The Flow Facility, in collaboration with a number of LC and valve manufacturing companies stepped in to help out with this multi-attribute process intensification problem.

The things we think and do not say: A high-throughput multi-attribute process intensification tool

High-throughput experiments (HTE) have changed the way we approach process intensification tasks today. HTE transformed how rapidly we can achieve a global solution to a complex multi-objective optimization problem. Multi-attribute process optimization, where all critical quality attributes (CQA) need to collectively achieve an optimum outcome, is a daunting task. More often than not the optimization of one CQA at a time fails to converge toward a similar set of optimal input parameters in a reasonable time frame.  Fortunately, recent advancement in multi-dimensional chromatography enabled us to monitor several CQAs in parallel. While multidimensional chromatography gives us a wealth of data relatively quickly, it is important to pay attention to what each individual chromatogram is telling us beyond just cataloging an attributes by numbers. For example, in the example chromatogram on the right we are investigating the yield of a product (peak P) from two reagents (peaks R1 and R2). When we see three peaks as the 'expected' chromatogram shows, the data appears well corroborated.

concept chromatograms; top has an unexpected impurity; bottom shows only expected reagents and the product
Fig. 1. The bottom chromatogram shows an impurity. The origin of such a peak is typically identified through additional runs using analytical standards

What happens when a new peak (the purple peak U) shows up! The question remains if this 'unknown' peak formed during analysis or in the process? For decades, scientists used peak spiking strategies to decide what is real and what is not. They reflected on their mechanistic expertise and experiential knowledge to infer how a particular process condition gives rise to an entity that fits the unknown ghost peak profile. And, more often than not they were right. That slow but steady rational approach, however, came at a cost, time. Making standards until the one fits the 'unknown' profile is not a routine task. It's up to the scientists to make a decision call on whether to take 'slow and steady' rational QbD approach, where the benefit of 'speed' may have to be compromised, or 'fast and risky' HTE approach, where we turn a blind eye to the devil in the details.

The Flow Facility, in collaboration with a number of LC and valve manufacturing companies stepped in to help out with this multi-attribute process intensification problem. We provided a unique multi-dimensional recirculatory platform that is exclusively designed to address the problem discussed above. More importantly, the platform eliminated the need for analytical standards and speeds up HT multidimensional process intensification for multi-attribute processes. Click below to learn more about this multi-attribute process optimization tool technique.