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.