Download Analytical Chromatography of Orencia™ (Abatacept, CTLA4-LG) ABSTRACT

Analytical Chromatography of Orencia™ (Abatacept,
CTLA4-LG)
Dave Kirkley, Senior Research Investigator II, Bristol-Myers Squibb
ABSTRACT
Biopharmaceutic molecules require an in-depth analytical
characterization and release testing in order to qualify as a
therapeutic drug. Different methods of chromatographic separation
can be performed to analyze, characterize, and assay biological drug
substances. Orencia™ (Abatacept, CTLA4-Ig) is a homodimer fusion
protein biotherapeutic that was FDA approved for use against
rheumatoid arthritis and is targeted for other autoimmune diseases
like lupus, MS, Crohn’s disease, and IBS.
To fulfill FDA requirements, many chromatographies were developed to assay and characterize this
molecule. Various testing methods were developed and validated which include affinity, size exclusion,
ion exchange, chromatofocusing, and reversed-phase chromatography. This presentation will center on
the use of these chromatographies to analytically assess the unique complexity in the production of
Orencia™ that insures quality, efficacy, and safety for patients.
BIOGRAPHY
Dave Kirkley is currently a Senior Research Investigator II at Bristol-Myers Squibb in Syracuse, NY. He is a
native of the Syracuse area having attended Fayetteville-Manlius High School. This was followed by
undergraduate work at the College of Wooster (in Ohio, BA in chemistry) and graduate school at
University of Texas at Arlington (MA in chemistry). He studied and worked on the biosynthesis of the
thiazole moiety of thiamine contributing two papers to the field. Following graduate school Dave taught
at colleges SUNY at Geneseo, Herkimer Community, and Hamilton and then switched to industry
concentrating on developing HPLC chromatography methods of small molecules in the pharmaceutical
industry. This started at Bristol-Myers in Syracuse followed by work at Ayerst in Rouses Point, NY and
Pennwalt Pharmaceuticals in Rochester, NY. In 1985 Dave moved on to perform large molecule HPLC
chromatography at Praxis Biologics in Rochester, NY and then back to Bristol-Myers Squibb until
present.
In the 23 years Dave has spent at BMS, he first introduced analytical size exclusion, protein A affinity,
hydrophobic interaction, ion exchange chromatography, and N-linked oligosaccharide analysis as well as
reversed-phase peptide mapping. By using these methods and more, the products which include
OrenciaTM, NulojixTM, and antibodies like YervoyTM became fully characterized and acceptable to the FDA
leading to these new licensed and marketed biologics.