Analytical Quality by Design Enabled Green RP‐HPLC Method Development and Validation for the Simultaneous Quantitation of the Cleaning Residues of Osimertinib, Binimetinib, and Erdafitinib: An Approach to Prevent the Cross‐Contamination in Shared Facilities of Pharmaceutical Manufacturing

Developed and validated a simple, robust, chemometric‐assisted, and green, reverse‐phase high‐performance liquid chromatography method for simultaneous quantification of three kinase inhibitors (osimertinib, binimetinib, and erdafitinib) to meet the maximum allowable carryover limits of residues in pharmaceutical cleaning validation. The method was developed on Waters HPLC Alliance e2695 using Xterra RP18 column, simpler mobile phase composition (0.1% formic acid:methanol; 51:49 v/v), detection at 254 nm and 15 min run time with the isocratic mode. Leveraging the analytical quality by design of ICH Q14, the method operable design regions were established by Taguchi screening and Box–Behnken optimization established a, ensuring robustness across chromatographic variables. Replaced acetonitrile with methanol as green solvent to reduce the environmental impact and achieved the analytical greenness metric approach (AGREE) score of 0.72. An assessment was performed for the cross‐contamination risks as per ICH Q3C(R9) for multi‐drug manufacturing (i.e., osimertinib, binimetinib, and erdafitinib) scenario. The method validation parameters performed successfully as per ICH Q2(R2) guideline, which demonstrated a good sensitivity for limit of detection (LOD: 0.5 µg/mL) and quantification (LOQ: 1.0 µg/mL). Considering the real industrial scenario, the recovery of residues performed from different surfaces (stainless steel, glass, and polytetrafluoroethylene plates) using both rinse and swab methods in‐line with the European Medical Agency guideline (1.5 µg/mL as 100% level) to represent the manufacturing of different pharmaceutical products in the shared facilities.