GMP-Grade Manufacturing and Quality Control of a Non-Virally Engineered Advanced Therapy Medicinal Product for Personalized Treatment of Age-Related Macular Degeneration

Biomedicines, vol. 10, pp. 2777

Abstract

The introduction of new therapeutics requires validation of Good Manufacturing Practice (GMP)-grade manufacturing including suitable quality controls. This is challenging for Advanced Therapy Medicinal Products (ATMP) with personalized batches. We have developed a person-alized, cell-based gene therapy to treat age-related macular degeneration and established a vali-dation strategy of the GMP-grade manufacture for the ATMP; manufacturing and quality control were challenging due to a low cell number, batch-to-batch variability and short production duration. Instead of patient iris pigment epithelial cells, human donor tissue was used to produce the transfected cell product ("tIPE"). We implemented an extended validation of 104 tIPE productions. Procedure, operators and devices have been validated and qualified by determining cell number, viability, extracellular DNA, sterility, duration, temperature and volume. Transfected autologous cells were transplanted to rabbits verifying feasibility of the treatment. A container has been engineered to ensure a safe transport from the production to the surgery site. Criteria for successful validation and qualification were based on tIPE's Critical Quality Attributes and Process Parameters, its manufacture and release criteria. The validated process and qualified operators are essential to bring the ATMP into clinic and offer a general strategy for the transfer to other manufacture centers and personalized ATMPs.

Authors 13

1. Martina Kropp corresponding

   University of Geneva · University Hospital of Geneva

   Affiliation as printed

   Department of Ophthalmology, University Hospitals of Geneva, 1205 Geneva, Switzerland

   Group of Experimental Ophthalmology, University of Geneva, 1205 Geneva, Switzerland

2. Nina Harmening

   University of Geneva · University Hospital of Geneva

   Affiliation as printed

   Department of Ophthalmology, University Hospitals of Geneva, 1205 Geneva, Switzerland

   Group of Experimental Ophthalmology, University of Geneva, 1205 Geneva, Switzerland

3. Thais Bascuas

   University of Geneva · University Hospital of Geneva

   Affiliation as printed

   Department of Ophthalmology, University Hospitals of Geneva, 1205 Geneva, Switzerland

   Group of Experimental Ophthalmology, University of Geneva, 1205 Geneva, Switzerland

4. Sandra Johnen Aachen Department of Ophthalmology

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Ophthalmology, University Hospital RWTH Aachen, 52074 Aachen, Germany

5. Eline Elodie Barbara De Clerck

   University of Geneva · University Hospital of Geneva

   Affiliation as printed

   Department of Ophthalmology, University Hospitals of Geneva, 1205 Geneva, Switzerland

   Group of Experimental Ophthalmology, University of Geneva, 1205 Geneva, Switzerland

6. Mattia Ronchetti
   Affiliation as printed

   BVI c/o Optikon 2000 S.p.A., 00138 Rome, Italy

7. Ruggero Cadossi
   Affiliation as printed

   IGEA S.p.A., 41012 Carpi, Italy

8. Cristina Zanini
   Affiliation as printed

   BioAir S.p.A., 20016 Pero, Italy

9. Daniel Scherman

   Centre National de la Recherche Scientifique · Inserm · Université Paris Cité · Unité de Technologies Chimiques et Biologiques pour la Santé

   Affiliation as printed

   CNRS, Inserm, UTCBS, Université Paris Cité, F-75006 Paris, France

10. Zoltán Ivics

    Paul Ehrlich Institut

    Affiliation as printed

    Division of Medical Biotechnology, Paul-Ehrlich-Institute, 63225 Langen, Germany

11. Corinne Marie

    Centre National de la Recherche Scientifique · Université Paris Sciences et Lettres · Inserm · Université Paris Cité · Chimie ParisTech - PSL · Unité de Technologies Chimiques et Biologiques pour la Santé

    Affiliation as printed

    CNRS, Inserm, UTCBS, Université Paris Cité, F-75006 Paris, France

    Chimie ParisTech, PSL Research University, F-75005 Paris, France

12. Zsuzsanna Izsvák

    Max Delbrück Center

    Affiliation as printed

    Max Delbrück Center for Molecular Medicine in the Helmholtz Association, 13125 Berlin, Germany

13. Gabriele Thumann corresponding

    University of Geneva · University Hospital of Geneva

    Affiliation as printed

    Department of Ophthalmology, University Hospitals of Geneva, 1205 Geneva, Switzerland

    Group of Experimental Ophthalmology, University of Geneva, 1205 Geneva, Switzerland