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, which is crucial for cell manufacturing.

The input raw materials for a cell-based manufacturing process include the cell media and any salts, buffers, and other nutrients 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 a 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 cell-based production 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 though 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.

Cell manufacturing processes require reliable methods to ensure the safety and integrity of raw materials. NGS can detect viral replication by identifying specific incorporation events into the viral genome. Using this technique, it is possible to discriminate between inactivated virus and virus capable of replication. This may prove advantageous to manufacturers who cannot use traditional methods to screen their raw materials, thereby enhancing the robustness of cell-based manufacturing.

Implementing NGS in product release testing can streamline the detection process, providing faster and more accurate results. This is especially critical in cell-based production, where the presence of active viral contaminants can compromise the entire manufacturing process. By integrating NGS into lot release procedures, manufacturers can ensure that only safe, uncontaminated materials are used, thus maintaining the high standards required in cell manufacturing.

Overall, using advanced techniques such as NGS for screening raw materials supports the stringent requirements of product release testing and lot release, ensuring the safety and efficacy of the final biologic products.