title: Nonclinical dose formulation: out of specification investigations.
abstract: Nonclinical safety studies are required to follow applicable Good Laboratory Practice (GLP) regulations. Nonclinical dose formulations are required to be analyzed to confirm the analyte concentration, homogeneity, and stability. Analytical samples that fall outside of the acceptance criteria are considered out of specification (OOS), and an investigation should be conducted. The US FDA has issued a guidance document for GMP studies on conducting OOS investigations. However, no regulatory guidance has been issued regarding nonclinical safety study (GLP) OOS investigations, which often vary in regard to content, assessment, and impact statements. There is opportunity to improve the quality of OOS investigations by defining expectations and providing guidance in several areas including root cause assessment, impact statements, and acceptable paths forward. This paper will provide recommendations of best practices for nonclinical dose formulation OOS investigations.
authors.affiliation: troyaappleton@gmail.com
authors.forename: Troy
authors.initials: T
authors.lastname: Appleton
authors.forename: Peter
authors.initials: P
authors.lastname: Bryan
authors.forename: Denise
authors.initials: D
authors.lastname: Contos
authors.forename: Teresa R
authors.initials: TR
authors.lastname: Henry
authors.forename: Paul
authors.initials: P
authors.lastname: Lehmann
authors.forename: Susan
authors.initials: S
authors.lastname: Ohorodnik
authors.forename: Dave
authors.initials: D
authors.lastname: Reed
authors.forename: Chantal
authors.initials: C
authors.lastname: Robichaud
authors.forename: John
authors.initials: J
authors.lastname: Schetter
authors.forename: Natalie
authors.initials: N
authors.lastname: South
authors.forename: John
authors.initials: J
authors.lastname: Weissmann
authors.forename: Monica Lee
authors.initials: ML
authors.lastname: Whitmire
mesh_terms: D002626:Chemistry, Pharmaceutical; D014481:United States; D014486:United States Food and Drug Administration