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U.S. Department of Health and Human Services

Animal & Veterinary

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NADA 141-100 DECCOX®,BMD®, 3-NITRO® - original approval

Approval Date: June 2, 1998

I. GENERAL INFORMATION:

NADA141-100
Sponsor:Alpharma, Inc.
One Executive Drive
Fort Lee, NJ 07024
Generic Name:Decoquinate, bacitracin methylene disalicylate, roxarsone
Trade Name:DECCOX®,BMD®, 3-NITRO®
Marketing Status:Over the Counter (OTC)

 

II. INDICATIONS FOR USE:

For the prevention of coccidiosis caused by Eimeria tenella, E. necatrix, E. mivati, E. acervulina, E. maxima, and E. brunetti, as an aid in the prevention of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin, and for increased rate of weight gain, improved feed efficiency, and improved pigmentation in broiler chickens.

 

III. DOSAGE

A.DOSAGE FORMThis original NADA provides for the combined use of these three Type A medicated articles, bacitracin methylene disalicylate as per 21 CFR § 558.76 (d)(1)(vi), decoquinate as per 21 CFR § 558.195 (d), and roxarsone as per 21 CFR § 558.530 (d)(1)(i). Bacitracin methylene disalicylate is supplied as Type A medicated articles in concentrations of 10, 25, 30, 40, 50, 60, and 75 grams bacitracin activity per pound. Decoquinate is supplied as a Type A medicated article containing 6 percent decoquinate. Roxarsone is supplied as Type A medicated articles in concentrations of 45.4, 90, and 227 grams of roxarsone activity per pound.
B.ROUTE OF ADMINISTRATIONOral, via the feed.
C.RECOMMENDED DOSAGES: 
 Decoquinate:Decoquinate is added to broiler chicken feed at a concentration of 27.2 g/ton for the prevention of coccidiosis caused by Eimeria tenella, E. necatrix, E. mivati, E. acervulina, E. maxima, and E. brunetti.
 Bacitracin methylene disalicylate:Bacitracin methylene disalicylate is added to broiler chicken feed at a concentration of 50 g/ton as an aid in the prevention of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin.
 Roxarsone:Roxarsone is added to broiler chicken feed at concentrations from 22.7 to 45.4 g/ton for increased rate of weight gain, improved feed efficiency, and improved pigmentation. Withdraw 5 days before slaughter. Do not feed to laying chickens. Use as the sole source of organic arsenic. Not for use in feeds for breeder chickens. Poultry should have access to drinking water at all times. Drug overdosage or lack of water intake may result in leg weakness or paralysis.

 

IV. EFFECTIVENESS:

In accordance with the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Animal Drug Availability Act of 1996, if the active ingredients or animal drugs intended for use in combination in animal feed have previously been separately approved for the particular uses and conditions of use for which they are intended for use in combination, FDA will not refuse to approve an NADA for the combination on effectiveness grounds unless the Agency finds that the NADA fails to demonstrate that 1) there is substantial evidence to demonstrate that any active ingredient or animal drug intended only for the same use as another active ingredient or animal drug in the combination makes a contribution to the labeled effectiveness, 2) each of the active ingredients or animal drugs intended for at least one use that is different from all other active ingredients or animal drugs used in the combination provides appropriate concurrent use for the intended target population, or 3) where the combination contains more than one nontopical antibacterial active ingredient or animal drug, there is substantial evidence that each of the nontopical antibacterial active ingredients or animal drugs makes a contribution to the labeled effectiveness (21 USC §512(d)(4)(D)).

Decoquinate, as provided by Alpharma Inc., has previously been separately approved for use in broiler chicken feed for the prevention of coccidiosis caused by Eimeria tenella, E. necatrix, E. mivati, E acervulina, E. maxima, and E. brunetti (21 CFR §558.195 (d)). Bacitracin methylene disalicylate, as provided by Alpharma Inc., has previously been separately approved for use in broiler chicken feed as an aid in the prevention of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin (21 CFR §558.76 (d)(1)(vi)). Roxarsone, as provided by Alpharma Inc., has previously been separately approved for use in growing chicken feed for increased rate of weight gain, improved feed efficiency and improved pigmentation (21 CFR §558.530 (d)(1)). Effectiveness for each drug, decoquinate, bacitracin methylene disalicylate, and roxarsone, when administered alone in accordance with its approved uses and conditions of use, is demonstrated in Alpharma Inc.’s approved NADAs 39-417, 46-592, and 7-891, respectively.

