Author Archives: Søren Kamstrup

A Challenge in Viral Clearance Determination: Estimation of Fifty-Percent Tissue Culture Infective Dose (TCID50) for Low Virus Concentrations

Performing viral clearance studies is an important safety element of manufacturing all biopharmaceuticals expressed from mammalian cells (1). Typically, viral clearance is described as a log reduction value (LRV) and calculated as the log10 of the ratio of input to output virus load. Amounts of virus load are calculated from the volume and concentration of input and output fractions. Virus concentration is often calculated as 50% of tissue-culture infective dose (TCID50) using the Spearman–Kärber (SK) equation (2, 3). In this…

Shared Clean-in-Place Systems: To Share or Not to Share?

Risk of viral contamination is a an accepted part of developing biopharmaceutical products derived from mammalian-cell culture. Viral safety is achieved through a combination of complementary approaches such as selecting non–animal-derived raw materials, testing cell banks, testing for adventitious virus contamination during cultivation, and demonstrating viral reduction capacity of a purification process (1). The latter commonly is referred to as viral clearance by orthogonal purification. Clearly, viral clearance and appropriate viral segregation are important considerations in biopharmaceutical manufacturing process and…

Virus Segregation During Purification Processes: Calculation of Critical Potential Carryover of Viruses

Before a pharmaceutical product is introduced into humans, either in a clinical trial or as a marketed product, virus safety must be evaluated carefully. Virus safety normally is ensured using a three step complementary approach: selecting and testing cell lines and/or raw materials for the absence of viruses, testing the product at appropriate steps of production, and assessing the capacity of a production process to clear infectious viruses (1). The latter (also referred to as viral clearance) is the subject herein. Spiking studies are conducted to evaluate the capacity of a purification…