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Scientific article
Open access
English

GMP-grade manufacturing and quality control of a non-virally engineered advanced therapy medicinal product for personalized treatment of age-related macular degeneration

Published inBiomedicines, vol. 10, no. 11, 2777
Publication date2022-11-01
First online date2022-11-01
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.

eng
Keywords
  • Personalized medicine
  • Autologous
  • Regenerative medicine
  • Cell product
  • Cell therapy
  • Advanced Therapy Medicinal Product (ATMP)
  • Good Manufacturing Practice (GMP)
  • Quality control
  • Non-viral gene therapy
  • Age-related macular degeneration (AMD)
  • Iris pigment epithelial cells (IPE)
Funding
  • European Commission - Transposon-based, targeted ex vivo gene therapy to treat age-related macular degeneration (AMD) [305134]
Citation (ISO format)
KROPP, Martina et al. GMP-grade manufacturing and quality control of a non-virally engineered advanced therapy medicinal product for personalized treatment of age-related macular degeneration. In: Biomedicines, 2022, vol. 10, n° 11, p. 2777. doi: 10.3390/biomedicines10112777
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Article (Published version)
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ISSN of the journal2227-9059
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Technical informations

Creation11/08/2022 8:18:00 AM
First validation11/08/2022 8:18:00 AM
Update time03/16/2023 9:05:26 AM
Status update03/16/2023 9:05:25 AM
Last indexation02/12/2024 12:27:22 PM
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