[Federal Register Volume 59, Number 72 (Thursday, April 14, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-9044]


[[Page Unknown]]

[Federal Register: April 14, 1994]


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 DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

21 CFR Part 520

 

Oral Dosage Form New Animal Drugs; Tetracycline Hydrochloride 
Soluble Powder

AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.

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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) for safe and effective use of tetracycline 
hydrochloride soluble powder. One supplemental NADA was filed by Wade 
Jones Co., Inc., and covers the use of the drug product in the drinking 
water of calves and swine for the control and treatment of certain 
bacterial diseases and in the drinking water of poultry for the control 
of certain bacterial diseases susceptible to the drug. The other 
supplemental NADA was filed by Pfizer, Inc., and also covers use of the 
drug in the drinking water of poultry for the control of certain 
susceptible bacterial diseases. Both approvals reflect compliance with 
the results of the National Academy of Sciences/National Research 
Council (NAS/NRC), Drug Efficacy Study Group's (DESI) evaluation of the 
drug's effectiveness and FDA's conclusions concerning that evaluation. 
Additionally, the agency is technically amending the regulations to 
make other needed corrections.

EFFECTIVE DATE: April 14, 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:

I. Background

Wade Jones Co., Inc., 409 North Bloomington, Lowell, AR 72745 (Wade 
Jones), filed a supplement to approved NADA 65-140 for a soluble powder 
containing 324 grams (g) of tetracycline hydrochloride (TC HCl) 
activity per pound (lb). The drug is available in several product 
container sizes, 2 and 5 lb tubs and 2.53, 5, and 10 ounce (oz) 
packets. The drug is indicated for use in chickens at 200 to 400 
milligrams per gallon (mg/gal) for control of infectious synovitis 
caused by Mycoplasma synoviae and at 400 to 800 mg/gal for control of 
chronic respiratory disease caused by M. gallisepticum and E. coli. The 
drug is indicated for use in turkeys at 400 mg/gal for control of 
infectious synovitis caused by M. synoviae and at 25 mg/lb of body 
weight for control of complicating bacterial organisms associated with 
bluecomb. It is also indicated for use in swine and calves at 10 mg/lb 
of body weight for control and treatment of bacterial enteritis 
(scours) and bacterial pneumonia. The NADA was originally approved July 
5, 1966.
    Pfizer, Inc., 235 East 42d St., New York, NY 10017 (Pfizer), filed 
supplemental NADA 65-123 for TC HCl soluble powder (6.4 ounce (oz) 
packet) to provide for use in chickens and turkeys under the same 
conditions of use expressed above for the Wade Jones application. The 
NADA was originally approved April 27, 1955.

