Cellular manufacturing for clinical applications.

Abstract

Rapid progress has been made in the development of novel cell-based approaches for the potential treatment of retinal degenerative diseases. As a result, one must consider carefully the conditions under which these therapeutics are manufactured if they are to be used in clinical studies or, ultimately, be approved as licensed cellular therapeutics. Here, we describe the principles behind the manufacturing of clinical-grade cellular products, as well as potential methods for large-scale expansion and processing according to Good Manufacturing Practice (GMP) standards sets by the United States Food and Drug Administration. Standards for personnel, materials, procedures, and facilities required for such manufacturing processes are reviewed. We also discuss current and future scale-up methods for the manufacturing of large doses of cellular therapeutics under GMP conditions and compare the use of conventional culture methods such as tissue culture flasks and multi-layered cell factories with novel systems such as closed system hollow-fiber bioreactors. Incorporation of these novel bioreactor systems into GMP facilities may enable us to provide adequate cell numbers for multi-center clinical trials and paves the way for development of cellular therapeutics with the potential to treat very large numbers of patients.