Approval Date: September 21, 1998
Freedom of Information Summary
NADA 200-259
I. GENERAL INFORMATION:
NADA 200-259 Sponsor: Alpharma, Inc.
Generic Name: Chlortetracycline, salinomycin sodium, roxarsone Trade Name: ChlorMax™, Sacox®, 3-Nitro® Marketing Status: Dosage Form: Type A Medicated Articles
Note: This ANADA provides for the combined use of three approved Type A Medicated Articles (ChlorMax chlortetracycline, Sacox salinomycin sodium, and 3-Nitro roxarsone) in Type C Medicated Feeds, rather than a premix incorporating all three of these compounds.
How Supplied:
Chlortetracycline: 5, 10 or 50-lb bags
Salinomycin sodium: 50-lb bags
Roxarsone: 50-lb bagsHow Dispensed: OTC
Label Claim of Amount of Active Ingredient(s):
Chlortetracycline- 50, 65, and 70 g/lb in Type A Medicated Articles
Salinomycin- 30 and 60 g/lb in Type A Medicated Articles
Roxarsone- 10, 20, and 50% (45.4, 90.8, 227 g/lb) in Type A Medicated ArticlesRoute of Administration: These drugs are administered orally by adding the Type A Medicated Articles to complete broiler feed (Type C Medicated Feed)
Recommended Dosage:
Chlortetracycline, 500 grams per ton (.055%)
Salinomycin, 40 to 60 grams per ton (.0044-.0066%)
Roxarsone, 45.4 grams per ton (.005%)
Species: Broiler ChickensIndications for use: For the prevention of coccidiosis in broiler chickens caused by Eimeria tenella, E. necatrix, E. acervulina, E. maxima, E. brunetti, and E. mivati, including some field strains of E. tenella that are more susceptible to roxarsone combined with salinomycin than salinomycin alone, and as an aid in the reduction of mortality due to E. coli infections susceptible to such treatments.
Equivalent Product:
ChlorMax
Chlortetracycline
NADA 46-699
Alpharma Inc.Pioneer Product/ Listed Product:
Aureomycin
Chlortetracycline
NADA 48-761
Roche Vitamins, Inc.Sacox
Salinomycin sodium
NADA 200-075
Roche Vitamins, Inc.
3-Nitro
Roxarsone (3-nitro-4-hydroxyphenylarsonic acid)
NADA 7-891
Alpharma Inc.AureomycinÒ -SacoxÒ -3-NitroÒ
Chlortetracycline/Salinomycin/Roxarsone
NADA 200-091
Roche Vitamins, Inc.II. EFFECTIVENESS AND TARGET ANIMAL SAFETY:
ChlorMax and Aureomycin were both found to comply with the results of NAS/NRC and DESI evaluation for effectiveness as published in the Federal Register (61 FR 35949-35958; July 9, 1996). These products approved under the DESI process were found to be equivalent at the codified level 21 CFR § 558.128(d)(1)(viii) of 500 g/ton for chickens (61 FR 35949-35958; July 9, 1996).
The Center’s fourth policy letter dated November 2, 1989, as published in the Federal Register on January 30, 1990 (55 FR 3107), states that the approval of a new generic Type A Medicated Article entitles the sponsor to approval of all the feed combinations for which the pioneer is approved. Bioequivalence and tissue residue studies are not required for approval of the feed use combinations.
Chlortetracycline (ChlorMax-Alpharma) is codified under 21 CFR § 558.128(a)(3). Chlortetracycline (Aureomycin-Roche) is codified under 21 CFR § 558.128(a)(1). Salinomycin sodium is codified under 21 CFR § 558.550. Roxarsone is codified under 21 CFR 558.530. The combination is codified under 21 CFR § 558.550(a)(2) and (d)(1)(xv).
III. HUMAN SAFETY:
- Tolerances and Safe Concentration of Residues
The tolerances established for the pioneer product apply to the generic product.
Tolerances for the sum of residues of the tetracycline, including chlortetracycline in tissues of chickens, are as follows: (a) 2 parts per million (ppm) in muscle; (b) 6 ppm in liver; (c) 12 ppm in fat (21 CFR § 556.150).
Under NADA 128-686 a tolerance for salinomycin was not required because residue levels in all three broiler tissues (muscle, liver, and skin/fat) were significantly below the established safe concentration.
Tolerances of arsenic (from roxarsone) are established at 0.5 ppm in uncooked muscle tissue and 2 ppm in uncooked edible by-products of broiler chickens with liver as the target tissue (21 CFR § 556.60).
b. Withdrawal Time
Based on the information in 21 CFR § 558.550(d)(1)(xv), a five-day withdrawal time is required for the combination of chlortetracycline, salinomycin and roxarsone.
c. Regulatory Methods for Residues
The regulatory analytical method for the determination of residue of chlortetracycline 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, National Center for Antibiotic and Insulin Analysis, FDA, Washington, DC 20204.
Under NADA 128-686 a regulatory method for salinomycin was not required because residue levels in all three broiler tissues (muscle, liver and skin/fat) were significantly below the established safe concentration for total residues.
The analytical method for the determination of roxarsone in tissues is a spectrophotometric method. The method, entitled "Arsenic (Total) Residues in Animal Tissues, Spectrophotometric Method," is published in the Official Methods of Analysis of AOAC International, 16th edition.
IV. AGENCY CONCLUSIONS:
This ANADA submitted under section 512(b) of the Federal Food, Drug and Cosmetic Act satisfies the requirements of section 512 (n) of the act and demonstrates that the combination of chlortetracycline, roxarsone and salinomycin, when used under its proposed conditions of use, is safe and effective for its labeled indications.
Attached labeling: Type C Medicated Feed (Blue Bird) - Generic
cc:Courtesy copy for the sponsor
HFV-199, ANADA 200-259, A0000 Orig.
HFV-2 (Special Mailing List)
HFV-12 (FOI Staff)
HFV-102 (GADQC Reserve Copy)
HFV-102 Green Book (NTurner)
HFA-305 (Dockets Management Branch)
HFR-MA350 (New Jersey NWJ-DO)
SHansard:HFV-102:301-827-0211:8/26/98ec: CVM Records\ONADE\\A200259\A0000foi.sum