ANADA 200-172 Nicarmix 25®, 3-Nitro® - original approval

Approval Date: March 5, 1996

I. GENERAL INFORMATION

1. Established Name:
   • Nicarbazin
   • Roxarsone (3-nitro-4-hydroxyphenylarsonic acid)
2. Trade/Proprietary Name:
   • Nicarmix 25®
   • 3-Nitro®

3. Dosage Form: Type A medicated articles

   NOTE: This ANADA provides for the combined use of two approved Type A medicated articles (Nicarmix 25® and 3-Nitro®) in Type C medicated feeds, rather than a premix incorporating all of these compounds.

4. How Supplied:
   • Nicarbazin: 50-lb bags
   • Roxarsone: 50-lb bags
5. How Dispensed: OTC
6. Label Claim of Amount of Active Ingredient(s):
   • Nicarbazin: 113.5 g/lb of Type A medicated article
   • Roxarsone: 10, 20, 50 and 80% roxarsone in Type A medicated article
7. Route of Administration: These drugs are administered orally by adding the Type A medicated articles to complete broiler feed (Type C medicated feed).
8. Labeled Dosage:
   • Nicarbazin: 113.5 g/ton
   • Roxarsone: 22.7 g/ton
9. Species: Broiler Chickens
10. Indications for Use: As an aid in preventing outbreaks of cecal (Eimeria tenella ) and intestinal (E. acervulina, E. maxima, E. necatrix, and E. brunetti ) coccidiosis and for increased rate of weight gain in broiler chickens.
11. Generic Product:
    • Nicarmix 25®
      Nicarbazin
      ANADA 200-027
      Planalquimica Industrial Ltda.
12. Pioneer Product/ "Listed" Product:
    • NICARB®
      nicarbazin
      NADA 009-476
      Merck Research Laboratories
    • 3-Nitro®
      Roxarsone (3-nitro-4-hydroxyphenylarsonic acid);
      NADA 7-891
      ALPharma
    • NICARB®/3-Nitro®
      Nicarbazin/Roxarsone
      NADA 108-115
      Merck Research Laboratories

II. TARGET ANIMAL SAFETY AND DRUG EFFECTIVENESS

In accordance with the Center's policy letter dated November 2, 1989, as published in the Federal Register on January 30, 1990 (55 FR 3107), following the approval of an ANADA for a generic Type A medicated article (ANADA 200-027; generic nicarbazin), Planalquimica Industrial Ltda. is entitled to the approval of generic nicarbazin in combination with roxarsone. Bioequivalence studies are not required for the approval of this generic combination (Type C medicated feed). Nicarbazin is codified under 21 CFR §558.366. Roxarsone (3-Nitro®) is codified under 21 CFR §558.530. The combination of nicarbazin and roxarsone is codified under 21 CFR §558.366(c).

III. HUMAN FOOD SAFETY

Tolerances for Marker Residues
The tolerance established for the pioneer product applies to the generic product.

A tolerance of 4.0 ppm is established for residues of nicarbazin in uncooked chicken muscle, liver, skin, and kidney under 21 CFR §556.445.

Tolerances for total residues of arsenic (calculated as As) from roxarsone are established for chicken tissues as 0.5 ppm in uncooked muscle and 2 ppm in uncooked edible by-products under 21 CFR §556.60.

Withdrawal Time
A 5-day withdrawal time is established for chickens receiving the combination of nicarbazin and roxarsone under 21 CFR §558.366. A tissue residue depletion study submitted under ANADA 200-027 supports the use of the pioneer drug withdrawal time for the generic nicarbazin product.

Regulatory Method for Residues
The analytical method for the determination of roxarsone in tissues is a spectrophotometric method. The method is titled "Arsenic (Total) Residues in Animal Tissues, Spectrophotometric Method," published in the 14th Edition of AOAC Official Methods of Analysis, Method 41.009, page 777.

The determinative procedure for quantifying nicarbazin residues in chicken tissues is a liquid chromatographic assay with UV detection of 4,4'-dinitrocarbanilide (DNC), the marker residue for nicarbazin. The identity of DNC is confirmed by thermospray liquid chromatography/mass spectrometry. The reference for the regulatory method is: J.L. Lewis, T.D. Macy, and D.A. Garteiz; J. Assoc. Off. Anal. Chem. 72(4): 577-581.

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 nicarbazin and roxarsone, when used under its proposed conditions of use, is safe and effective for its labeled indications.

Attachments:

Facsimile generic labeling and currently approved pioneer labeling are attached, as shown:

1. Blue Bird label for the generic Type C medicated feed for broiler chickens
2. Blue Bird label for the pioneer Type C medicated feed for broiler chickens

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