Good Practices in Bioanalysis of Biotherapeutics Using LC-MS Based Approaches

The presentation will discuss the regulatory requirements for bioanalysis of biotherapeutics using LC-MS based approaches and the critical questions that need to be addressed during method development, validation and implementation to clinical studies. The critical questions include but are not limited to:
• What’s the scientific justification for the use of LC-MS based approaches (strategical, technical and practical considerations)?
• Does the selected signature peptide readily differentiate the targeted biotherapeutics and its endogenous counterparts?
• Does the assay have sufficient sensitivity to assess the pharmacokinetics of the product adequately (feasibility of using nano flow hybrid LC-MS/MS)?
• Does biotransformation impact in-study assay performance? Which kinds of mitigating strategies can be implemented?
• Rationale for the using of immunocapture procedure during sample preparation (anti-ID Ab, anti-peptide Ab, soluble target, etc).
• Selection of internal standard(s) and control strategy for in-study matrix effect.
• Acceptance criteria for accuracy and precision.
• Automation for increasing reproducibility and throughput.
The presentation will focus on two case studies, Trastuzumab and REGN10933 + REGN10987, to thoroughly elaborate how these critical questions were addressed. It can be clearly seen from the discussion and case studies presented in the presentation that communication between FDA and sponsors at critical junctures in drug development may ultimately facilitate successful adoption of novel technologies to address the structural complexity and the manufacturing of biotherapeutics.