Developing Assays to Address Identity, Potency, Purity and Safety: Cell Characterization in Cell Therapy Process Development

Abstract

A major challenge to commercializing cell-based therapies is developing scalable manufacturing processes while maintaining the critical quality parameters (identity, potency, purity, safety) of the final live cell product. Process development activities such as extended passaging and serum reduction/elimination can facilitate the streamlining of cell manufacturing process as long as the biological functions of the product remain intact. Best practices in process development will be dependent on cell characterization; a thorough understanding of the cell-based product. Unique biological properties associated with different types of cell-based products are discussed. Cell characterization may be used as a tool for successful process development activities, which can promote a candidate cell therapy product through clinical development and ultimately to a commercialized product.

Standard Requirement of a Microbiological Quality Control Program for the Manufacture of Human Mesenchymal Stem Cells for Clinical Use

“…Medicines are generally subjected to end-product batch testing as a means of quality control; in the case of a biologic medicine using stem cell, for clinical use, this control must be amplified due to limitations inherent in the cells, such as viability, genetic stability related to extended culture time, and microbiological contamination [33,34]. Microbiological contamination is one of the major risks associated with the administration of a CTMP.…”

The Potential Impact of Bone Tissue Engineering in the Clinic

“…Bone tissue in the clinic Review others), angiogenic (PDGF, VEGF, among others), inflammation-control (TNFα, interleukins, interferon-γ, among others) and systemic factors (Vitamin D, growth hormone, calcitonin, parathyroid hormone, among others) [44][45][46][47]. These cell signaling molecules have been studied extensively in the laboratory but few have been used in therapies that have gone through clinical trials.…”

Cell and gene therapy manufacturing: the necessity for a cost-based development approach

“…It is anticipated that the adoption of automated manufacture will decrease variability in the quality of manufactured cell products, resulting in more consistent clinical outcomes that exhibit both reproducibility and, importantly, dose-responsiveness. Poor understanding of the link between potency and product characteristics makes it challenging to develop a series of assays which reliably predict the result of a batch in vivo [27,28]. This situation is further complicated by the fact any assays of a fresh-preserved product must be completed rapidly as non-frozen cell-based products are not stable.…”