[Federal Register Volume 59, Number 148 (Wednesday, August 3, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-18926]


[[Page Unknown]]

[Federal Register: August 3, 1994]


=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 520

 

Oral Dosage Form New Animal Drugs; Chlortetracycline Soluble 
Powder

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is amending the animal 
drug regulations to reflect approval of two supplemental new animal 
drug applications (NADA's) filed by the American Cyanamid Co. The 
supplemental NADA's provide for the safe and effective use of 
chlortetracycline hydrochloride (CTC HCl) soluble powder in both the 
drinking water of chickens and turkeys for control of certain bacterial 
diseases susceptible to CTC, and the drinking water of swine and cattle 
for control and treatment of certain bacterial diseases susceptible to 
CTC. The approvals reflect compliance with results of the National 
Academy of Sciences/National Research Council (NAS/NRC), Drug Efficacy 
Study Group's (DESI) evaluation of the drugs' effectiveness and FDA's 
conclusions concerning that evaluation.

EFFECTIVE DATE: August 3, 1994.

FOR FURTHER INFORMATION CONTACT: Dianne T. McRae, Center for Veterinary 
Medicine (HFV-102), Food and Drug Administration, 7500 Standish Pl., 
Rockville, MD 20855, 301-594-1623.

SUPPLEMENTARY INFORMATION: American Cyanamid Co., Berdan Ave., Wayne, 
NJ 07470, submitted a supplement to its approved NADA 65-071 for 
Aureomycin (chlortetracycline hydrochloride (CTC HCl)) 
Soluble Powder (available in 181 gram (g) (6.4 ounce (oz) packets and 
2.3 kilogram (kg) (5 pound (lb) bags, with a concentration of 25 g CTC 
HCl/lb) and NADA 65-440 for Aureomycin (CTC HCl) Soluble 
Powder Concentrate (available in 181 g (6.4 oz) and 726 g (25.6 oz) 
packets, with a concentration of 64 g CTC HCl/lb). The drug products 
are used to medicate drinking water to be administered to chickens, 
turkeys, swine, calves, beef cattle, and nonlactating dairy cattle in 
accordance with Sec. 520.445b(d)(4) (21 CFR 520.445b(d)(4)). Both 
NADA's were originally approved on June 23, 1953, as antibiotic Form 6 
applications.
    The drugs were the subject of a NAS/NRC DESI evaluation of 
effectiveness (DESI 0113NV). The findings were published in the Federal 
Register of July 21, 1970 (35 FR 11646). NAS/NRC evaluated the drugs as 
probably effective for growth promotion and feed efficiency and for the 
treatment of animal diseases caused by pathogens sensitive to 
chlortetracycline. NAS/NRC stated:
    (1) Claims made regarding ``for prevention of'' or ``to 
prevent'' should be replaced with ``as an aid in the control of'' or 
``to aid in the control of'';
    (2) claims for growth promotion or stimulation are disallowed 
and claims for faster gains and/or feed efficiency should be stated 
as ``may result in faster gains and/or improved feed efficiency 
under appropriate conditions'';
    (3) each disease claim should be properly qualified as 
``appropriate for use in (name of disease) caused by pathogens 
sensitive to (name of drug)''; if the disease cannot be so qualified 
the claim must be dropped;
    (4) claims pertaining to egg production and hatchability should 
be changed to ``May aid maintaining egg production and hatchability, 
under appropriate conditions, by controlling pathogenic 
microorganisms'';
    (5) the labels should warn that treated animals must actually be 
consuming enough medicated water or medicated feed to provide a 
therapeutic dosage under the conditions that prevail and, as a 
precaution, state the desired oral dose per unit of animal weight 
per day for each species as a guide to effective usage of the 
preparation in drinking water or feed; and
    (6) effective blood levels are required for each recommended 
dosage.
    FDA concurred with the NAS/NRC findings.
    The NAS/NRC evaluation is concerned only with the drugs' 
effectiveness and safety to the treated animal. It does not take into 
account the safety for food use of food derived from drug-treated 
animals. Nothing herein will constitute a bar to further proceedings 
with respect to questions of safety of the drugs or their metabolites 
in food products derived from treated animals.
    The American Cyanamid Co. filed supplemental NADA's which revised 
