A Global GLP Approach to Formulation Analysis Method Validation and Sample Analysis

Abstract

Nonclinical pharmacokinetic (PK) and toxicokinetic (TK) toxicology safety studies are performed using good laboratory practice (GLP) regulations to ensure the availability of safe medicines. International GLP regulations uniformly require that dose concentration, homogeneity/uniformity and stability be known prior to administration. However, the United States Food and Drug Administration (US FDA) and the Organisation for Economic Cooperation and Development (OECD) both confirmed that GLPs do not apply to validation of analytical methods used to determine the concentration of GLP test article in drug dosage forms. It is our assertion that the outcome of nonclinical toxicology safety studies is inherently dependent upon accurate and precise dose formulations. In this paper, we attempt to provide supporting evidence as to why formulation method validation and sample analysis for supporting nonclinical toxicology studies should be consistently conducted under the framework of GLP principles across the globe. GLP studies are planned, performed, monitored, recorded, reported and archived according to a protocol, study plan or standard operating procedure (SOP) which is authorized prior to performing the experiments. All applicable experimental parameters and associated acceptance criteria are pre-defined. The FDA asked for responses to the Advance Notice of Proposed Rulemaking for 21 CFR Part 58 GLPs for Nonclinical Laboratory Studies [Docket No. FDA–2010–N–0548] on December 21, 2010. Several comments were received stating that guidance regarding the validation of formulation analysis methods and subsequent use for supporting GLP toxicology study sample analysis is warranted at this time and should be conducted consistently. Adherence to GLP principles for method validation and sample analysis would inherently improve the quality of nonclinical safety studies. Furthermore, the recently published White Paper titled, “Nonclinical dose formulation analysis method validation and sample analysis” should be the keystone of this effort.