Effort to address challenges to the manufacturing scale-up of cell-based therapies follows release of Project A-Gene for gene therapy in 2021
The Alliance for Regenerative Medicine (ARM) and the National Institute for Innovation in Manufacturing BioPharmaceuticals (NIIMBL) today released Project A-Cell, a multistakeholder collaboration to incorporate Quality by Design (QbD) principles into a manufacturing case study of a Chimeric Antigen Receptor T-cell (CAR-T) therapy.
A-Cell brings best practices and a standard methodology for Chemistry, Manufacturing and Controls (CMC) to the cell-based therapy field, which has produced six FDA-approved CAR-T therapies to treat blood cancers but still faces challenges to manufacturing scale-up. Many of the hurdles to the streamlined, cost-effective manufacture of cell and gene therapy products derive from a lack of standardized methodologies and training around CMC programs.
A-Cell emulates previous QbD efforts that were applied to the manufacturing of monoclonal antibodies (A-Mab), vaccines (A-Vax), and more recently, gene therapies (A-Gene). Antibodies and vaccines faced similar hurdles to those now faced by the cell and gene therapy sector when developers sought to advance from small-batch manufacturing for clinical trials to full-scale commercial production. A-Mab and A-Vax helped to lower barriers to technology transfer and to better prepare new entrants to the industry. Educational institutions including the University College of London are already using A-Gene as an educational tool, while more than 500 representatives from ARM members attended a series of webinars to share the report’s findings. The A-Gene document has been viewed more than 5,000 times on ARM’s website.
“A-Gene is already making a significant impact as an educational and workforce development tool for the gene therapy sector,” said Michael Lehmicke, ARM’s vice president for science and industry affairs and lead on the A-Gene and A-Cell projects. “We think A-Cell will similarly advance the cell therapy field and help to deliver durable and potentially curative treatments for a range of serious cancers and other diseases.”
More than 50 industry experts from over 30 leading therapeutic developers, as well as regulatory experts and the Standards Coordinating Body, contributed to A-Cell. A-Cell focuses on an autologous CAR-T therapy because of early regulatory successes and significant investor interest in this therapeutic approach. But many of the concepts from this study are applicable and beneficial to a broader profile of cell-based therapy products, including mesenchymal stem/ stromal cell therapies and pluripotent stem cell-based therapies.
QbD is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.
“We are very excited about the project because cell therapies have demonstrated a transformational impact on patients,” said Gene Schaefer, NIIMBL senior fellow. “Now is a critical time to have the biopharmaceutical manufacturing community share best practices to accelerate access to these treatments for patients in need.”
ARM and NIIMBL are making the A-Cell report publicly available via ARM’s website. ARM will host a webinar series in 2022 and early 2023 highlighting specific A-Cell chapters, the first of which will be held in September.
Source – Alliance for Regenerative Medicine