Demonstrating the Equivalence of Traditional Versus Automated Buffer Preparation Methods Using In-Line Conditioning Control Modes to Manage Incoming Stock Solution Variability

by Karolina Busson, Robbie Kamperveen, and Enrique Carredano
Volume 20, Open Access (Apr 2021)

In-line conditioning (IC) is a form of dilution where a process buffer is formulated in-line from concentrated stock solutions of acids, bases, and salts that are mixed with the correct amount of water-for injection (WFI). This new buffer preparation strategy must prove its equivalency to buffers made the traditional way (i.e., weighing salts, stirring in water, titrating with acid or base). In this paper, such a demonstration is presented using two control modes: (1) ratio control with flow feedback; and (2) pH/conductivity feedback. To obtain the necessary parameters for an error propagation analysis, a robustness study has been performed. Our analysis showed that with low incoming variability, or when the uncertainty of the stock solutions is below 2%, the two modes of control give comparable performance. When the uncertainty increases, so does the uncertainty of ratio control with flow feedback, more with respect to conductivity than pH, while the precision of pH/conductivity feedback remains at the same level. The choice of control should therefore take into consideration the critical process parameters, their tolerances, and the input variability in the stock solution concentration. In situations where there are higher variabilities in stock solution concentrations or process temperatures, this study suggests that pH/conductivity feedback might be a better option.

Busson K, Kamperveen R, Carredano E. Demonstrating the equivalence of traditional versus automated buffer preparation methods using in-line conditioning control codes to manage incoming stock solution variability. BioProcess J, 2021; 20.

Posted online April 27, 2021.