CFR - Code of Federal Regulations Title 21

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For the most up-to-date version of CFR Title 21, go to the Electronic Code of Federal Regulations (eCFR).

[Code of Federal Regulations]

[Title 21, Volume 6]

[CITE: 21CFR556]

TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER E - ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS

PART 556 TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD

Subpart A - General Provisions

Sec. 556.1 Scope.

(a) The Federal Food, Drug, and Cosmetic Act requires an applicant seeking approval or conditional approval of a new animal drug to submit a proposed tolerance as part of its new animal drug application when such a tolerance is needed to assure that the proposed use of the new animal drug will be safe (see sections 512(b)(1)(H) and 571(a)(2)(A) of the Federal Food, Drug, and Cosmetic Act). FDA assigns tolerances for animal drugs used in food-producing animals as part of the application approval process. Tolerances for approved and conditionally approved new animal drugs are codified in subpart B of this part.

(b) Compounds that have been found to be carcinogenic are regulated under subpart E of part 500 of this chapter.

Sec. 556.3 Definitions.

As used in this part:

Acceptable daily intake (ADI) means the daily intake which, during up to an entire life of a human, appears to be without adverse effects or harm to the health of the consumer. The ADI most often will be set on the basis of the drug's toxicological, microbiological, or pharmacological properties. It is usually expressed in micrograms or milligrams of the chemical per kilogram of body weight per day.

Acute reference dose (ARfD) means an estimate of the amount of residues expressed on a body weight basis that can be ingested in a period of 24 hours or less without adverse effects or harm to the health of the human consumer.

Edible tissues means muscle, liver, kidney, fat, skin with fat in natural proportions, whole eggs, whole milk, and honey.

Marker residue means the residue whose concentration is in a known relationship to the concentration of total residue in an edible tissue.

mg/kg means milligrams per kilogram.

Not required, in reference to tolerances in this part, means that at the time of approval:

(1) No withdrawal period was necessary for residues of the drug to deplete to or below the concentrations considered to be safe, or an adequate withdrawal period was inherent in the proposed drug use, and there was a rapid depletion of residues, so there was no concern about residues resulting from misuse or overdosing; or

(2) No withdrawal period was necessary because the drug was poorly absorbed or metabolized rapidly so as to make selection of an analyte impractical or impossible.

ppb means parts per billion (equivalent to nanograms per gram (ng/g) or [micro]g/kg).

ppm means parts per million (equivalent to micrograms per gram ([micro]g/g) or mg/kg).

ppt means parts per trillion (equivalent to picograms per gram (pg/g) or nanograms per kilogram (ng/kg)).

Residue means any compound present in edible tissues that results from the use of a drug, and includes the drug, its metabolites, and any other substance formed in or on food because of the drug's use.

Target tissue means the edible tissue selected to monitor for residues in the target animals.

Tolerance means the maximum concentration of a marker residue, or other residue indicated for monitoring, that can legally remain in a specific edible tissue of a treated animal.

Total residue means the aggregate of all compounds that results from the use of an animal drug, including the drug, its metabolites, and any other substances formed in or on food because of such drug use.

[micro]g/kg means microgram per kilogram.

Zero, in reference to tolerances in this part, means any residues detected in the edible tissue renders it unsafe.

Sec. 556.5 General considerations.

(a) The tolerances listed in subpart B of this part pertain only to the species and production classes of the animal for which the drug use has been approved or conditionally approved. Approved and conditionally approved conditions of use in parts 516, 520, 522, 524, 526, 529, and 558 of this chapter, including the species and production classes of animals, are referenced in each tolerance section in subpart B of this part.

(b) All tolerances refer to the concentrations of a marker residue, or other residue indicated for monitoring, permitted in uncooked tissues.

(c) After a tolerance is listed, the finding that the concentration of the marker residue in the target tissue from a tested animal is at or below the tolerance indicates that all edible tissues (excluding milk and eggs unless otherwise indicated) from that tested animal are safe for human consumption. If a listed tolerance is not expressly linked to a target tissue, then the tolerance is specific only for the named edible tissue and inferences cannot be made about the safety of the other edible tissues from the tested animal.

(d) FDA requires that a drug sponsor submit a practicable method as part of their new animal drug application. FDA uses the practicable method to determine the quantity of the drug residues that can safely remain in edible tissues (i.e., the tolerance), the withdrawal period, and any other use restrictions necessary to ensure that the proposed use of the drug will be safe.

Authority: 21 U.S.C. 342, 360b, 371.
Source: 84 FR 32993, July 11, 2019, unless otherwise noted.