A Knowledge Management Framework and Approach for Clinical Development.

A knowledge management (KM) framework enhances knowledge gathering, sharing, application, and retention within clinical development and enables the effective and successful implementation of a clinical quality management system (QMS). The goal of managing knowledge is to improve organizational performance by getting the right information to the right people at the right time. The concepts of KM have been around for decades but, to date, have not been widely adopted within the clinical development arena.

Use of a quality-by-design approach to justify removal of the HPLC weight % assay from routine API stability testing protocols.

Due to the high method variability (typically > or = 0.5%, based on a literature survey and internal Merck experience) encountered in the HPLC weight percent (%) assays of various active pharmaceutical ingredients (APIs), it is proposed that the routine use of the test in stability studies should be discouraged on the basis that it is frequently not sufficiently precise to yield results that are stability-indicating. The high method variability of HPLC weight % methods is not consistent with the current ICH practice of reporting impurities/degradation products down to the 0.

Evaluation of chiral purity for a substituted imidazole p38 MAP kinase inhibitor and its intermediates using a single chiral capillary electrophoresis method.

The chiral separation of a substituted imidazole p38 MAP kinase inhibitor and its intermediates was investigated using capillary electrophoresis (CE) with various sulfated cyclodextrins. After initial screens, a single CE chiral method with a randomly sulfated beta-CD was selected for the evaluation of chiral purity for all three compounds. Operational parameters, such as the concentration of the chiral selectors, background electrolyte (or mobile phase) pH, organic modifiers, and temperature were varied in order to achieve an optimized method.

Comparison study of Chiralpak AD-H with AD columns in chromatographic enantioseparation of dihydropyrimidinone acid and its methyl ester.

This paper reports a comparison study of the difference between Chiralpak AD-H and AD columns in enantioseparation of dihydropyrimidinone (DHP) acid and its methyl ester under normal phase LC conditions. Unlike those of the AD phase, the van't Hoff plots of retention factors for DHP acid on the AD-H phase were linear. The cyclic van't Hoff plots of selectivity factors for DHP acid on the AD-H phase were non-linear and slightly non-superimposable.

Characterization of a thermally induced irreversible conformational transition of amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase in enantioseparation of dihydropyrimidinone acid by quasi-equilibrated liquid chromatography and solid-state NMR.

A thermally induced irreversible conformational transition of amylose tris(3,5-dimethylphenylcarbamate) (i.e., Chiralpak AD) chiral stationary phase (CSP) in the enantioseparation of dihydropyrimidinone (DHP) acid racemate was studied for the first time by quasi-equilibrated liquid chromatography with cyclic van't Hoff and step temperature programs and solid-state ((13)C CPMAS and (19)F MAS) NMR using ethanol and trifluoroacetic acid (TFA)-modified n-hexane as the mobile phase.