Animal & Veterinary
NADA 065-252 Strep-SoL - supplemental approval (September 5, 1993)
I. GENERAL INFORMATION
|Sponsor:||Veterinary Services, Inc.|
Modesto, CA 95394
|Generic Name:||streptomycin sulfate 25% solution|
|Marketing Status:||Over the Counter (OTC)|
|Effect of Supplement:|
II. INDICATIONS FOR USE
Treatment of non-specific infectious enteritis caused by organisms susceptible to streptomycin sulfate.
Swine and calves:
Treatment of bacterial enteritis caused by Escherichia coli and Salmonella spp. susceptible to streptomycin sulfate.
A. DOSAGE FORM: Liquid
B. ROUTE OF ADMINISTRATION: Oral (medicated drinking water)
C. RECOMMENDED DOSAGES: 10 to 15 mg/pound body weight.
NADA 065-252 was originally approved as safe for use as labeled on February 18, 1954. The drug was the subject of National Academy of Sciences/National Research Council (NAS/NRC) reports which were published in the FEDERAL REGISTER of November 21, 1969 (FR 69-13826).
The Academy evaluated these products as probably effective for the treatment of bacterial diseases involving the gastrointestinal tract in poultry, swine, and calves.
The Academy stated that:
- Each disease claim should be properly qualified as "appropriate for use in (name of disease) caused by pathogens sensitive to (name of drug)." If the disease cannot be so qualified, the claim must be dropped.
- Label claims for these preparations must be restricted to diseases involving the gastrointestinal tract because of the chemical and pharmacological properties of the streptomycin sulfate.
- The label should warn that treated animals must actually consume sufficient medicated water to provide a therapeutic dose under the conditions that prevail. As a precaution, the label should declare the desired oral dose in terms of the amount of drug per pound of animal weight per day for each species as a guide to effective use of the preparation in drinking water.
- Label claims made "for prevention of" or "to prevent" should be replaced with "as an aid in the control of" or, "to aid in the control of."
- Labeling should carry a warning pertaining to the development of streptomycin resistant organisms.
- Dosage levels recommended in the labeling are low.
The Food and Drug Administration concurs with the Academy's evaluation. This evaluation is concerned only with the drug's effectiveness and safety to the animal to which administered. It does not take into account the safety for food use of food derived from drug-treated animals. Nothing herein will constitute a bar to further proceedings with respect to questions of safety of these drugs or their metabolites as residues in food products derived from treated animals.
The Food and Drug Administration proceeded to review all available data relating to the effectiveness of products subject to NADA 065-252 to determine which label claims were supported by the requisite proof of effectiveness. That review resulted in a letter to the sponsor dated September 23, 1992, in which the agency stated that it had "concluded that such data supported effectiveness for bacterial enteritis in chickens, swine and calves."
Thereafter, the sponsor complied with the evaluation of NAS / NRC / DESI and FDA's conclusions in the following manner:
- Each disease claim on the label has been properly qualified with the appropriate genus and species of bacteria susceptible to streptomycin sulfate. Except for poultry the disease was defined as non-specific. Disease claims which were not so qualified have been deleted.
- Label claims for this preparation have been restricted to infectious bacterial enteritis. The appropriate oral dose of 10-15 mg per pound body weight daily in each species has been incorporated in the labeling.
- The manufacturer's label carries the warning statement that treated animal must have the medicated water adjusted to compensate for variation in age and the weight of the animal, the nature and severity of disease signs, and environmental temperature and humidity, each of which affects water consumption.
- Claims made for prevention have been dropped completely.
- The label carries a warning statement pertaining to the development of streptomycin resistant organisms.
V. ANIMAL SAFETY
NADA 065-252 was originally approved as safe on February 18, 1954. No further safety data are required.
VI. HUMAN FOOD SAFETY
The NAS/NRC evaluation of the drug is concerned only with the effectiveness and safety of the drug for the treated animal. FDA's approval of the supplemental applications did not involve reevaluation or reaffirmation of the human food safety data in the parent application.
The supplemental application providing for the revision of the tolerance from "zero" to 2.0 ppm in kidney and 0.5 ppm in all other edible tissues of calves, swine, and poultry reflects the change in FDA policy regarding the concept of residue tolerance. No new toxicity data are submitted in support of the change because the values cited above are consistent with the tolerance level that would have been established when the drug was originally approved ( February 18, 1954).
Under the zero tolerance concept, no detectable residues of a new animal drug were permissible in edible tissues of treated food animals when tissues were assayed using available analytical methods. However, as analytical technologies advanced, methodologies became increasingly sensitive and capable of measuring progressively smaller amounts of drug residues in tissues. Therefore, FDA adopted the concept of maximum negligible, or permissible, residues which reflect the lower level of quantitative sensitivity of the official regulatory analytical method. Also, considered in this process is the relative consumption of various tissues.
The levels of 2.0 ppm in kidney and 0.5 ppm in other tissues reflects the levels of streptomycin which FDA considers to be safe and at which USDA has been monitoring for residues for a number of years. The requested tolerances have already been determined to be scientifically acceptable to the agency. Revision of 21 CFR 556.610 formally acknowledges the reality of streptomycin residue monitoring.
VII. AGENCY CONCLUSIONS
The DESI finalization supplemental NADA satisfies the requirements of section 512 of the Act and demonstrates that Strep SoL, when used under its proposed conditions of use, is safe and effective for the labeled indications. The approval provides for use of Strep SoL for the treatment of infectious enteritis in chickens, swine, and calves.
The "probably effective" finding of the NAS/NRC/DESI regarding Strep SoL which was published in the FEDERAL REGISTER of November 21, 1969, was subsequently reviewed by FDA, resulting in the upgrade to "effective" status with respect to the claims noted in the previous paragraph. The firm submitted revised labeling to conform and, therefore, this supplemental NADA complies with the NAS / NRC / DESI evaluation and FDA's conclusions.
Strep SoL for use in food-producing animals is currently on the market as an over-the-counter product. When the NADA was reviewed under NAS/NRC/DESI program, it was an over-the-counter product and this marketing status remains unchanged. Therefore, the Center for Veterinary Medicine has concluded that this product should retain overthe-counter marketing status.
Additionally, the supplemental application providing for revision of the tolerance from "zero" to 2.0 ppm in the kidney and 0.5 ppm in the edible tissues of calves, swine, and chickens is acceptable and is approved.
Under the Center's supplemental approval policy (21 CFR 514.106(b)(2)), these are Category II changes. The approval of these changes are not expected to have any adverse effect on the safety or effectiveness of this new animal drug and, therefore, did not require a reevaluation of the human food or target animal safety data in the parent application.
Under the Generic Animal Drug and Patent Term Restoration Act of 1988, these approvals do not qualify for an exclusivity period under section 512(c)(2)(F)(iii) of the Federal, Food, Drug, and Cosmetic Act U.S.C.360b (c)(2)(F)(iii)) because the supplemental applications do not contain reports of new clinical or field investigations (other than bioequivalence or residue studies) and in the case of food producing animals, human food safety studies (other than bioequivalence or residue studies) essential to the approvals and conducted or sponsored by the applicant.
VIII. LABELING (Attached)
Copies of applicable labels may be obtained by writing to the:
Food and Drug Administration
Freedom of Information Staff (HFI-35)
5600 Fishers Lane
Rockville, MD 20857
Or requests may be sent via fax to: (301) 443-1726. If there are problems sending a fax, call (301) 443-2414.