In the creation of biopharmaceutical drugs, cells are genetically modified to produce some compound to have a desired effect in a treatment program. Essentially the cell becomes a chemical factory secreting a certain compound. The cells are then grown in a manner similar to how beer is produced in vats called “bioreactors”.
These cells typically produce very big macromolecules (ranging in molecular weight from 50,000 to well over 100,000), most are proteins and peptides. This differs from traditional pharmaceuticals which are generally made from much smaller molecules.
The manufacture of biological drugs is a fairly long process, but basically consists of 2 parts:
Sepragen’s products and services concentrate on these two manufacturing steps making them faster, scalable and more cost effective and reliable. Our customers thus realize the benefits of reduced cost of development and manufacture as well as faster time to market.
After growing the cells in the bioreactors, the compound (protein, peptide, etc) needs to be separated from all the other things (cells, nutrients, etc) using a series of centrifugation, membrane filtration and chromatography steps. The process is almost like petroleum refining/fractionation, where distillation or temperature is used to separate different compounds from oil, e.g., gasoline, diesel, etc. In biotechnology, it is the biochemical properties of the molecules such as molecular size or molecular charge that are used to affect the separation. Additionally, in this industry the process called isolation, purification or separation is targeted towards recovering the product in a pure state, often suitable for injection.
Separation/purification may start with a centrifugation step to remove the cells because they’re big and the liquid can be forced out. Alternatively, filters with pores small enough to stop the cells, but large enough to allow the compound of interest to flow through (“micro-filters” with pores of a few microns in size) are sometimes used for this step. Next, very fine “Ultra filters” are employed to remove water and concentrate the compound. The product of these filtration steps is a clear soup which includes as one of its components, the concentrated compound of interest.
The concentrated compound is then applied to a chromatography step wherein it is selectively adsorbed relative to all the other components and then released to affect a separation.
In one example for instance, at the beginning of the isolation process, a batch may start out with 20,000-30,000 liters of fluid which is concentrated and purified to produce an output of only a single liter. This one liter could be sufficient to provide the drug to the entire US. A dose may be as small as 100 micro-grams.