Tools to evaluate pharmacokinetics data for establishing maximum residue limits for approved veterinary drugs: examples from JECFA's work

Abstract

Maximum residue limits (MRLs) for residues of veterinary drugs are the maximum concentrations of residues permitted in or on a food by national or regional legislation. In the process of MRLs recommendations by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), analysis of pharmacokinetic data describing the ADME process (absorption, distribution, metabolism and excretion) is a crucial step and requires the use of different pharmacokinetic tools. The results of animal metabolism studies are the prime determinants of the residue definition in food commodities. Substances labelled with radioactive isotopes are used so that the disposition of the residue can be followed as total residue and main metabolites concentrations. Residue depletion studies with radiolabelled parent drug will lead to the estimate of the time course of the total residue and to determine a marker residue. Depletion studies with an unlabelled drug provide more information on the time course of the marker residue in raw commodities after administration under approved practical conditions of use. By use of this information and after conversion with the total/residue marker ratio, MRLs are derived by comparison of the acceptable daily intake with the daily intakes calculated with different scenarios of dietary exposure. Progress in pharmacokinetic model such as physiologically based pharmacokinetics and population pharmacokinetics will drive the future research in this field to improved veterinary drug development.

A history of antimicrobial drugs in animals: Evolution and revolution

“…The FAO/WHO Joint Expert Committee on Food Additives (JECFA) was established in 1956. It enunciates principles and develops tools (Sanders, Henri, & Laurentie, 2016) for evaluating safety and quantifying risks of residues of veterinary drugs in food. JEFCA also recommends MRLs for target tissues and determines criteria for, and evaluates methods of, analysis for detecting and/or quantifying residues in food.…”

Screening and Analysis of Multiclass Veterinary Drug Residues in Animal Source Foods using UPLC-Q-Exactive Orbitrap/MS

“…In recent years, food contamination by veterinary drug residue has become public health concern worldwide (Beyene 2016;Organization 2016;Song et al 2016). Hence, the maximum residue limits of veterinary drugs in food products must be set (Sanders et al 2016;Tang et al 2017).…”

Preface to the proceedings of the SASKVAL III international workshop on validation and regulatory analysis

“…Under Theme 7 – Pharmacokinetics and Depletion Studies – Sanders et al . reviewed the general principles and methods for chemical risk assessment described in Environmental Health Criteria 240, Principles and methods for the risk assessment of chemicals in food approaches which the Joint WHO/FAO of the UN Expert Committee on Food Additives (JECFA), follows to conduct risk assessments.…”

“…The studies that need to be completed in the process are very well laid out and in all the studies there is a requirement to use suitably sensitive methods for the studies being conducted. [15] reviewed the general principles and methods for chemical risk assessment described in Environmental Health Criteria 240, Principles and methods for the risk assessment of chemicals in food approaches which the Joint WHO/FAO of the UN Expert Committee on Food Additives (JECFA), follows to conduct risk assessments. Following a request from the CCRVDF, JECFA will assess veterinary drugs which are currently used under national marketing authorization or unregulated compounds which are used as a veterinary treatment (e.g.…”