(205a) Development and Scale-up of a PEGylated Human Growth Hormone Manufacturing Process

PEGylation is known to increase the therapeutic half-life of proteins. One currently marketed recombinant protein therapeutic, human growth hormone (hGH), could see improved patient acceptance from modifications such as PEGylation that could potentially extend dosing periods from once daily to once weekly or better. While PEGylation is a powerful tool for improving the pharmacokinetic properties of a protein, unique challenges are encountered during the development of a robust, scalable manufacturing process. The technology development efforts to define an optimized process for PEGylated human growth hormone and scale-up to a 200 g production scale will be described. This will include optimization of a one-step ion exchange chromatography operation to produce mono-PEGylated hGH as well as the challenges encountered during ultrafiltration/diafiltration of a PEGylated protein.