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.
Highlights
The concept of quality by design (QbD) in chemical analysis method development is becoming increasingly demanded by regulatory bodies to mitigate risks and optimize the performance of quality control protocols applied in pharmaceutical manufacturing [1,2,3]
While analytical QbD is neither an entirely new nor unique approach and largely is based on tools that for long have been applied in chemical analysis [1], the structured concept still catalyzes a change of mindset and influence how separation method development is performed in laboratories, leading to better fit-for-purpose analysis procedures
The list contains more than one thousand entries [10], and among them is the call for monograph methods for foscarnet sodium injection solution
Summary
The concept of quality by design (QbD) in chemical analysis method development is becoming increasingly demanded by regulatory bodies to mitigate risks and optimize the performance of quality control protocols applied in pharmaceutical manufacturing [1,2,3]. While analytical QbD is neither an entirely new nor unique approach and largely is based on tools that for long have been applied in chemical analysis [1], the structured concept still catalyzes a change of mindset and influence how separation method development is performed in laboratories, leading to better fit-for-purpose analysis procedures. Publications of QbD applied to ion chromatography (IC) seem to be very scarce or even non-existent despite the increased importance of IC in pharmaceutical quality control [8]. The list contains more than one thousand entries [10], and among them is the call for monograph methods for foscarnet sodium injection solution
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