From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product

Frontiers in Medicine

Sylvie Miot¹  Ivan Martin¹  Anke Wixmerten¹  Sebastian Haeusner²  Oliver Pullig²  Ulrich Blache³  Chris Henze⁴  Marc Mauermann⁴  Jelena Ochs⁵  Laura Herbst⁵  Robert Schmitt⁶  Thomas Schwarz⁷  Patrick Bittorf⁷ 

[1] Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland;Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany;Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany;Fraunhofer Institute for Process Engineering and Packaging IVV, Dresden, Germany;Fraunhofer Institute for Production Technology IPT, Aachen, Germany;Laboratory for Machine Tools and Production Engineering (WZL), RWTH Aachen University, Aachen, Germany;Translational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research, Wuerzburg, Germany;

关键词: ATMP;    tissue engineering;    GMP;    manufacturing;    autologous;    cartilage regeneration;   

DOI  :  10.3389/fmed.2021.712917

来源: DOAJ

【 摘 要 】

Advanced Therapy Medicinal Products (ATMP) provide promising treatment options particularly for unmet clinical needs, such as progressive and chronic diseases where currently no satisfying treatment exists. Especially from the ATMP subclass of Tissue Engineered Products (TEPs), only a few have yet been translated from an academic setting to clinic and beyond. A reason for low numbers of TEPs in current clinical trials and one main key hurdle for TEPs is the cost and labor-intensive manufacturing process. Manual production steps require experienced personnel, are challenging to standardize and to scale up. Automated manufacturing has the potential to overcome these challenges, toward an increasing cost-effectiveness. One major obstacle for automation is the control and risk prevention of cross contaminations, especially when handling parallel production lines of different patient material. These critical steps necessitate validated effective and efficient cleaning procedures in an automated system. In this perspective, possible technologies, concepts and solutions to existing ATMP manufacturing hurdles are discussed on the example of a late clinical phase II trial TEP. In compliance to Good Manufacturing Practice (GMP) guidelines, we propose a dual arm robot based isolator approach. Our novel concept enables complete process automation for adherent cell culture, and the translation of all manual process steps with standard laboratory equipment. Moreover, we discuss novel solutions for automated cleaning, without the need for human intervention. Consequently, our automation concept offers the unique chance to scale up production while becoming more cost-effective, which will ultimately increase TEP availability to a broader number of patients.

【 授权许可】

Unknown