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. T he potential of packed-column SFC (pSFC) instrumentation in the pharmaceuti cal industry is demonstrated along with different qualification parameters influencing chromatographic results, methods for their determination, and s pecifications defined in light of the ICH (International Conference on Harm onisation) Guideline for industry. Standard Operation Procedures (SOPs) are described for measuring flow rate, pressure, temperature, linearity and pr ecision, sample carry-over, noise and drift, composition gradient, and wave length accuracy of the pSFC instrumentation. The strong requirements for im purity and/or assay methods lead to a relative high effort of validation: b eside selectivity, linearity and precision must be demonstrated over a wide range of concentrations for several repeated injections; limit of detectio n (LOD) and limit of quantitation (LOQ) must be in compliance with the spec ifications for impurity methods. A system suitability test (SST), filed tog ether with the testing instructions of the drug, ensures that the pSFC inst rumentation can be used for the analysis, Finally, method transfer between different systems and further instrumental improvements are discussed.