SC18: NEXT GENERATION SEQUENCING AS A DIAGNOSTICS PLATFORM
Monday, March 7 | 8:00 – 11:00 am
ABOUT THIS COURSE:
Next generation sequencing is entering its second decade as a commercial technology. A diversity of clinical diagnostic assays are now being routinely performed on a variety of NGS platforms, spanning from single gene to multi-gene sequencing, to genome wide analyses for the detection of germline and somatic mutations. The diversity of diagnostic applications has been accompanied by multiple implementation approaches being used by clinical laboratories for specific NGS diagnostic assays. For clinical laboratories with NGS experience, and especially for those just starting to use the technology, designing and operationalizing robust NGS assays remains a challenge. This short course will review validation principles relevant to NGS assays including intended use to drive assay design, establishment of performance metrics, and post-clinical launch quality monitoring. Case studies will be presented for germline and somatic mutation diagnostic assays. Integrated into the course will be discussion of current regulatory viewpoints on NGS assays and the College of American Pathologists' accreditation requirements and proficiency testing for NGS.
COURSE AGENDA:
8:00 am Moderator's Remarks
Validation and Implementation of NGS Diagnostic Assays: The Continuing Challenge
Karl V. Voelkerding, M.D., Professor of Pathology, University of Utah School of Medicine
8:05 Bringing up NGS Assays in the CLIA Lab: Considerations for Coping with an Evolving Regulatory Landscape
Jamie Platt, Ph.D., Vice President of Genomic Solutions, Molecular Pathology Laboratory Network
A decade of commercially available NGS technology has not only brought us major clinical insights in diagnostics, prognostics and theranostics, but has also given us platforms suited to various throughputs and applications. These platforms now have streamlined workflows that are better suited to a variety of clinical lab environments with varied levels of technical capabilities. In addition, labs also now have the option of choosing FDA cleared NGS systems and clinical in vitro diagnostic (IVD) assays. While bringing up an NGS IVD assay lessens the overall R&D burden, there are still important development considerations in terms of the entire testing process. Examples from the MiSeqDx Cystic Fibrosis 139-Variant Assay and Cystic Fibrosis Clinical Sequencing Assay will be provided. Key considerations for delivering Laboratory Developed Testing Procedures (LDPs or LDTs) and FDA cleared assays (IVDs) will be discussed in the context of an evolving regulatory environment and FDA regulation of assay development.
8:55 Selection, Development and Analytical Validation of a Targeted NGS Assay for the Support of the NCI-MATCH Trial
Mickey Williams, Ph.D., Director of the Molecular Characterization Laboratory at Frederick National Laboratories for Cancer Research
NGS assays are rapidly becoming a standard of cancer patient management. The complexity of this technology requires clear description of the specific parameters comprising the assay systems, methods used to establish analytical validity and guidance for clinicians and patients on how assay reports should be used. A discussion of the NCI-MATCH NGS assay development and analytical validation will serve as a case study.
9:35 Refreshment Break
9:50 Validation and Implementation of NGS Assays within the Framework of CAP Accreditation and Proficiency Testing Requirements
Karl V. Voelkerding, M.D., Professor of Pathology, University of Utah School of Medicine
Clinical laboratories offering NGS based diagnostic assays are required to meet regulatory requirements under CLIA. To date, the only NGS specific accreditation requirements in the U.S. are those developed by the College of American Pathologists and New York State. This presentation will describe the NGS validation and implementation accreditation and proficiency testing framework developed by the CAP emphasizing a methods-based validation approach that is customized by intended use.
INSTRUCTORS:
Karl V. Voelkerding, M.D. FCAP, Professor of Pathology, University of Utah; Medical Director, Genomics and Bioinformatics, ARUP Laboratories; Chair, CAP Next Generation Sequencing Project Team
Karl V. Voelkerding, M.D., received his Bachelor of Science from the Ohio State University in 1978 and his Medical Degree from the University of Cincinnati College of Medicine in 1983. Subsequently, he completed post-doctoral research and clinical training in molecular biology and clinical pathology. In 1990, he joined the faculty of the Department of Pathology and Laboratory Medicine at the University of Wisconsin in Madison, Wisconsin, where he developed and directed a molecular diagnostics laboratory while also practicing transfusion medicine. In 2001, Dr. Voelkerding served as President of the Association for Molecular Pathology, and in 2002 he moved to Salt Lake City, Utah to join the ARUP Laboratories. Currently, he is a Professor of Pathology at the University of Utah and a Medical Director of Genomics and Bioinformatics at the ARUP Laboratories. Dr. Voelkerding is board certified in clinical pathology and molecular genetic pathology. He has a longstanding involvement in the translation of new technologies into molecular diagnostics, and this interest has focused over the past few years on next generation sequencing. Dr. Voelkerding’s current funded research focuses on the utilization of genomic approaches to elucidate the genetic basis of primary immune deficiencies. He is currently the Chair of the College of American Pathologists Project Team on Next Generation Sequencing which is responsible for developing laboratory accreditation requirements and proficiency testing programs for clinical next generation sequencing.
Jamie L. Platt, Ph.D., Vice President, Genomic Solutions, Geneuity
Dr. Platt received her Ph.D. in Molecular & Cellular Biology from Oregon State University and completed postdoctoral training in population genetics at the University of California, Berkeley. She has extensive expertise in sequencing and molecular systematics, including population genetics. During her 15 years in clinical diagnostics, Dr. Platt has developed, validated, and commercialized numerous high complexity sequencing assays in the clinical areas of Infectious Diseases, Oncology, and Molecular Genetics. Dr. Platt has spent nearly 10 years overseeing development of next generation sequencing assays for both clinical diagnostics and clinical trials, resulting in at least 18 commercially available NGS-based tests. In addition to contributing to clinical NGS guidelines (CLSI MM09), she serves on several sequencing and genomics advisory boards, including Genomics England. Dr. Platt has special interest in transitioning emerging technologies to regulated molecular clinical diagnostics and applying advancing sequencing technologies (NGS) to improve personalized healthcare.
P. Mickey Williams, Ph.D., Director, Molecular Characterization Laboratory, Frederick National Laboratory for Cancer Research
Dr. Williams received his doctorate from the University of Virginia, and did postdoctoral work at Stanford University. He spent thirteen years at Genentech, where he developed novel assays to support clinical studies and discover new therapeutic targets and contributed to the development of “real-time” PCR technology. Prior to joining CDP in 2010, he was a senior research group leader at Roche Molecular Diagnostics, managing two large multi-national clinical assay studies: The MILE Study (microarray innovations in leukemia) and a collaboration with the LLMPP (leukemia and lymphoma molecular profiling project) and also led projects that led to two FDA approved companion diagnostic tests. In his current position he continues to make contributions to the use of molecular technologies for use as clinical assays.
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