cvm s procedure for setting tolerances l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
CVM’s Procedure for Setting Tolerances PowerPoint Presentation
Download Presentation
CVM’s Procedure for Setting Tolerances

Loading in 2 Seconds...

play fullscreen
1 / 26

CVM’s Procedure for Setting Tolerances - PowerPoint PPT Presentation


  • 262 Views
  • Uploaded on

CVM’s Procedure for Setting Tolerances. Lynn G. Friedlander, Ph. D. Division of Human Food Safety Residue Chemistry Team. Tolerance Setting. Chemical residues Other approaches. Tolerance Setting. Residue:

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'CVM’s Procedure for Setting Tolerances' - adamdaniel


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
cvm s procedure for setting tolerances

CVM’s Procedure for Setting Tolerances

Lynn G. Friedlander, Ph. D.

Division of Human Food Safety

Residue Chemistry Team

tolerance setting
Tolerance Setting
  • Chemical residues
  • Other approaches
tolerance setting3
Tolerance Setting

Residue:

Any compound present in the edible tissues of the target animal which results from the use of the sponsored compound, including the sponsored compound, its metabolites, and any other substances formed in or on food because of the sponsored compound’s use. 21 CFR 500.82 (b)

tolerance setting4
Tolerance Setting
  • Office of New Animal Drug Evaluation
  • Division of Human Food Safety
    • Toxicity data from the model species
    • Microbial safety data
    • Residue data from the target food-producing species
    • Analytical methodology
    • Good Laboratory Practices (GLP)
tolerance setting toxicology
Tolerance Setting-Toxicology
  • Basic Toxicology Package
  • Additional/special toxicology studies
  • Calculate the No Observable Effect Level (NOEL)
  • Determine the appropriate safety factor
  • Calculate the Allowable Daily Intake (ADI)
tolerance setting toxicology6
Tolerance Setting-Toxicology

ADI = No Observable Effect Level Safety Factor

tolerance setting toxicology calculating the safe concentration
Tolerance Setting-ToxicologyCalculating the Safe Concentration

Safe Concentration = ADI x 60 kg consumption factor

tolerance setting toxicology8
Tolerance Setting-Toxicology

The safe concentration is the amount of residue that can be eaten in any edible tissue each day for an entire lifetime without exposing the consumer to residues in excess of the ADI.

tolerance setting residue chemistry
Tolerance Setting-Residue Chemistry
  • Risk = Hazard X Exposure
  • Mitigates the hazard identified in the toxicology safety studies by controlling exposure to the hazard through the assigning of tolerances and withdrawal periods or milk discard periods, where needed.
tolerance setting residue chemistry10
Tolerance Setting-Residue Chemistry
  • Basic Studies
    • Comparative Metabolism-Toxicology Species
    • Total Residue and Metabolism-Target Species
    • Analytical Method
    • Residue Depletion/Withdrawal-Target Species
tolerance setting residue chemistry11
Tolerance Setting-Residue Chemistry
  • Comparative Metabolism Study
    • Did the toxicology testing evaluate the right compound(s)?
      • Qualitative comparison of the metabolic profiles in the toxicological and food-producing species
      • Ensures that the toxicological species has been exposed to the same residues to which humans will be exposed when they consume products derived from treated food-producing animals
    • If profiles are not comparable, more toxicology testing may be indicated.
tolerance setting residue chemistry12
Tolerance Setting-Residue Chemistry
  • Total Residue and Metabolism Study
    • Radiolabeled drug
    • 1-1.5X the proposed dose
    • Proposed route of administration
    • Intended duration of treatment/steady state
    • Intended species; males and females
tolerance setting residue chemistry13
Tolerance Setting-Residue Chemistry
  • Total Residue and Metabolism Study
    • Determines the MARKER RESIDUE
      • the residue that monitors the depletion of total residues in a tissue
    • Determines the TARGET TISSUE
      • generally, the edible tissue from which residues deplete most slowly
      • often, liver or kidney
      • rarely, muscle or fat
tolerance setting residue chemistry14
Tolerance Setting-Residue Chemistry
  • Total Residue and Metabolism Study
    • Provides a METABOLISM PROFILEin the food-producing animal
      • for comparison with the metabolism profile of the toxicological species
    • Establishes the MARKER:TOTAL ratio
      • to calculate the tolerance
tolerance setting residue chemistry15
Tolerance Setting-Residue Chemistry
  • Analytical Methodology
    • Determinative
      • measures concentrations of drug residues in tissue
    • Confirmatory
      • verifies the identity of the drug residue
    • Screening
      • assesses impact the new drug on pre-existing residue tests
      • not required
slide16

1000.0

Total Residue

100.0

Safe Concentration

10.0

Drug Concentration

1.0

Marker Residue

0.1

0.01

1

2

3

4

5

Time (days)

tolerance setting residue chemistry17
Tolerance Setting-Residue Chemistry
  • Determine the time at which the concentration of total radiolabeled residues in the target tissue is less than the target tissue safe concentration
  • Determine the concentration of the marker residue in the target tissue at that time using the proposed analytical methodology
tolerance setting residue chemistry18
Tolerance Setting-Residue Chemistry
  • The concentration of the marker residue in the target tissue at the time the total radiolabeled residue in the target tissue has depleted to less than the target tissue safe concentration is the target tissue TOLERANCE
tolerance setting residue chemistry19
Tolerance Setting-Residue Chemistry
  • Can establish tolerances for more than one tissue, i.e., target tissue and muscle
    • must have data for the tissue(s) to support the tolerance assignment(s)
    • often these data are available as part of the total residue and metabolism study
slide20

1000.0

Total Residue

100.0

Safe Concentration

10.0

Drug Concentration

1.0

Marker Residue

Tolerance

0.1

0.01

1

2

3

4

5

Time (days)

tolerance setting residue chemistry21
Tolerance Setting-Residue Chemistry
  • Target tissue tolerance is a monitor for the depletion of residues from all the edible tissues
  • When the concentration of the marker residue in the target tissue is less than the target tissue tolerance, total residues in all of the edible tissues are less than their respective safe concentrations
tolerance setting residue chemistry22
Tolerance Setting-Residue Chemistry
  • Non-target tissue tolerance monitors depletion of residues only from the specific non-target tissue
  • For example, if we assign a muscle tolerance and muscle is not the target tissue:
    • Muscle tolerance monitors the depletion of residues from the muscle
    • When the concentration of the marker residue in the muscle is less than the muscle tolerance, the total residues in the muscle are less than the muscle safe concentrations
    • Muscle tolerance does not monitor any other edible tissues
tolerance setting residue chemistry23
Tolerance Setting-Residue Chemistry
  • Tolerance
    • links the ADI and safe concentrations of total radiolabeled residues to “cold” residues that result from the use of the proposed market formulation as measured with the regulatory analytical method
tolerance setting residue chemistry applying the tolerance
Tolerance Setting-Residue ChemistryApplying the Tolerance
  • The preslaughter withdrawal period and, if applicable, the milk discard period
    • on the product labeling
    • in the relevant section of 21 CFR Part 500
  • The established tolerance is codified under 21 CFR 556