Validation scientists in bioanalytical or clinical laboratories

August 12, 2020 - CA US


Overview: Validation of test methods is a critical requirement for the drug development process. Bioassays are used to support biologics in the drug development process and in post-market analytical support. Unlike analytical test methods for small molecules, bioassays have unique requirements due to the variable nature of some critical components. Although some variability may be inherent, careful attention to setting appropriate limits and to robust qualification of critical components enhances the likelihood of success during validation. Regulatory agencies expect pharmaceutical companies and biopharmaceutical companies to use validated methods for late phase work. The methods are used to test large molecule drug substance or drug product for identity, purity, and potency. Poorly developed and inadequately validated methods often have high failure rates when in production. Data submitted from poorly developed/validated methods is subject to additional scrutiny due to the excessively high failure rate that lowers confidence in the data that is produced. Cell-based methods may be difficult to validate due to a lack of extensive testing during the development phase. Method validation requires careful design of the method during development and seamless implementation to meet regulatory agency expectations for the quality of assay methods used in testing of biopharmaceutical or pharmaceutical compounds. Cell-based methods have additional complexities that may contribute to variability. With appropriate controls in place in the method variability can be minimized leading to successful validation and sample analysis using the cell-based method. This webinar will address several parameters that are important for the successful validation of a bioassay. Included in this discussion are multiple challenges that often lead to rework and failure that if appropriately addressed during development should not become issues that hinder validation. This webinar addresses the importance of method development in successfully overcoming difficult validations. Specific topics are unique challenges for cell-based methods, use of DOE to define method parameters, and creating unambiguous methods. This webinar will provide attendees with an understanding of handling critical reagents as well as challenges faced in cell culture. Details important in the written method as well as details for the validation that reduce analyst variability and improve efficiency will also be addressed. This webinar will not just define challenges but will also guide professionals working with cell-based methods toward important concepts that promote success in method validation. Appropriate training and documentation of the method are critical elements for successful transfer of a method from the development phase into the validation procedure. Accomplishing the validation of a cell-based method with little or no rework can occur with careful planning and attention to an appropriate timeline. An important factor that contributes to failure is rushing into validation without collecting the data required to support fully a decision to move toward validation. This webinar addresses those issues that may lead to failure of validations of cell-based methods while providing solid suggestions for best practices that support success. Why you should Attend Bioassays, especially cell-based methods are a necessary component of assays providing data supporting large molecule therapeutics. Typically, these methods are required to establish potency, a critical quality attribute, in either release or stability assays. The live cell quality of these assays may introduce a layer of uncertainty regarding the ability to build a method that meets requirements for ruggedness. Cells that express the receptor responsible for the mechanism of action may be a transfected clonal line or may be a cell expressing the native protein. The growth characteristics of the cell that promote expression levels with good signal-to-background in the method are an important quality to address as development of the assay begins. A key question may be how much prework to perform to guide development of the assay. Live cells are not as simple to control as individual reagents in a method. Live cells respond to components in media, environmental factors, and seeding densities in a manner that may have an impact on growth characteristics, receptor expression, and signals in cell-based methods. These issues should be assessed fully and examined in early development work to direct the lab toward the parameters likely to produce an assay with a low rate of failure. This complexity often leads to problems when factors that contribute to ruggedness in cell-based methods are not assessed and addressed during the development phase. Successful validation is achievable with careful consideration of the cells as the primary critical reagent. Control of the assay starts with control of the cells. While sufficient time is needed to perform development using design of experiments, moving from development to validation should be based on the quality of the data observed in the assay and not inordinately pushed forward. Areas Covered in the Session Method selection Understanding the variable nature of cell-based methods Understanding the critical characteristics of cell-based assays that may affect performance Characterization of the cell line Details of cell maintenance, cell culture prior to performing the method Defining parameters to monitor Defining critical reagents Selection and certification of the reference standard Setting appropriate limits for reagents Reagent supply and sample handling Pre-test of critical reagents Setting intermediate performance controls Testing robustness/ruggedness/selectivity/specificity prior to validation Analyst training Peer review of the test method Statistical analysis Validation protocol and templates Preplanning Documentation of deviations and failures Who Will Benefit Validation scientists in bioanalytical or clinical laboratories Development scientists in bioanalytical or clinical laboratories QA Documentation Specialists Regulatory Specialists Consultants Directors of Outsourcing Method trainers Statistical staff Speaker Profile Gwen Wise-Blackman, Ph.D. has over 20 years of combined experience in Cell-Based Assays and Quality Systems. She has worked at DuPont Pharmaceuticals, Catalent Pharma Solutions (formerly Magellan Laboratories and Cardinal Health), and Salix Pharmaceuticals where she successfully managed multiple projects and held positions of increasing accountability for scientific and quality expertise. Currently she is the owner of Gwen Wise-Blackman Consulting, LLC, a biopharmaceutical consulting firm.

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