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

Frontiers in Medicine, vol. 8, pp. 712917

Abstract

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.

Authors 12

1. Sebastian Haeusner corresponding

   University of Würzburg · Universitätsklinikum Würzburg · Fraunhofer Institute for Silicate Research

   Affiliation as printed

   Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany

   Translational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research, Wuerzburg, Germany

2. Laura Herbst corresponding Aachen Fraunhofer Institute for Production Technology IPT

   Fraunhofer Institute for Production Technology IPT

   Affiliation as printed

   Fraunhofer Institute for Production Technology IPT, Aachen, Germany

3. Patrick Bittorf

   Fraunhofer Institute for Silicate Research

   Affiliation as printed

   Translational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research, Wuerzburg, Germany

4. Chris Henze

   Fraunhofer Institute for Process Engineering and Packaging Dresden

   Affiliation as printed

   Fraunhofer Institute for Process Engineering and Packaging IVV, Dresden, Germany

5. Marc Mauermann

   Fraunhofer Institute for Process Engineering and Packaging Dresden

   Affiliation as printed

   Fraunhofer Institute for Process Engineering and Packaging IVV, Dresden, Germany

6. Jelena Ochs Aachen Fraunhofer Institute for Production Technology IPT

   Fraunhofer Institute for Production Technology IPT

   Affiliation as printed

   Fraunhofer Institute for Production Technology IPT, Aachen, Germany

7. Robert Heinrich Schmitt Aachen Fraunhofer Institute for Production Technology IPT Laboratory for Machine Tools and Production Engineering (WZL)

   Fraunhofer Institute for Production Technology IPT · RWTH Aachen University

   Affiliation as printed

   Fraunhofer Institute for Production Technology IPT, Aachen, Germany

   Laboratory for Machine Tools and Production Engineering (WZL), RWTH Aachen University, Aachen, Germany

8. Ulrich Blache

   Fraunhofer Institute for Cell Therapy and Immunology

   Affiliation as printed

   Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany

9. Anke Wixmerten

   University of Basel · University Hospital of Basel

   Affiliation as printed

   Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland

10. Sylvie Miot

    University of Basel · University Hospital of Basel

    Affiliation as printed

    Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland

11. Iván Martín

    University of Basel · University Hospital of Basel

    Affiliation as printed

    Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland

12. Oliver Pullig corresponding

    University of Würzburg · Universitätsklinikum Würzburg · Fraunhofer Institute for Silicate Research

    Affiliation as printed

    Department of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, Germany

    Translational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research, Wuerzburg, Germany