Process challenges with the scale up and purification of a potential antibacterial candidate

ORGN 72

Daniel J Watson, daniel.watson@arraybiopharma.com, D David Hennings, dhennings@arraybiopharma.com, Brian Wong, Matthew Medina, and John DeMattei. Process Research and Development, Array Biopharma Inc, 3200 Walnut Street, Boulder, CO 80301
The challenge with the development and scale-up of this antibacterial candidate was the fact that the starting material is a natural product containing a mixture of four components in an approximate ratio of 45:45:5:5. The major components were differentiated by having either a serine or alanine amino acid handle. This enabled derivatisation and separation by chromatography utilizing in-line UV monitoring together with HPLC analysis and was demonstrated on scale to separate multi-kilogram quantities of this advanced intermediate. The impurity profile of the API also provided both an analytical and engineering challenge and a robust process and controlled drying process was developed to ensure reproducibly high quality product.