Cell Therapies

Automation of CAR-T Cell Adoptive Immunotherapy Bioprocessing: Technology Opportunities to Debottleneck Manufacturing

Continued clinical efficacy demonstrations of cell-based immunotherapies (iTx) such as chimeric antigen receptor T cell (CAR-T) therapies has made the prospect increasingly likely of an immunotherapy product achieving conditional market authorization in the short term. For example, Novartis and the University of Pennsylvania’s lead candidate (CTL019) for treating a range of hematological malignancies received breakthrough status from the US Food and Drug Administration (FDA) in 2014, permitting access to an expedited drug development pathway for high unmet medical needs (1).…

Development of a Novel Cell-Separation Platform: Discussion with Quad Technologies CEO Sean Kevlahan

Releasing and separating cells from surfaces and capture molecules are critical steps in cell therapy development. Research into such therapies as chimeric antigen receptor T cells (CAR-T) cancer therapies and stem-cell regenerative medicines demand the isolation and purification of viable and functional target cells. A number of cell-separation strategies can be used to produce such cells, but they are not able to deliver the required efficiency or scalability and can also cause damage to cells or affect their phenotype. Since…

Therapeutic Gene Editing: Tools to Facilitate Basic Science or Stimuli for a Paradigm Shift in Biomanufacturing?

Historically, fundamental science and process engineering were separated by distinct vernaculars and a decade or more in the translation pathway of candidate therapeutics from laboratory to bedside (1). This crude metric holds true for the origins of the modern pharmaceutical industry, namely fine chemicals that supported the high-margin small molecules that constitute the majority of the pharmacopoeia even today. But as illustrated by deeply interwoven careers, companies, and technologies — including those related to monoclonal antibodies (MAbs) — that classic…

Collaboration Will Drive Regenerative Medicine: Toronto Development Center Will Help to Advance the Field

With support from the federal government of Canada, GE Healthcare and the Centre for Commercialization of Regenerative Medicine (CCRM) are pushing into new frontiers to advance the progress of cell therapy and regenerative medicine. When I first met Michael May, president and chief executive officer (CEO) of CCRM, both our organizations had been exploring opportunities in parallel to drive the cell therapy industry forward. CCRM’s mission is to create and sustain a global nexus for company creation, technology and cell…

Decision-Support Tools for Monoclonal Antibody and Cell Therapy Bioprocessing: Current Landscape and Development Opportunities

Industrial-scale manufacturers in a number of fields — from automobiles to biotherapeutics — have long relied on powerful computational and mathematical tools to aid in the scale-up, optimization, quality control, and monitoring of product development (1–5). Typical process pathways are highly multifactorial, with numerous branch points, feedback steps, instrumental attributes, and target parameters. Moreover, margins for error are minimal for most industrial processes, requiring high standards of precision from industrial and operational pathways (6). For those reasons, the complexity of…

Quantitative Risk Assessment of Bioaccumulation Attributable to Extractables and Leachables in Cellular Immunotherapy Biomanufacturing

Precious patient samples, contamination concerns, and limited product purification options have compelled manufacturers of cellular immunotherapies (iTx) such as chimeric antigen receptor T cells (CAR-T) and T-cell receptor (TCR) technologies toward the disposables industry. Such companies are implementing single-use technologies (SUTs) almost exclusively (1). But despite the dominance of disposable bioprocess platforms and their extraordinary growth in the iTx marketplace, researchers have made limited efforts to understand the perennial and critical bioprocessing risks of leachables and extractables. Here we outline…

Manufacturing Strategies for Regenerative Medicine Success

Just a few years ago, my requests for manuscripts detailing logistical considerations for cell-therapy manufacturing were met with puzzlement. The assumption seemed to be that such processes already existed for commercial biopharmaceuticals and would simply be adapted later. In quite a few cases, adopting a commercial mind-set did not appear to be a goal at all, with hands-on practitioners used to applying procedures in hospital settings. For those of us who remember early discussions about commercialization and cost-containment for protein…

Cell Therapy Scaling: Beyond the Biology

Few other areas of medical research have been the source of as much promise (and hype) as cell therapies. Therapies that use engineered or repurposed versions of our own cells have inspired researchers and media alike. However, the pace at which effective therapies have made it out of laboratories and into clinical practice has not met the world’s high expectations. Although the biology has continued to press onward, the gap between R&D and commercialization remains substantial. In 1957, the first…

Manufacturing Human Induced-Pluripotent Stem Cells for Clinical Application

The reprogramming of human somatic cells into induced pluripotent stem cells (iPSCs) offers tremendous potential for cell therapy, basic research, disease modeling, and drug development. Human iPSCs can be generated in culture, expanded, and then used to manufacture clinical-grade cells of almost any adult cell type. Given their great capacity for self-renewal, they are attractive as input materials for current good manufacturing practice (CGMP) operations. For human iPSCs to fulfill their therapeutic potential, however, it is necessary to develop a…

Cost-Effective Process Development for Plasmid DNA Manufacture: Evaluation of Single-Use Technologies to Support Escherichia coli Culture

DNA-based gene therapy products have been in clinical development since the 1990s. But over the past 24 months, the overall demand and therapeutic applications for plasmid DNA (pDNA) have rapidly grown and expanded. Currently, pDNA can be used directly as a therapeutic agent (e.g., in gene therapy or generation of vaccine antigens) and indirectly for a range of applications. Those include its use as a critical starting material for transient transfection to produce both viral-vector constructs (e.g., lentivirus or adenoassociated…