P. Bennett, DVM, MS, DACVPM, MPP Office of Public Health Science Food Safety and Inspection Service 1.

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Update: National Residue Program

P. Bennett, DVM, MS, DACVPM, MPPOffice of Public Health Science

Food Safety and Inspection Service

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Historical Perspectives

NRP Initiatives◦ Restructure NRP◦ Establish public health safety levels◦ Establish methods framework

Questions

Outline

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NRP Mission StatementTo protect consumers from unsafe exposure to chemical

residues in meat, poultry, and egg products

http://www.culinate.com/hunk/29180

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History of the NRP

1967-8 Wholesome Meat and Poultry Acts 1975-1984 Memorandums of Understanding: Give authority to

Surveillance Advisory Team (SAT) & Interagency Residue Control Group (IRCG)

1979 Implementation of Swab Test on Premises (STOP)

1980 First Compound Ranking System 1981 FDA executes first successful prosecution

as a result of STOP

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1995 FSIS Implementation of Fast Antimicrobial Screen Test (FAST)

1996 HACCP Implementation2009 Begin Kidney Inhibition Swab (KIS) Implementation2011 Begin using Multi-class method for

testing pesticides 2012 Begin using Multi-class method for

testing veterinary drugs

History of the NRP

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NRP GoalsRevise residue

sampling & scheduling algorithms

Improve documentation

of chemical hazards

Identify trends and high-priority

compounds to research

Establish protocol for

recall decisions

Develop analytical techniques and

improve analysis

Respond to public and

stakeholder concern

Monitor chemical

exposure in the industry

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Collaborative Efforts

-Manages farm-to-fork testing and feed analysis

-Conducts on-farm

investigations

-Prevents violations through testing and regulatory action

-Enforces the tolerances of animal drugs in meat, poultry, and egg products and prevents improper use of these drugs on farm

-Provides data for continuous baseline sampling

-Uses residue data to

adjust or establish tolerances and safety limits

-Regulates the use of pesticides through establishment of tolerances in meat, poultry and egg products and prevents improper use of these chemicals

FDA EPA

-Improved coordination

andcommunicatio

n between tiers

- Share residue data, safety limits, and analytical

methods

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Collaborative Efforts

MOU: Memorandum of Understanding:• Working relationship

between FSIS, AMS, FDA, EPA to coordinate regulatory activities for residues

• FSIS consults mainly with FDA/EPA to compare information on regulations

IRCG: Interagency Residue Control Group:• FSIS/FDA/EPA/AMS/

CDC/ARS; monthly meetings for updates and collaborating relative to the NRP

SAT: Surveillance Advisory Team:• Interagency

committee that determines the chemical compounds and production classes of public health concern

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Why propose new initiatives?

To minimize risks to consumers from chemical hazards

To “catch the next melamine” and detect new hazards

To more efficiently collect necessary residue data for risk assessments

To develop NRP processes that are easily translated for smooth import and export

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NRP Initiatives

Restructure NRP

Establish public health safety levels

Establish methods

framework

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Restructure NRP

Tiered approach

Hazard ID and ranking

New methods

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Restructure NRP

Tiered approach

Hazard ID and ranking

New methods

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Modern approach to residue testing Collaboration with Agricultural Research

Service

FSIS labs received new methods in 2011 The MRM methods be implemented as part

of overall improvements to NRP

Multi-Residue Method (MRM)

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Distinguishindividualanalytes

Screen many types of analytes

First time FSIS method to analyze multiple chemicals per sample

Screen up to 120+ analytes

NOT JUST ANTIBIOTICSFirst time FSIS to use this type of method

MRM: a Significant Improvement

• Chemical method

MRM ClassesMRM ClassesBeta-Agonists

Beta-Lactams & Cephalosporins

Hormones

Macrolides & Lincosamides

Analgesics & Anti-inflammatory

Phenicols

Fluoroquinolones

Sulfas

Tetracyclines

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Analytes in the MRM Classes

FluoroquinoloneDesethylene CiprofloxacinNorfloxacinCiprofloxacinDanofloxacinEnrofloxacinSarafloxacin