the labeling of its products to comply with the results of the NAS/NRC 
DESI review and FDA's conclusions. The supplemental NADA's are approved 
as of June 15, 1994, and the regulations are amended by revising 
Sec. 520.445b (21 CFR 520.445b) to reflect the approvals.
    Additionally, Sec. 520.445b(b) is amended to reflect sponsor 
approvals as a result of this latest DESI finalization:
    1. Drug sponsor no. 053389 (Pennfield Oil Co.) is currently 
codified for the uses provided in Sec. 520.445b(d)(3) and (d)(4). 
Actually, the approval is limited to the uses provided only in 
Sec. 520.445b(d)(2)(i)(D) and (d)(3)(i)(A).
    2. Drug sponsor no. 010042 (American Cyanamid Co.) is currently 
codified for the uses provided in Sec. 520.445b(d)(1) and (d)(2). 
However, approval of its applications is now limited to the uses 
listed in Sec. 520.445b(d)(4).
    3. Drug sponsor no. 054273 (Fermenta Animal Health Co.) is 
codified for all of the current uses in Sec. 520.445b(d)(4), which 
is being amended because the sponsor does not hold an approval for 
the claim added in paragraph (d)(4)(i)(C) of Sec. 520.445b.
    4. Drug sponsor no. 017274 (Feed Specialties Co., Inc.) is 
currently codified for the uses provided in Sec. 520.445b(d)(4)(i) 
through (d)(4)(iii). However, this is being amended because the 
sponsor does not hold an approval for the claim added in paragraph 
(d)(4)(i)(C).
    As a result of the DESI finalization, Sec. 520.445b(d)(1) and 
(d)(2) are being removed (for claims no longer acceptable) and new 
paragraph (d)(4)(i)(C) is being added to reflect a claim for control of 
mortality due to fowl cholera caused by Pasteurella multocida.
    Section 520.445b is further amended in paragraphs (d)(4)(iii)(B) 
and (d)(4)(iv)(B) to change the name of one of the causative agents, 
Hemophilus, to Actinobacillus pleuropneumoniae, the current scientific 
name.
    Finally, Sec. 520.445b is amended in paragraph (d)(4)(iv)(C) to add 
warning statements now required on the labeling.
    The agency has carefully considered the potential environmental 
effects of this action. FDA has concluded that the action will not have 
a significant impact on the human environment, and that an 
environmental impact statement is not required. The agency's finding of 
no significant impact and the evidence supporting that finding, 
contained in an environmental assessment, may be seen in the Dockets 
Management Branch (HFA-305), Food and Drug Administration, rm. 1-23, 
12420 Parklawn Dr., Rockville, MD 20857, between 9 a.m. and 4 p.m., 
Monday through Friday.
    Under section 512(c)(2)(F)(iii) of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 360b(c)(2)(F)(iii)), these approvals for food 
producing animals do not qualify for marketing exclusivity because the 
supplemental applications do not contain reports of new clinical or 
field investigations (other than bioequivalence or residue studies) and 
new human food safety studies (other than bioequivalence or residue 
studies) essential to the approvals and conducted or sponsored by the 
applicant.
    In accordance with the freedom of information provisions of part 20 
(21 CFR part 20) and Sec. 514.11(e)(2)(ii) (21 CFR 514.11(e)(2)(ii)), a 
summary of safety and effectiveness data and information submitted to 
support approval of this application may be seen in the Dockets 
Management Branch (address above) between 9 a.m. and 4 p.m., Monday 
through Friday.

List of Subjects in 21 CFR Part 520

    Animal drugs.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs and 
redelegated to the Center for Veterinary Medicine, 21 CFR part 520 is 
amended as follows:

PART 520--ORAL DOSAGE FORM NEW ANIMAL DRUGS

    1. The authority citation for 21 CFR part 520 continues to read as 
follows:

    Authority: Sec. 512 of the Federal Food, Drug, and Cosmetic Act 
(21 U.S.C. 360b).

    2. Section 520.445b is amended in paragraph (a) by adding ``, 
64,'' after ``25.6'' and ``, 141,'' after ``56.4''; by revising 
paragraphs (b), (d)(1), (d)(2), (d)(4)(iii)(B), (d)(4)(iii)(C), 
(d)(4)(iv)(B), and (d)(4)(iv)(C); by removing and reserving 
paragraph (d)(3); and by adding new paragraph (d)(4)(i)(C) to read 
as follows:


Sec. 520.445b  Chlortetracycline powder (chlortetracycline 
hydrochloride or chlortetracycline bisulfate).

