AOF or non-AOF? That is the question...

by Marian L. McKee, Ph.D., Vice President, Biosafety

Whether or not to request cell banking in an animal origin free (AOF) or non-AOF suite is a decision that many of our clients are making these days. The decision to produce a master or working cell bank in one of our two AOF suites should come from a risk assessment of the overall manufacturing process from cell bank to bioreactor through downstream processing and purification. While there is currently no specific regulatory requirement driving the move to serum-free, animal-derived supplement-free cell culture, more manufacturers are moving to AOF production methods as part of the overall contaminant risk mitigation strategy to assure the safety of biological products, drugs, and vaccines for human and animal use.

Animal-derived components in cell culture are the most frequent source of contaminants in the biopharmaceutical industry. In fact, in a recent survey across biologics manufacturers, the vast majority of contaminants in mammalian cell culture operations were traced back to the animal serum and other medium components used in the manufacturing process. Overall, the three main risk factors for adventitious agent contamination in biologics manufacturing are the cell sources, materials used in cell culture, and exposure of the cell culture during manufacturing to the environment or the operator. All three of these risks center on the use of cells in culture for the production of biologic drugs.

This awareness of the risk of introduction of adventitious agents via raw materials from animal sources has contributed to a move toward AOF medium components and adaptation of cell lines for production of biologics and vaccines to these AOF media. The move to an AOF production method should be addressed early in the development process as it takes time to adapt cells to these conditions. Plant origin and recombinant medium supplements must be identified and tested to replace serum and other animal-derived material that have been traditionally used in cell culture maintenance and bioprocessing.

Once identified, the cells must be transitioned to the new conditions over time and multiple passages. This adaptation should be completed and reproducible growth conditions established prior to laying down the master cell bank. Characterization of the adapted cells is also important in order to demonstrate that any critical attributes have not been compromised. Aspects of this characterization testing will be performed alongside safety testing as part of the master cell bank release program.

As new therapeutic modalities emerge in the biopharmaceutical industry, the amount of purification and downstream processing required is changing, too. This is an area where we are seeing increased demand for AOF production of the cell banks to support these cell and gene therapy products.

When you chose Eurofins BPT for production of an AOF Master or Working Cell Bank, all work will be performed in one of two Grade A/B clean room suites dedicated to AOF banking. Cleanroom production banks are performed on a campaign basis. The rooms and equipment are cleaned at the start and end of each bank campaign, monitored, and cleared by QA before and after each project. For more information visit: Cell Bank Preparation - Eurofins BioPharma Product Testing