PMID- 30350921 OWN - NLM STAT- MEDLINE DCOM- 20190718 LR - 20190718 IS - 1860-7314 (Electronic) IS - 1860-6768 (Linking) VI - 14 IP - 4 DP - 2019 Apr TI - Scale-Down Model Development in ambr systems: An Industrial Perspective. PG - e1700766 LID - 10.1002/biot.201700766 [doi] AB - 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. CI - (c) 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Sandner, Viktor AU - Sandner V AUID- ORCID: 0000-0003-1886-7561 AD - Process Design, Process Development, FUJIFILM Diosynth Biotechnologies, Belasis Avenue, Billingham, TS23 1LH, United Kingdom. AD - School Engineering, Merz Court University of Newcastle, Newcastle Upon Tyne, NE1 7RU, United Kingdom. FAU - Pybus, Leon P AU - Pybus LP AD - Mammalian Cell Culture, Process Development, FUJIFILM Diosynth Biotechnologies, Belasis Avenue, Billingham, TS23 1LH, United Kingdom. FAU - McCreath, Graham AU - McCreath G AD - Process Design, Process Development, FUJIFILM Diosynth Biotechnologies, Belasis Avenue, Billingham, TS23 1LH, United Kingdom. FAU - Glassey, Jarka AU - Glassey J AD - School Engineering, Merz Court University of Newcastle, Newcastle Upon Tyne, NE1 7RU, United Kingdom. LA - eng GR - 643056/H2020 Marie Sklodowska-Curie Actions/ PT - Journal Article PT - Review DEP - 20181126 PL - Germany TA - Biotechnol J JT - Biotechnology journal JID - 101265833 RN - H2D2X058MU (Cyclic GMP) SB - IM MH - Animals MH - Batch Cell Culture Techniques/*trends MH - *Bioreactors MH - CHO Cells MH - Cricetinae MH - Cricetulus MH - Cyclic GMP/biosynthesis/*chemistry MH - High-Throughput Screening Assays/*trends MH - Hydrodynamics MH - Industry/trends OTO - NOTNLM OT - high-throughput systems OT - miniature bioreactors OT - process characterization OT - regulatory qualification OT - scale-down models EDAT- 2018/10/24 06:00 MHDA- 2019/07/19 06:00 CRDT- 2018/10/24 06:00 PHST- 2017/10/17 00:00 [received] PHST- 2018/10/16 00:00 [revised] PHST- 2018/10/24 06:00 [pubmed] PHST- 2019/07/19 06:00 [medline] PHST- 2018/10/24 06:00 [entrez] AID - 10.1002/biot.201700766 [doi] PST - ppublish SO - Biotechnol J. 2019 Apr;14(4):e1700766. doi: 10.1002/biot.201700766. Epub 2018 Nov 26.