Scale-Down Model Development in ambr systems: An Industrial Perspective.

Autor: Sandner V; Process Design, Process Development, FUJIFILM Diosynth Biotechnologies, Belasis Avenue, Billingham, TS23 1LH, United Kingdom.; School Engineering, Merz Court University of Newcastle, Newcastle Upon Tyne, NE1 7RU, United Kingdom., Pybus LP; Mammalian Cell Culture, Process Development, FUJIFILM Diosynth Biotechnologies, Belasis Avenue, Billingham, TS23 1LH, United Kingdom., McCreath G; Process Design, Process Development, FUJIFILM Diosynth Biotechnologies, Belasis Avenue, Billingham, TS23 1LH, United Kingdom., Glassey J; School Engineering, Merz Court University of Newcastle, Newcastle Upon Tyne, NE1 7RU, United Kingdom.
Jazyk: angličtina
Zdroj: Biotechnology journal [Biotechnol J] 2019 Apr; Vol. 14 (4), pp. e1700766. Date of Electronic Publication: 2018 Nov 26.
DOI: 10.1002/biot.201700766
Abstrakt: High-Throughput (HT) technologies such as miniature bioreactors (MBRs) are increasingly employed within the biopharmaceutical manufacturing industry. Traditionally, these technologies have been utilized for discrete screening approaches during pre-clinical development (e.g., cell line selection and process optimization). However, increasing interest is focused towards their use during late clinical phase process characterization studies as a scale-down model (SDM) of the cGMP manufacturing process. In this review, the authors describe a systematic approach toward SDM development in one of the most widely adopted MBRs, the ambr 15 and 250 mL (Sartorius Stedim Biotech) systems. Recent efforts have shown promise in qualifying ambr systems as SDMs to support more efficient, robust and safe biomanufacturing processes. The authors suggest that combinatorial improvements in process understanding (matching of mass transfer and cellular stress between scales through computational fluid dynamics and in vitro analysis), experimental design (advanced risk assessment and statistical design of experiments), and data analysis (combining uni- and multi-variate techniques) will ultimately yield ambr SDMs applicable for future regulatory submissions.
(© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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