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Teresa HenryTeresa R. Henry, Ph.D., currently serves as the associate director of quality control at Optimer Pharmaceuticals, Inc.

Nonclinical pharmacokinetic and toxicokinetic 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 established prior to administration.

But the Food and Drug Administration and the Organisation for Economic Cooperation and Development both proclaim that GLPs do not apply to validation of analytical methods used to determine the concentration of GLP test article in drug dosage forms. Yet the outcome of nonclinical toxicology safety studies is fundamentally dependent upon accurate and precise dose formulations. Therefore, formulation method validation and sample analysis for supporting nonclinical toxicology studies should be consistently conducted around the world under the framework of GLP principles.

Guidance regarding the validation of formulation analysis methods and subsequent use for supporting GLP toxicology study sample analysis is warranted to ensure such studies are consistently conducted. Adherence to standard principles for method validation, sample analysis, and out-of-specification (OOS) investigations would inherently improve the quality of nonclinical safety studies. Furthermore, the recently published white papers Nonclinical Dose Formulation Analysis Method Validation and Sample Analysis and Nonclinical Dose Formulation: Out of Specification Investigations should be the keystones of this effort.

The April AAPS Newsmagazine cover article, developed by the Pharmacokinetics, Pharmacodynamics and Drug Metabolism section, reviews this topic. Read the article and then participate in the discussion question below.

Discussion Point: What regulatory gaps do you see related to the application of GLP principles, and how would you rectify them?