Packed-column SFC in the pharmaceutical industry: cGMP aspects

General aspects of drug development are discussed in the context of current Good Manufacturing Practice (cGMP) specified by various administrations. The potential of packed-column SFC (pSFC) instrumentation in the pharmaceutical industry is demonstrated along with different qualification parameters influencing chromatographic results, methods for their determination, and specifications defined in light of the ICH (International Conference on Harmonisation) Guideline for industry. Standard Operation Procedures (SOPs) are described for measuring flow rate, pressure, temperature, linearity and precision, sample carry-over, noise and drift, composition gradient, and wavelength accuracy of the pSFC instrumentation. The strong requirements for impurity and/or assay methods lead to a relative high effort of validation: beside selectivity, linearity and precision must be demonstrated over a wide range of concentrations for several repeated injections; limit of detection (LOD) and limit of quantitation (LOQ) must be in compliance with the specifications for impurity methods. A system suitability test (SST), filed together with the testing instructions of the drug, ensures that the pSFC instrumentation can be used for the analysis, Finally, method transfer between different systems and further instrumental improvements are discussed.