Cell/Gene Therapies

Viral Safety of Viral Vectors:
Special Concerns Arise When the Virus Is the Product

As anyone who has focused on host-cell proteins as process contaminants can tell you, trying to purify a specific type of molecule from a large mixture of many similar molecules is like trying to find a few particular needles in a huge pile of varied needles. The same could be said for purifying viral vectors from cell culture fluids. When viruses are the products, unwanted viruses are contaminants that must be separated away — or better yet, prevented from being…

Formulation, Fill and Finish of Lentiviral Vectors: Part 1 — Case Study in Facility and Process Design

Over the past few years, Oxford Biomedica Ltd. (OXB) has developed and implemented a fill–finish platform (“Oxbox,” Figure 1) at its viral vector processing facility in the United Kingdom. The facility includes four segregated bulk viral-vector drug substance (VS) suites, where closed systems and bioburden control processes apply, and two viral-vector drug product (VP) fill–finish suites that apply aseptic processing, with space for expansion by scale-out as product output demand increases. Segregated suites enable the facility to process different viral…

Spurring on Innovation in Gene Therapy Development

Gene therapies based on adenoassociated virus (AAV) vectors hold promise for treating myriad conditions. Immunogenicity remains a challenge for such products, however. With support from PerkinElmer, Roland W. Herzog (professor of pediatrics and Riley Children’s Foundation professor of immunology at the Indiana University School of Medicine) joined Nagendra Venkata Chemuturi (scientific director of global research for drug metabolism and pharmacokinetics, DMPK, at Takeda Pharmaceuticals) to deliver a BPI “Ask the Expert” presentation exploring strategies for minimizing immune responses to AAV-based…

Transfection Best Practices for AAV Gene Therapy Programs

As viral vectors continue to push gene therapy innovations closer to market, many researchers are setting their sights on optimizing transfection, the process of delivering corrective genetic material into cells. It’s not just a question of how to transfect them, but also how to do so efficiently and at high volumes. Approaches that work for one cell line might not perform well for others, and transfection protocols can have different implications for scalability and cost during production for clinical trials.…

Focusing on the Patient Journey Can Increase Access to Lifesaving Therapies

Cell and gene therapies (CGTs) are positioned currently as last-chance, “miracle” cures for patients who have severe illnesses. Such promises require innovation. Despite the cutting-edge science and significant investment that goes into CGT development, fundamental challenges remain, including patient access. The highly personalized nature of autologous-therapy development presents myriad logistical, financial, and manufacturing challenges to ensuring global access to treatment. Understanding a patient’s journey to treatment is vitally important to achieving that goal. Barriers to Cell and Gene Therapy Access…

Recombinant Proteins for Cell and Gene Therapy Research: A Conversation with Shenandoah Biotechnology

Recombinant proteins such as growth factors and cytokines are essential for cell therapy, gene therapy and regenerative medicine research, development and manufacturing. These proteins are critical in the production of desired cell types and subsequent differentiation of cells, to deliver the desired effect. Founded 15 years ago, Shenandoah Biotechnology applies a proprietary method of folding and purifying recombinant proteins from both bacterial and mammalian systems to enable cost-effective, large-scale production of Cell Therapy Grade proteins to support these groundbreaking treatments.…

No More Sleepwalking: New Mindsets for Manufacturing Cell and Gene Therapies at Commercial Scale

Cell and gene therapies (CGTs) offer potential cures to some of the most challenging illnesses of our time. The number of such therapies approved for market is set to surge in the next 10 years (1). Yet current manufacturing approaches are not fit for purpose. Biomanufacturing must adapt to prevent the industry from unintentionally sleepwalking into causing harm to patients. Some urgently needed changes could come with learning about the mindset of the medical-devices industry. Background and Current State After…

eBook: CAR-T Cell Therapy — Mitigating Clinical and Bioprocess Limitations

Developers of chimeric antigen receptor (CAR) T-cell therapies are working in a state of tempered optimism. As of September 2021, the US Food and Drug Administration has approved only five such products, two coming this year. Now that those approved products have demonstrated the viability of CAR-based immunotherapies, drug developers are trying to address significant limitations that have come to light with increases in available clinical data and bioprocess knowledge. One shortcoming concerns therapeutic efficacy. Blood cancer patients who have…

Strategizing Scale-Up and Scale-Out for Cell Therapy Production

When considering strategies for expanding the number of cells being grown to support cell therapy development, companies often focus on decisions regarding scale-up and scale-out: increasing capacity either by using larger vessels to increase production volume or by implementing more units of the same vessel, respectively. Complete workflows often involve both. Figure 1 shows an example of scaling out from one to multiple cell culture flasks of the same dimension before transitioning to a larger format. Scale-out can be straightforward…

Ask the Expert: Streamlining Mesenchymal Stem Cell Production — From Expansion Through Removal of Cryoprotectant

The number of cell therapy product candidates based on mesenchymal stem cells (MSCs) has grown steadily since their clinical debut in 1995. As of June 2020, clinical investigators were evaluating more than 1,100 such therapies. Scaling up MSC production remains challenging, however. On 31 May 2021, Hilary Sherman (senior scientist at Corning Life Sciences) presented an “Ask the Expert” webinar describing her company’s efforts to facilitate MSC workflows. Sherman’s Presentation Easing Expansion: MSCs have strong differentiation capability and can be…