Focus of Regulatory Concerns Regarding Pharmacometric Review in the
Development and Evaluation of Antimicrobial Agents
Abstract
Pharmacometrics is an emerging science that interprets drug, disease and
trial information in a mathematical fashion to inform and facilitate
efficient drug development and/or regulatory decisions. Pharmacometric
study is increasingly adopted in the regulatory review of new
antimicrobial agents. We summarized and reviewed the 31 antimicrobial
agents approved by the US Food and Drug Administration (FDA) and the 26
antimicrobial agents approved by European Medicines Agency (EMA) from
January 2001 to May 2019. Regulatory concerns in pharmacometric review
of antimicrobial agents were expounded with examples, including modeling
and simulation methods, effects of internal/external factors on PK
parameters, safety and efficacy evaluation in terms of exposure-response
analysis, refinement of the wording of product labeling and package
leaflet, and possible post-marketing clinical trial. Ongoing
communication among regulators, academia, and industry regarding
pharmacometrics is encouraged to streamline and facilitate the
development of new antimicrobial agents. The industry can maximize its
benefit in drug development through continued pharmacometric
education/training.