 II. The NAS/NRC DESI Evaluation

    The drug products were subject to a NAS/NRC DESI evaluation of 
effectiveness (DESI 0012NV). The findings were published in the Federal 
Register of July 8, 1970 (35 FR 10966). NAS/NRC evaluated the products 
as ``probably effective'' for oral treatment of animal diseases when 
such diseases are caused by pathogenic microorganisms sensitive to 
tetracycline hydrochloride, diseases such as: (1) Enteric and 
respiratory diseases in poultry; (2) gastrointestinal and respiratory 
diseases in swine; (3) infected wounds, gastrointestinal and 
respiratory diseases in calves, sheep, and goats; (4) digestive system 
and respiratory diseases, pyelonephritis, peritonitis, infected wounds, 
abscesses, ulcers, and secondary bacterial invaders in dogs and cats; 
(5) coccidiosis in dogs; and (6) hexamitiasis in turkeys.
    NAS/NRC reached the following conclusions applicable to the subject 
TC HCl drug products:
    (1) Most of the dosage directions provide for a less than effective 
dose, and the recommended minimum oral dose for large animals is 10 mg/
lb of body weight daily in divided doses and for small animals 25 mg/lb 
body weight daily in divided doses;
    (2) claims for the treatment of viral diseases must be limited to 
microorganisms belonging to the psittacosis-lymphogranuloma group;
    (3) each disease claim should be properly qualified as 
``appropriate for use in (name of disease) caused by pathogens 
sensitive to (name of drug),'' and if the disease cannot be so 
qualified the claim must be dropped;
    (4) claims made ``for prevention of'' or ``to prevent'' should be 
replaced with ``as an aid in the control of'' or ``to aid in the 
control of'';
    (5) as applicable, the manufacturer's label should warn that 
treated animals must consume enough medicated water or medicated feed 
to provide a therapeutic dose under the conditions that prevail--as a 
precaution, the label should state the desired oral dose per unit of 
animal weight per day for each species as a guide to effective use of 
the preparation in drinking water or feed.
    FDA concurred with the NAS/NRC findings, interpreting the phrase 
``cannot be so qualified'' in item (3) of the paragraph immediately 
above to mean ``is not supported by adequate data.'' FDA proceeded to 
review all available data relating to the effectiveness of similar 
products to determine which label claims were supported by the 
requisite proof of effectiveness. The review resulted in the agency 
concluding that the data supported effectiveness only for the control 
and treatment of certain bacterial diseases susceptible to TC HCl in 
calves, swine, chickens, and turkeys.
    Subsequently, Wade Jones and Pfizer complied with the NAS/NRC 
evaluation and FDA's conclusions by filing supplemental NADA's which 
revised the drug products' labeling as follows: (1) Adopting the dosage 
recommended by NAS/NRC; (2) dropping all claims for viral diseases; (3) 
properly qualifying disease claims; (4) revising prevention claims to 
read ``Control of''; and (5) adding to the manufacturer's label the 
warning statement concerning factors influencing adequate consumption 
of medicated water.
    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 human food use of food derived from drug-treated 
animals.
    Wade Jones' supplemental NADA is approved as of September 15, 1993, 
and Pfizer's supplemental NADA is approved as of March 18, 1994. The 
regulations are amended by revising Sec. 520.2345d (21 CFR 520.2345d) 
to reflect the approvals.
    FDA's approval of the supplemental NADA's does not involve a 
reevaluation or reaffirmation of the human food safety data in the 
parent applications. Tolerances for residues of the drug and its 
metabolites in chickens, turkeys, swine, and calves of 0.25 part per 
million are currently codified in 21 CFR 556.720.

III. Environmental Impact

    The agency has carefully considered the potential environmental 
effects of approving the Wade Jones Supplement. 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.
    With regard to approving the Pfizer supplement, the agency has 
determined under 21 CFR 25.24(d)(1)(i) that this action is of a type 
that does not individually or cumulatively have a significant effect on 
the human environment. Therefore, neither an environmental assessment 
nor an environmental impact statement is required.
    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 do not 
qualify for exclusivity periods because their applications do not 
contain reports of new clinical or field investigations (other than 
bioequivalence or residue studies) and, in the case of food-producing 
animals, human food safety studies (other than bioequivalence or 
residue studies) essential to approval of the supplements and conducted 
or sponsored by the applicants.
    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)), 
summaries of safety and effectiveness data and information submitted to 
support approval of these applications may be seen in the Dockets 
Management Branch (address above) between 9 a.m. and 4 p.m., Monday 
through Friday.

IV. The Technical Amendments

    In conjunction with amending Sec. 520.2345d to codify the NAS/NRC 
DESI finalization of Wade Jones' and Pfizer's NADA's the agency is 
using this occasion to rewrite Sec. 520.2345d to clarify the 
regulations. Section 520.2345d is the recodified version of section 
546.180d(c). This latter section was one of many antibiotic drug 
sections affected by the final rule that published in the Federal 
Register of August 18, 1992 (57 FR 37318) for the purpose of: (1) 
Removing the technical regulations that included the requirements for 
certification and tests and methods of assay and (2) recodifying, based 
on route of administration, the remaining provisions concerning 
conditions of marketing. However, when Sec. 546.180d was recodified, 
the agency did not include other technical changes to update changes in 
the approved conditions of marketing. Accordingly, FDA is revising 
Sec. 520.2345d to codify the currently approved conditions of marketing 
and to make the following needed corrections: (1) The section heading 
is revised to fully identify the drug as the hydrochloride; (2) the 
``Specifications'' paragraph is removed and information concerning drug 
concentrations is incorporated into the ``Sponsors'' paragraph; (3) the 
second sentence of the NAS/NRC status paragraph is removed because it 
has been superseded by enactment of the Generic Animal Drug and Patent 
Term Restoration Act of 1988; (4) the drug labeler code for Upjohn Co. 
(000009) is removed because the firm was incorrectly listed as the 
sponsor of approvals for the use of TC HCl soluble powder in the 
drinking water of calves, swine, chickens, and turkeys; (5) the drug 
labeler code for Vetri-Tech, Inc. (058752), has been changed to that 
for Arkansas Micro Specialties, Inc. (047863), since Vetri-Tech, Inc., 
has transferred ownership of its NADA (use of drug in chickens) to 
Arkansas Micro Specialties, Inc., (57 FR 12711, April 13, 1992), and 
(6) in the calf and swine claims, the name of the causative agent, 
Hemophilus is changed to Actinobacillus pleuropneumoniae, the current 
scientific name.

