Flow Cytometry Validation for Drug Development: Instruments and Methods

December 5, 2011
12:30 pm–2:00 pm

Ligand Binding Assay Bioanalytical focus group–Flow Cytometry Action Program Committee
Presented by Cherie Green, Thomas McCloskey, Ph.D., Yaunxin  Xu, Ph.D.
Moderated by Virginia Litwin, Ph.D., Covance  

About the Webinar

Flow cytometry is a powerful and flexible analytical tool used during all stages of drug development. While substantial effort is invested in development and validation of analytical methods for biomarkers, instrument validation is often neglected. Rapid technological advances and extended timelines for bringing a drug from discovery to the clinic often create unique challenges for ensuring data integrity. This webinar will provide an overview of key concepts for validation of flow cytometry platforms in regulated environments (pre-clinical, early phase clinical). The focus will be on understanding the key issues for ensuring data integrity across instruments, analysts, time, and geographic locations.

The Flow Cytometry APC has recently published two manuscripts: one on method validation and one on instrument validation (JIM, 363:104-119, 2011. JIM, 363:120-134, 2011.) As a follow-up to these two important papers we would like to present a series of three webinars between June and December, 2011: 1) Introduction to Flow Cytometry; 2) Flow Cytometer Instrument Validation; 3) Flow Cytometric Assay Validation.

Although the value of utilizing flow cytometry in drug discovery and development is gaining recognition, the technology is still under-utilized. This may be due in part to a general lack of understanding about the technology as well as the complexities associated with validation.

The focus of the three webinars will be to increase the understanding of flow cytometry and its application in the drug development process. The webinars will be of interest to both novice and advanced users of the technology.

Webinar Agenda
  • Understanding regulations and industry guidance: GLP, GCP, CLIA, ISO and beyond 
  • What is validation and why should we do it?
  • Principles of instrument validation (standardized methods and change control, installation and performance qualification, life cycle maintenance and system retirement
  • Documentation
About the Presenters

GreenCherie Green is a scientist in the Clinical Immunology department at Amgen Inc., based in Thousand Oaks, Calif. She has been actively engaged in the field of regulated flow cytometry since 1994. At Amgen, she and her team are responsible for developing, implementing, and monitoring high complexity flow cytometric assays to measure cellular changes in response to investigational therapeutics with an emphasis in the areas of autoimmunity and hematological malignancies. Prior to Amgen, she spent many years cultivating expertise in the areas of leukemia and lymphoma immunophenotyping at Hematologics Inc. and T-cell therapeutics at Xcyte Therapies in Seattle, Wash. She has presented her work in publications and through domestic and international presentations.

McCloskeyThomas W. Mc Closkey, Ph. D., joined ICON Central Laboratories in October of 2007 as associate director, Research and Development. Mc Closkey obtained his bachelor's in biology from Hofstra University in New York and his doctorate in immunology from Rutgers University in New Jersey. At North Shore University Hospital in New York, he served as director of Flow Cytometry for the Department of Pediatrics from 1993–2004 and as scientist-in-charge for the Flow Cytometry Core Facility from 2004–2007.

Mc Closkey has written more than 40 manuscripts and book chapters related to flow cytometry and has presented his research at both national and international conferences. He is a member of the New York/New Jersey Flow Cytometry Society and the International Society for Analytical Cytology. In 1998, Mc Closkey won the Presidential Award of Excellence, which recognized him as the Top Young Investigator in Flow Cytometry in a worldwide competition.

Yuanxin Xu2Yuanxin Xu, Ph.D., is currently senior scientific director at Clincial Laboratory Sciences at Genzyme, a Sanofi company. Her group is responsible for development/validation of clinical assays to support clinical trials and postmarket programs for pharmacokinetics (PK), pharmacodynamics, safety, immunogenicity, and biomarkers. The group has validated flow cytometric methods for detection of anti-drug neutralizing antibodies, PK, full panel of lymphocyte phenotyping (T, B, NK/Activated NK, CD4/CD8 T, Activated T, Naive/Memory T, Treg, DC, etc), cell surface receptor occupancy, and biomarkers (such as HLA tetramer for Ag specific T cells). Before joining Genzyme in 2002, she had worked at BioTransplant on allo and xeno organ/cell transplantation and induction of immune tolerance. She has received her doctorate from Iowa State University majoring in biochemistry and her Bachelor of Medicine from Beijing Medical University (now part of Peking University).

LitwinVirginia Litwin obtained a doctorate in virology/immunology from the University of Iowa. As a graduate student, she was a pioneer in the application of flow cytometry to the characterization of virally infected cells and the function of viral glycoproteins. During her post-doctoral fellowship at DNAX Institute for Cellular and Molecular Biology, she identified one of the first KIR receptors (KIR3DL1) on human NK cells. This was followed by research on HIV viral entry and fusion at Progenics Pharmaceuticals. Since 1997 when she joined the clinical armacology/experimental medicine department at Bristol-Myers Squibb, she has focused primarily on the development and validation of flow cytometry-based biomarker methods for clinical trials. She is currently the global lead flow cytometry scientist at Covance Central Laboratory Services.

She founded the Flow Cytometry Action Program Committee of the AAPS Ligand Binding Assay Bioanalytical focus group, and is an active contributor to the International Clinical Cytometry Society (ICCS), and the International Society for Analytical Cytology (ISAC). She is an editor for Clinical and Vaccine Immunology, and serves on the editorial board of Cytometry Part B, Clinical Cytometry. She recently edited the book, Flow Cytometry in Drug Discovery and Development (John Wiley & Sons), and the Special Issue of the Journal of Immunological Methods on Flow Cytometry Biomarkers and Translational Medicine.