HormonesPrednisone*

Macrolide/LincosamideLincomycinPirlimycinClindamycinGamithromycin*TilmicosinErythromycinTylosin

Analgesic/Anti-inflammatory

Oxyphenylbutazone (pork only)*

Flunixin Phenylbutazone (pork only) Beta/Dexa-methasone*

Tetracycline Oxytetracline Tetracyline Chlortetracycline

Phenicol Florfenicol Amine (pork only) Florfenicol Chloramphenicol

* Indicates analytes not tested/not tested in recent years.

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Analytes in the MRM Classes

SulfonamideSulfanilamide (pork only)*SulfadiazineSulfathiazoleSulfapyridineSulfamerazineSulfamethiazoleSulfamethazineSulfamethoxypyridazineSulfachloropyridazineSulfadoxineSulfamethoxazoleSulfaethoxypyridazineSulfadimethoxineSulfaquinoxalineSulfanitran*

β-Agonist Salbutamol Cimaterol Ractopamine

Β-Lactam/ Cephalosporin

Cefazolin DCCD Ampicillin Difloxacin Penicillin G Oxacillin Cloxacillin Nafcillin Dicloxacillin

* Indicates analytes not tested/not tested in recent years.

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Screening method◦ Specific screening◦ Improved sensitivity◦ Level assessment

Confirmatory method◦ Multi class method reduces time and need for

class-specific confirmation tests

Impact of MRM

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Aminoglycosides AnalytesNeomycin

Gentamicin

Spectinomycin

Apramycin

Dihydrostreptomycin

Hygromycin B

Amikacin

Streptomycin

Kanamycin

Analytes in the Aminoglycosides Method

Pesticide ClassesPesticide Classes

Benzimidazole

Carbamate

Conazoles/Triazoles

Halogenated

Imidazoles

Organonitrogen

Organophosphates

Pyrethroids

Triazines

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BenzimidazoleThiabendazole

CarbamateCarbarylCarbofuranMethomyl

Organophosphorus Acephate

Azinphos-methylChlorpyrifosChlorpyrifos-methyl Dichlorvos (DDVP) EthofumesateTetrachlorvinphos

Organonitrogen Metalaxyl Tebufenozide

Pyrethroids Bifenthrin Cyhalothrin-L Cypermethrin Deltamethrin Permethrin (cis & trans) Tefluthrin

Triazines Simazine

Conazoles / Triazoles Difenoconazole Myclobutanil Propiconazole Tetraconazole

Analytes in the Pesticide Classes

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Halogenated◦ Alachlor ◦ Aldrin ◦ Boscalid ◦ Carfentrazone-ethyl ◦ Chlordane, cis- ◦ Chlordane, trans- ◦ Clofentezine ◦ Dieldrin ◦ Diflubenzuron ◦ Diuron ◦ Endosulfan I ◦ Endosulfan II ◦ Endosulfan sulfate ◦ Fipronil ◦ Heptachlor

HalogenatedHeptachlor epoxide (cis & trans)Imidacloprid Linuron Nonachlor, trans- Norflurazon Oxychlordane Pronamide Propachlor Propanil Pyridaben Thiamethoxam

Imidazoles

Imazalil

Other Compounds Indoxacarb

Methoxyfenozide

Mirex

Piperonyl butoxide

Analytes in the Pesticide Classes

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Metals ElementsLead

Cadmium

Manganese

Thallium

Selenium

Cobalt

Molybdenum

Elements in the Metals Method

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Sulfa

dimeth

oxine (

SUL)

Sulfa

methazi

ne (SU

L)

Sulfa

thiazole

(SUL)

Sulfa

diazine (

SUL)

Sulfa

methoxa

zole

(SUL)

Sulfa

dimeth

oxine

(SUL2

)

Sulfa

methazi

ne (SU

L2)

Sulfa

thiazole

(SUL2

)

