SFC for pharmaceutical quality control: Opportunities, challenges and fears

Supercritical Fluid Chromatography (SFC) could be presented as an emerging analytical technique, especially in the field of pharmaceutical analysis. Indeed, despite the launch of modern SFC instrumentation in 2012 and the continuous increase of publications, SFC is still considered as a niche technique for pharmaceutical quality control. In this context, SFC implementation for several QC applications was studied from the perspective of the analytical method lifecycle and GMP compliance to highlight the potential of this technique.
Firstly, we evaluated in depth the performance of this technique for the determination of impurities in API, especially in terms of robustness and method precision criteria. This evaluation was performed at three different stages of the analytical method lifecycle. After systematic method development and robustness assessment according to Quality by Design principles (ICH Q8), the method was validated according to the total error approach (ICH Q2) [1]. The main challenge of this project was focused on the evaluation of the applicability and transferability of this method in various laboratories around the world. Two consecutive inter-laboratory studies were performed following ISO 5725-2 guidelines for the measurement of method precision [2-3]. In the first study, the method was transferred to several laboratories equipped with the same instrumentation. The method reproducibility was then calculated taking into account several sources of variability, i.e., replicates, days, and laboratories. The second study includes several instrumentation types (vendors) and required technical and/or method adjustments to be able to properly transfer the method. The latter highlights the challenges of SFC method transfer regarding the instrumentation. Another aspect to be addressed with was the poor implementation of this technology in pharmaceutical QC laboratories.
The second objective was to evaluate the routine (daily) use of SFC QC method. In this context, A generic SFC-MS was developed and used to analyze several vitamin D medicines and food supplements. Qualitative and quantitative system suitability tests (SST) were implemented and monitored using a control chart. In conclusion, these studies demonstrated the potential of modern SFC as QC technique and overcome several fears. Some challenges regarding the instrumentation (qualification and transfer) and widespread implementation of the technique should be considered in the future.