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U.S. Department of Health and Human Services

Animal & Veterinary

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NADA 011-315 Neomycin 325/Neomix Ag 325 Soluble Powder - supplemental approval (Date of Approval: April 3, 1996)

Date of Approval: April 3, 1996

I. GENERAL INFORMATION:

NADA011-315
Sponsor:The Upjohn Company
Agricultural Division
Kalamazoo, Michigan 49001-0199
Generic Name:neomycin sulfate
Trade Name:Neomycin 325/Neomix Ag 325 Soluble Powder
Marketing Status:Over the Counter (OTC)
Effect of Supplement:To increase the tolerance in the target tissue, kidneys, to 7.2 ppm and to decrease the withdrawal periods to 1 day in cattle, 2 days in sheep, and 3 days for swine and goats

 

II. INDICATIONS FOR USE

See below

 

III. DOSAGE

A. DOSAGE FORM: Soluble powder

B. HOW SUPPLIED: 3.5 oz (100 g) and 50 Lb (22.6 kg) packages

C. AMOUNT OF ACTIVE INGREDIENT: 50 gm neomycin per 3.5 oz (100 g) package and 227.5 gm neomycin per 50 Lb (22.6 kg) package

D. ROUTE OF ADMINISTRATION: Orally in drinking water or milk

E. SPECIES: Cattle (excluding veal calves), Swine, Sheep, and Goats

F. LABELED DOSAGES: 10 mg/lb body weight daily in divided doses for a maximum of 14 days

G. INDICATIONS FOR USE: For the treatment and control of colibacillosis (bacterial enteritis) caused by Escherichia colisusceptible to neomycin sulfate.

 

IV. TARGET ANIMAL SAFETY AND DRUG EFFECTIVENESS:

The basis for the original approval of this NADA was published in 57 FR 19085, May 4, 1992.

 

V. HUMAN FOOD SAFETY:

Tolerance
The tolerance for neomycin residues in the uncooked edible tissues of cattle, swine, sheep, and goats was originally established at 0.25 ppm (21 CFR 556.430). The tolerance is being revised using the new food consumption factors as described in the FDA/CVM July 1994 publication entitled, "General Principles for Evaluating the Safety of Compounds Used in Food-Producing Animals" (59 FR 37499). A tolerance of 7.2 ppm is established for residues of parent neomycin (marker residue) in the kidney (target tissue) of cattle (except veal calves), swine, sheep, and goats. A tolerance of 0.15 ppm is established for neomycin in milk.

Studies Establishing the Withdrawal Period
Four separate residue depletion studies were conducted by Colorado Animal Research Enterprises Inc. (CARE), Fort Collins, Colorado under VMF 5154. The purpose of the studies was to determine the depletion of neomycin in swine, cattle, sheep, or goats following administration of 10 mg neomycin sulfate/pound body weight/day through drinking water for 14 days.

  1. Ten male and ten female swine weighing approximately 100 lbs each were administered neomycin sulfate at 10 mg/lb/day for 14 days through the drinking water. One male and one female swine served as controls. The swine were sacrificed in groups of four (2M, 2F) at 0, 1, 3, 7, and 14 days after the last dose. Samples of kidney, liver, muscle, and fat were taken and assayed for residues. Only kidney had detectable amounts of residues.

    (Eds. note: The following table consists of 3 columns.)

    Geometric Mean Kidney Tissue Neomycin Residues from Swine Medicated with 10 mg/lb/day for 14 Days through Drinking Water (n=2)

    Geometric Mean Neomycin Levels (ppm)

    Withdrawal Time in DaysFemaleMale
    01.632.52
    10.792.92
    30.461.34
    70.440.65
    140.340
    Limit of Quantitation is 0.5 ppm.
  2. Ten steers and ten heifers weighing approximately 525 lbs each were administered neomycin sulfate at 10 mg/lb/day for 14 days through drinking water. One steer and one heifer served as controls. The treated cattle were sacrificed in groups of four (2M, 2F) at 0, 1, 3, 7, and 14 days after the last dose (only 3 animals were sacrificed on day 7 of withdrawal due to the death of one heifer). Kidneys, liver and samples of muscle and fat were assayed for residues. Only kidney had detectable amounts of residues.

    (Eds. note: The following table consists of 3 columns.)

