The translation of cell-based therapies:clinical landscape and manufacturing challenges

Cell-based therapies have the potential to make a large contribution toward currently unmet patient need and thus effective manufacture of these products is essential. Many challenges must be overcome before this can become a reality and a better definition of the manufacturing requirements for cell-based products must be obtained. The aim of this study is to inform industry and academia of current cell-based therapy clinical development and to identify gaps in their manufacturing requirements. A total of 1342 active cell-based therapy clinical trials have been identified and characterized based on cell type, target indication and trial phase. Multiple technologies have been assessed for the manufacture of these cell types in order to facilitate product translation and future process development

On the process capability of the solid free-form fabrication: a case study of scaffold moulds for tissue engineering.

This study applies the methodology and procedure of process capability to investigate a solid free-form fabrication technique as a manufacturing method to produce scaffold moulds for tissue engineering. The process capability Cpk and process performance Ppk of scaffold mould manufacture using a solid free-form fabrication technique has been analysed with respect to the dimension deviations. A solid free-form fabrication machine T66 was used to fabricate scaffold moulds in this study and is able to create features that ranged from 200 microm to 1000 microm. The analysis showed that the printing process under the normal cooling conditions of the printing chamber was in statistical control but gave low process capability indices, indicating that the process was 'inadequate' for production of 'dimension-consistent' scaffold moulds. The study demonstrates that, by lowering the temperature of the cooling conditions, the capability Cpk of the printing process can be improved (about threefold) sufficiently to ensure the consistent production of scaffold moulds with dimension characteristics within their specification limits

A Quality-by-Design Approach to Risk Reduction and Optimization for Human Embryonic Stem Cell Cryopreservation Processes

Final publication is available from Mary Ann Liebert, Inc., publishers: https://doi.org/10.1089/ten.tec.2013.0595.It is well documented that cryopreservation and resuscitation of human embryonic stem cells (hESCs) is complex and ill-defined, and often suffers poor cell recovery and increased levels of undesirable cell differentiation. In this study we have applied Quality-by-Design (QbD) concepts to the critical processes of slow-freeze cryopreservation and resuscitation of hESC colony cultures. Optimized subprocesses were linked together to deliver a controlled complete process. We have demonstrated a rapid, high-throughput, and stable system for measurement of cell adherence and viability as robust markers of in-process and postrecovery cell state. We observed that measurement of adherence and viability of adhered cells at 1h postseeding was predictive of cell proliferative ability up to 96h in this system. Application of factorial design defined the operating spaces for cryopreservation and resuscitation, critically linking the performance of these two processes. Optimization of both processes resulted in enhanced reattachment and post-thaw viability, resulting in substantially greater recovery of cryopreserved, pluripotent cell colonies. This study demonstrates the importance of QbD concepts and tools for rapid, robust, and low-risk process design that can inform manufacturing controls and logistics