[Federal Register Volume 67, Number 25 (Wednesday, February 6, 2002)]
[Rules and Regulations]
[Pages 5470-5471]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-2751]

[[Page 5470]]



Food and Drug Administration

21 CFR Part 530

[Docket No. 01N-0499]

Topical Nitrofurans; Extralabel Animal Drug Use; Order of 

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.


SUMMARY: The Food and Drug Administration (we) is issuing an order 
prohibiting the extralabel use of topical nitrofuran animal and human 
drugs in food-producing animals. We are issuing this order based on 
evidence that extralabel use of topical nitrofuran drugs in food-
producing animals may result in the presence of residues that we have 
determined to be carcinogenic and to not have been shown to be safe. We 
find that such extralabel use ``presents a risk to the public health'' 
for the purposes of the Animal Medicinal Drug Use Clarification Act of 
1994 (AMDUCA).

DATES: This rule is effective May 7, 2002. We invite your written or 
electronic comments. We will consider all comments that we receive by 
April 8, 2002.

ADDRESSES: Submit your written comments to the Dockets Management 
Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 
1061, Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT: Gloria J. Dunnavan, Center for 
Veterinary Medicine (HFV-6), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-827-1726, 
e-mail: gdunnava@cvm.fda.gov.



    AMDUCA (Public Law 103-396) was signed into law on October 22, 
1994. It amended the Federal Food, Drug, and Cosmetic Act (the act) to 
permit licensed veterinarians to prescribe extralabel uses of approved 
animal and human drugs in animals. However, section 512(a)(4)(D) of the 
act (21 U.S.C. 360b(a)(4)(D)) gives us authority to prohibit an 
extralabel drug use in animals if, after affording an opportunity for 
public comment, we find that such use presents a risk to the public 
    We published the implementing regulations (codified at part 530 (21 
CFR part 530)) for AMDUCA in the Federal Register of November 7, 1996 
(61 FR 57732). The sections regarding prohibition of extralabel use of 
drugs in food-producing animals are found at Secs. 530.21 and 530.25. 
These sections describe the basis for issuing an order prohibiting an 
extralabel drug use in food-producing animals and the procedure to be 
followed in issuing an order of prohibition. We may issue a prohibition 
order if we find that extralabel use in animals presents a risk to the 
public health. Under Sec. 530.3(e), this means that we have evidence 
that demonstrates that the use of the drug has caused or likely will 
cause an adverse event.
    Section 530.25 provides for a public comment period of not less 
than 60 days. It also provides that the order of prohibition will 
become effective 90 days after the date of publication, unless we 
revoke the order, modify it, or extend the period of public comment. 
The list of drugs prohibited from extralabel use is found in 
Sec. 530.41. The current list of drugs prohibited from extralabel use 
in food-producing animals includes furazolidone and nitrofurazone, but 
it contains the parenthetical statement ``(except for approved topical 

