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Title: Improved Stability of a Model IgG3 by DoE-Based Evaluation of Buffer Formulations

Formulating appropriate storage conditions for biopharmaceutical proteins is essential for ensuring their stability and thereby their purity, potency, and safety over their shelf-life. Using a model murine IgG3 produced in a bioreactor system, multiple formulation compositions were systematically explored in a DoE design to optimize the stability of a challenging antibody formulation worst case. The stability of the antibody in each buffer formulation was assessed by UV/VIS absorbance at 280 nm and 410 nm and size exclusion high performance liquid chromatography (SEC) to determine overall solubility, opalescence, and aggregate formation, respectively. Upon preliminary testing, acetate was eliminated as a potential storage buffer due to significant visible precipitate formation. An additional 2 4full factorial DoE was performed that combined the stabilizing effect of arginine with the buffering capacity of histidine. From this final DoE, an optimized formulation of 200 mM arginine, 50 mM histidine, and 100 mM NaCl at a pH of 6.5 was identified to substantially improve stability under long-term storage conditions and after multiple freeze/thaw cycles. Therefore, our data highlights the power of DoE based formulation screening approaches even for challenging monoclonal antibody molecules.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [2] ;  [3]
  1. Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality's (OPQ) Division II
  2. Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality's (OPQ) Division of Product Quality Research, Office of Testing
  3. Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality's (OPQ) Division II
  4. Food and Drug Administration (FDA), Silver Spring, MD (United States). Center for Drug Evaluation and Research (CDER), Office of Pharmaceutical Quality's (OPQ) Division of Pharmaceutical Analysis, Office of Testing and Research
Publication Date:
Grant/Contract Number:
CDER-Grant-No.1500
Type:
Accepted Manuscript
Journal Name:
BioMed Research International
Additional Journal Information:
Journal Volume: 2016; Journal ID: ISSN 2314-6133
Publisher:
Hindawi
Research Org:
Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States)
Sponsoring Org:
USDOE Office of Science (SC); US Food and Drug Administration (FDA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1376192