Traditional and Current Approaches and Relevance to Regulatory Guidance
Pharmaceutical companies are under tremendous pressure to minimize costs during drug development. In an attempt to accomplish this, some companies choose to defer radiosynthesis and nonclinical radiolabeled ADME studies until they achieve proof-of-concept (POC).
Followers of this approach thus face the challenge of meeting the MIST and ICH M3(R2) recommendations to assess the safety of metabolites earlier in drug development without, however, the benefit of the most facile and reliable means to achieve– radiometric detection. Non-radiolabeled approaches to metabolite characterization, used increasingly in non-clinical development as part of the approach outlined above, have risks associated with them. This is due in part to the increased likelihood of metabolites remaining undetected, for example, in the preclinical toxicology species.
During clinical development, these unidentified metabolites could potentially give rise to seemingly unique or disproportionate human metabolites of which the regulatory agencies expect a safety assessment. However, recent advancements in analytical hardware and software technology have significantly reduced the probability of metabolites of significant importance remaining unidentified.
This presentation will discuss traditional and current approaches to metabolite characterization, including advantages and disadvantages, and their relevance to the regulatory guidance. Furthermore, we will present examples of how inexpensive additions to non-clinical studies provide metabolite information that potentially helps you to avoid delays during clinical development.
Presented by
Joseph Marini, PhD,
Principal Investigator, Metabolite Identification
Dr Marini received his PhD in Chemistry from Texas A&M University in College Station, Texas. He began his carrier in the pharmaceutical industry with Wyeth Research (now Pfizer) where he was responsible for developing and supporting high-throughput ADME assays in support of over 65 different project teams. In 2009, he joined the Drug Metabolism Department at Covance in Madison, Wisconsin. He is one of eight principal investigators responsible for small molecule drug metabolite identification in support of discovery, development and clinical research studies.
Richard Clayton,
Staff Scientist, Metabolite Identification
Richard received his HNC in Chemistry from Reading College of Technology and began his career with Reading Scientific Services in Analytical Chemistry. Richard joined the Covance Metabolism Department at Harrogate, UK in 1991 and was involved in the formation of the Mass Spectrometry Group in 1993. Richard led the transition to high resolution mass spectrometry and Ultra High Performance Liquid Chromatography, particularly in the application of non-radiolabeled metabolite identification. Now a Staff Scientist in the Metabolite Identification Group, he is responsible for implementing new technologies and overseeing a team that performs metabolite identification studies using LC-MS/MS.
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Key Learning Objectives
- Understand traditional approaches to metabolite characterization and how they address regulatory guidance recommendations
- Learn about how current technologies in mass spectrometry address regulatory guidance recommendations
- Obtain insights into the advantages and disadvantages of current approaches to metabolite characterization
- Learn about simple, inexpensive approaches to studies that can help you avoid delays during clinical development
Audience
- CEO/President/Chairman/Executive Director
- CEO/President/Chairman/Executive Director
- Pharmaceutical Companies
- Corporate Management
- Senior R&D/Lab R&D
- Therapeutic Area Leaders
