title: Quality by design for a vaccine release immunoassay: a case study.
abstract: BACKGROUND
  As quality by design (QbD) for pharmaceutical product development is being expanded to include analytical methods, we applied QbD to the development of antigenicity assays measuring in vitro relative potency of a quadrivalent vaccine candidate.
  
  
  RESULTS
  After establishing development targets together with customers, immunoassays were developed to meet objectives. Statistical design of experiments was used to optimize method parameters and establish a design space. Systematic risk analysis enabled identification of potential risks to method performance that were mitigated by investigating the available design space around risk factors and by establishing appropriate control strategies.
  
  
  CONCLUSIONS
  We found QbD-based method development was a more efficient and systematic approach that could also potentially facilitate assay transfers and life cycle management.
authors.affiliation: Merck & Co., Inc., 770 Sumneytown Pike, P.O. Box 4, West Point, PA 19486, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Yarovoi
authors.forename: Tina
authors.initials: T
authors.lastname: Frey
authors.forename: Silikhone
authors.initials: S
authors.lastname: Bouaraphan
authors.forename: Mary
authors.initials: M
authors.lastname: Retzlaff
authors.forename: Thorsten
authors.initials: T
authors.lastname: Verch
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000302:isolation & purification; D000918:Antibody Specificity; D000941:Antigens / Q000032:analysis*; D005163:Factor Analysis, Statistical; D019085:Fluorescent Antibody Technique, Direct / Q000592:standards*; D019084:Fluorescent Antibody Technique, Indirect / Q000592:standards*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000302:isolation & purification; D011817:Rabbits; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014612:Vaccines / Q000032:analysis* / Q000276:immunology; D054928:Validation Studies as Topic
chemical_list: D000911:Antibodies, Monoclonal; D000941:Antigens; D007074:Immunoglobulin G; D014612:Vaccines