Semisynthetic model calibration for monitoring glucose in mammalian cell culture with in situ near infrared spectroscopy英文电子书.pdf

A RTICLE Semisynthetic Model Calibration for Monitoring Glucose in Mammalian Cell Culture with In Situ Near Infrared Spectroscopy Michael Milligan,1 Nicholas Lewin-Koh,2 Daniel Coleman,2 Adeyma Arroyo, 1 Victor Saucedo 1 1Process Development Engineering, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080; telephone: þ650-467-7117; e-mail: saucedo.victor@ 2Non-Clinical Biostatistics, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080 Introduction ABSTRACT: Near infrared (NIR) spectroscopy has the Mammalian cell cultures are widely used in the biotechnolo- capability of providing real-time, multi-analyte monitoring gy industry to produce valuable biological therapeutic of the complex reaction mixture associated with cell culture processes. However, the development of robust models to products. Their process environment must be carefully predict the concentration of key analytes has proven difficult. monitored and controlled to maximize important factors like In this study, a modeling methodology using semisynthetic product yield and quality. Cell culture monitoring currently process samples was used to predict glucose concentrations in requires manual sampling operations at specific time points, Chinese Hamster Ovary (CHO) cell culture processes. Partial with the associated necessary sample preparation and an Least Squares (PLS) regression models were built from in situ NIR spectra, and glucose levels between 4.0 and 14.0 g/L. Two array of technologies to characterize the chemical