Implementing Process Controls for Cell-Based Assays

Bioassays are used to demonstrate that a biological product performs per the stated function and potency.

Typically, these methods are performed in living systems. Cell-based methods can have inherent variability due to the nature of living systems. Minimizing potential variability can be achieved through careful documentation and analysis of assay performance on control charts. Monitoring numerous parameters may assist laboratory scientists, laboratory managers, QC, and QA personnel to identify and manage trends that could lead to OOS/OOT results. Monitoring also decreases failure rates by trending parameters that have a direct impact on cell-based methods meeting acceptance criteria. A significant consideration for these methods is setting appropriate system suitability that is consistent with methods that experience higher variability. Since the number of parameters evaluated is dependent on the cell type, assay type, and a number of critical components or reagents, this webinar will provide a general overview of the topic as well as specific examples of successful monitoring of cell-based methods leading to a reduction in assay failures. Cell-based methods are known for variability. Living systems introduce complexity that is not present in simple in vitro methods. Cells respond to the culture medium and control environmental conditions at different levels depending on receptor expression, cell passage number, and density in the flask or on the plate. Responses to small changes in reagents, analyst techniques, and the environment can have a major impact on cell-based systems. Cells are the primary critical reagent in any cell-based system, whether in production or in a test method. As in any method, control of the critical reagent is essential for reducing variability. Proper handling of cells and the implementation of controls that are an integral part of the method can reduce variability in cell-based methods. Control is not just achievable during the performance of the method. Process controls must also be considered during cell thaw and seeding, and when seeding of stock cultures used to seed assay plates. Attendees of this webinar will be introduced to concepts designed to assist with developing cell-based methods focused on a reduction in assay failures. We will address understanding sources of variability and examine the critical characteristics of cell-based assays. Specifically, the webinar addresses the characterization of the cell line, cell maintenance, culturing cells prior to assay set-up as well as for assay set-up. Although the cells are the primary critical reagent, this webinar will also review other critical reagents important in cell culture and cell-based methods. To assist with monitoring we will discuss intermediate performance controls assessed by control charts. Additionally, the webinar will examine and highlight the handling of other critical reagents necessary for cell culture. This includes certification of critical reagents prior to use in method validation or sample analysis. The use of alert and action limits with control charts will also be addressed for effective monitoring. Finally, writing of the methods and training of analysts to decrease variability will be addressed.