Manufacturing models permitting roll out/scale out of clinically led autologous cell therapies: regulatory and scientific challenges for comparability
journal contributionposted on 12.11.2014, 11:49 by Paul Hourd, Patrick J. Ginty, Amit Chandra, David Williams
Manufacturing of more-than-minimally manipulated autologous cell therapies presents a number of unique challenges driven by complex supply logistics and the need to scale out production to multiple manufacturing sites or near the patient within hospital settings. The existing regulatory structure in Europe and the United States imposes a requirement to establish and maintain comparability between sites. Under a single market authorization, this is likely to become an unsurmountable burden beyond two or three sites. Unless alternative manufacturing approaches can be found to bridge the regulatory challenge of comparability, realizing a sustainable and investable business model for affordable autologous cell therapy supply is likely to be extremely demanding. Without a proactive approach by the regulators to close this “translational gap,” these products may not progress down the development pipeline, threatening patient accessibility to an increasing number of clinician-led autologous cellular therapies that are already demonstrating patient benefits. We propose three prospective manufacturing models for the scale out/roll out of more-than-minimally manipulated clinically led autologous cell therapy products and test their prospects for addressing the challenge of product comparability with a selected expert reference panel of US and UK thought leaders. This paper presents the perspectives and insights of the panel and identifies where operational, technological and scientific improvements should be prioritized. The main purpose of this report is to solicit feedback and seek input from key stakeholders active in the field of autologous cell therapy in establishing a consensus-based manufacturing approach that may permit the roll out of clinically led autologous cell therapies.
This study, conducted as part of the “Exploring the Feasibility of a New Regulatory Paradigm for the Manufacture of Autologous Cell Therapies” project funded by EPSRC Centre for Innovative Manufacturing in Regenerative Medicine, acknowledges the contributions of Robert Deans, Ian Rees, Alison Wilson and Mahendra Rao. The authors would like to acknowledge support from the ISCT for a workshop at the ISCT Regional Meeting, Philadelphia, Pennsylvania, on September 9, 2013, titled “Manufacturing Comparability Workshop.”
- Mechanical, Electrical and Manufacturing Engineering