Ractopam

ine

Carbad

ox

Aldrin

Alpha-BHC

Mirex

p,p'-DDE

Flunixi

n

Flunixi

n Lea

d Lea

d

Cadmium

Cadmium

Moxidecti

n

Moxidecti

n

Doramecti

n

Doramecti

n

Iverm

ectin

Iverm

ectin

Arsenic

*** P

enicil

lin

*** C

hlortetra

cyclin

e

Chloramphen

icol

*** A

mpicillin

Florfe

nicol

Florfe

nicol

Desfuro

ylceft

iofur (as

DCA or DCCD)

*** O

xytet

racycl

ine

*** T

etracy

cline

Tilmico

sin

*** N

eomyci

n

*** T

ylosin

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60

100

140

180

MU (normalized) for quantitative FSIS CLG methods

Rela

tive

%

*** denotes 7-plate bioassay

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Methods for the analysis of food composition, food additives, nutrients, veterinary drug and pesticide residues.

Methods provide analysts with documentation to facilitate training, performance, quality assessment, and interpretation of data.

The contents are continuously revised and updated.

http://www.fsis.usda.gov/Science/Chemistry_Lab_Guidebook/index.asp

Chemistry Laboratory Guidebook

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2012 •MRM method: Targeted sampling •Aminoglycosides Method: Scheduled and Targeted sampling programs•Metals method: Exploratory program

2013 •MRM as a screening method in Eastern and Western labs for Scheduled sampling program

FSIS Method Implementation:

Proposed Timetable

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Restructure NRP

Tiered approach

Hazard ID and ranking

New methods

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Scheduled Sampling Program◦ Headquarters generated◦ Across production classes

Targeted Sampling Program◦ (Field)Inspector generated◦ Directed at a particular plant/production

class/chemical◦ Focused

National Residue Program

3-Tiered Model

May direct samplefor Tier 3 Testing

Tier 1 – Scheduled Sampling:

Appropriate Methods Violative Residues

Tier 2 – Targeted Sampling:

Violative Residues

Tier 3 – Targeted Flock/Herd:

May direct sample

for Tier 2 Testing

Appropriate Methods

Violative Residues

Appropriate Methods

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Additional testing

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Restructure NRP

Tiered approach

Hazard ID and ranking

New methods

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Hazard IDand Ranking

Define the Universe of Chemical Hazards

Screen to Establish a Priority List

National Residue Program

Enter into scheduling algorithm

Risk Management

Risk Based Priority List

Select compounds from Priority List

Determine appropriatePublic Health Safety Level

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NRP Initiatives

Restructure NRP

Establish public health safety levels

Establish methods

framework

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Developing

policies

Methodology

to determine PH safety levels

Public Health Safety Levels -Cadmium

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NRP Initiatives

Restructure NRP

Establish public health safety levels

Establish methods framewor

k

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FDA/FSIS collaboration

Develop a process to expedite approval of new testing methodologies for FSIS.

Develop a comparison protocol to facilitate using new analytical methods while retaining the linkage to the safety package prepared to support the new animal drug approval

Performance-based methods

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Conclusions

The NRP initiatives will result in:

Identify emerging

contaminants

Prevent adulterated meat, poultry, and egg products from entering

the marketplace

Discourage improper behavior by

producers, processors, and importers

Close regulatory gaps between

Agencies

http://www.quicklabel.com/blog/wp-content/uploads/2011/07/iStock_000011997708Small.jpghttp://media.treehugger.com/assets/images/2011/10/cute-kid-eating-meat-steak-photo.jpg

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Terry Dutko

Patricia Nedialkova

Lynn Cruikshank

Lou Bluhm

Emilio Esteban

Sarah Edwards

Janell Kause

Alice Thaler

Pat Basu

Kerry Dearfield

Vivian Chen

David Goldman

Allie Miraglia

Margaret O’Keefe

Naser Abdelmajid

David LaBarre

Alex Domesle

Jade Mitchell-Blackwood

Acknowledgements

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Questions?

Patty [email protected]

202-690-6189