Raw Material Testing

What is RAW MATERIAL TESTING and why is it important?

The regulators require that the manufacturing process for all biologics be rigorously defined and strictly controlled. Clearly this begins with defining and controlling the input and in-process raw materials.

The input raw materials for a cell based manufacturing process will include the cell media and any salts, buffers and other nutrients which are required for the manufacturing cells to grow and produce the biologic. While common in a research setting, the use of animal derived materials has long been known to be of specific concern for GMP manufacturing. For example, non-irradiated bovine serum is known to present significant risk of containing high levels of live virus. Indeed, animal derived enzymes such as porcine trypsin carry similar viral risks to serum. Due to these significant risks, manufacturers have tried to remove the highest risk raw materials such as serum and trypsin from their manufacturing processes.

Raw materials are most often screened for viral contamination using molecular detection, specifically PCR, as it is highly sensitive and rapid.  The issue with PCR is that it cannot discriminate between live-replicating virus and virus which has been inactivated through, for example irradiation. PCR would therefore identify serum as containing virus even through it was fully inactivated, presenting no risk. More traditional cell-based methods can be used, but these can take weeks. Cell-based methods also run the risk of being permissible to infection without showing any cytopathic or histochemical indications.

NGS can detect viral replication, for example as specific incorporation events into the viral genome. Using this technique it is therefore possible to discriminate between inactivated virus and virus which is capable of replication. This may prove advantageous to manufacturers who cannot use traditional methods to screen their raw materials.