Because decoquinate, bacitracin methylene disalicylate and roxarsone each have at least one use that is different from all other animal drugs used in the combination, the NADA must also demonstrate that decoquinate plus bacitracin methylene disalicylate plus roxarsone provide appropriate concurrent use for the intended target population. The use of decoquinate plus bacitracin methylene disalicylate plus roxarsone provides appropriate concurrent use because these drugs are intended to treat different conditions (decoquinate, coccidiosis; bacitracin methylene disalicylate, necrotic enteritis; roxarsone, pigmentation problems) likely to occur simultaneously with sufficient frequency in broiler chickens. There is no more than one nontopical antibacterial (bacitracin methylene disalicylate) contained in this combination animal drug intended for use in Type C medicated feed. Decoquinate is not considered to be an antibacterial animal drug for use in broiler chickens for the purposes of §512(d)(4) of the FFDCA, because decoquinate is approved only for prevention of a protozoal disease in broiler chickens. Roxarsone is not considered to be an antibacterial animal drug for use in broiler chickens for the purposes of §512(d)(4) of the FFDCA, because roxarsone is not approved for use in broiler chickens for the diagnosis, cure, mitigation, treatment or prevention of bacterial disease and is not approved for any other use the Center for Veterinary Medicine deems attributable to its antibacterial properties.

 

V. ANIMAL SAFETY

In accordance with the Federal Food, Drug, and Cosmetic Act (FFDCA), as amended by the Animal Drug Availability Act of 1996, if the active ingredients or animal drugs intended for use in combination have previously been separately approved for the particular uses and conditions of use for which they are intended for use in combination, FDA will not refuse to approve an NADA for the combination on target animal safety grounds unless there is a substantiated scientific issue specific to an active ingredient or animal drug used in the combination or a scientific issue is raised by target animal observations contained in studies submitted to the NADA for the combination and FDA finds that the application fails to establish that such combination active ingredient or animal drug is safe for the target animal.

Decoquinate, as provided by Alpharma Inc., has previously been separately approved for use in broiler chicken feed for the prevention of coccidiosis caused by Eimeria tenella, E. necatrix, E. mivati, E acervulina, E. maxima, and E. brunetti (21 CFR §558.195 (d)). Bacitracin methylene disalicylate, as provided by Alpharma Inc., has previously been separately approved for use in broiler chicken feed as an aid in the prevention of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin (21 CFR §558.76 (d)(1)(vi)). Roxarsone, as provided by Alpharma Inc., has previously been separately approved for use in growing chicken feed for increased rate of weight gain, improved feed efficiency and improved pigmentation (21 CFR §558.530 (d)(1)). Target animal safety for each drug, decoquinate, bacitracin methylene disalicylate, and roxarsone, when administered alone in accordance with its approved uses and conditions of use, is demonstrated in Alpharma Inc.’s approved NADAs 39-417, 46-592, and 7-891, respectively. The Agency has found no substantiated scientific issue relating to the target animal safety of decoquinate, bacitracin methylene disalicylate, or roxarsone when used in combination under this NADA and no scientific issue has been raised by target animal observations submitted as part of the NADA for this combination. Thus, pursuant to FFDCA, as amended by the Animal Drug Availability Act of 1996, no specific target animal safety study(ies) are required for approval of NADA 141-100.

 

VI. HUMAN SAFETY:

A. Tolerances

Tolerances for residues of decoquinate in uncooked edible tissues of chickens at 2 ppm in tissues other than skeletal muscle and 1 ppm in skeletal muscle in 21 CFR §556.170. Tolerances for residues of bacitracin in uncooked edible tissues of chickens are established at 0.5 ppm (0.02 unit/g) in 21 CFR §556.70. Tolerances for residues of arsenic from roxarsone in chickens are established at 0.5 ppm in uncooked muscle tissue, 2 ppm in uncooked edible by-products and 0.5 ppm in eggs (21 CFR §556.60).

