Approval Date: June 29, 1998
I. GENERAL INFORMATION:
Hoechst Roussel Vet
30 Independence Blvd.
P.O. Box 4915
Warren, NJ 07059
Over the Counter (OTC)
Effect of Supplement:
provides for the removal of the caution statement "Not for Use in Animals Intended for Breeding" in feedlot and pasture cattle, and the addition of dairy and beef replacement heifers to the indications for use in pasture cattle.
Effect of Action:
21 CFR 558.95 provides for the use of bambermycins in complete feeds for increased rate of weight gain and improved feed efficiency of cattle fed in confinement for slaughter (feedlot cattle) and for increased rate of weight gain in pasture cattle (slaughter, stocker and feeder cattle).
This supplement provides for the removal of the caution statement "Not for Use in Animals Intended for Breeding" in feedlot and pasture cattle, and the addition of dairy and beef replacement heifers to the indications for use in pasture cattle.
II. INDICATIONS FOR USE
For increased rate of weight gain and improved feed efficiency in cattle fed in confinement for slaughter (feedlot cattle). For increased rate of weight gain in pasture cattle (slaughter, stocker and feeder cattle, and dairy and beef replacement heifers).
III. DOSAGE FORM(S), ROUTE(S) OF ADMINISTRATION, AND RECOMMENDED DOSAGES
GAINPRO ™ medicated premix is supplied as a Type A Medicated Article in 50 lb. multi-walled bags. The Type A Medicated Article contains 10 g bambermycins per pound. The drug is administered orally by mixing the Type A Medicated Article into cattle feeds (Type C Medicated) to provide not less than 10 nor more than 20 mg bambermycins per head per day. The resultant feed containing bambermycins is to be fed continuously throughout the feeding period.
|GAINPRO ™ Dosage:||Use Level For Use||Indications|
Feed continuously in a Type C medicated feed at a rate of 10 to 20 mg bambermycins per head per day.
Feed continuously at a rate of not less than 10 mg nor more than 20 mg of bambermycins per head per day when on pasture. The drug must be contained in at least one pound and not more than ten pounds of supplement [21 CFR 558.95(b)(4)(ii)], or the drug may be fed on a free-choice basis [21 CFR 558.95(b)(4)(iii)] in a formulation that is the subject of an approved FDA 356.
For increased rate of weight gain and improved feed efficiency in cattle fed in confinement for slaughter.
For increased of weight gain in pasture cattle (slaughter, stocker and feeder cattle, and dairy and beef replacement heifers).
Freedom of Information summaries were prepared with applications to NADA 141-034 for the continuous feeding of 10 to 20 mg/head/day of bambermycins to pasture cattle (slaughter, stocker and feeder cattle) that are: (1) hand fed [21 CFR 558.95 (b)(4)(ii), approved 3/4/94]; and (2) free-choice [21 CFR 558.95 (b)(4)(iii), approved 7/9/96] to increase rate of weight gain. The current application is for the use of bambermycins in pasture cattle of like weight and age. Therefore, the efficacy data presented in the cited FOIs are applicable to dairy and beef replacement heifers.
V. ANIMAL SAFETY
Freedom of Information summaries were prepared with applications to NADA 44-759 for the continuous feeding of 10 to 20 mg/head/day of bambermycins to cattle fed in confinement for slaughter [21 CFR 558.95(b)(4)(i), approved 9/21/93]; and pasture cattle (slaughter, stocker and feeder cattle) that are: (1) hand fed [21 CFR 558.95 (b)(4)(ii), approved 3/4/94]; and (2) free-choice fed [21 CFR 558.95 (b)(4)(iii), approved 7/9/96]. The current application provides for the use of 10 to 20 mg/head/day of bambermycins in pasture cattle of like weight and age. Therefore, the target animal safety data in the cited FOIs are applicable to dairy and beef replacement heifers. In 21 CFR Section 558.95 "Required label statements", precludes the use of bambermycins in breeding animals. Data have been provided the Agency encompassing toxicity and reproduction studies in laboratory animals. A reproduction safety study in cattle has been conducted and set forth below.