* * * * *
    (b) Sponsors. See No. 053389 in Sec. 510.600(c) of this chapter for 
conditions of use as in paragraphs (d)(1)(i)(A) and (d)(2)(i)(A) of 
this section; No. 010042 for conditions of use as in paragraph (d)(4) 
of this section; No. 054273 for conditions of use as in paragraphs 
(d)(4)(i)(A) and (B) and (d)(4)(ii) through (iv) of this section; No. 
017274 for conditions of use as in paragraphs (d)(4)(i)(A) and (B) and 
(d)(4)(ii) and (iii) of this section.
* * * * *
    (d) Conditions of use. (1) Use as chlortetracycline hydrochloride 
in drinking water as follows:
    (i) Swine. (A) Amount. Ten milligrams per pound of body weight 
daily in divided doses.
    (1) Indications for use. Control and treatment of bacterial 
enteritis (scours) caused by Escherichia coli and bacterial pneumonia 
associated with Pasteurella spp., Actinobacillus pleuropneumoniae 
(Hemophilus spp.), and Klebsiella spp.
    (2) Limitations. Prepare a fresh solution twice daily; as sole 
source of chlortetracycline; administer for not more than 5 days; do 
not slaughter animals for food within 5 days of treatment.
    (B) [Reserved]
    (ii) [Reserved]
    (2) Use as chlortetracycline hydrochloride in a drench or drinking 
water as follows:
    (i) Calves. (A) Amount. Ten milligrams per pound of body weight 
daily in divided doses.
    (1) Control and treatment of bacterial enteritis (scours) caused by 
E. coli and bacterial pneumonia (shipping fever) associated with 
Pasteurella spp., A. pleuropneumoniae (Hemophilus spp.), and Klebsiella 
spp.
    (2) Limitations. Prepare fresh solution daily; as sole source of 
chlortetracycline; administer for not more than 5 days; do not 
slaughter animals for food within 24 hours of treatment; do not 
administer this product with milk or milk replacers; administer 1 hour 
before or 2 hours after feeding milk or milk replacers; a withdrawal 
period has not been established in preruminating calves; do not use in 
calves to be processed for veal.
    (B) [Reserved]
    (ii) [Reserved]
    (3) [Reserved]
    (4) * * *
    (i) * * *
    (C) Amount. One thousand milligrams per gallon.
    (1) Indications for use. Control of mortality due to fowl cholera 
caused by Pasteurella multocida susceptible to chlortetracycline.
    (2) Limitations. See paragraph (d)(4)(i)(A)(2) of this section.
* * * * *
    (iii) * * *
    (B) Indications for use. Control and treatment of bacterial 
enteritis (scours) caused by E. coli and Salmonella spp. and bacterial 
pneumonia associated with Pasteurella spp., Actinobacillus 
pleuropneumoniae (Hemophilus spp.), and Klebsiella spp.
    (C) Limitations. Prepare fresh solution daily; as sole source of 
chlortetracycline; do not use for more than 5 days; for 017274, 053389, 
and 054273 do not slaughter animals for food within 5 days of 
treatment; for 010042 do not slaughter animals for food within 24 hours 
of treatment.
    (iv) * * *
    (B) Indications for use. Control and treatment of bacterial 
enteritis (scours) caused by E. coli and Salmonella spp. and bacterial 
pneumonia (shipping fever complex) associated with Pasteurella spp., A. 
pleuropneumoniae (Hemophilus spp.), and Klebsiella spp.
    (C) Limitations. Prepare fresh solution daily; use as a drench; as 
sole source of chlortetracycline; do not use for more than 5 days; do 
not slaughter animals for food within 24 hours of treatment; do not use 
in lactating cattle; do not administer this product with milk or milk 
replacers; administer 1 hour before or 2 hours after feeding milk or 
milk replacers; a withdrawal period has not been established in 
preruminating calves; do not use in calves to be processed for veal.

    Dated: July 27, 1994.
Robert C. Livingston,
Director, Office of New Animal Drug Evaluation, Center for Veterinary 
Medicine.
[FR Doc. 94-18926 Filed 8-2-94; 8:45 am]
BILLING CODE 4160-01-F