PHARMACOMETRICS INFORMS LABELING AND PACKAGE LEAFLET OF
ANTIMICROBIAL AGENTS
The EMA-approved labelling of antimicrobial agents is concise in
content, but the package leaflet provides an easy-to-understand summary
of product characteristics for patients and healthcare professionals
separately, and detailed information about storage, usage, and
precautions. However, the data and information relevant to
pharmacometrics are infrequently described in EMA-approved labeling and
package insert. This is consistent with EMA Guideline on theReadability of the Labelling and Package Leaflet of Medicinal
Products for Human Use published in 2009 [40].
The FDA-approved labeling of antimicrobial agents has relatively profuse
content. The pharmacology section includes the data of drug absorption,
distribution, metabolism, and excretion in healthy subjects and
patients, including those with impaired hepatic/renal function. The
effect of covariates on exposure and population PK analysis (if any) is
also described. The results of in vivo and in vitro DDI
studies are also summarized in labeling to inform if there is any drug
incompatibility or contraindication. FDA also issued a series of
guidelines, such as Clinical Studies Section of Labeling for Human
Prescription Drug and Biological Products - Content and Format in 2006
and Clinical Pharmacology Labeling for Human Prescription Drug and
Biological Products - Content, and Format (2016) [41, 42]. These
guidelines provide clear-cut guidance and specifications for the
industry regarding the content and format of the pharmacology section of
drug product labeling. At the Precision Dosing Public Workshop held on
August 12, 2019, Robert Temple from Center for Drug Evaluation and
Research (CDER) of FDA also advised FDA to consider adding the content
of PK-PD modeling analysis to drug labeling for guiding individualized
dosing.
NMPA also highly values the importance of the standardization and
management of drug package leaflet and labeling and provides a clear
guidance to the industry in relevant policies, includingRegulations for Management of Drug Package Leaflet and Labeling,
Detailed Specifications for Package Leaflet of Chemical Drugs and
Biological Products , and Technical Guidance for Drafting Package
Leaflet of Antimicrobial Agents . We can see that NMPA clearly advises
applicants to include the information regarding antimicrobial
susceptibility testing, results of PK and PD parameters, DDI study,
precautions in special population, and the effect of various covariates
on PK in the package leaflet, for better clinical use of the drug by
patients and healthcare professionals.