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Deborah A. Cera - Division of Compliance

Center for Veterinary Medicine, FDA

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RVIS

• Interagency Database

TRIMS

• An Interactive Database Containing Information

Obtained During FDA/State Inspections of Firms

Involved/Responsible for Tissue Residue

Violations.

• Attachment C Ensures Consistent Data

Collection by both Federal and State

Investigators

• Attachment G Drug Inventory

Databases

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DRUG 2006 2007 2008 2009 2010 Total Percent

Amikacin 2 0 1 0 0 3 0.07%

Ampicillin 10 13 8 14 10 55 1.24%

Ceftiofur * * 71 116 70 257 5.79%

Dihydrostreptomycin 10 8 3 1 1 23 0.52%

Fenbendazole 0 0 0 1 0 1 0.02%

Florfenicol 0 0 0 0 1 1 0.02%

Flunixin 133 262 233 182 167 977 22.02%

Furazolidone 1 0 0 1 0 2 0.05%

Gentamicin 95 58 50 66 55 324 7.30%

Kanamycin 1 0 0 0 0 1 0.02%

Lincomycin 0 1 0 0 0 1 0.02%

Neomycin 28 23 21 15 19 106 2.39%

Dairy Cow Tissue Residues

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DRUG 2006 2007 2008 2009 2010 Total Percent

Oxytetracycline 30 21 32 9 21 113 2.55%

Penicillin 358 413 304 267 210 1552 34.98%

Phenylbutazone 0 4 3 2 0 9 0.20%

Sulfachlorpyridazine 1 0 0 0 0 1 0.02%

Sulfadiazine 0 0 0 0 1 1 0.02%

Sulfadimethoxine 158 159 135 114 124 690 15.55%

Sulfamethazine 33 33 22 37 28 153 3.45%

Sulfathiazole 2 0 0 0 1 3 0.07%

Tetracycline 16 7 15 6 15 59 1.33%

Tilmicosin 27 14 4 22 33 100 2.25%

Tulathromycin 0 0 0 2 0 2 0.05%

Tylosin 0 1 1 0 1 3 0.07%

Total 905 1017 903 855 757 4437

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Additional Background

• It is an FDA priority to ensure the safety of

animal-derived foods for human consumption

• FDA works with USDA and the States to monitor

meat, poultry, and milk for unapproved or unsafe

drug and chemical residues

• Although only 7.7% of the cattle slaughtered in

the United States are adult dairy cattle they

represent 67% of the tissue residue violations

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Poor Practices Leading to Tissue Residues

• Drug residue violations in dairy cattle often result from

poor husbandry practices on the farm. These practices

include:

– Failure to maintain treatment records

– Failure to identify treated animals

– Failure to follow labeled withdrawal times

– Increasing the labeled dosage

– Increasing the length of treatment

– Giving the drug by an unapproved route of

administration

– Drug given in unapproved species

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Importance of Following Label

Directions

• FDA approved animal drugs are labeled with the approved species, dosage, route of administration, frequency of use, condition to be treated, and meat and milk withdrawal times. When the directions for use on the approved label are followed, drug residues in meat and milk should not exceed the established drug tolerance.

• Good management practices at dairy farms include maintaining records of each animal treated, what drug it was treated with, when it was treated, and how it was treated, for example the route of administration, dosage and duration of treatment. Such records can be used by producers to ensure that treated cows put back into the milking string or sold for slaughter have met appropriate drug withdrawal times in order to prevent illegal drug residues in milk and meat.

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Federal/State Cooperative

Program • FDA and the States currently participate in

the National Conference on Interstate Milk

Shipments (NCIMS).

• NCIMS is a voluntary coalition of

regulators established to ensure the safety

and wholesomeness of fresh milk in the

U.S.

• FDA publishes the Grade A Pasteurized

Milk Ordinance (PMO) as a model

ordinance for States to adopt.

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Current Milk Testing

Requirements

• The PMO currently requires the sampling

and testing of milk from bulk milk pick-up

tankers when the milk is received at dairy

plants. This sampling consists of

commingled raw milk collected from

various dairy farms.

• The PMO only requires that bulk milk pick-

up tankers be tested for the presence of at

least four of six specific Beta Lactam class

drugs.

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Additional Compound Classes

of Concern

• There are many other classes of drugs used on farms that are not tested for on a routine basis such as sulfonamide antibiotics like sulfadimethoxine, aminoglycoside drugs such as gentamicin, and anti-inflammatory drugs like flunixin.

• USDA/FSIS tissue residue data for calendar years 2005-2010 indicates that over 50% of the violative drug residues in edible tissues reported in culled dairy cows are from drugs other than beta-lactam class drugs.

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FDA’s Concern

• FDA is concerned that the same poor

practices that lead to drug residues in

tissues might also be leading to drug

residues in milk, especially of non-beta

lactam drugs.

• In November 2010 FDA announced that it

had developed a milk sampling

assignment to determine whether our

concern has merit.

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Feedback

• FDA received feedback from State regulators and milk industry associations that because of the on-farm sample collection approach, the proposed plan would have a negative impact on producers and would cause milk to be dumped.

• FDA then participated in three listening sessions to seek input on revising the plan in an effort to avoid disruption to the milk supply.

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Revised Sampling Plan

In response to input received at these

Listening Sessions, informal face to face

meetings, and many individual concerns of

our stakeholders the Agency has completely

revised its sample assignment strategy.

