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U.S. Department of Health and Human Services

Animal & Veterinary

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NADA 048-761 Aureomycin; Type A Medicated Article - supplemental approval (July 31, 1998)

I. GENERAL INFORMATION

NADA048-761
Sponsor:Roche Vitamins, Inc.
Parsippany, NJ 07054
Generic Name:Chlortetracycline Pre-mix
Trade Name:Aureomycin; Type A Medicated Article
Marketing Status:Over the Counter (OTC)
Effect of Supplement:Deletion of limitations statement, "Do not feed to chickens producing eggs for human consumption" and establishment of a Tolerance for chlortetracycline in eggs.

 

II. INDICATIONS FOR USE

See below.

 

III. DOSAGE

A. DOSAGE FORM: Type A Medicated Article

B. ROUTE OF ADMINISTRATION: Oral - For use in Type C medicated chicken feeds.

C. RECOMMENDED DOSAGES:

CHICKENS

10-50 g/tBroiler/fryer chickens:
For increased rate of weight gain and improved feed efficiency.
100-200 g/tControl of infectious synovitis caused by Mycoplasmasynoviae susceptible to chlortetracycline. (Feed continuously for 7 to 14 days)
200-400 g/tControl of chronic respiratory disease (CRD) and air sac infection caused by Mycoplasma gallisepticum and Escherichia coli susceptible to chlortetracycline. (Feed continuously for 7 to 14 days)
WARNING: Zero-day withdrawal period.
500 g/tReduction of mortality due to Escherichiacoli infections susceptible to chlortetracycline. (Feed for 5 days)
WARNING: Withdraw 24 hours prior to slaughter.

 

IV. EFFECTIVENESS

No further effectiveness data were required.

 

V. ANIMAL SAFETY

No further safety data were required.

 

VI. HUMAN FOOD SAFETY

A. Safe Concentrations of Total Residues

Recently, the Center for Veterinary Medicine (CVM) revised the tolerances for tetracycline drugs (61 FR 67453). Based on an ADI (ADI) of 0.025 mg/kg of body weight (bw) per day, reserving 60% of the ADI for milk and eggs, unified tolerances of 2 ppm for muscle, 6 ppm for liver and 12 ppm for kidney and fat now are codified for total tetracycline residues (i.e., tetracycline, oxytetracycline and chlortetracycline). The ADI for milk and eggs is calculated as follows:

Using the above ADI, reserving 50% of the nontissue ADI for eggs, and applying the current consumption factors, the tolerance for total tetracyclines in eggs is calculated as follow:

While the toxicology data would support a tolerance as high as 4.5 ppm for eggs, we are unable to build a relationship between this tolerance value and the tolerances in the other edible tissues. A tolerance of 400 ppb is established for residues of chlortetracycline in the eggs of laying hens. This value is consistent with both the incurred residues seen in the eggs of treated hens and the tolerances in other tissues.

B. Studies to Establish a Withdrawal Time

  1. "Aurofac 100: Determination of Chlortetracycline Residues in Eggs from Hens Fed 300ppm Chlortetracycline for Seven Consecutive Days," PE Gingher, January 20, 1989.

    Study Director: PE Gingher

    Study Location:

    American Cyanamid Company
    Agricultural Research Division
    Princeton, NJ 08540

    Twenty Hubbard White Leghorn laying hens were treated with 300 ppm CTC in the diet for seven consecutive days. Ten birds served as untreated controls. Eggs were collected from the treated birds from 0 through 12 days withdrawal and assayed microbiologically for residues of CTC. Eggs from control birds were assayed for CTC on days 0 and 5 of the withdrawal period. Eggs were assayed in order of collection until residues at two consecutive withdrawal days were less than 0.05 ppm. The study results are summarized in Table 1.

    Table 1: Mean residues (ppm) of CTC in whole eggs from laying hens treated with 300 ppm CTC in the feed for seven consecutive days.

    Withdrawal (days)Treatment Group ControlsTreatment Group CTC, 300 ppm
    0Negative*Neg.-0.040
    1**Neg.-0.038
    2**Negative
    3**Negative
    4**Negative
    5NegativeNegative

    * Negative = activity £ 0.0375 ppm ** Not assayed

  2. "Aureomycin Soluble Powder: Chlortetracycline Residues in Eggs from Hens Given 120ppm Chlortetracycline in Drinking Water for Seven Consecutive Days," PE Gingher, January 20, 1989.

