Manufacturing

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…

Planning for Commercial Scale of Cell Therapy and Regenerative Medicine Products, Part 2: Clinical Efficacy, Reimbursement, and Needle-to-Needle Logistics

Cell therapy is an emerging pillar in healthcare with the potential to provide curative solutions to a wide range of indications. The biological complexities through which cell technologies exert their clinical impact (especially those used in immunotherapies for cancer) provide opportunities for novel modes of immune regulation, cell targeting, and payload delivery. Cells also can serve as vehicles for genetic content, which the gene therapy industry is now investigating. Since early 2004, Invetech has worked with organizations dedicated to cell…

Mapping Success for Commercial Cell Therapy Manufacturing

Commercializing cell therapies can be much more challenging than commercializing traditional pharmaceuticals and biologics. Cell-based drug products are significantly more complex than protein or small-molecule drug products. Their mechanisms of action and product attributes are also more complex. Cell therapy product attributes rely heavily on the associated manufacturing processes. Process changes can influence products in ways that may not be discernible until their effects on efficacy effects become evident. Product characterization is critical, but cell therapy products are living organisms…

The Cell Therapy Supply Chain: Logistical Considerations for Autologous Immunotherapies

Among the basics of building a successful logistics strategy for the management of cell-based material, some better-known and important factors to consider include selecting the right dry-shipping unit, qualifying that container for a particular payload and shipping configuration, choosing an appropriate data logger, creating a chain of custody, evaluating a transit carrier, and anticipating potential problems inherent in shipping at cryogenic temperatures (1). Here, I’d like to go beyond those basics to address some lesser-known considerations. These factors may be…

Comprehensive Hands-On Training for Biopharmaceutical Manufacturing: BTEC’s Program to Deliver Training to FDA Investigators

Training and continuing education play a vital role in carrying out the US Food and Drug Administration’s mission to protect and promote the public health — not only for consumers, health professionals, and industry, but also for the agency’s own personnel. Since 2008, the Golden LEAF Biomanufacturing Training and Education Center (BTEC) at North Carolina State University has filled a niche in the agency’s internal training program and provided a series of courses to more than 100 FDA investigators. The…

Enabling Cell Therapy Manufacturing

As this special Pall supplement of BioProcess International issue goes to press, progress continues in the field of cell therapy research. The revival of cell (and gene) therapy has been driven by some positive achievements that have occurred over the past decade. Cell therapy products differ in many ways from traditional small-molecular and biologic products. The main difference is that, contrary to traditional biopharmaceutical applications in which cells secrete the product of interest, in cell therapy applications cells are the…

Positioning for Success: An Interview with Mario Philips

On 12 March 2015, BPI met with Mario Philips, president, single-use technologies, at Pall’s Port Washington, NY, facility, to learn about Pall’s reasons for entering the cell therapy market. Also participating in the discussion was Alain Fairbank, director of marketing for cell therapies at Pall Life Sciences. Read the full text of this article in the PDF (Login required).

Meeting Lot-Size Challenges of Manufacturing Adherent Cells for Therapy

Adherent cells such as adult primary cell lines and human multipotent (MSCs) and pluripotent stem cells (hPSCs) present a manufacturing challenge as lot sizes increase from 109 (billions) to 1012 (trillions) cells (1). Typically, manufacturing platforms are good for one log of expansion. So new methods will be required to achieve commercially relevant lot sizes. Traditional two-dimensional culture methods have been used to grow anchorage-dependent cell types. Although such methods are reliable and well defined, they are very labor intensive…