03-23891. Implantation or Injectable Dosage Form New Animal Drugs; Oxytetracycline Injection

AGENCY:

Food and Drug Administration, HHS.

ACTION:

Final rule.

SUMMARY:

The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a hybrid new animal drug application (NADA) filed by Norbrook Laboratories, Ltd. The NADA provides for the prescription and over-the-counter use of a 300 milligram per milliliter (mg/mL) oxytetracycline injectable solution for the treatment of various bacterial diseases of cattle and swine, and for the control of respiratory disease in cattle at high risk of developing bovine respiratory disease (BRD).

DATES:

This rule is effective September 19, 2003.

FOR FURTHER INFORMATION CONTACT:

Joan C. Gotthardt, Center for Veterinary Medicine (HFV-130), Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 301-827-7571, e-mail: [e-mail].

SUPPLEMENTARY INFORMATION:

Norbrook Laboratories, Ltd., Station Works, Newry, BT35 6JP, Northern Ireland, filed NADA 141-143, a hybrid application that provides for veterinary prescription use of TETRADURE 300 (oxytetracycline) Injection and over-the-counter use of Oxytetracycline Injection 300 mg/mL for the treatment of various bacterial diseases of cattle and swine. Norbrook Laboratories' TETRADURE 300 Injection and Oxytetracycline Injection 300 mg/mL are approved as generic copies of Pfizer's LIQUAMYCIN LA-200, approved under NADA 113-232. TETRADURE 300 Injection is also indicated for the control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia (Pasteurella) haemolytica. The application is approved as of July 25, 2003, and the regulations in part 522 (21 CFR part 522) are amended to reflect the approval by revising § 522.1660 and by adding § 522.1660b. The basis of approval is discussed in the freedom of information summary.

NADA 141-143 is a hybrid application as defined in the Center for Veterinary Medicine's Seventh Generic Animal Drug Policy Letter, dated March 20, 1991. The data submitted in support of this hybrid NADA satisfy the requirements of section 512(b)(1) and (b)(2) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 360b(b)(1) and (b)(2)) and 21 CFR part 514 of the regulations. This hybrid application relies on the approval of the pioneer animal drug product, a 200 mg/mL solution of oxytetracycline, to the extent that such reliance is allowed under section 512(n) of the act, to establish the safety and effectiveness of the active ingredient, oxytetracycline. This is the section 512(b)(2) portion of the hybrid application. It also contains data to support a change from the pioneer product formulation to a generic product of greater concentration, 300 mg/mL; to support use in cattle at a higher dosage of 13.6 mg/lb bodyweight; and to support use for the control of respiratory disease in cattle at high risk of developing BRD. These are the section 512(b)(1) portions of the hybrid application.

In accordance with the freedom of information provisions of 21 CFR part 20 and 21 CFR 514.11(e)(2)(ii), a summary of safety and effectiveness data and information submitted to support approval of this application may be seen in the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852, between 9 a.m. and 4 p.m., Monday through Friday.

Under section 512(c)(2)(F)(ii) of the act (21 U.S.C. 360b(c)(2)(F)(ii)), this approval qualifies for 3 years of marketing exclusivity beginning July 25, 2003. This marketing exclusivity applies only to the increase in formulation concentration to 300 mg/mL, to the veterinary prescription use of the product in cattle at dose ranges of 9 to 13.6 mg/lb bodyweight, and for the control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia (Pasteurella) haemolytica for which new data were required.

The agency has determined under 21 CFR 25.33(a)(1) and (d)(5) that this action is of a type that does not individually or cumulatively have a significant effect on the human environment. Therefore, neither an environmental assessment nor an environmental impact statement is required.

This rule does not meet the definition of “rule” in 5 U.S.C. 804(3)(A) because it is a rule of “particular applicability.” Therefore, it is not subject to the congressional review requirements in 5 U.S.C. 801-808.

List of Subject in 21 CFR Part 522

• Animal drugs

Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs and redelegated to the Center for Veterinary Medicine, 21 CFR part 522 is amended as follows:

PART 522—IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS

1. The authority citation for 21 CFR part 522 continues to read as follows:

Authority: 21 U.S.C. 360b.

