[Federal Register: August 6, 2001 (Volume 66, Number 151)]
[Page 40964-40965]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]



Food Safety and Inspection Service

[Docket No. 00-026N]

Residue Policy

AGENCY: Food Safety and Inspection Service, USDA.

ACTION: Notice; request for comment.


SUMMARY: The Food Safety and Inspection Service (FSIS) is announcing 
its intention to harmonize its procedures with those of the Food and 
Drug Administration (FDA) with respect to the target tissue/marker 
residue policy in testing animal tissues for residues of new animal 
drugs. FSIS has reviewed its approach regarding the disposition of 
carcasses containing residues and has determined that its approach is 
not consistent with FDA's approach. To ensure that meat containing 
unsafe levels of chemical residues is not being released into commerce, 
FSIS intends to modify its approach to testing and disposition of 
carcasses for violative residues to be more consistent with FDA's 
target tissue/marker residue policy.

DATES: Comments may be submitted by no later than September 5, 2001. 
FSIS will review comments and address them in another notice. That 
notice will announce when the procedural changes addressed in this 
notice are effective.

ADDRESSES: Submit one original and two copies of written comments to: 
FSIS Docket Clerk, Docket # 00-026N, Room 102, Cotton Annex Building, 
300 12th Street, SW., Washington, DC 20250-3700. All comments received 
in response to this notice will be considered part of the public record 
and will be available for viewing in the FSIS Docket Room between 8:30 
a.m. and 4:30 p.m., Monday through Friday.

FOR FURTHER INFORMATION CONTACT: Daniel L. Lazenby, Acting Director, 
Technical Analysis Staff, Office Policy, Program Development and 
Evaluation; (202) 205-0210.



    When a new animal drug is given to an animal, some of the parent 
drug and resulting metabolites remain in the animal as residues. A new 
animal drug is defined under 21 CFR 510.3(g) and examples of 
``newness'' are specified in 21 CFR 510.3(i).
    For new animal drugs approved prior to 1976, tolerances were 
assigned for each of the edible tissues. Collection and testing of 
multiple tissues is routine for these new animal drugs. As each tissue 
is tested, it is either released or condemned, depending on whether it 
is found to have an acceptable level of residue.
    Since 1976, FDA has been establishing tolerance levels for new 
animal drugs using a ``marker residue.'' The term ``marker residue'' is 
defined in the Food and Drug Administration's (FDA) Center for 
Veterinary Medicine's Guideline, ``General Principles for Evaluating 
the Safety of Compounds Used in Food-Producing Animals,'' (CVM 
Guideline #3, http://www.fda.gov/cvm/guidance/guideline3toc.html) as 
being the residue selected for assay whose concentration is in a known 
relationship to the total residue of toxicological concern in the last 
tissue to deplete to its permitted concentration.
    These marker residues serve as a sentinel for the levels of all 
residues associated with that drug (parent and metabolites) in all 
edible tissues of the food animal. CVM's Guideline 3 defines 
target tissue as being the edible tissue selected to monitor for 
residues in the target animals, including, where appropriate, milk or 
eggs. When the FDA-approved conditions of use for a new animal drug are 
followed, the concentration of marker residue in the target tissue 
should be below the target tissue tolerance when the animal is sent to 
slaughter. To establish an appropriate tolerance for the marker 
residue, FDA must know the relationship between the concentration of 
the marker residue in the target tissue and the concentrations of total 
residues in each of the edible tissues (CVM Guideline 3). FDA 
obtains this information from the drug's sponsor who, in submitting a 
New Animal Drug Application (NADA), includes total residue depletion 
and metabolism studies with radiolabeled compound in species for which 
approval is sought (CVM's Guideline #3). The target tissue is usually 
liver, kidney, or fat because residues generally deplete from these 
tissues more slowly than from other tissues, i.e., muscle tissue.
    In those cases where FDA has established a marker residue tolerance 
in target tissue, when the marker residue in the target tissue depletes 
to a concentration equal to or less than the target tissue 
tolerance(based on the total residue depletion and metabolite data),it 
can be reliably anticipated that the concentration of total residue in 
each edible tissue has reached its respective permitted safe 
concentration. In other words, when the concentration of the marker 
residue is at or below its tolerance in the target tissue, the entire 
carcass is considered safe to eat, without additional testing of the 
individual edible parts of the animal carcass. Similarly, if the level 
of the marker residue in the target tissue exceeds the tolerance, FDA 
will consider the entire carcass to be adulterated, because the residue 
in the target tissue is imputed to the rest of the animal.
    In addition, for 15 new animal drugs FDA has specifically 
established tolerances for residues found in muscle tissue and 
analytical methods for detecting those residues. Therefore, the muscle 
tissue may be released for human consumption if it meets the muscle 
residue tolerance level. This is true even when the marker residue 
tolerance in the target tissue has been exceeded. The target tissue, 
however, would be condemned. In this situation, documenting that the 
drug residues in muscle are less than the muscle tolerance will only 
demonstrate that the muscle tissue is safe, and does not imply that any 
other part of the animal carcass is safe, except in those few instances 
where muscle has been designated to be the target tissue.

