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Published case study of analytical quality by design method development and validation

Diduco has published a scientific peer-reviewed case study on how modern analytical method development can be performed in the pharmaceutical industry. The work was performed according to analytical quality by design (AQbD) principles to establish the design space and robust setpoint of the ion chromatography assay, and then validated according to the guidelines established by the International Council for Harmonization (ICH).

All details about the method development and validation are available in the scientific paper “Validated modernized assay for foscarnet in pharmaceutical formulations using suppressed ion chromatography developed through a quality by design approach”, published under the creative commons attribution license in the open access scientific journal Separations (year 2021, volume 8, issue 11, page 209) and is available for download at: doi.org/10.3390/separations8110209

Image displays the graphical abstract which illustrates the calculated design space and robust setpoint of the assay. Abstract: Inspired by the United States Pharmacopoeia (USP) “monograph modernization” initiative, we developed and validated an assay for foscarnet sodium injection solution (“foscavir”), following quality by design (QbD) principles, incorporating design of experiments (DoE) and multivariate data analysis to establish the design space and robust setpoint of the method. The resulting analytical procedure was based on ion chromatography (IC) with suppressed conductivity detection, employing an isocratic carbonate–bicarbonate eluent system. The assay was successfully validated at the robust setpoint conditions, according to the guidelines established by the International Council for Harmonization (ICH). The linear range stretched at least from 5 to 100 mg/L with high repeatability (relative standard deviation, RSD ≤ 0.3%) both at the target concentration (60 mg/L) and at 50% and 150% from this level. Special attention was given to establish a rugged assay that would be easily transferable between laboratories, and the recorded recoveries of 98.2–100.5% for both the formulated drug product and the drug substance during intermediate precision evaluation at different analysis situations indicated that this mission was accomplished. A multivariate assessment of intermediate precision data acquired using an experimental design scheme revealed that the assay was not adversely affected by any of the situation variables, including the use of different liquid chromatography instrument types, regardless of if they were constructed from inert materials or stainless steel that had been passivated, even though such problems have been reported in several previous methods for analysis of foscarnet.

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