Approval Date: April 18, 1989
I. GENERAL INFORMATION:
Veterinary Research and Development, Inc.
P.O. Box 1299
Truckee, CA 95734
copper disodium edetate
II. INDICATIONS FOR USE:
For use in beef cattle and beef calves to prevent copper deficiency alone on or in association with molybdenum toxicity.
Injection, 60 mg Cu per ml.
ROUTE OF ADMINISTRATION
Subcutaneously in the neck area.
Nursing calves-1 ml
Calves over 300 pounds-2 ml
Older cattle-2 ml
The efficacy of Copper glycinate has been established by the National Academy of Sciences and the National Research Council (NAS/NRC) which evaluated the drug to be effective in the prevention of copper deficiency alone or in association with molybdenum toxicity in beef cattle.
The Food and Drug Administration concurred with the findings of the NAS/NRC, which were published in the Federal Register on April 8, 1969, 34 FR 6259.
Accordingly, a bioequivalency study was conducted by Veterinary Research and Development, Inc. to demonstrate the bioequivalency of its product, copper disodium edetate as a source of copper, to the NAS/NRC/DESI reviewed copper glycinate product.
This study was conducted in 1982 by V.R. Bohman D.V.M. at the University of Nevada. Compliance with the Good Laboratory Practices regulation was shown.
Twelve Hereford steers, averaging 568 lbs, were assigned at random to two treatment groups. One group received 120 mg of copper as Cu-glyc and the other 120 mg of copper as Cu disodium edetate by subcutaneous injection. Immediately prior to administering the copper salts, blood and liver (biopsy) samples were taken as well as at 28-day intervals over a 112-day period after administration. The copper levels in the samples were determined by atomic absorption spectrophotometric methods.
The plasma copper levels remained relatively constant throughout the study. This was in agreement with several other studies supplied by the sponsor which indicated that plasma copper remains fairly constant after liver stores reach 40 parts per million (ppm) or higher on a dry matter basis. The liver copper residues in the Veterinary Research and Development, Inc. study were around 33 ppm at the beginning. Following the administration of either form of copper, the liver copper stores were significantly increased (4x) and decreased logarithmically thereafter. The following table contains the liver concentrations of copper obtained in this study:
(Eds. note: The following table consists of 6 columns.)
Copper Levels (µg/g wet liver tissue)
Cu disodium edetate
The data submitted in support of this approval show that copper disodium edetate as a source of copper is the bioequivalent of copper glycinate when used in accordance to the needs of the animal and at recommended dosages. Copper disodium edetate promotes similar growth, tissue levels of copper and synthesis of ceruloplasmin to copper glycinate. Liver stores of copper from both compounds are similar.
V. TARGET ANIMAL SAFETY:
Copper glycinate was evaluated by NAS/NRC and found to be safe for use in cattle. FDA concurred with the findings of the NAS/NRC, which were published in the Federal Register on April 8, 1969, 34 PR 6259.
Target animal safety study is not required for this copper disodium edetate product.
VI. HUMAN SAFETY:
In the bioequivalency study described previously, six cattle were injected with Veterinary Research and Development's copper disodium edetate injection preparation, and six were given the cupric glycinate injection preparation. For purposes of comparing the relative levels of copper in cattle liver, biopsy samples were taken at 28 day intervals. The mean levels of copper (µg/g wet tissue) in the cattle liver were as follows:
(Eds. note: The following table consists of 6 columns.)
Mean Levels (6 Animals)
|Copper disodium edetate||8.61||39.12||39.27||21.56||19.82|
Although CVM's Bioequivalency Guidelines do not provide for biopsy sampling to measure tissue residues for the purpose of bioequivalency determinations, the Guidelines do not foreclose biopsy sampling for that purpose. Moreover, CVM recognizes that the results of biopsy sampling may be used for comparisons, where appropriate. In this case, CVM determined that the sponsor showed that its copper disodium edetate product is bioequivalent to the DESI reviewed (and FDA approved) copper glycinate product, because all the residue values were within normal limits for copper in cattle liver. Therefore, Veterinary Research and Development's copper disodium edetate injection will have the same 30 day withdrawal period as the approved copper glycinate product.
VII. AGENCY CONCLUSIONS:
The data submitted in support of this NADA satisfy the requirements of 512 of the Act and demonstrate that Bovi-Cu (copper disodium edetate), when used under its proposed conditions of use, is safe and effective for its labeled indications.
Copper products that carry only the prevention claim and not the treatment claim are marketed over the counter. Adequate directions for use have been written for the layman and the conditions of use prescribed on the labeling are likely to be followed in practice. Therefore, the agency has concluded that this copper product labeled only for the prevention of copper deficiency alone or in association with molybdenum toxicity be granted over the counter marketing status.
New animal drug applications for NAS/NRC/DESI reviewed compounds are eligible for approval based upon demonstration of bioequivalence at the same withdrawal time as the NAS/NRC/DESI accepted preparation. Therefore, Bovi-Cu has the approved 30 day withdrawal period.
- Bovi-Cu package insert
- Bovi-Cu package label
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