title: Semiautomated Sample Preparation for Protein Stability and Formulation Screening via Buffer Exchange.
abstract: A novel semiautomated buffer exchange process workflow was developed to enable efficient early protein formulation screening. An antibody fragment protein, BMSdab, was used to demonstrate the workflow. The process afforded 60% to 80% cycle time and scientist time savings and significant material efficiencies. These efficiencies ultimately facilitated execution of this stability work earlier in the drug development process, allowing this tool to inform the developability of potential candidates for development from a formulation perspective. To overcome the key technical challenges, the protein solution was buffer-exchanged by centrifuge filtration into formulations for stability screening in a 96-well plate with an ultrafiltration membrane, leveraging automated liquid handling and acoustic volume measurements to allow several cycles of exchanges. The formulations were transferred into a vacuum manifold and sterile filtered into a rack holding 96 glass vials. The vials were sealed with a capmat of individual caps and placed in stability stations. Stability of the samples prepared by this process and by the standard process was demonstrated to be comparable. This process enabled screening a number of formulations of a protein at an early pharmaceutical development stage with a short sample preparation time.
authors.affiliation: Bristol-Myers Squibb, Drug Product Science & Technology, New Brunswick, NJ, USA.
authors.forename: William
authors.initials: W
authors.lastname: Ying
authors.affiliation: Bristol-Myers Squibb, Drug Product Science & Technology, New Brunswick, NJ, USA jaquan.levons@bms.com.
authors.forename: Jaquan K
authors.initials: JK
authors.lastname: Levons
authors.affiliation: Bristol-Myers Squibb, Drug Product Science & Technology, New Brunswick, NJ, USA United States Pharmacopeial Convention, Rockville, MD, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Carney
authors.affiliation: Bristol-Myers Squibb, Drug Product Science & Technology, New Brunswick, NJ, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Gandhi
authors.affiliation: Bristol-Myers Squibb, Late Phase Chemical Development, New Brunswick, NJ, USA.
authors.forename: Vicky
authors.initials: V
authors.lastname: Vydra
authors.affiliation: Bristol-Myers Squibb, Late Phase Chemical Development, New Brunswick, NJ, USA.
authors.forename: A Erik
authors.initials: AE
authors.lastname: Rubin
mesh_terms: D057205:Automation, Laboratory / Q000379:methods*; D002021:Buffers; D004339:Drug Compounding / Q000379:methods*; D008403:Mass Screening / Q000379:methods*; D055550:Protein Stability; D011506:Proteins / Q000737:chemistry*
chemical_list: D002021:Buffers; D011506:Proteins
keywords: automation; biologics; buffer exchange; formulation screening; protein; stability