Many of the leading biopharmaceuticals are produced using animal cell culture and Pall® products are used from filter-sterilizing the cell culture media to purifying by chromatography and ultrafiltration of the resulting product.
The products, mostly proteins, are secreted by the cells into the culture medium. A variety of cell types are used, derived from many animal tissues. The commonest are CHO (Chinese Hamster Ovary) cells and BHK which are pure cell lines adapted for suspension or adherent cell culture and NS0 and other myeloma or hybridoma lines. Insect cell lines may also be used, especially for viral vector production, and some yeasts, such as Pichia pastoris are also able to express molecules of interest exogenously.
Smaller volume processes – typically up to 2000 liters – may be performed in fully single-use or disposable bioreactors, with all upstream and downstream processes utilizing single-use systems.
Large volume processes utilize all-stainless steel, hard-piped, fully engineered and often fully-automated production systems.
Pall Life Sciences offers system and component capability for all types of process equipment, as well as hybrid systems with Allegro™ Single-use System components integrated to fixed systems for maximum flexibility.
Downstream Processes Include These Main Areas:
As expression levels continue to improve, with 1 to 2 grams per liter of protein being considered 'normal', and some processes and cell lines capable of producing in excess of 10 g/L, downstream processes need to be able to handle increasing concentrations of product. This also means that for some proteins, where large quantities are not required as a therapeutic dose, process volumes can be reduced, leading to an easier process fit with single-use technologies.
Following this, the final bulk product may be further processed by being concentrated to a target formulation strength, sterile-filtered and filled, lyophilized or otherwise prepared for patient use.