FSIS Practice

    FSIS regulations regarding residues state that ``* * *Animal drug 
residues are permitted in meat and meat food products if such residues 
are from drugs which have been approved by the Food

[[Page 40965]]

and Drug Administration and any such drug residues are within tolerance 
levels approved by the Food and Drug Administration * * *''(9 CFR 
318.20). FSIS has not strictly applied FDA's marker residue/target 
tissue approach in determining whether drug residues are within 
tolerance levels.
    Specifically, FSIS has condemned only the organ with a violative 
residue level and has conducted a laboratory analysis of the muscle 
tissue to determine whether the muscle portion of the carcass can be 
salvaged. This has been the practice even for residues of those new 
animal drugs for which FDA has not established a tolerance or testing 
methodology for the muscle tissue. Historically, if no drug residue was 
detected in the muscle, FSIS released the muscle portion of the carcass 
for human consumption.
    FSIS's practice has generated on-going questions regarding whether 
or not the muscle or other organs are safe. FSIS has referred these 
questions to FDA, which addresses them on an ad hoc basis.
    FSIS needs to modify its procedures to be consistent with the 
determinations that underlie FDA's approach. Therefore, for those new 
animal drugs for which FDA has established a marker residue tolerance 
in a specified target tissue without establishing a tolerance for a 
residue in muscle and an official analytical method for muscle 
residues, FSIS will only test the target tissue that is identified in 
FDA regulations. If the residues found in the target tissue exceed the 
FDA tolerances, FSIS will condemn the entire carcass. If FDA has also 
established a tolerance for a residue in muscle and an official 
analytical method for muscle residues, FSIS will test the muscle using 
the official methodology to determine whether the concentration of 
residues in the muscle is at or below the muscle tolerance. If 
acceptable, FSIS will permit the release of the muscle. For those new 
animal drugs for which a marker residue tolerance in a specified target 
tissue has not been identified, FSIS will continue to collect and 
monitor multiple edible tissues.
    FSIS is aware that the change in its procedures announced in this 
notice will affect the industry. To ensure that animals do not have 
violative amounts of residues, establishments may change their 
purchasing practices. Establishments should consider incorporating 
controls into their HACCP plans to avoid exceeding residue tolerances. 
Exceeding residue tolerances may result in the condemnation of more 
product than is currently being condemned. FSIS invites comment on this 
impact and will welcome any cost data. FSIS will consider these data 
and consider in what ways it may lessen the impact.

Additional Public Notification

    Public awareness of all segments of rulemaking and policy 
development is important. Consequently, in an effort to better ensure 
that minorities, women, and persons with disabilities are aware of this 
notice, FSIS will announce it and provide copies of this Federal 
Register publication in the FSIS Constituent Update. FSIS provides a 
weekly FSIS Constituent Update, which is communicated via fax to over 
300 organizations and individuals. In addition, the update is available 
on-line through the FSIS web page located at http://www.fsis.usda.gov. 
The update is used to provide information regarding FSIS policies, 
procedures, regulations, Federal Register notices, FSIS public 
meetings, recalls, and any other types of information that could affect 
or would be of interest to our constituents/stakeholders. The 
constituent fax list consists of industry, trade, and farm groups, 
consumer interest groups, allied health professionals, scientific 
professionals, and other individuals that have requested to be 
included. Through these various channels, FSIS is able to provide 
information to a much broader, more diverse audience. For more 
information and to be added to the constituent fax list, fax your 
request to the Congressional and Public Affairs Office, at (202) 720-

    Done at Washington DC, on: July 31, 2001.
Thomas J. Billy,
[FR Doc. 01-19597 Filed 8-3-01; 8:45 am]