Use of online Process Analytical Technology (PAT) to monitor Maytansinoid conjugation to modified antibodies: Implications in establishing robust processes for manufacturing disulfide-linked immunoconjugates

BIOT 168

Ian M. Schwartz, ian.schwartz@immunogen.com1, Sanjiv Gohain1, Dana C. Pentia1, Godfrey Amphlett2, Deborah H. Meshulam1, and Gennady Malin1. (1) Process Science and Engineering, ImmunoGen, Inc, 128 Sidney Street, Cambridge, MA 02139, (2) Process and Product Development, ImmunoGen, Inc, 128 Sidney Street, Cambridge, MA 02139
Process Analytical Technologies (PATs) are used primarily in the biotechnology industry during cell culture, filtration and column chromatography. A new application of PAT was established for the development and manufacture of immunoconjugates. Our PAT monitors reaction progression during disulfide exchange between a bispecific linker on the modified antibody and small molecule cytotoxic agent (Maytansinoid, DM4) by absorbance of released thiopyridine at 343 nm. The absorbance reaches a plateau upon saturation of available conjugation sites on the antibody. The presented approach will not only facilitate the process development for protein conjugates by determining time to reaction completion, reagent excess, and effects of environmental variables including pH and temperature, but will also improve process robustness by interfacing online monitoring with automated reagent addition. This methodology will establish a more robust “self tuning” process that will respond in real time to variations in raw materials and manufacturing variables during protein conjugation.
 

Commercialization of Biologics: Impact of Design Space Philosophy & Emerging Regulations on Process Validation
3:00 PM-5:20 PM, Tuesday, August 21, 2007 BCEC -- 108, Oral

Division of Biochemical Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007