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Samples to be Collected

• As required in the Pasteurized Milk

Ordinance (PMO), when certified bulk milk

hauler/samplers collect raw milk samples,

the “Universal Sampling System” is

employed, whereby samples are collected

every time milk is picked up at the farm.

• It is these “Universal Samples” that will be

collected during this sampling assignment.

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Revised Sampling Plan cont.

FDA Investigators will visit laboratories holding Universal Samples and collect 900 samples from farms that have had tissue residue violations and 900 cohort samples from dairy farms not known to have had previous tissue residue violations.

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Revised Sampling Plan cont.

The origin of all samples collected, whether from the targeted group of known tissue residue violators or the cohort sample group, will be blinded utilizing an independent third party, the Institute for Food Safety and Health (IFSH) in Summit Argo, IL.

The milk samples from all farms will be analyzed by one of three FDA laboratories for a broad range of drugs to determine if the milk contains violative drug residues.

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How Will Targeted Farms be

Selected?

• The sampling assignment will include the

violators that have had tissue residues with the

highest risk scores in culled dairy cows.

• The Risk Model takes into account the hazard

associated with the drug, the likelihood of

exposure, and the exposure level.

• FDA Investigators will be given an alphabetical

list of selected violators by state of origin.

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Methods

• A fully validated multi-class, multi-residue liquid chromatography/tandem mass spectrometry screening and confirmation method will be used to identify violative drug residues in milk.

• Additionally ELISA technology will be used to detect the presence of several aminoglycoside class drugs.

• All residues of drugs with established tolerances will be quantitated to confirm the level of drug present.

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DRUG SAFE/TOLERANCE LEVEL (ppb) Ampicillin (AMP) 10 Cephapirin (CEPH) 20 Cloxacillin (CLOX) 10 Penicillin G (PEN G) 5 Erythromycin (ERY) 50 Tylosin (TYL) 50 Ciprofloxacin (CIP) None a Sarafloxacin (SAR) None a Chlortetracycline (CTC) 300 b Oxytetracycline (OTC) 300 b Tetracycline (TC) 300 b Doxycycline (DC) None a Sulfachloropyridazine (SCP) 10 Sulfadiazine (SDZ) 10 Sulfamerazine (SMR) 10 Sulfadimethoxine (SDM) 10 • a no tolerance set for milk; method target level set at 100 ppb for VIR and TIL and DC; 10 ppb for

TUL; and 5 ppb for CIP, SAR, CAP and FF

• b Tolerance includes sum and individual residues; method target levels set at 100 ppb each, the

sum of the tetracylines present should not exceed 300 ppb.

• c Amount listed is a “safe level” from 9/27/05 FDA/CFSAN Milk Safety Branch Memo

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DRUG SAFE/TOLERANCE LEVEL (ppb) Sulfamethazine (SMZ) 10 Suflaquinoxaline (SQX) 10 Sulfathiazole (STZ) 10 Tripelennamine (TRIP) 20 Thiabendazole (THBZ) 50 Flunixin (FLU) (Flunixinhydroxide) 2 Bacitracin (BAC) 500 Virginiamycin (VIR) 100 Tilmicosin (TIL) 100 Florfenicol 0 Chloramphenicol 0 Tulathromycin 0 Gentamicin 30 Neomycin 150 a no tolerance set for milk; method target level set at 100 ppb for VIR and TIL and DC; 10 ppb for

TUL; and 5 ppb for CIP, SAR, CAP and FF

b Tolerance includes sum and individual residues; method target levels set at 100 ppb each, the sum

of the tetracylines present should not exceed 300 ppb. c Amount listed is a “safe level” from 9/27/05 FDA/CFSAN Milk Safety Branch Memo

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Samples to be Collected cont.

• The State Milk Regulatory Agency shall be

advised of this assignment and

laboratories involved prior to the collection

of any samples.

• The State Milk Regulatory Agency will be

invited to participate in any sampling

conducted in their state. Such participation

is totally at the discretion of the State.

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Violative Samples

• No enforcement actions will be taken in

response to violative levels of residues in

these samples because the purpose of the

assignment is to determine if a problem

exists.

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Findings • FDA will use the resulting data to inform the ongoing

Milk Drug Residue Risk Assessment.

• Depending on the findings, FDA in active consultation with the National Conference on Interstate Milk Shippers, may expand the requirements for milk testing under the PMO to include additional compounds.

• FDA may also revise Compliance Program 7371.006 to routinely require the testing of farm bulk milk tanks during the inspection of a farm due to a violative tissue residue.

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Timeline

• Prior to implementing the Milk Sampling Assignment the Agency will hold teleconferences with the Commissioners, Secretaries, and Directors of State Departments of Agriculture, and State Milk Regulatory Officials.

• The Agency will also notify the Executive Board of the National Conference on Interstate Milk Shippers and other affected stakeholders, i.e., Industry, Consumer Groups, etc., prior to starting the assignment.

• There is no specific timeline but the assignment is expected to start within the next few months and will take approximately 12 months to complete.

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In Conclusion

• FDA’s Milk Sampling Assignment is targeting the few members of an otherwise compliant industry in order to ensure that the public can have the utmost confidence in the dairy products that they consume.

• FDA continues to believe that the nation’s milk supply is safe. Efforts such as this sampling assignment will ensure that potential problems, if they exist, remain minor and are quickly mitigated by education and enforcement, as appropriate.