    Geometric Mean Kidney Tissue Neomycin Residues from Cattle Medicated with 10 mg/lb/day for 14 Days through Drinking Water (n=2)

    Geometric Mean Neomycin Levels (ppm)

    Withdrawal Time in DaysFemaleMale
    02.403.16
    13.352.37
    31.871.48
    7---0.5
    1400
    Limit of Quantitation is 0.5 ppm.
  3. Ten wethers and ten ewes weighing approximately 110 lbs each were administered neomycin sulfate at 10 mg/lb/day for 14 days through drinking water. One wether and one ewe served as controls. The treated sheep were sacrificed in groups of four (2M, 2F) at 1, 3, 7, 14, and 21 days after the last dose. Kidneys, liver and samples of muscle and fat were assayed for residues. Only kidney had detectable amounts of residues.

    (Eds. note: The following table consists of 3 columns.)

    Geometric Mean Kidney Tissue Neomycin Residues from Sheep Medicated with 10 mg/lb/day for 14 Days through Drinking Water (n=2)

    Geometric Mean Neomycin Levels (ppm)

    Withdrawal Time in DaysFemaleMale
    11.280.62
    300.45
    7---0
    Limit of Quantitation is 0.5 ppm.
  4. Ten female and ten male goats weighing approximately 65 lbs each were administered neomycin sulfate at 10 mg/lb/day for 14 days through drinking water. One female goat and one male goat served as controls. The treated goats were sacrificed in groups of four (2M, 2F) at 12, 24, 48, 72, and 96 hours after the last dose. Kidneys, liver and samples of muscle and fat were assayed for residues. Only kidney had detectable amounts of residues.

    (Eds. note: The following table consists of 3 columns.)

    Geometric Mean Neomycin Levels (ppm)

    Withdrawal Time in DaysFemaleMale
    121.0020.732
    241.502.61
    481.092.20
    720.811.04
    960.360.84

    Limit of Quantitation is 0.5 ppm.

    A weighted least squares regression line was fit to tobit maximum likelihood (ML) estimates of central location for each time point. The weights were based on ML estimates of dispersion. This accommodates values below the limit of quantitation and above the limit of detection. Using a statistical tolerance limit for the 99th percentile of the population with 95% confidence, the following withdrawal times were calculated for animals treated with 10 mg/lb/day neomycin sulfate for 14 days through drinking water:

    Animals treated with 10 mg/lb/day
    neomycin sulfate for 14 days through drinking water
    Withdrawal Time in Days
    swine3
    goats3
    sheep2
    cattle (excluding veal calves)1
    Regulatory Method for Residues
    The regulatory analytical method for detection of residues of the drug is a microbiological test using Staphylococcus epidermidissuspension. The method is published by the Food and Drug Administration, "Antibiotic Residues in Milk, Dairy Products and Animal Tissues: Methods, Reports, and Protocols", revised October 1968, reprinted December 1974.

 

VI. AGENCY CONCLUSIONS:

Neomycin sulfate, codified in 21 CFR Parts 520.1484(c)(3) and 556.430, is approved for marketing as a soluble powder for the treatment and control of colibacillosis (bacterial enteritis) caused by Escherichia coli susceptible to neomycin sulfate in cattle (excluding veal calves), swine, sheep, and goats.

The data submitted in support of this supplemental NADA requesting an increase in the tolerance satisfy the requirements of section 512 of the Act and demonstrate that neomycin sulfate (Neomycin 325 Soluble Powder) at a dose of 10 mg/lb/day for 14 days orally in the drinking water, will produce concentrations of residues in the kidneys (target tissue) in cattle, swine, sheep, and goats which are below the accepted tolerance (7.2 ppm) by the following revised withdrawal periods. The withdrawal period for cattle is 1 day, sheep is 2 days, and swine and goats is 3 days.

Under the Center's supplemental approval policy, this is a Category II change [21 CFR 514.106(b)(2)(x) and (xi)]. The approval of this change, a recalculation of the tolerance, is not expected to have any adverse effect on the safety or effectiveness of this new animal drug. The change in tolerance allows for a decrease in the withdrawal period. Accordingly, this approval did not require a reevaluation of the safety or effectiveness data in the parent application.

Under section 512(c)(2)(F)(iii) of the Federal Food , Drug, and Cosmetic Act (21 U.S.C. 360b(c)(2)(F)(iii)), this approval does not qualify for marketing exclusivity because the application does not contain reports of new clinical or field investigations (other than bioequivalence or residue studies) or new human food safety studies (other than bioequivalence or residue studies) essential to the approval and conducted or sponsored by the applicant.

 

VII. LABELING:

The following labeling is attached.

Facsimile package label for neomycin sulfate - Neomycin 325 Soluble Powder- 3.5 ounces and 50 pound packages.

Copies of these 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.