B. Residue Data

Cobb broiler chickens were fed medicated feed containing 0.003% decoquinate, roxarsone at 45 g/ton, penicillin at 50 g/ton as procaine penicillin, and bacitracin at 50 g/ton as zinc bacitracin and were raised in floor pens for 61 days. All tissues of chickens killed at zero withdrawal of medication contained less than the established tolerance for decoquinate [muscle (range 0.22-0.40 ppm), skin-fat (range 0.88-1.18 ppm), liver (range 0.76-1.04 ppm), and kidney (0.92-0.86 ppm)]. All tissues of chickens killed after a five day withdrawal of medication contained less than the established tolerance for arsenic [muscle (<0.1 ppm), skin-fat (range <0.1-0.1 ppm), liver (range 0.3-1.0 ppm), and kidney (0.1 ppm)]. There were no positive findings for bacitracin in any of the edible tissues taken at zero withdrawal. This study also provided data to show assay noninterference among decoquinate, bacitracin, and roxarsone.

Substantial scientific information provided by Alpharma Inc. shows that the likelihood of other drugs in combination with bacitracin methylene disalicylate altering the bacitracin residues in tissues of animals is extremely improbable. There are no longer requirements for conducting studies demonstrating tissue residue and analytical method non-interference for Alpharma Inc.’s bacitracin methylene disalicylate where each is included at already approved levels - such is the case for this combination. Data generated over many years show that residues of bacitracin methylene disalicylate are not detected, whether the drugs are used alone or in combination. Studies using radiolabeled drugs confirm that bacitracin is recovered mostly with the feces, with only small amounts of radioactivity associated with urine.

The available residue chemistry information supports the assignment of a five day withdrawal period for broiler chickens fed the combination of decoquinate (27.2 g/ton), bacitracin methylene disalicylate (50 g/ton) and roxarsone (22.7-45.4 g/ton).

C. Regulatory Methods for Residues

A fluorometric method is used to assay tissues for decoquinate. The method entitled "AOAC Official Method 973.79, Decoquinate Residues in Animal Tissues, Fluorometric Method" is published in the AOAC Official Methods of Analysis (1995), Chapter 23, p. 4.

A microbiological method is used to assay tissues for bacitracin residues. The method entitled "Modified Microbiological Method for Determination of Bacitracin in Tissues" is on display in the Food and Drug Administration’s Freedom of Information Publication Room, 5600 Fisher’s Lane, Rockville, MD 20857.

A spectrophotometric method is used to assay tissues for roxarsone residues. The method entitled "Arsenic (Total) Residues in Animal Tissues, Spectrophotometric Method" is published in the AOAC, 15th Edition 973.78, page 626.

 

VII. AGENCY CONCLUSIONS

The data submitted in support of this NADA comply with the requirements of Section 512 of the FFDCA and demonstrate that decoquinate (27.2 g/ton) plus bacitracin methylene disalicylate (50 g/ton) plus roxarsone (22.7 to 45.4 g/ton) are safe and effective for the claims indicated in Section II of this FOI summary.

Pursuant to 21 CFR §514.106 (b)(2)(vi), this combination NADA approval is regarded as a Category II supplemental change which did not require a reevaluation of safety and efficacy data in the parent NADAs. The drugs are to be fed in Type C medicated feeds, in accordance with Section II and III of the FOI Summary and the Blue Bird labeling that is attached to this document.

Residue data show that decoquinate is within the established safe concentrations in edible chicken tissues [muscle (range 0.22-0.40 ppm), skin-fat (range 0.88-1.18 ppm), liver (range 0.76-1.04 ppm), and kidney (0.92-0.86 ppm)]. Residue data show that roxarsone (as residues of arsenic in edible tissues of chickens) is well below the tolerances of 0.5 ppm arsenic in muscle and 2.0 ppm arsenic in edible chicken tissues. Bacitracin was undetectable in any of the edible tissues assayed.

Under section 512(c)(2)(F)(ii) of the FFDCA, this approval for food producing animals does not qualify for marketing exclusivity beginning on the date of approval because the application does not contain substantial evidence of the effectiveness of the drugs involved, any studies of animal safety, or, in the case of food producing animals, human food safety studies (other than bioequivalence or residue studies) required for the approval of the application and conducted or sponsored by the applicant.

 

VIII. LABELING (Attached)

  1. Type C medicated Feed (Blue Bird).

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

Freedom of Information Office
Center for Veterinary Medicine, FDA
7500 Standish Place
Rockville, MD 20855