Cellular therapy is currently generating great interest in the treatment of a variety of diseases. In turn, this interest has stimulated the Center of Biologics Evaluation and Research of the Food and Drug Administration to examine its regulatory approach to the products used for these therapies. As a result, facilities preparing cell therapy products are now regarded as manufacturers, and are expected to comply with current Good Manufacturing Practices and/or the proposed current Good Tissue Practices. Compliance with these practices can be a culture shock to some academic centers whose background is firmly in research. The FDA has indicated that there is a sliding scale of compliance depending on the phase of the clinical study. The difficulty for centers is deciding where they fall on the compliance scale, as well as determining what changes must be made to come into compliance. This article reviews some of the factors that must be considered when making these decisions…
BioProcessing Journal Posts
As product development proceeds in the field of cellular therapies, adequate product characterization remains a challenge for both IND Sponsors and FDA/CBER. Cellular therapy products are not considered to be well-defined products, and therefore the control and characterization of each stage of the production process helps to ensure product safety and consistency. Product characterization of cellular products includes demonstration of safety, plus determination of identity, purity, potency, and product stability. Development of appropriate specifications for each of these parameters is necessary for lot release, and also provides an important database of knowledge for addressing regulatory issues, such as lot-to-lot consistency and potential issues with product comparability, should the manufacturing process, or other aspects of product development, change over time…
The characterization of a batch cell culture process to produce a monoclonal antibody from a GS-NS0 mouse myeloma cell line is described. Productivity and cellular metabolism were monitored during scale-up to both characterize the process and aid in assessing cell culture stability. During fermentation scale-up studies, it was found that as culture generation number increased, productivity declined. In both flask and bioreactor cultures, declining production started abruptly at approximately generation 60. In this study, we assessed whether the decline in productivity was due to genetic instability of the cell line, which resulted in the generation of a non-producer sub-population, or a shift to a less productive state of cellular metabolism…
The K562 cell line is a human myelogenous leukemic cell which has been used by several groups, including ours, as a vehicle for cell-based vaccines and immuno-gene therapies. The attractiveness of K562 cells is the ease with which they can be cultured, plus the fact that they express very low levels of MHC proteins. Low MHC expression facilitates the use of these cells in patients with different MHC backgrounds, and it may improve the in vivo survival of the cells by delaying immune rejection. Based largely on these properties, we have been developing the K562 cell line as a universal platform for expressing cytokines, tumor antigens, and other immuno-modulating proteins…