Characterization of Cell Therapies: Challenges and Opportunities

Malcolm Moos Jr., M.D., Ph.D.
Medical Officer, Senior Investigator
U.S. Food and Drug Administraion, Office of Tissues
and Advanced Therapies
Division of Cellular and Gene Therapies

Development of cell-based therapies has been hindered by the difficulty of identifying cellular characteristics that predict in vivo performance reliably, an essential step in developing tests for use in control of the manufacturing process, for release of finished products for clinical use, and meeting other regulatory requirements. Cells are complex analytically, and many products being evaluated for therapeutic potential contain more than one cell type. This difficulty is compounded by the fact that many analytical methods are performed on material from a sample of many cells—so-called “population-average methods”—rather than on single cells. These methods are likely to obscure differences between similar cell types and miss the presence of rare cell types altogether. Since
comparatively minor fractions of a heterogeneous cell population may be responsible for significant biological actions, including both therapeutic and deleterious effects, population-average methods may have limited utility in evaluating cell preparations for safety and potential therapeutic effectiveness. We propose that concepts from developmental, cell, and systems biology, and control theory, in combination with emerging analytical tools and advanced computational methods, may offer an approach to analysis of cell populations with discriminating power sufficient to help overcome these obstacles that will be of use not only in developing improved testing strategies, but in design of improved products and manufacturing processes.

Bio-sketch

Dr. Moos majored in Biological Sciences at Stanford University and obtained his M.D. and Ph.D. at the University of Minnesota. His graduate major was pharmacology, with a supporting program in biophysics and spectroscopy. He completed residency training in Laboratory Medicine and Pathology, with a fellowship in Clinical Chemistry, at the same institution. Dr. Moos then came to FDA/CBER to continue his work in the area of cyclic nucleotide-mediated signal transduction, and became a recognized expert in protein microsequencing, separation techniques, and protein analytical biochemistry. When he began independent investigations as a Medical Officer, he changed fields to support regulatory decisions in the emerging area of cellular therapy. His current research interests are to define how evaluating the status of major cell signaling pathways (BMP, Wnt, etc.) can be used in conjunction with recent developments in systems biology, single cell analytical technology, and computational biology to characterize cell-based products more accurately to facilitate improved product design and testing. His work has resulted in seven patents issued, one allowed, and two pending. While at CBER, he has been CMC reviewer on hundreds of IND submissions (Original Submissions plus Amendments) and five BLAs, been primary or contributing author on various FDA and International Conference on Harmonisation guidance documents dealing with recombinant protein and cellular products, organized various meetings dealing with cell and gene therapy regulatory issues, and participated in criminal investigations and prosecutions when needed. His awards include the Harvey W. Wiley Medal, the FDA Award of Merit, the Center Director’s Targeted Research Award (twice), the Center Director’s Distinguished Service Award, and thirty-two others.