Establishing a GMP manufacturing site for nanoparticles

An active clinical trial at MD Anderson Cancer Center uses DOTAP:Chol liposomes as a non-viral vector for gene therapy. This therapeutic product needs to be produced fresh for each administration. Originally, the manufacture of the liposomes, the purified plasmid Fus-1 DNA as well as the Liposome-DNA complex for this trial was completed at a collaborating institution. With the recent opening of MDACC's state of the art GMP facility the manufacture of the DOTAP:Chol-Fus-1 complex was transferred to our facilities. This transfer took the collaborative efforts of regulatory groups, the original manufacturing site, the clinical team, the GMP technical laboratory, QC and QA groups, and various reference laboratories. During this technology transfer process it was discovered that the original liposomes had begun to degrade. Our GMP facility had to therefore validate the manufacturing of both the liposome and DNA-liposome complexes. The release specifications of the liposome and final DNA-liposome product were equivalent to lots previously produced at our collaborating institution. To date, 10 doses have been manufactured for the treatment of 4 patients.