II. Nitrofurans

    In 1991, and after a full evidentiary hearing, we withdrew the 
approvals for furazolidone and nitrofuranzone labeled for antiprotozoal 
use in a wide variety of conditions in poultry and swine. (See the 
Federal Register of August 23, 1991 (56 FR 41902).) These withdrawals 
were based on our determination that use of the drugs resulted in 
residues in edible tissues for human food and that residues of these 
drugs were not shown to be safe, in part because both drugs are 
carcinogenic. We did not, however, withdraw the approvals of these 
products for use in nonfood animals or for topical use in food-
producing animals. Moreover, while our current regulations in 
Sec. 530.41 prohibit extralabel use of approved furazolidone and 
nitrofurazone products in food-producing animals, this prohibition does 
not extend to topical use in food-producing animals. These topical uses 
in food-producing animals were allowed because there was no evidence 
that such use of furazolidone and nitrofuranzone resulted in residues 
in edible tissues.
    However, a recent carbon-14 (C-14) radio-label residue depletion 
study that we conducted showed that detectable levels of nitrofuran 
derivatives are present in edible tissues (milk, meat, kidney, liver) 
of cattle treated by the ocular (eye) route (Ref. 1). This study, 
coupled with our findings in our prior withdrawal action, means that 
residues, which are carcinogenic and have not been shown to be safe, 
will likely be present at slaughter as a result of topical uses of 
nitrofurans, including furazolidone and nitrofurazone, in food-
producing animals.
    We advised all manufacturers of nitrofuran drugs that were approved 
for ocular use in food-producing animals of the evidence and the 
manufacturers revised their labels to remove those indications. (See, 
for example, 65 FR 41587 (July 6, 2000).) Some lot numbers of these 
drugs may remain in commercial distribution channels with the former 
labels that contain indications for food-producing animals. These 
products, however, are not approved for use in food-producing animals 
and, therefore, are adulterated and misbranded. Some topical and 
ophthalmic nitrofuran products are still approved for certain uses in 
nonfood animals. Under the current regulations governing extralabel 
use, these remaining approved topical and ophthalmic products are not 
prohibited from extralabel topical use in food-producing animals. 
However, as stated previously, there is evidence that these uses will 
result in residues in edible tissues. Because of the likelihood of this 
adverse event, by this order of prohibition, we are prohibiting all 
extralabel uses, including extralabel topical use, in food-producing 
animals of nitrofuran products that are approved for use in nonfood 
animals or humans. Therefore, no nitrofuran product may be legally used 
in food-producing animals.

III. Request for Comments

    We are providing 60 days from the date of this publication for you 
to comment. The order will become effective May 7, 2002, unless we 
revoke or modify the order or extend the comment period. You may submit 
written or electronic comments to the Dockets Management Branch 
(address above) by April 8, 2002. Please identify your comments with 
the docket number found in brackets in the heading of this document. 
You may read any comments that we receive at our Dockets Management 
Branch reading room (address above). The reading room is open from 9 
a.m. to 4 p.m., Monday through Friday, except for Federal holidays.

IV. Order of Prohibition

    Therefore, I hereby issue the following order under section 
512(a)(4)(D) of the act and 21 CFR 530.21 and 530.25. We find that 
extralabel use of nitrofurans in food-

[[Page 5471]]

producing animals likely will cause an adverse event, which constitutes 
a finding under section 512(a)(4)(D) of the act that extralabel use of 
these drugs in food-producing animals presents a risk to the public 
health. Therefore, we are prohibiting all extralabel uses of these 
drugs in food-producing animals.

V. Reference

    The following information has been placed on display in the Dockets 
Management Branch (address above). You may view it between 9 a.m. and 4 
p.m., Monday through Friday.
    1. Smith, D. J., G. D. Paulson, and G. L. Larsen, ``Distribution 
of Radiocarbon After Intermammary, Intrauterine or Ocular Treatment 
of Lactating Cows With Carbon-14 Nitrofurazone,'' Journal of Dairy 
Science, vol. 81, pp. 979-988, 1998.

List of Subjects in 21 CFR Part 530

    Administrative practice and procedure, Advertising, Animal drugs, 
Labeling, Reporting and recordkeeping requirements.

    Accordingly, under the Federal Food, Drug, and Cosmetic Act and 
under authority delegated to the Commissioner of Food and Drugs and 
redelegated to the Director of the Center for Veterinary Medicine, 21 
CFR part 530 is amended as follows:


    1. The authority citation for 21 CFR part 530 continues to read as 

    Authority: 15 U.S.C. 1453, 1454, 1455; 21 U.S.C. 321, 331, 351, 
352, 353, 355, 357, 360b, 371, 379e.

Sec. 530.41  [Amended]

    2. Section 530.41 Drugs prohibited for extralabel use in animals is 
amended in paragraphs (a)(7) and (a)(8) by removing the parenthetical 
phrase ``(except for approved topical use)''.

    Dated: November 9, 2001.
Stephen F. Sundlof,
Director, Center for Veterinary Medicine.
[FR Doc. 02-2751 Filed 2-5-02; 8:45 am]