rAAV Manufacturing: The Challenges of Soft Sensing during Upstream Processing

Autor: Cristovão Freitas Iglesias, Milica Ristovski, Miodrag Bolic, Miroslava Cuperlovic-Culf
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Bioengineering, Vol 10, Iss 2, p 229 (2023)
Druh dokumentu: article
ISSN: 2306-5354
DOI: 10.3390/bioengineering10020229
Popis: Recombinant adeno-associated virus (rAAV) is the most effective viral vector technology for directly translating the genomic revolution into medicinal therapies. However, the manufacturing of rAAV viral vectors remains challenging in the upstream processing with low rAAV yield in large-scale production and high cost, limiting the generalization of rAAV-based treatments. This situation can be improved by real-time monitoring of critical process parameters (CPP) that affect critical quality attributes (CQA). To achieve this aim, soft sensing combined with predictive modeling is an important strategy that can be used for optimizing the upstream process of rAAV production by monitoring critical process variables in real time. However, the development of soft sensors for rAAV production as a fast and low-cost monitoring approach is not an easy task. This review article describes four challenges and critically discusses the possible solutions that can enable the application of soft sensors for rAAV production monitoring. The challenges from a data scientist’s perspective are (i) a predictor variable (soft-sensor inputs) set without AAV viral titer, (ii) multi-step forecasting, (iii) multiple process phases, and (iv) soft-sensor development composed of the mechanistic model.
Databáze: Directory of Open Access Journals
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