2. Section 522.1660 is amended by revising the section heading to read as follows:

§ 522.1660

Oxytetracycline injection, 200 milligram/milliliter.

3. Section 522.1660a is added to read as follows:

§ 522.1660a

Oxytetracycline injection, 300 milligram/milliliter.

(a) Specifications. Each milliliter (mL) of solution contains 300 milligrams (mg) oxytetracycline base.

(b) Sponsor. See No. 055529 in § 510.600(c) of this chapter.

(c) Related tolerances. See § 556.500 of this chapter.

(d) Special considerations. When labeled for use as in paragraph (e)(1)(i)(D) or (e)(1)(i)(E) of this section, labeling shall also bear the following: “Federal law restricts this drug to use by or on the order of a licensed veterinarian.”.

(e) Conditions of use—(1) Beef cattle, nonlactating dairy cattle, and calves including preruminating (veal) calves—(i) Amounts and indications for use—(A) 3 to 5 mg per pound of bodyweight (mg/lb BW) per day (/day) intramuscularly, subcutaneously, or intravenously for treatment of pneumonia and shipping fever complex associated with Pasteurella spp. and Haemophilus spp., foot-rot and diphtheria caused by Fusobacterium necrophorum, bacterial enteritis (scours) caused by Escherichia coli, wooden tongue caused by Actinobacillus lignieresii, leptospirosis caused by Leptospira pomona, wound infections and acute metritis caused by Staphylococcus spp. and Streptococcus spp.

(B) 5 mg/lb BW/day intramuscularly, subcutaneously, or intravenously for treatment of severe foot-rot, and advanced cases of other indicated diseases.

(C) 9 mg/lb BW intramuscularly or subcutaneously as single dosage where retreatment of calves and yearlings for bacterial pneumonia is impractical or for treatment of infectious bovine keratoconjunctivitis (pinkeye) caused by Moraxella bovis.

(D) 9 to 13.6 mg/lb BW intramuscularly or subcutaneously as single dosage where retreatment of calves and yearlings for bacterial pneumonia is impractical or for treatment of infectious bovine keratoconjunctivitis (pinkeye) caused by Moraxella bovis.

(E) 13.6 mg/lb BW intramuscularly or subcutaneously as a single dosage for control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia (Pasteurella) haemolytica.

(ii) Limitations. Treatment should be continued 24 to 48 hours following remission of disease signs, however, not to exceed a total of four consecutive days. Do not inject more than 10 mL per site in adult cattle, reducing the volume according to age and body size to 1 to 2 mL in small calves. Exceeding the highest recommended level of drug/lb BW/day, administering more than the recommended number of treatments, and/or exceeding 10 mL intramuscularly or subcutaneously per injection site may result in antibiotic residues beyond the withdrawal time. Rapid intravenous administration in cattle may result in animal collapse. Oxytetracycline should be administered intravenously slowly over a period of at least 5 minutes. Discontinue treatment at least 28 days prior to slaughter. Not for use in lactating dairy animals.

(2) Swine—(i) Amount. 3 to 5 mg/lb BW/day; 9 mg/lb BW as a single dosage where retreatment for pneumonia is impractical. Sows: Administer once 3 mg/lb BW, approximately 8 hours before farrowing or immediately after completion of farrowing.

(ii) Indications for use. For treatment of bacterial enteritis (scours, colibacillosis) caused by Escherichia coli, pneumonia caused by Pasteurella multocida, and leptospirosis caused by Leptospira pomona. Sows: as an aid in control of infectious enteritis (baby pig scours, colibacillosis) in suckling pigs caused by E. coli.

(iii) Limitations. Administer intramuscularly. Treatment should be continued 24 to 48 hours beyond remission of disease signs, however, not to exceed a total of 4 consecutive days. Exceeding the highest recommended level of drug/lb BW/day, administering more than the recommended number of treatments, and/or exceeding 5 mL intramuscularly per injection site may result in antibiotic residues beyond the withdrawal time. Discontinue treatment at least 28 days prior to slaughter.

Dated: August 27, 2003.

Stephen F. Sundlof,

Director, Center for Veterinary Medicine.