Approval Date: June 3, 1998
Freedom of Information Summary
NADA 141-085
I. GENERAL INFORMATION:
NADA 141-085 Sponsor: Alpharma, Inc.
One Executive Drive
Fort Lee, New Jersey 07024Generic Name: zoalene, bacitracin methylene disalicylate Trade Name: ZOAMIX®,BMD® Marketing Status: Over the Counter (OTC) II. INDICATIONS FOR USE:
For prevention and control of coccidiosis, and for increased rate of weight gain and improved feed efficiency in growing turkeys.III. DOSAGE
A. DOSAGE FORM This NADA provides for the combined use of these two Type A medicated articles, zoalene as per 21 CFR § 558.680 (c)(1)(iii), bacitracin methylene disalicylate as per 21 CFR § 558.76 (d)(1)(i). Zoalene is supplied as a Type A medicated article in a single concentration of 25 percent zoalene. Bacitracin methylene disalicylate is supplied as a Type A medicated article in concentrations of 10, 25, 30, 40, 50, 60, or 75 grams bacitracin activity per pound. B. ROUTE OF ADMINISTRATION Oral, via the feed. C. RECOMMENDED DOSAGES: Zoalene Zoalene is added to growing turkey feed at concentrations from 113.5 to 170.3 g/ton for the prevention and control of coccidiosis. Bacitracin methylene disalicylate Bacitracin methylene disalicylate is added to growing turkey feed at concentrations from 4 to 50 g/ton for increased rate of weight gain and improved feed efficiency. CAUTION:
For turkeys grown for meat purpose only. Not to be fed to laying birds. 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)).Zoalene, as provided by Alpharma Inc., has previously been separately approved for use in growing turkey feed for the prevention and control of coccidiosis (21 CFR §558.680 (c)(1)(iii)). Bacitracin methylene disalicylate, as provided by Alpharma Inc., has previously been separately approved for use in growing turkey feed for increased rate of weight gain and improved feed efficiency (21 CFR §558.76 (d)(1)(i)). Effectiveness for each drug, zoalene and bacitracin methylene disalicylate, when administered alone in accordance with its approved uses and conditions of use, is demonstrated in Alpharma Inc.’s approved NADAs 11-116 and 46-592, respectively. Because zoalene and bacitracin methylene disalicylate each have at least one use that is different from all other animal drugs used in the combination, the NADA must also demonstrate that zoalene plus bacitracin methylene disalicylate provide appropriate concurrent use for the intended target population. The use of zoalene plus bacitracin methylene disalicylate provides appropriate concurrent use because these drugs are intended to treat different conditions (zoalene, coccidiosis; bacitracin methylene disalicylate, performance) likely to occur simultaneously with sufficient frequency in growing turkeys. 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. Zoalene is not considered to be an antibacterial animal drug for use in growing turkeys for the purposes of §512(d)(4) of the FFDCA, because zoalene is approved only for prevention of a protozoal disease in growing turkeys.
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.Zoalene, as provided by Alpharma Inc., has previously been separately approved for use in growing turkey feed for the prevention and control of coccidiosis (21 CFR §558.680 (c)(1)(iii)). Bacitracin methylene disalicylate, as provided by Alpharma Inc., has previously been separately approved for use in growing turkey feed for increased rate of weight gain and improved feed efficiency (21 CFR §558.76 (d)(1)(i)). Target animal safety for each drug, zoalene and bacitracin methylene disalicylate, when administered alone in accordance with its approved uses and conditions of use, is demonstrated in Alpharma Inc.’s approved NADAs 11-116 and 46-592, respectively. The Agency has found no substantiated scientific issue relating to the target animal safety of zoalene or bacitracin methylene disalicylate 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) is (are) required for approval of NADA 141-085.VI. HUMAN SAFETY:
A. Tolerances
Data establishing the safety of bacitracin methylene disalicylate (BMD) and zoalene have been submitted to NADA 46-592 and NADA 11-116, respectively. Tolerances for residues of bacitracin in uncooked edible tissues of turkeys are established at 0.5 ppm (0.02 unit/g) in 21 CFR 556.70. Tolerances for zoalene and its metabolite 3-amino-5-nitro-o-toluamide (ANOT) are established at 3 ppm in uncooked muscle and liver in 21 CFR 556.770.
B. Residue Data
Three-week old turkeys were fed zoalene (at 170.3 g/ton) in combination with bacitracin zinc (at 49.5 g/ton) for 9.5 weeks. Analyses of muscle samples from birds killed at zero withdrawal showed an average of 0.5 ppm zoalene (range 0.36 to 0.66 ppm) and 0.6 ppm ANOT (3-amino-5-nitro-o-toluamide, range 0.50 to 0.68 ppm). In liver samples, no zoalene was found while ANOT averaged 0.9 ppm (range 0.87 to 0.88 ppm). The observed residues were well below the tolerances of 3 ppm in liver and muscle for zoalene and ANOT at zero withdrawal.
On the basis of substantial scientific information showing 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 noninterference for bacitracin methylene disalicylate where it 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 drug is used alone or in combination. Studies using radiolabeled drug confirm that bacitracin is recovered mostly with the feces, with only small amounts of radioactivity associated with the urine.
The available residue chemistry information supports the assignment of a zero withdrawal period for growing turkeys fed the combination of bacitracin methylene disalicylate (4 to 50 g/ton) and zoalene (113.5 to 170.3 g/ton).VII. AGENCY CONCLUSIONS:C. Regulatory Methods for Residues
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 zoalene residues. The method entitled "Zoalene Residues in Animal Tissues, Spectrophotometric Method" is published in the AOAC, 15th Edition 973.78, page 635.
A spectrophotometric method is used to assay tissues for ANOT residues. The method entitled "ANOT Residues in Animal Tissues, Spectrophotometric Method" is published in the AOAC, 15th Edition 961.23, page 625.
The data submitted in support of this NADA comply with the requirements of Section 512 of the FFDCA and demonstrate that zoalene (113.5 to 170.3 g/ton) plus bacitracin methylene disalicylate (4 to 50 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 zoalene and its metabolite (ANOT) are within the established safe concentrations (3 ppm) in edible turkey tissues [liver (zoalene - 0; ANOT - 0.87-0.88 ppm); muscle (zoalene - 0.36-0.66 ppm; ANOT - 0.50-0.68 ppm)].VIII. LABELING (Attached)
Type C medicated Feed (Blue Bird)
Copies of applicable labels may be obtained by writing to the:
Freedom of Information Office
Center for Veterinary Medicine, FDA
7500 Standish Place
Rockville, MD 20855