Cell Culture Automation and Quality Engineering: A Necessary Partnership to Develop Optimized Manufacturing Processes for Cell-Based Therapies

Abstract

The translation of experimental cell-based therapies to volume produced commercially successful clinical products that satisfy the regulator requires the development of automated manufacturing processes to achieve capable and scaleable processes that are both economic and able to meet the unpredictable demands of the market place. The Healthcare Engineering group at Loughborough has conducted novel demonstrators of the transfer of manual human cell culture processes to the CompacT SelecT (The Automation Partnership) automated cell culture platform, including an osteoblast cell line, embryonic carcinoma cell line, primary bone marrow-derived mesenchymal stem cells, primary umbilical cord-derived progenitor cells, and human embryonic stem cells. The work aims to develop and optimize automated cell culture processes for manufacturing cell-based therapies in a quality system and current good manufacturing practice (cGMP) compliant manner and is underpinned by the application of a six-sigma inspired quality engineering approach. In this technical brief, we outline the need for automated cell culture systems and automated process engineering for the manufacture of cell populations for therapeutic applications. We review the transfer of a manual cell culture process to an automated process and the subsequent methodology for process improvement using examples from our laboratory of the application of these principles to an important regenerative medicine cell type, the human mesenchymal stem cell. We believe that systematic process improvement methodologies combined with the process stability provided by automation are essential to engineer optimized cGMP compliant manufacturing processes that will be required to realize the promise of cell-based therapies.