Is the way cell cultures are currently monitored in the biopharmaceutical industry satisfying ?

Various parameters turn out to be effective to control Upstream Cell culture (USP): presence of chemical elements, product of interest concentration, temperature, osmolality, pH, etc.

During a culture process, pH, dissolved oxygen and temperature are usually controlled by a PID controller (in-line data).

Additionally, biological parameters, such as cell densities and nutrient or amino acids concentrations are measured at-line or off-line, requiring a daily sampling. Cell densities and viability are assessed using an automated cell counter while nutrient and metabolite concentrations are measured using enzyme-coupled reactions and electrochemical detection. Depending of the analysis complexity, data could be acquired after a delay of several weeks.

Generally, measurements are formally accepted when accuracy is better than 20%. But the desired accuracy is rather 10%.

Many different techniques, poor in-line information… This situation seems to be far from ideal.

Upstream Cell culture (USP)