Continuing a deeper dive into analytical development, we’ll start by talking about my favorite characterization assay (experiment/method/protocol) – the functional potency assessment!
This particular characterization method is a way of quantifying how well the drug is able to execute the desired biochemical interactions within the cell in order to result in the expected therapeutic effect. For example, some drugs bind to a membrane protein which initiates a signaling pathway, other drugs (i.e. viral gene therapy) are to infect the nucleus of the cell, introduce their genome, and produce a new or missing protein. In any case, the functional potency assay aims to measure this very specific, and often highly complex, intracellular mechanism of action.
Because the mechanism of action differs for each drug, no one potency assay looks alike! They all take different amounts of time to execute, require detailed optimization of parameters, and utilize varying kinds of signal readouts (polymerase chain reaction, plate-based immunoassay, fluorescence readouts, binding kinetics, etc.). You can also imagine, that since they require the use of cells, the kind of baseline variability you’re working with is higher. But because these measurements are eventually used for batch release of commercial product, the final precision and accuracy of the analytical assays must be really high – the potency assay no exception! It’s (almost always) the most challenging analytical development characterization assay – but I find it the most rewarding.
I mentioned this assay is eventually used to characterize individual batches of commercial drug before releasing them to be used in humans, but these assays are also very important even prior to clinical trials when the research and process teams are working hard to optimize the production and purification process. Each time a step is adjusted, the potency assay can be used to ensure that the change did not have a detrimental effect (or conversely improved) the therapeutic effect of the drug.
I hope over time you are enjoying learning a bit more about how drugs are characterized in industry.