Year: 2009-10

Company: BioMarin Pharmaceuticals

Liaison(s): Nick Zecherle

BioMarin Pharmaceuticals Inc. develops and commercializes innovative enzyme replacement therapies for rare diseases. The company’s product portfolio is comprised of three FDA approved products (Kuvan®, Naglazyme®, Aldurazyme®) and several investigational product candidates. The focus of our project was to develop a quantification assay and purification strategy for reduction or removal of a trace protease impurity found in some of BioMarin’s purification process intermediates derived from mammalian cell culture. The BioMarin Team Masters Project (TMP) designed a twophase plan to address the main goal of the project. During Phase I, the team worked on multiple proof-of-principle, sensitive blotting technique experiments for accurate quantification of the impurity. In Phase I the team developed an analytical assay which will be of significant importance to validate the effectiveness of Phase II methodology. During Phase II of the project, the BioMarin Team tested different membrane chromatography approaches to sufficiently reduce or eliminate the protease impurity without concomitant loss of the target therapeutic enzyme molecule. Additionally, we considered factors regarding the ease of implementation of a membrane chromatography step in an otherwise pre-defined purification process.