1. Type of Study: Reproduction safety
2. Study Director:
Mr. Dan Ronning
Colorado Animal Research Enterprises, Inc.
6200 East County Road 56
Fort Collins, CO 80524
3. General Design of Study:a. Purpose of study: To determine the reproductive and health effects of bambermycins when administered daily at 0 and 30 mg/head/day to replacement beef heifers beginning from postweaning growth and development phase and continuing until their first parity calves attain weaning age.b. Test animals: Spring-born (March-April 1994) weaned Angus heifer calves 5 to 7 months of age, approximately 570 pounds at start of treatment.c. Dosage form: Bambermycins was provided in a commercially available GAINPRO ™ premix containing 10 grams bambermycins per pound.d. Dosage used: Bambermycins was administered at the level of 0 and 30 mg/head/day. To assure that the cattle consumed at least the maximum approved dosage level of 20 mg/head/day during the reproduction safety study, the medicated supplement was formulated to provide 30 mg/head/day which represented a 50% overage of the maximum approved feeding rate.e. Route of administration: Bambermycins dose was fed daily in 2 pounds of molasses-sweetened ground corn supplement.f. Preacclimation and acclimation period was 77 days, starting September 26, 1994. Bambermycins treatment and observation period was 677 days; starting December 12, 1994, and ending October 18, 1996. g. Treatments: One hundred-ten heifer calves (55 per treatment group) were allotted randomly by weight to the following treatments: 1. Non-medicated control (0 mg bambermycins/head/day); 2. Medicated (30 mg bambermycins/head/day).h. Pertinent parameters measured:
1. Individual body weights of breeding females were obtained at the following critical time points:
1) Beginning of treatment period (Study Day -4) for selection and assignment to study;
2) Prebreeding (Study Day 141) which represented the start of breeding phase to produce first parity calves;
3) Precalving (Study Day 390) which occurred approximately 3 weeks before the first calving date;
4) Postcalving which occurred 7 days after calving;
5) Second pregnancy check (Study Day 611) which was coincident with pregnancy determination;
6) End of study (Study Day 677) when the youngest calf reached 205 days of age.
2. Interval body weight changes were determined at the following times:
1) Precalving interval which represented the precalving weight minus the prebreeding weight; 2) Calving interval which represented the postcalving weight minus the precalving weight; 3) Lactation interval which represented the end of study weight minus the postcalving weight.
3. Individual body condition scores of breeding females were obtained at several critical time points during the conduct of the study. The scores ranged from 1 (thin) to 9 (fat).
4. Rate of body weight gain of the first parity calves was determined using birth weight and weaning weight at 205 days of age.
5. Individual reproduction observations were obtained for determination of breeding performance.
1) For detection of first estrus, study heifers were observed for signs of estrus twice daily from Study Day 1 until Study Day 141 at which time the heifers were approximately 13 months of age and the first breeding phase of the study began.
2) During the nulliparous period only, the length of interestrus interval was an average of the days to subsequent estruses from the first observed estrus. Estrus observations were performed three times daily during the 25-day artificial insemination phase of the 60-day breeding period. Estrus observations were discontinued once the nulliparous females were exposed to clean-up bulls.
3) To monitor for days to postpartum return to estrus, observations were performed twice daily from two weeks after the first calf was born. The observations were increased to three times daily upon commencement of the breeding phase for conception of second parity calves.
4) To establish nulliparous pregnancy rate, females were examined for pregnancy by rectal palpation of the reproductive tract at approximately 47 days after last exposure to clean-up bulls.
5) Calving rate was calculated as the number of calves born compared with the number of females exposed to breeding.
6) No calving difficulty was calculated as the number of females not having difficulty calving when compared with the total number of females calving. A calving difficulty score was recorded for each parturient female after delivery of each calf, based on the following scale:
1 = No calving difficulty (unassisted or unobserved);2 = Slight difficulty (assisted birth, with or without obstetrical devices;3 = Moderate difficulty (required moderate force with obstetrical devices;4 = Pronounced difficulty (required considerable force with obstetrical devices;5 = Extreme difficulty (required surgery).
