Concise Review: Mind the Gap: Challenges in Characterizing and Quantifying Cell- and Tissue-Based Therapies for Clinical Translation

Abstract

There are many challenges associated with characterizing and quantifying cells for use in cell- and tissue-based therapies. From a regulatory perspective, these advanced treatments must not only be safe and effective but also be made by high-quality manufacturing processes that allow for on-time delivery of viable products. Although sterility assays can be adapted from conventional bioprocessing, cell- and tissue-based therapies require more stringent safety assessments, especially in relation to use of animal products, immune reaction, and potential instability due to extended culture times. Furthermore, cell manufacturers who plan to use human embryonic stem cells in their therapies need to be particularly stringent in their final purification steps, due to the unrestricted growth potential of these cells. This review summarizes the current issues in characterization and quantification for cell- and tissue-based therapies, dividing these challenges into the regulatory themes of safety, potency, and manufacturing quality. It outlines current assays in use, as well as highlights the limits of many of these product release tests. Mode of action is discussed, with particular reference to in vitro surrogate assays that can be used to provide information to correlate with proposed in vivo patient efficacy. Importantly, this review highlights the requirement for basic research to improve current knowledge on the in vivo fate of these treatments; as well as an improved stakeholder negotiation process to identify the measurement requirements that will ensure the manufacture of the best possible cell- and tissue-based therapies within the shortest timeframe for the most patient benefit.

Hematopoietic Stem Cell Potency for Cellular Therapeutic Transplantation

“…First, unlike biopharmaceutical products, where relatively large quantities of the material would be available to establish several batches of reference standards, it might be extremely difficult to establish cell reference standards (Strong et al 2009;Rayment & Williams, 2010). There are several alternatives to establishing reference standards for cell therapeutics that have already been discussed above.…”

Introductory Chapter: Multi-Aspect Bibliographic Analysis of the Synergy of Technical, Biological and Medical Sciences Concerning Materials and Technologies Used for Medical and Dental Implantable Devices

“…Stem cells originating from bone marrow and fatty tissue may be used for breeding mesenchymal cells and tissues, in adipocytes, chondrocytes, osteoblasts and skeletal myocytes and can be used for producing tissues, e.g., muscles fat, gristle and bones [168][169][170][171]. Stringent safety requirements must be considered in cell-based therapies because raw materials of the animal origin are used, which poses a potential threat of transmitting a pathogen to a recipient or of immunological complications [172] and as post-production cleaning is required [173]. Progress in this domain seen since 2004 requires further detailed considerations concerning the mechanism of in vivo therapeutic activity, to facilitate the development and optimisation and for the development of automated processes, with improved efficiency and with quality control and with reference standards established [174][175][176][177].…”

Precision manufacturing for clinical-quality regenerative medicines

“…Specifically, there is a need to demonstrate safety, efficacy and purity of manufacture of regenerative therapies [35]. Safety is of prime concern to ensure therapies do not have a deleterious effect on the patient.…”