Chapter 621 of the USP explains the allowable adjustments to chromatography systems while staying within quality requirements. It is important to consider these criteria before beginning to optimize assays for APIs and related substances to ensure that methods meet requirements during regulatory filing.
In this case, Cambrex had a short time frame of only 7 weeks to complete assay optimization and conduct pre-validation studies within the confines of USP<621>. The additional challenges they faced from inherent properties of the API included a narrow pH window (± 0.05 of the pKa), and controlling reaction conditions to allow use of an ion pairing agent. In addition, the analysis time was lengthy (72 minutes), and required evaluation of multiple peaks and PDA spectral evaluation during system suitability.