title: Efficient biological process characterization by definitive-screening designs: the formaldehyde treatment of a therapeutic protein as a case study.
abstract: As part of the process-characterization campaign of a candidate vaccine product, a recently developed class of three-level designs-definitive-screening designs-was employed to select a quadratic model that describes the effect of six input process parameters, including protein concentration, formaldehyde-to-protein ratio, lysine concentration, reaction duration, pH, and reaction temperature, on a formylation protein-crosslinking reaction. This design requires only 17 experimental runs. The resulting model was then used to simulate 10,000 runs that account for the variability in the inputs expected on manufacturing scale. The extent of protein polymerization was predicted to be within specifications for all simulated runs, demonstrating the robustness of the unit operation for subsequent process validation and future commercial manufacturing.
authors.affiliation: Microbial Custom Manufacturing-Process Development, Lonza AG, 3930, Visp, Switzerland. axel.erler@lonza.com
authors.forename: Axel
authors.initials: A
authors.lastname: Erler
authors.forename: Nuria
authors.initials: N
authors.lastname: de Mas
authors.forename: Philip
authors.initials: P
authors.lastname: Ramsey
authors.forename: Grant
authors.initials: G
authors.lastname: Henderson
mesh_terms: D001688:Biological Products / Q000302:isolation & purification* / Q000378:metabolism*; D001709:Biotechnology / Q000379:methods*; D011506:Proteins / Q000302:isolation & purification* / Q000378:metabolism*; D012107:Research Design; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D001688:Biological Products; D011506:Proteins