Author Archives: Emma Bolduc

Characterizing Oxygen Mass Transfer and Shear During Cell Culture: Calculating the Maximum Cell Density Supported By a 20,000-Liter Stirred-Tank Bioreactor

Increasing demand for biologics and continuing limitations with single-use bioreactors (up to 5,000 L) compel some biopharmaceutical manufacturers to transfer their production processes into large-scale (20,000-L) stainless-steel bioreactors. Over decades of advancement, the industry has developed high–cell-density (HCD) cell-culture processes. When transferring an HCD cell culture from 2,000-L to 20,000-L production bioreactors, process engineers first must assess whether the larger bioreactors can meet the high oxygen demands required for high-density cultures. If so, the next consideration is whether the process…

Validating Prefiltration Dirty-Hold Times for Upstream Media and Feed Solutions: Implications for Establishing In-Process Microbial Control

Biopharmaceutical manufacturing processes require that prepared raw materials and product intermediates be held at different stages. During hold times, however, process and product intermediates are susceptible to microbial risks from bioburden, endotoxins, and exotoxins. Such risks arise from multiple sources, including bioproduction facilities, equipment, operations, and raw materials. Even a prepared intermediate can help microbes to grow. The US Food and Drug Administration’s (FDA’s) guidance on Sterile Drug Products Produced By Aseptic Processing states that “the time limits established for…