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The cell therapy industry (CTI) is poised to grow rapidly over the next decade, treating millions of patients and generating annual revenues into the tens of billions of US dollars ( 1 , 2 ). To meet that high-growth demand, large CTI system manufacturers (e.g., Corning, Nunc/Nalgene, and GE Healthcare) and leading contract manufacturing organizations (CMOs, such as Lonza) are developing and integrating new upstream technology platforms such as gas-permeable membranes and microcarrier-based bioreactors to significantly increase therapeutic cell culture productivity. As those upstream technologies mature, following the path that protein therapeutics took decades ago, cell yields are expected to increase to hundreds of billions to trillions of cells per lot ( 3 ). Increasing the number of cells per lot raises harvest volumes from current tens of liters to more than 100 L in one to five years (a conservative estimate) and up to 1,000 L over the following 10 years. Such large-quantity cell harvests will need...
As children growing up, we could barely contain our anticipation for those banner, milestone years: entering first grade, becoming a teenager, turning 16 and then 18, high-school graduation. But even the most innocuous “in-between” years saw notable change and maturation, and 2012 was just such a year for the growing cell therapy sector. Although it is not likely to be noted as a pivotal or breakthrough year, 2012 nonetheless delivered some significant and welcome signposts of continued sector maturation. Here is a summary of what I believe to be the most notable of such events. I’ve liberally borrowed from the annual “Top 10” list delivered in January by Edward L. Field, chief operating officer of Cytomedix, Inc. and an executive committee member of the Alliance for Regenerative Medicine. He presented his list — voted on by the attending conference goers — in Washington, DC at Phacilitate’s Cell and Gene Therapy Forum ( www.cgt-forum.com ) held at the end of January 2013. Perhaps the highest-profile even...
Single-use technologies (SUTs) are tools that can be used in producing cell therapies and personalized medicines. Such products must meet specific requirements because of the way they are used. To meet those criteria, the cell therapy industry simply has no alternatives to single-use systems. SUT applications are rapidly changing. Traditional uses for single-use systems in cell therapy include processing in clinical settings (e.g., blood bags, transfer sets) and research and development (e.g., T-flasks, pipettes). Although such applications continue, the commercialization of both autologous and allogeneic cell therapies presents new challenges with SUT scale-out and scale-up. Fortunately for those of us working in cell therapy, the biopharmaceutical industry has been actively addressing the effect of SUTs in manufacturing. Resulting studies provide a wealth of supporting data and guidance documents. They have also led to SUT manufacturers having a stronger awareness of such production issues. SUTs are wid...
With an increasing number of cell therapies becoming available for patient use, the need for controlled and consistent manufacturing and delivery of cell products is increasingly important. A closed cell culture process not only offers control and consistency, but may also relieve labor demands. Single-use components within a closed process also can reduce contamination risk. Closed systems with single-use platforms may reduce the risk of biological contamination and cross-contamination that could inadvertently be introduced into cell-culture processes. Such contaminants use culture nutrients to produce unwanted proteins and limit the growth of (or destroy) a cell culture. Slow-growing adventitious agents can be subtle and may become apparent only when unwanted proteins are detected. Detection of contamination will result in unusable product, and depending on the circumstances, entire lots may have to be discarded. This can be incredibly costly in both materials and time. Manual cell culture processes can...
Human mesenchymal stem cells (hMSCs) are a self-renewing population of adherent, multipotent progenitor cells that can differentiate into several lineages. The current definition of MSCs includes adherence to standard tissue culture plastic ware, expression of various surface antigens, and multilineage in vitro differentiation potential (osteogenic, chondrogenic, and adipogenic). hMSCs hold great promise as therapeutic agents because of their potential ability to replace damaged tissue and their immunomodulatory properties. Consequently, many clinical trials using hMSCs are currently under way in a number of indications, including bone and cartilage disease, cancer, heart disease, gastrointestinal disease, diabetes, and autoimmunity and neurodegenerative diseases ( 1 ). In addition, hMSCs are being used in drug discovery applications as replacements for primary cells and animal models for initial toxicity and effector function screening of new compounds ( 2 ). However, for both drug discovery and therapeu...
Biomanufacturing automation is an established mission-critical step in the commercialization pathway for conventional therapeutics, including small molecules and monoclonal antibodies (MAbs) ( 1 ). The prospect of a potential biologic progressing into late-stage clinical trials without a robust biomanufacturing strategy to support at least pilot-plant scale bioprocessing is simply unthinkable. Conversely, the cell therapy industry (or at least a significant proportion of it) regard this as a trend that is unlikely to be mirrored as the industry develops. The aim of this piece is to assess the risks and benefits of the automation of cell therapy biomanufacturing by focusing in particular on the feasibility of process automation and its impact on regulatory compliance and return on investment. Interestingly, the authorship — composed of academia and industry — spans the product development pathway. One author will make the case that in some respects it is challenging to translate lab-scale processes into au...
In a 2006 report, the US Department of Health and Human Services hailed regenerative medicine as “the vanguard of 21st century healthcare” and “the first truly interdisciplinary field that utilizes and brings together nearly every field in science” ( 1 ). To fuel support for regulatory, legislative, and reimbursement initiatives in this new therapeutic class, a small group of scientists, life science business executives, patient advocates, and other experts formed the Alliance for Regenerative Medicine (ARM, http://alliancerm.org ). Starting with 17 charter members, the organization now includes more than 130 participants. Here, I discuss ARM’s objectives and current projects with cofounder and executive director Michael Werner and managing director Morrie Ruffin. Objectives and Organization BPI: What are ARM’s primary objectives? How does it differ from other groups? Ruffin: ARM was formed in September 2009 as the first organization in the regenerative medicine space to focus on the clinical advanceme...