¹FDA, Rockville, MD, USA

Abstract

The FDA Guidance for Industry on population pharmacokinetics (PPK) was published in early 1999. We surveyed the IND and NDA submissions with population analysis/studies (PAS) between 1997 and 2000 to summarize how PAS impacts the regulatory decisions and to address its strength and weakness. From 1997 to 2000, the total number of PAS increased from 18 to 35/yr. Most of these PAS determined PPK parameters for various populations include pediatrics, screened covariates, and modeled exposure-response relationships. Optimal sampling design was well utilized. Most of the submissions used NONMEM for data analyses whereas a small number of submissions used other commercial softwares. The most important impact of PAS is the inclusion of its results in product labelings, which increased over the years. PAS with existing data also reduced the need of additional rich-sampling traditional PK studies. Various reasons led to the rejection of PAS, such as inappropriate study design, incomplete model building, insufficient data, unbalanced demographic distribution and lack of objectives. The utilities, barriers, and limitations of PAS in making valuable impact on drug development and regulatory decisions will be discussed.