Continuing a deeper dive into analytical development, let’s talk about residual impurity assays!
It’s important to understand that during the production of biologics (proteins, nucleic acids, viruses) and small molecules it is inevitable that things will be introduced throughout that you want to remove through purification. For example, viruses are produced by cells in culture (in a dish in a lab). The viruses have to be extracted from the cells – this means that proteins, DNA/RNA, and small molecules used in the growth media used on the cells need to be removed during purification. While in this image I depict a single filtration step, in reality there are many steps that utilize different mechanisms (both specific and general filtration) to remove impurities. Regulatory agencies have requirements for these impurities and it is the job of the industry to ensure that the production process meets these requirements.
Developing residual nucleic acid assays can often be a bit easier to develop because there are standardized ways to measure nucleic acids (pcr using specific primer sets). The difficult piece is confirming that the assay can detect incredibly low values (lower limit of detection), that the buffers used throughout the drug purification process don’t interfere with the assay (matrix interference), and that the accuracy and precision is high. Residual protein and small molecule assays do require more optimization and depend heavily on the kinds of proteins or small molecules you are trying to measure – these can be highly specific to the drug of interest.
Needless to say, there is a large group of characterization assays used to confirm that the final drug product has process impurities removed!
Does this all make sense? Stay tuned for future posts about other analytical assays! I hope over time you are enjoying learning a bit more about how drugs are characterized in industry.