In this time of dire need, Sepragen team is doing its part to solve the problem of COVID-19. We are providing equipment on an expedited basis to a company developing a vaccine for COVID- 19.

Biologics Drug Manufacturing

Enabling Biological Drugs Scale Up & Production

Sepragen’s products are used to manufacture over 30+ FDA approved drugs including Kogenate®, Alphanate®, Neupogen®, and GammaGrand®* along with a multitude of other drugs currently in clinical trials. Sepragen’s customers range from manufacturers of recombinant biological protein and peptides, vaccines manufacturers, genetic therapy vectors, monoclonal antibody producers for diagnostic and therapeutic use and enzyme producers. In one instance, over 40,000 liters of human plasma is being treated every 6 hours on 2,800 liters of Sepragen columns to produce tens of kilograms of an injectable protein drug.

Case Study 1: Plasma Separation: 9X Higher Flow

Superflo® Columns can dramatically reduce separation times and costs of both labor and materials. The data below was obtained from a plasma fractionation facility. The study was performed in order to compare the performance of a Superflo®-20L Column with that of a 16L axial flow column. Table 1 shows a comparison of the performance of the two columns. With the Superflo® Column, flow rates increased over 3 fold with a corresponding increase in separation speed from three shifts to one shift without affecting product recovery or purity
RFC installation processing 20,000 liters of human plasma every shift. Courtesy: Baxter
RFC installation processing 20,000 liters of human plasma every shift. Courtesy: Baxter
Scale-up on radial flow columns resulted in 1/3 column size, 1/3 processing time and 1/3 media cost.
Scale-up on radial flow columns resulted in 1/3 column size, 1/3 processing time and 1/3 media cost.

Case study 2: Purification of an Intracellular Bacterial Enzyme

The example below shows the isolation of a recombinant protein. Not only is the processing time decreased dramatically, but the recovery is enhanced due to reduction of on column proteolytic degradation.

Biologic Drug Manufacturing

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:

  1. Growing Cells genetically engineered to secrete a compound and
  2. Isolation/Purification, separating/purifying the compound.

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.

Growing Cells

Cells are the micro factories of biologic compounds that are grown in “bioreactors” which provide the nutrients necessary for the cells to reproduce and secrete the compound of interest. Traditional bioreactors are something like beer vats, in which the cells are suspended in a liquid bath of nutrients. Cells are feeding, multiplying and secreting until the batch reaches a terminal condition and is harvested.

Isolation/Purification

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.

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