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 520.2345d is revised to read as follows:


Sec.  520.2345d  Tetracycline hydrochloride soluble powder.

    (a) Sponsors. The following sponsors listed in Sec. 510.600(c) of 
this chapter hold approvals for the drug concentrations (i.e., grams of 
tetracycline hydrochloride per pound) and conditions of use indicated:
    (1) 047864 and 054273, 102.4 and 324 grams per pound as in 
paragraph (d) of this section.
    (2) 000069, 25 grams per pound as in paragraphs (d)(3) and (d)(4) 
of this section.
    (3) 010042, 102.4 and 324 grams per pound as in paragraphs (d)(1) 
and (d)(2) of this section.
    (4) 047863, 102.4 and 324 grams per pound as in paragraph (d)(3) of 
this section.
    (b) Related tolerances. See Sec. 556.720 of this chapter.
    (c) National Academy of Sciences/National Research Council (NAS/
NRC) status. The conditions of use specified in paragraph (d) of this 
section were NAS/NRC reviewed and found effective.
    (d) Conditions of use in drinking water--(1) Calves--(i) Amount. 10 
milligrams per pound of body weight per day in divided doses.
    (ii) Indications for use. Control and treatment of bacterial 
enteritis (scours) caused by Escherichia coli and bacterial pneumonia 
(shipping fever complex) associated with Pasteurella spp., 
Actinobacillus pleuropneumoniae (Hemophilus spp.), and Klebsiella spp., 
susceptible to tetracycline.
    (iii) Limitations. Administer for 3 to 5 days; do not slaughter 
animals for food within 4 days of treatment for sponsor 010042 and 
within 5 days of treatment for sponsors 047864 and 054273; prepare a 
fresh solution daily; use as the sole source of tetracycline.
    (2) Swine--(i) Amount. 10 milligrams per pound of body weight per 
day in divided doses.
    (ii) Indications for use. Control and treatment of bacterial 
enteritis (scours) caused by E. coli and bacterial pneumonia associated 
with Pasteurella spp., A. pleuropneumoniae (Hemophilus spp.), and 
Klebsiella spp., susceptible to tetracycline.
    (iii) Limitations. Administer for 3 to 5 days; do not slaughter 
animals for food within 7 days of treatment for sponsor 010042 and 
within 4 days of treatment for sponsors 047864 and 054273; prepare a 
fresh solution daily; use as the sole source of tetracycline.
    (3) Chickens--(i) Amount. Chronic respiratory disease: 400 to 800 
milligrams per gallon. Infectious synovitis: 200 to 400 milligrams per 
gallon.
    (ii) Indications for use. Control of chronic respiratory disease 
(CRD or air-sac disease) caused by Mycoplasma gallisepticum and E. 
coli; control of infectious synovitis caused by M. synoviae susceptible 
to tetracycline.
    (iii) Limitations. Administer for 7 to 14 days; do not slaughter 
for food within 4 days of treatment; not for use in chickens producing 
eggs for human consumption; prepare a fresh solution daily; use as the 
sole source of tetracycline.
    (4) Turkeys--(i) Amount. For infectious synovitis: 400 milligrams 
per gallon. For complicating bacterial organisms associated with 
bluecomb (transmissible enteritis or coronaviral enteritis): 25 
milligrams per pound of body weight per day.
    (ii) Indications for use. Control of infectious synovitis caused by 
M. synoviae; control of bluecomb complicated by organisms sensitive to 
tetracycline.
    (iii) Limitations. Administer for 7 to 14 days; do not slaughter 
for food within 4 days of treatment; not for use in turkeys producing 
eggs for human consumption; prepare a fresh solution daily; use as the 
sole source of tetracycline.

    Dated: April 7, 1994.
Robert C. Livingston,
Director, Office of New Animal Drug Evaluation, Center for Veterinary 
Medicine.
[FR Doc. 94-9044 Filed 4-13-94; 8:45 am]
BILLING CODE 4160-01-F