][19][20] The potential CPPs that were identified by this risk assessment of the production culture step in the cell culture process were experimentally evaluated on a scaled down model by a multivariate study using DoE. A design space was established on the basis of those results and checked by Monte Carlo simulation.…”

Applying the Quality by Design to Robust Optimization and Design Space Define for Erythropoietin Cell Culture Process

“…There is still a contrast in the way different industries apply QbD as depicted in the guidance, and solid contextual investigations of QbD in biopharmaceutical industry are still limited. A few studies have shown unique QbD system that emphasizes risk analysis and design of experiment for cell culture process and purification procedures . Adoption of this approach by companies has, typically, been an process in progress, with a lot of prominent biopharmaceutical companies testing this approach according to their specific needs .…”