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Development of a scale down cell culture model using multivariate analysis as a qualification tool
Author(s) -
Tsang Valerie Liu,
Wang Angela X.,
YusufMakagiansar Helena,
Ryll Thomas
Publication year - 2013
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1002/btpr.1819
Subject(s) - quality by design , scale (ratio) , univariate , process (computing) , multivariate statistics , process engineering , computer science , scale up , multivariate analysis , biochemical engineering , industrial engineering , scale analysis (mathematics) , manufacturing engineering , reliability engineering , engineering , machine learning , operations management , physics , classical mechanics , quantum mechanics , downstream (manufacturing) , operating system , thermodynamics
In characterizing a cell culture process to support regulatory activities such as process validation and Quality by Design, developing a representative scale down model for design space definition is of great importance. The manufacturing bioreactor should ideally reproduce bench scale performance with respect to all measurable parameters. However, due to intrinsic geometric differences between scales, process performance at manufacturing scale often varies from bench scale performance, typically exhibiting differences in parameters such as cell growth, protein productivity, and/or dissolved carbon dioxide concentration. Here, we describe a case study in which a bench scale cell culture process model is developed to mimic historical manufacturing scale performance for a late stage CHO‐based monoclonal antibody program. Using multivariate analysis (MVA) as primary data analysis tool in addition to traditional univariate analysis techniques to identify gaps between scales, process adjustments were implemented at bench scale resulting in an improved scale down cell culture process model. Finally we propose an approach for small scale model qualification including three main aspects: MVA, comparison of key physiological rates, and comparison of product quality attributes. © 2013 American Institute of Chemical Engineers Biotechnol. Prog ., 30:152–160, 2014