Seed Expansion & Cell Banking System

Cell banking is normally a rather laborious manual process using centrifuges and a series of concentration, separation and resuspension operations, subject to much variariability. The cell bank produced is generally vials containing 1ml or 10ml of cell suspension of similar concentration (and viability). Since this cell bank creation takes several hours (or up to a day depending on the number of vials), it is impossible to expect the first and last vial to be the same.

The cells in these vials are critical since they are the first step in the manufacturing process, whether for small scale research purposes or for eventual inoculation to a 20,000L reactor. Generally for manufacturing, several vials will be thawed and a series of cell expansions will occur in parallel so that a choice of the best from them will be used to inoculate the first bioreactor. This is unavoidable due to the inherent variation caused by the inefficient manual process that created the cell bank.

There is risk, uncertainty and variation in these steps and there is a significant time involved.

Cell Banking with the ATF System solves all the problems with the existing procedures. This is done by ensuring the cells always stay in a healthy environment within the sterile reactor, for example they never suffer stress through a lack of oxygen, centrifugation or being starved of nutrients. The media exchanges and freezing fluid introduction all occur rapidly inside the reactor and the cell bank is transferred to disposable bags without any open handling nor individual manual testing of cell concentrations. The entire process can be automated and completed within an hour: the first cell bag banked will be identical to the last – and this can be validated.

Seed Expansion with the ATF System removes the variation from the first passages from cell bank to bioreactor. The cell bank can inoculate directly a small bioreactor from the freezer without the need for centrifugation and DMSO removal in advance. No open handling is needed. The bioreactor can be from 5L to 50L or larger depending on your facility (disposable or traditional), and the expansion of the cells occurs in concentrated fed-batch mode to ultra-high cell densities, e.g. 70-150m/ml. This first seed reactor can then inoculate a large reactor (20-50x) without intervening scale-up steps, saving a significant amount of time and capital and reducing manufacturing risk for each batch. The larger reactors can then be operated in standard batch or fed-batch mode, or further productivity improvements can be made by implementing concentrated perfusion or concentrated fed-batch.