Development of new media formulations for cell culture operations based on regression models.

The paper discusses modelling and optimization of multi-component cell culture medium. The specific productivity (Qp) was considered a function of the medium components and possible interactions described by linear factors, two-way interactions and squared terms that results in a high dimensional problem where the number of variables p (represented by the medium components and their interactions) is much larger than the number of observations n. Principal Components Regression (PCR), Partial Least Squares (PLS), Lasso and Elastic Net regressions were compared as modelling tools to deal with a high dimensional [Formula: see text] problem. PCR and PLS regression models resulted in better prediction results and were used for robust optimization of the medium composition by a nonlinear optimization. The case studies show that it is possible to formulate new media that result in higher Qp than the ones provided by the initial media experiments available. Also, the multivariate statistical approach permitted us to select media that is most informative about the optimum thus permitting modelling and optimization with a reduced set of initial experiments.