    Study Director: PE Gingher

    Study Location:
    American Cyanamid Company
    Agricultural Research Division
    Princeton, NJ 08540

    Twenty White Leghorn laying hens were treated with 120 ppm CTC in the drinking water for seven consecutive days. Ten birds served as untreated controls. Eggs were collected from the treated birds from 0 through 12 days withdrawal and assayed microbiologically for residues of CTC. Eggs from control birds were assayed for CTC on days 0 and 5 of the withdrawal period. Eggs were assayed in order of collection until residues at two consecutive withdrawal days were less than 0.05 ppm. The study results are summarized in Table 2.

    Table 2: Mean residues (ppm) of CTC in whole eggs from laying hens treated with 120 ppm CTC in the drinking water for seven consecutive days.

    Withdrawal (days)Treatment Group ControlsTreatment Group CTC, 120 ppm
    0Negative*Neg.-0.041
    1**Neg.-0.041
    2**Negative
    3**Negative
    4**Negative
    5NegativeNegative

    * Negative = activity £ 0.0375 ppm ** Not assayed

C. Confirming zero withdrawal for eggs

The reported residues in the eggs of treated hens are generally low. In the feeding study, birds were dosed at 60% of the maximum labeled dose. If residues for the study are corrected to the maximum codified dose of 500 ppm, they would range from negative to 0.07 ppm. In the drinking water study, birds were dosed at 45% of the maximum labeled dose. If residues for the study are corrected to the maximum codified dose of 1000mg/gallon (263 ppm), they would range from negative to 0.09 ppm.

The 99th percentile/95% confidence intervals were calculated for residues of chlortetracycline administered via feed and water. For feed administration, the upper confidence limit is 90 ppb for untransformed data and 95 ppb for log transformed data. For drinking water administration, the upper confidence limit is 105 ppb for untransformed data and 106 ppb for log transformed data. For both studies, residues in eggs at zero withdrawal are well below the tolerance of 400 ppb.

D. Regulatory Analytical Methods for Residues

The regulatory analytical method for detection of residues of the drug is a microbiological test using Bacillus cereus var mycoides (ATCC 11778). The method is found in Antibiotic Residues in Milk, Dairy Products, and Animal Tissues: Methods, Reports and Protocols, Revised October 1968, Reprinted December 1974, Nation Center for Antibiotic and Insulin Analysis, FDA, Washington, DC 20204.

 

VII. AGENCY CONCLUSIONS

This supplemental NADA satisfies the requirements of section 512 of the Act and demonstrates that AUREOMYCIN Type A Medicated Article when used under its proposed conditions of use, is safe and effective for the labeled indications. The supplemental approval provides for the use of this Type A Medicated Article in the treatment of chickens producing eggs for human consumption and the establishment of a tolerance for chlortetracycline in eggs (0.4 ppm).

The "probably effective"finding of the NAS/NRC/DESI regarding chlortetracycline hydrochloride was published in the FEDERAL REGISTER of July 21, 1970, subsequently reviewed by FDA, resulting in the upgrade to "effective status" and was DESI-finalized and codified in the FEDERAL REGISTER on July 9, 1996.

When NADA 48-761 was reviewed under NAS/NRC/DESI program, it was an over-the-counter product and this marketing status remains unchanged. Other Chlortetracycline Type A Medicated Articles for use in food-producing animals are also currently on the market as over-the-counter products. Therefore, the Center for Veterinary Medicine has concluded that this product should retain over-the-counter marketing status.

Under the Center's supplemental approval policy [21 CFR 514.106(b)(2)(ix)] this is a Category II change. The approval of this change is not expected to have any adverse effect on the safety or effectiveness of this new animal drug. However, the approval did require a re-evaluation of the human food safety data in the parent application.

Under the Generic Animal Drug and Patent Term Restoration Act of 1988, this supplemental approval for food producing animal qualifies for THREE years of marketing exclusivity beginning on the date of approval under Section 512(c)(2)(F)(iii) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 360b(c)(2)(F)(iii)] because the supplemental application contains reports of new human food safety studies (establishing the tolerance for eggs) essential to the approval of the application and conducted by the sponsor.

 

VIII. LABELING (Attached)

Aureomycin® 50, 90, and 100 premix bags

Copies of applicable labels may be obtained by writing to the:

Food and Drug Administration
Freedom of Information Staff (HFI-35)
5600 Fishers Lane
Rockville, MD 20857

Or requests may be sent via fax to: (301) 443-1726. If there are problems sending a fax, call (301) 443-2414.