ABSTRACT
Supercritical fluid chromatography (SFC) has been historically used for non-Good Manufacturing Practice (GMP) activities in drug development because its low sensitivity and insufficient accuracy and precision could hardly meet GMP testing method requirements. In recent years, with the improvement in the sensitivity and the advancement of the instrumentation, SFC can now meet the method requirements thus to be applied for GMP release and stability testing. This chapter presents how to implement SFC methods in GMP testing. First, the chapter provides the pioneer experience on how to qualify the SFC system for GMP use, including the system qualification protocol write up and acceptance criteria definition. Second, the chapter demonstrates the feasibility of chiral SFC methods being applied in GMP testing by passing method validation requirements with side-to-side comparison with the corresponding
HPLC methods. The successful validation of the SFC methods proves that SFC can meet the requirements for chromatographic purity methods, thus can be a potential replacement for HPLC in chiral API GMP release and stability testing. Third, the method transferability among different SFC systems has been studied and confirmed the suitability of the chiral SFC as a regulatory filing method. Along with the continuous improvement in SFC instrumentation and further exploration on how to better apply the technology in pharmaceutical analysis, SFC has been increasingly implemented as a the fast and efficient separation tool for pharmaceutical analysis in the regulated analytical laboratories.
