A Data-Driven Approach for Leveraging Inline and Offline Data to Determine the Causes of Monoclonal Antibody Productivity Reduction in the Commercial-Scale Cell Culture Process.

Abstract

The monoclonal antibody (mAb) manufacturing process comes with high profits and high costs, and thus mAb productivity is of vital importance. However, many factors can impact the cell culture process, and lead to mAb productivity reduction. Nowadays, the biopharma industry is actively employing manufacturing information systems, which enable the integration of both online data and offline data. Although the volume of data is large, related data mining studies for mAb productivity improvement are rare. Therefore, a data-driven approach is proposed in this study to leverage both the inline and offline data of the cell culture process to discover the causes of mAb productivity reduction. The approach consists of four steps, namely data preprocessing, phase division, feature extraction and fusion, and cluster comparing. First, data quality issues are solved during the data preprocessing step. Next, the inline data are divided into several phases based on the moving window k-nearest neighbor method. Then, the inline data features are extracted via functional data analysis and combined with the offline data features. Finally, the causes of mAb productivity reduction are identified using the contrasting clusters via the principal component analysis method. A commercial-scale cell culture process case study is provided in this research to verify the effectiveness of the approach. Data from 35 batches were collected, and each batch contained nine inline variables and seven offline variables. The causes of mAb productivity reduction were identified to be the lack of nutrients, and recommended actions were taken according to the result, which was subsequently proven by six validation batches.