Cell/Gene Therapies

Using Regulatory T Cells for Treatment of Type 1 Diabetes, Part 2: Drug Development and the Transition to Clinical Trials

In the April 2023 issue of BPI, Leonardo Ferreira discussed the biology of type 1 diabetes and how he has worked toward developing a cure for that disease at his laboratory at the Medical University of South Carolina using chimeric antigen receptor (CAR) T regulatory cells (Tregs) (1). He spoke about industry-wide advances in developing Treg technology and how lessons learned during preclinical trials can be applied in human trials. He also discussed what the industry needs to develop Treg…

Viral Safety for Biotechnology Products, Including Viral Vectors: ICH Q5A Revision 2 Brings Updated and More Comprehensive Guidance

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) provides guidance on the testing and evaluation of viral safety of biotechnological products derived from characterized cell lines of human or animal origin through its harmonized guideline ICH Q5A (1). The latest revision, released for consultation in October 2022, maintains the key principles of previous versions while introducing key changes in response to important advances in the field. Those advances are covered in new sections that…

Quantitative Risk Assessment of Limits for Residual Host-Cell DNA: Ensuring Patient Safety for In Vitro Gene Therapies Produced Using Human-Derived Cell Lines

Viral-vector gene therapies (GTs) manufactured from cell-substrate production systems can contain residual amounts of host-cell DNA (hcDNA), which in a final product presents safety risks to treated patients. Therefore, drug manufacturers monitor and control residual hcDNA levels in purified products (1, 2). The US Food and Drug Administration (FDA) and other global regulatory agencies recommend tight, quantifiable limits for hcDNA levels: 10 ng/dose, with DNA fragments smaller than the functional gene size of 200 base pairs (bp) (3). However, because…

Strengthening Data Management and Integrity for CGT Applications

The specialized nature of cell and gene therapies (CGTs) requires that they be delivered to single patients or in low batch numbers. Manufacturing CGTs at scale is critical to industry success, but doing so at an economically viable cost is a key obstacle. Today’s therapies cost between US$400,000 and $3.5 million per patient, largely because of the need for highly skilled workers to deliver those innovative drugs. The CGT industry has innovated across all areas of production, from collection of…

Cryopreserving Hematopoietic Stem Cells — Part 2: Methods, Materials, and Operations

Bone marrow (BM) remains a critical source of hematopoietic progenitors used in stem-cell transplantation. Currently, however, it is obtained almost exclusively from living donors. That approach limits what quantities of cells can be extracted during an aspiration procedure, in turn reducing the number of opportunities available for treating blood-cancer patients. In BPI’s November 2022 eBook on cryopreservation, I presented part of my conversation with Erik Woods (cofounder, chief science officer, and executive vice president of Ossium Health) about ways to…

Meeting the Unique Needs of Rare-Disease Patients

The growth of gene and cell therapies (CGTs) and specialty pharmaceuticals represents a radical shift in the treatment of rare diseases. By changing the parameters for care coordination, such innovations are improving patient outcomes and leading to a better quality of life. Treatments for rare diseases have been shown to provide more significant health benefits on average than can drugs that are formulated for more common conditions. Regrettably, over 95% of rare-disease patients in the United States lack a US…

Overcoming AAV Manufacturing Challenges: Movement Toward Plug-and-Play Solutions

Discovered in the mid-1960s, adenoassociated viruses (AAVs) have become the leading vector for gene therapy in recent years. In October 2012, the first European market authorization for a human gene-therapy product was granted for UniQure’s Glybera (alipogene tiparvovec), which contains an AAV1 vector for treating patients who have lipoprotein lipase deficiency. (The product has been withdrawn from the market because of limited demand.) Both gene therapies currently approved in the United States — Luxturna (voretigene neparvovec) from Spark Therapeutics, approved…

eBook: Cell Therapy — Lessons Learned from Working with Vectors and Cells

Gene-modified cell therapies hold much promise for cancer treatment. Currently, the most popular approach leverages T cells expressing chimeric antigen receptors (CARs), which give immune cells the specificity needed to bind with and destroy malignancies. Despite rapid progress in drug discovery and development, the biopharmaceutical industry still has much to learn about manufacturing CAR T-cell therapies in commercially feasible ways. In this eBook, BPI’s managing editor speaks with subject-matter experts from VIVEbiotech, Castle Creek Biosciences, and Bristol Myers Squibb (BMS)…

Cell Therapy — Supply Chain Discussions

The 2017 approval of Kymriah (tisagenlecleucel) has paved the way for other cell therapy products to reach the patients who need them. Each passing year promises to open the regulatory floodgates to more product approvals, but technical and manufacturing issues continue to keep initially high expectations from being realized. One barrier is supply chain complexity, especially for the subset of autologous cell therapies. This eBook features expert commentary from Be The Match BioTherapies, a company providing more than 50 product…

Improving Scalability of AAV and Lentivirus Production: Tailored Transfection Reagents Enable Large-Scale Manufacturing

Scientific advances have increased the safety and efficacy of recombinant viral-vector technology for cell and gene therapies. In this special report, we will discuss how tailored transfection reagents improve the scalability of AAV and lentivirus production. We will also focus on the challenges of scaling up viral vector production platforms and the importance of selecting the right transfection reagent for this process to increase the titer and quality of viral production to generate more therapeutic doses per run. Fill out…