Development toward rapid and efficient screening for high performance hydrolysate lots in a recombinant monoclonal antibody manufacturing process


  • Ying Luo,

    Corresponding author
    1. Product and Process Development, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320
    • Product and Process Development, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91320
    Search for more papers by this author
  • Karisa M. Pierce

    1. Dept. of Chemistry and Biochemistry, Seattle Pacific University, 3307 Third Avenue West, Suite 205, Seattle, WA 98119
    Search for more papers by this author


Plant-derived hydrolysates are widely used in mammalian cell culture media to increase yields of recombinant proteins and monoclonal antibodies (mAbs). However, these chemically varied and undefined raw materials can have negative impact on yield and/or product quality in large-scale cell culture processes. Traditional methods that rely on fractionation of hydrolysates yielded little success in improving hydrolysate quality. We took a holistic approach to develop an efficient and reliable method to screen intact soy hydrolysate lots for commercial recombinant mAb manufacturing. Combined high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy and partial least squares (PLS) analysis led to a prediction model between product titer and NMR fingerprinting of soy hydrolysate with cross-validated correlation coefficient R2 of 0.87 and root-mean-squared-error of cross-validation RMSECV% of 11.2%. This approach screens for high performance hydrolysate lots, therefore ensuring process consistency and product quality in the mAb manufacturing process. Furthermore, PLS analysis was successful in discerning multiple markers (DL-lactate, soy saccharides, citrate and succinate) among hydrolysate components that positively and negatively correlate with titer. Interestingly, these markers correlate to the metabolic characteristics of some strains of taxonomically diverse lactic acid bacteria (LAB). Thus our findings indicate that LAB strains may exist during hydrolysate manufacturing steps and their biochemical activities may attribute to the titer enhancement effect of soy hydrolysates. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 28: 1061–1068, 2012