Accelerating development of engineered T cell therapies in the EU: current regulatory framework for studying multiple product versions and T2EVOLVE recommendations

Frontiers in Immunology, vol. 14, pp. 1280826

Abstract

To accelerate the development of Advanced Therapy Medicinal Products (ATMPs) for patients suffering from life-threatening cancer with limited therapeutic options, regulatory approaches need to be constantly reviewed, evaluated and adjusted, as necessary. This includes utilizing science and risk-based approaches to mitigate and balance potential risks associated with early clinical research and a more flexible manufacturing paradigm. In this paper, T2EVOLVE an Innovative Medicine Initiative (IMI) consortium explores opportunities to expedite the development of CAR and TCR engineered T cell therapies in the EU by leveraging tools within the existing EU regulatory framework to facilitate an iterative and adaptive learning approach across different product versions with similar design elements or based on the same platform technology. As understanding of the linkage between product quality attributes, manufacturing processes, clinical efficacy and safety evolves through development and post licensure, opportunities are emerging to streamline regulatory submissions, optimize clinical studies and extrapolate data across product versions reducing the need to perform duplicative studies. It is worth noting that this paper is focusing on CAR- and TCR-engineered T cell therapies but the concepts may be applied more broadly to engineered cell therapy products (e.g., CAR NK cell therapy products).

Authors 13

1. Delphine Ammar corresponding Aachen Regulatory Affairs

   Astellas Pharma (Netherlands)

   Affiliation as printed

   Regulatory Affairs, Astellas Pharma B.V., Leiden, Netherlands

2. Inga Schapitz corresponding

   Bayer (Germany)

   Affiliation as printed

   Regulatory Affairs, Bayer Vital GmbH, Leverkusen, Germany

3. Maik Luu

   University of Würzburg · Universitätsklinikum Würzburg

   Affiliation as printed

   Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany

4. Michael Hudecek

   University of Würzburg · Universitätsklinikum Würzburg

   Affiliation as printed

   Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany

5. Miriam Elsa Meyer

   Immatics Biotechnologies (Germany)

   Affiliation as printed

   Regulatory Affairs, Immatics Biotechnologies GmbH, Tuebingen, Germany

6. Timmothy Taps

   Century Therapeutics (United States)

   Affiliation as printed

   Regulatory Affairs, Century Therapeutics Inc., Philadelphia, PA, United States

7. Zoltán Ivics

   Paul Ehrlich Institut

   Affiliation as printed

   Research/Division of Hematology, Gene and Cell Therapy, Paul Ehrlich Institute, Langen, Germany

8. Carmen Sanges

   University of Würzburg · Universitätsklinikum Würzburg

   Affiliation as printed

   Lehrstuhl für Zelluläre Immuntherapie, Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany

9. Paul Franz

   Fraunhofer Institute for Cell Therapy and Immunology

   Affiliation as printed

   Department of Cell and Gene Therapy Development, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany

10. Ulrike Koehl

    Fraunhofer Institute for Cell Therapy and Immunology · Leipzig University

    Affiliation as printed

    Department of Cell and Gene Therapy Development, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany

    Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany

11. Hélène Trebeden‐Negre

    Institut de Recherches Internationales Servier (France)

    Affiliation as printed

    Institut de Recherches Internationales Servier, Gif-sur-Yvette, France

12. Inez Johanna

    University Medical Center Utrecht

    Affiliation as printed

    Department of Hematology and Innovation Center for Advanced Therapy (ICAT), Universitair Medisch Centrum (UMC) Utrecht, Utrecht, Netherlands

13. Jacquelyn Awigena-Cook corresponding

    Bristol-Myers Squibb (United Kingdom)

    Affiliation as printed

    Global Regulatory Sciences, Bristol Myers Squibb, Uxbridge, United Kingdom