Single-Use Technologies Applied Throughout The Development And Manufacturing Of Biopharmaceuticals

By Michiel Ultee, Laureate Biopharmaceutical Services

While much has been written about specific applications of single-use technologies (SUT) in biopharmaceutical production, the breadth of their involvement is sometimes overlooked. From the earliest thaws of frozen cells to the final filling of protein-product solutions, SUT are in widespread use. The reasons for this extensive adoption are numerous, ranging from faster turnaround times and lower capital and utility costs, to reduced opportunities for cross-contamination and hence need for cleaning validation. Taking a step back to view the broader picture from a historical perspective shows just how much SUT has crept into biopharmaceutical production in the past 25 years.

In the distant past cell cultures were performed in sterilized glass vessels, but these were displaced by disposable plastic bottles and flasks more than 20 years ago. Similarly, pipettes and other liquid dispensing equipment become largely single use, saving the effort and time needed for cleaning and sterilization. The next step, the bioreactor, was traditionally occupied by glass and stainless steel vessels. In the past decade, however, plastic has made major inroads into this hard-material turf. Use of multi-laminate sterile bags, either with impellers or an external rocker-type platform (i.e., Wave-type bioreactors) for mixing of the cell culture, has allowed growth of cells in what heretofore had been glass or stainless vessels.

While most production cell lines will grow well in plastic bags, there have been some exceptions. These have sometimes been traced to a necessary media component being removed by adsorption to the plastic, such as the well-known issue of cholesterol adsorption onto plastic bags preventing growth of NS0 cell lines requiring this lipid nutrient.