PMF 005-646 - Target Animal Safety Letter
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PMF 005646 C 0015
December 19, 2003
William H. Gingerich, Ph.D.
Interim Registration Officer
USGS, Upper Midwest Environmental Sciences Center
2630 Fanta Reed Road
La Crosse, WI 54603
Dear Dr. Gingerich:
By letter dated February 19, 2003, you submitted a target animal safety study and draft labeling to the Public Master File (PMF), PMF 005646, for oxytetracycline. The drug is proposed as an antimicrobial. The submission requested review of a study to determine the safety of oxytetracycline to cool and warmwater finfish when administered in feed at the label dose of 3.75 g/100 pounds of fish/day for 10 consecutive days.
Based on the information in this submission and the information contained in PMF 005646, the Division of Therapeutic Drugs for Food Animals considers the TARGET ANIMAL SAFETY technical section to be complete for oxytetracycline when administered in feed at doses up to 3.75 g/100 pounds of fish/day for 10 consecutive days to freshwater reared cool and warmwater finfish. Please provide a brief chronology of our correspondence pertaining to this technical section and a copy of this letter in Section 8, EVIDENCE TO ESTABLISH SAFETY AND EFFECTIVENESS, of your administrative New Animal Drug Application (NADA).
A final decision on whether the application can be approved will be made when all the data for all technical sections submitted as part of an administrative NADA, NADA, or supplemental NADA are viewed as a whole and it is determined that:
1) the information contained in and referenced by the application supports approval;
2) the GMP status of each manufacturing facility is current and satisfactory;
3) if a claim for categorical exclusion was made, conditions for the categorical exclusion are still applicable;
4) there is no new information that would preclude the approval of the application.
COMMENTS ON THE STATISTICAL ANALYSIS OF THE STUDY
We prefer the analysis using the general linear mixed model because the model handles the tank as the experimental unit and block location as a random effect appropriately. However, some of the general linear mixed models did not converge in our analysis. We reran the analyses using a normal distribution for arcsin transformed data instead of binomial distribution. The analysis results are consistent with the Fisher's test results. We recommend reporting our analysis results in the Freedom of Information summary as shown below.
Table 1. Histopathology results from the walleye portion of the study.
| Variable | Lesion Dose | Lesion Number of Observations (%) | Lesion P-Value* |
|---|---|---|---|
| Anterior Kidney Hematopoeitic/Lymphopoetic |
Control 1x 3x 5x |
1 (10.0) 2 (20.0) 3 (33.3) 7 (77.8) |
0.4545 0.1855 0.0106 |
| Gill filament, Epithelial hyperplasia |
Control 1x 3x 5x |
0 (0.0) 0 (0.0) 1 (11.1) 5 (55.6) |
1.0000 0.2619 0.0023 |
| Posterior kidney, Tubular epithelium, Eosinophilic droplets |
Control 1x 3x 5x |
7 (70.0) 4 (40.0) 1 (11.1) 0 (0.0) |
0.1578 0.0361 0.0160 |
*Comparison between the treated groups and the controls. Bold p-values are statistically significant at α=0.10.
Future correspondence regarding your submission to the Public Master File should include the date of this correspondence and our file number, PMF 005646 C 0015. A copy of this technical section complete letter should be included in the administrative NADA.
If you need further information regarding this letter, please contact Dr. Donald Prater, Leader, Aquaculture Drugs Team, at 301-827-7567.
Sincerely yours,
/s/
Joan C. Gotthardt, D.V.M.
Director, Division of Therapeutic
Drugs for Food Animals
Office of New Animal Drug Evaluation
Center for Veterinary Medicine