From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product
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 b...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2021.712917/full |
| _version_ | 1818438159600451584 |
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| author | Sebastian Haeusner Sebastian Haeusner Laura Herbst Patrick Bittorf Thomas Schwarz Chris Henze Marc Mauermann Jelena Ochs Robert Schmitt Robert Schmitt Ulrich Blache Anke Wixmerten Sylvie Miot Ivan Martin Oliver Pullig Oliver Pullig |
| author_facet | Sebastian Haeusner Sebastian Haeusner Laura Herbst Patrick Bittorf Thomas Schwarz Chris Henze Marc Mauermann Jelena Ochs Robert Schmitt Robert Schmitt Ulrich Blache Anke Wixmerten Sylvie Miot Ivan Martin Oliver Pullig Oliver Pullig |
| author_sort | Sebastian Haeusner |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T17:36:08Z |
| format | Article |
| id | doaj.art-c11340d575854feb954af216d01e1212 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-12-14T17:36:08Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-c11340d575854feb954af216d01e12122022-12-21T22:52:58ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2021-08-01810.3389/fmed.2021.712917712917From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage ProductSebastian Haeusner0Sebastian Haeusner1Laura Herbst2Patrick Bittorf3Thomas Schwarz4Chris Henze5Marc Mauermann6Jelena Ochs7Robert Schmitt8Robert Schmitt9Ulrich Blache10Anke Wixmerten11Sylvie Miot12Ivan Martin13Oliver Pullig14Oliver Pullig15Translational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research, Wuerzburg, GermanyDepartment of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, GermanyFraunhofer Institute for Production Technology IPT, Aachen, GermanyTranslational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research, Wuerzburg, GermanyTranslational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research, Wuerzburg, GermanyFraunhofer Institute for Process Engineering and Packaging IVV, Dresden, GermanyFraunhofer Institute for Process Engineering and Packaging IVV, Dresden, GermanyFraunhofer Institute for Production Technology IPT, Aachen, GermanyFraunhofer Institute for Production Technology IPT, Aachen, GermanyLaboratory for Machine Tools and Production Engineering (WZL), RWTH Aachen University, Aachen, GermanyFraunhofer Institute for Cell Therapy and Immunology, Leipzig, GermanyDepartment of Biomedicine, University Hospital Basel, University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital Basel, University of Basel, Basel, SwitzerlandDepartment of Biomedicine, University Hospital Basel, University of Basel, Basel, SwitzerlandTranslational Center Regenerative Therapies TLC-RT, Fraunhofer Institute for Silicate Research, Wuerzburg, GermanyDepartment of Tissue Engineering and Regenerative Medicine, University Hospital Wuerzburg, Wuerzburg, GermanyAdvanced 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.https://www.frontiersin.org/articles/10.3389/fmed.2021.712917/fullATMPtissue engineeringGMPmanufacturingautologouscartilage regeneration |
| spellingShingle | Sebastian Haeusner Sebastian Haeusner Laura Herbst Patrick Bittorf Thomas Schwarz Chris Henze Marc Mauermann Jelena Ochs Robert Schmitt Robert Schmitt Ulrich Blache Anke Wixmerten Sylvie Miot Ivan Martin Oliver Pullig Oliver Pullig From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product Frontiers in Medicine ATMP tissue engineering GMP manufacturing autologous cartilage regeneration |
| title | From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product |
| title_full | From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product |
| title_fullStr | From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product |
| title_full_unstemmed | From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product |
| title_short | From Single Batch to Mass Production–Automated Platform Design Concept for a Phase II Clinical Trial Tissue Engineered Cartilage Product |
| title_sort | from single batch to mass production automated platform design concept for a phase ii clinical trial tissue engineered cartilage product |
| topic | ATMP tissue engineering GMP manufacturing autologous cartilage regeneration |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2021.712917/full |
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