Chemist US Food and Drug Administration Silver Spring, Maryland
The presentation will first discuss the BsUFA III Regulatory Research Pilot Program: Research Roadmap (https://www.fda.gov/media/164751/download) that was published earlier this year, with public comments provided from 01/25/2023 to 04/05/2023 (https://www.regulations.gov/document/FDA-2023-N-0254-0001). As part of BsUFA III commitments, FDA has identified two research priorities that will help support the development of biosimilars: 1) Increase the accuracy and capability of analytical (structural and functional) and CMC characterization and 2) Develop alternatives to and/or reduce the size of studies involving human subjects. As such, the quality of analytical data which supports analytical comparability assessment, and bioanalytical data which supports clinical studies, might be more crucial during the development of biosimilars and interchangeable products.
Next, the presentation will discuss how the scientific principles described in ICHQ2(R2) Validation of Analytical Procedure Guideline (draft), ICHQ2(R2) Annex 2 Illustrative Examples of Analytical Techniques (draft), and ICHQ14 Analytical Procedure Development (draft) can be applied to facilitate analytical and bioanalytical method development and help improve in-study method performance. The discussion will endeavor to focus on the following topics: • Analytical target profiles (ATP) and technology selection • Technology inherent justification • Challenges due to possibly different formulation used in biosimilars • Risk assessment and mitigating strategies • Orthogonal procedure comparison • Method robustness
The presentation will then discuss the recently published FDA M10 Bioanalytical Method Validation and Study Sample Analysis Guidance, to highlight the differences between the current Guidance and previous version and discuss how the recommendations in Guidance will strengthen bioanalytical data quality. Potentially, the discussion will focus on the following topics: • Understanding the analyte of interest and considering aspects of any prior analytical methods • Documenting changes to the method and the rationale • Choosing stable isotope-labeled analogs as the IS • Specificity: detecting and differentiating the analyte from other substances especially its related substances • Monitoring the IS responses of the quality control and study samples • Understanding the potential and real differences among different bioanalytical technologies
The presentation will use recent regulatory examples and literatures as case studies to elaborate rationale and application of testing strategies, as well as how the critical questions mentioned above were addressed. The discussion and case studies highlight that communication between FDA and sponsors at critical junctures in drug development may help facilitate the successful adoption of novel technologies to address the structural complexity, better understand clinical data requirements and thus improve the efficiency of biotherapeutics/biosimilars development.
Learning Objectives:
Participants will better understand how the recommendations in FDA M10 Bioanalytical Method Validation and Study Sample Analysis Guidance and ICHQ2(R2) Validation of Analytical Procedure Guideline (draft) will strengthen data quality.
Participants will understand the importance of good practices in the systematic and rigorous implementation of BMV guidance, especially when adopting new technologies and implementing new technologies for new applications.
Participants will be able to identify and access evolving practices in LC-MS based bioanalytical methods for biotherapeutics which can assure the quality of bioanalytical data to support regulatory decision.