Residues (Part 5A)

When applying to register new veterinary chemical products to be used in or on food-producing animal species, in support of your application you should submit appropriate pharmacokinetic, residue kinetic and residues depletion data, or relevant scientific argument. Pharmacokinetic and residue kinetic data are used for maximum residue limit determinations, while residue depletion data are used to establish withholding periods.

Types of data

Pharmacokinetic, residue kinetic and residues depletion data are submitted to enable maximum residue limits and withholding periods to be established. As the APVMA is responsible for registering both agricultural and veterinary chemicals, it has a harmonised approach to assessing the intake of residues as part of its evaluation of safety. In the interest of obtaining outcomes that are aligned with those of other countries for maximum residue limit decisions for veterinary chemicals, the APVMA follows the procedure used by the Joint Food and Agriculture Organization/World Health Organization Expert Committee on Food Additives for determining maximum residue limit values.

Pharmacokinetic data comprise information on the absorption of a veterinary chemical, its distribution in tissues, its metabolism or biotransformation, and excretion over time. The purpose of pharmacokinetic studies is not one of mass balance (that is, to achieve quantitative recovery of the administered dose), but rather to provide information on the concentration–time profile of the veterinary chemical and its metabolites in the target animal species, and on subsequent planning of residue depletion studies. The recommended considerations when performing pharmacokinetic studies are described in Veterinary drug residues—comparative metabolism studies, selection of marker residue(s), and ratios of marker residues to total residues.

Additionally, the pharmacokinetic profiles of the veterinary chemical and its metabolites in the target animal species are compared qualitatively with those of the laboratory animal species used to establish the health standards, to verify the relevance of the toxicological effects and the no-observed-adverse-effect levels, and thereby validate the dietary exposure assessments.

Residue kinetic studies provide information on the concentration profile of total residues in edible tissues over time, and the corresponding concentration profile of marker residue(s). These data are used to:

  • define the relationship between the marker residue(s) and total residues in edible commodities
  • calculate maximum residue limits.

The recommended considerations when performing residue kinetic studies are described in Veterinary drug residues—comparative metabolism studies, selection of marker residue(s), and ratios of marker residues to total residues.

Food-safety (marker residue depletion) data are used to

  • establish maximum residue limits
  • demonstrate compliance with existing maximum residue limits
  • determine appropriate withholding periods

The guideline Food-safety studies for veterinary drugs used in food-producing animals provides study design recommendations that will facilitate the generation of food-safetydata that are likely to satisfy the data recommendations for establishing maximum residue limits and recommending appropriate withdrawal periods for a specific product.

Residues data submissions

The types of pharmacokinetic, residue kinetic and marker residue(s) depletion data that should be provided in support of an application to register a veterinary chemical product will depend on whether:

  • the veterinary chemical has been previously approved by the APVMA
  • the APVMA-approved veterinary chemical has been previously registered in a product for use in or on the target animal species
  • the dose form, treatment regimen, and route of administration of the veterinary chemical product has been considered previously by the APVMA.

Details of the types of data that should be submitted to address the veterinary residues aspects of an application are provided in Table 1.

Table 1: Pharmacokinetic and residues data needed based on type of product application
Registration status Data
Veterinary chemical Use of veterinary chemical in target animal species Dose form, route of administration, and treatment regimen
New veterinary chemical
(not currently approved by the APVMA)
N/A N/A Full pharmacokinetic, residue kinetic and residue depletion package
Existing veterinary chemical
(previously approved by the APVMA)
Not currently registered N/A Full pharmacokinetic, residue kinetic and residue depletion package
Existing veterinary chemical
(previously approved by the APVMA)
Currently registered by the APVMA Not currently registered Full pharmacokinetic, residue kinetic and residue depletion package
Existing veterinary chemical
(previously approved by the APVMA such as a generic registrations)
Currently registered by the APVMA Currently registered Residue depletion package only

N/A = not applicable

Application layout

A checklist of data for Part 5A (pharmacokinetics and residues) of an application for veterinary chemical products is shown in Table 2, along with a brief description of how the data should be set out.

Table 2: Data submission checklist for Part 5A
Submission Comments
Table of contents List the sections included in the submission and their page numbers

Pharmacokinetic and residue kinetic studies (for the determination of marker residue, marker residue to total residue ratios and maximum residue limits):

  • summary of studies
  • proposed acceptable daily intake
  • proposed marker residues
  • proposed target tissues
  • ratios of marker residues to total residues at specified times post treatment
  • proposed maximum residue limits for edible commodities.
A single summary of all pharmacokinetic and residue kinetic studies, along with an interpretation of the results, clearly outlining the reasons for the proposed marker residues and target tissues, and the proposed maximum residue limits for each edible commodity. Full copies of each of the studies should be provided in the appendices. Where maximum residue limits have already been established, details of the previously established marker residues, target tissues, ratios of marker residues to total residues, and maximum residue limits should be provided.

Food-safety (marker residue depletion) trials (for the estimation of withholding periods):

  • summary of studies
  • proposed withholding periods.
A single summary collating all the relevant residues decline data, along with an interpretation of the results, which give rise to the proposed withholding periods. Full copies of each of the residue decline studies should be provided in the appendices.

Analytical methodology:

  • summary of the analytical methods and validation data for methods used in pharmacokinetic and residue kinetic studies
  • summary of the analytical methods and validation data for the methods used in the marker residues depletion trials.
Copies of the full reports for each analytical method, including validation reports, should be provided in the appendices.

Appendices:

  • copies of the full reports for pharmacokinetic, residue kinetic and residue trials, along with complete details of the analytical methods and validation reports.
 

 

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