7) Weaning rate was calculated as the number of calves reaching 205 days of age when compared with the number of calves born.8) To establish primiparous pregnancy rate, females were examined for pregnancy by rectal palpation of the reproductive tract at approximately 45 days after last exposure to clean-up bulls and again study end.
|Parameter||Bambermycins (mg/head/day)- 0||Bambermycins (mg/head/day)- 30|
Body weights: 1
Beginning treatment period
Second pregnancy check
End of study
Interval body weight changes: 1
Body condition scores: 7
Beginning treatment period
Second pregnancy check
End of study
Calf performance: 1
Ending weight, 205 days
Average daily gain, 205 days
Days to first estrus
Length of interestrus interval 8
Postpartum return to estrus 8
Nulliparous pregnancy rate 9
Calving rate 9
No difficulty calving 9
Weaning rate 9
Primiparous pregnancy rate 9
1 pounds; 2 3-12 weeks prior to anticipated calving; 3 7 days after calving; 4 precalving wt. - prebreeding wt.; 5 postcalving wt. - precalving wt.; 6 end of study wt. - postcalving wt.; 7 Score: 1 = thin, 9 =fat; 8 days; 9 percent; * (P=0.0144).
5. Conclusion: No significant effects were observed for any of the parameters measured except for postpartum return to estrus. The number of days for return to estrus following parturition were significantly reduced in the medicated treatment group. Therefore, bambermycins did not adversely effect reproductive function or performance when fed at 30 mg/head/day.
VI. HUMAN FOOD SAFETY:
A Freedom of Information summary was prepared with the original application to NADA 44-759, approved 9/21/93, providing for the use of bambermycins in complete feeds for cattle in confinement at the rate of 10 to 20 mg/head/day as detailed in 21 CFR 558.95. The application was approved for the use of bambermycins in cattle fed in confinement for slaughter at a dose of 10 to 20 mg/head/day without a withdrawal period, tolerance, or regulatory methods for tissue residues. The residue study for the feedlot approval was done in confined cattle at a dose of 400 mg/head/day. No additional toxicology or residue testing were required to support the original pasture cattle approval [21 CFR 558.95(b)(4)(ii), approved 3/4/94]. The previous FOI covers toxicity, safe concentrations of residues and total residues aspects for the use of bambermycins in nonconfined cattle. Because the dose in the residue study was 20 times the dose to be used in confined and nonconfined cattle, there was no concern that the differences in diet and dosing method between confined and nonconfined cattle could cause residues of toxicological concern to be present in tissues of nonconfined cattle. Therefore, bambermycins was approved for use in nonconfined cattle at a dose of 10 to 20 mg/head/day without a withdrawal period, tolerance, or regulatory methods for tissue residues.
VII. AGENCY CONCLUSIONS:
Under the Center’s supplemental approval policy (21 CFR 514.106 (b)(2)), this is a Category II change. This action did not require a reevaluation of the safety and effectiveness data in the parent applications (NADA 44-759, NADA 141-034) for the removal of the caution statement "Not for Use in Animals Intended for Breeding" in feedlot and pasture cattle, and the addition of dairy and beef replacement heifers to the indications for use in pasture cattle.This NADA satisfies the requirements of section 512(b) of the Federal Food, Drug and Cosmetic Act, and demonstrates that bambermycins (GAINPRO ™ ) when used under the proposed conditions of use is safe and effective for the labeled indications.
Under the Center's supplemental approval policy (21 CFR 514.106(b)(2)), this is a Category II change. However, this action did not require a reevaluation of the safety and effectiveness data in the parent application.
VIII. LABELING (Attached)
GAINPRO ™ -10 (Type A Medicated Article)
Blue Bird Liquid Cattle Supplement - Type B Medicated Feed
Blue Bird Cattle - Type C Medicated Feed
Blue Bird Supplemental Pasture Cattle Feed - Type B Medicated Feed
Blue Bird Supplemental Pasture Cattle Feed - Type C Medicated Feed
Blue Bird Ruminant Free-Choice - Type C Medicated Feed
Vigortone GP Grazer - Type C Free-Choice Medicated Feed
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