title: Accelerating Vaccine Formulation Development Using Design of Experiment Stability Studies.
abstract: Vaccine drug product thermal stability often depends on formulation input factors and how they interact. Scientific understanding and professional experience typically allows vaccine formulators to accurately predict the thermal stability output based on formulation input factors such as pH, ionic strength, and excipients. Thermal stability predictions, however, are not enough for regulators. Stability claims must be supported by experimental data. The Quality by Design approach of Design of Experiment (DoE) is well suited to describe formulation outputs such as thermal stability in terms of formulation input factors. A DoE approach particularly at elevated temperatures that induce accelerated degradation can provide empirical understanding of how vaccine formulation input factors and interactions affect vaccine stability output performance. This is possible even when clear scientific understanding of particular formulation stability mechanisms are lacking. A DoE approach was used in an accelerated 37(°)C stability study of an aluminum adjuvant Neisseria meningitidis serogroup B vaccine. Formulation stability differences were identified after only 15 days into the study. We believe this study demonstrates the power of combining DoE methodology with accelerated stress stability studies to accelerate and improve vaccine formulation development programs particularly during the preformulation stage.
authors: Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033. Electronic address: patrick_ahl@merck.com.
authors: Patrick L
authors: PL
authors: Ahl
authors: Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors: Christopher
authors: C
authors: Mensch
authors: Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors: Binghua
authors: B
authors: Hu
authors: Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors: Heidi
authors: H
authors: Pixley
authors: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033; Infectious Diseases and Vaccines Discovery, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486.
authors: Lan
authors: L
authors: Zhang
authors: Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors: Lance
authors: L
authors: Dieter
authors: Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors: Ryann
authors: R
authors: Russell
authors: Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors: William J
authors: WJ
authors: Smith
authors: Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033; Infectious Diseases and Vaccines Discovery, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486.
authors: Craig
authors: C
authors: Przysiecki
authors: Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors: Mike
authors: M
authors: Kosinski
authors: Vaccine Bioprocess Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486; Merck Research Laboratories, Merck & Co., Inc., Kenilworth, New Jersey 07033.
authors: Jeffrey T
authors: JT
authors: Blue
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry*; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding / Q000379:methods* / Q000639:trends; D015195:Drug Design; D004355:Drug Stability; D005260:Female; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D009345:Neisseria meningitidis / Q000187:drug effects / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D014612:Vaccines
keywords: analytical biochemistry; biotechnology; excipients; stability; vaccine adjuvants; vaccines