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U.S. Department of Health and Human Services

Animal & Veterinary

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NADA 141-018 SaraFlox® Injection - supplemental approval (January 21, 1997)

Approval Date: January 21, 1997

I. GENERAL INFORMATION:

NADA 141-018
Sponsor: Abbott Laboratories
1401 Sheridan Road
North Chicago, IL 60064
Generic Name: sarafloxacin hydrochloride
Trade Name: SaraFlox® Injection
Marketing Status: prescription (Rx) product which carries the following caution statement "Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian."
Effect of Supplement: This supplement provides for the addition of a new dose for in ovo administration to 18-day embryonated broiler eggs, to be added to the previously approved product, SaraFlox® Injection.
Diagnosis: Diagnosis of E. coli infections that may be present in 18-day embryonated eggs is based on the presumptive identification of the organism in the day-old broiler as part of chick quality monitoring program. This presumptive identification may be based on such considerations as breeder flock history, physical examination, necropsy and yolk sac culture.

 

II. INDICATIONS FOR USE

SARAFLOX® INJECTION is indicated for use in 18-day embryonated broiler eggs for the control of early chick mortality associated with Escherichia coli organisms susceptible to sarafloxacin.

 

III. DOSAGE

A. DOSAGE FORM SARAFLOX® INJECTION is available as an 80 mL sterile-solution-fill in a 100 mL glass bottle at a concentration of 50 mg sarafloxacin base per mL. The contents of one bottle will be sufficient to inject 80,000 broiler eggs.
B. ROUTE OF ADMINISTRATION SARAFLOX® INJECTION is to be mixed with sterile water or physiologic saline for administration as a single injection to 18-day embryonated broiler chicken eggs.
C. RECOMMENDED DOSAGES: Each 18-day embryonated broiler egg should be given a single in ovo injection with SARAFLOX INJECTION diluted with sterile water or physiologic saline to provide 0.05 mg sarafloxacin in a volume of 0.1 mL.

 

IV. EFFECTIVENESS

In support of this supplemental application, three well-controlled dose confirmation/clinical field studies were conducted to establish the efficacy of this product when administered in ovo to 18-day embryonated broiler eggs for the control of early chick mortality associated with E. coli.

A. Pivotal Studies

  1. Dose Confirmation/Field Study
    1. Type of Study: A dose confirmation/clinical field study was conducted using sarafloxacin injection in broiler chick eggs from a breeder flock with a history of high early mortality due to E. coli in their progeny.
    2. Investigator:

      Terry N. TerHune, D.V.M., Ph.D.
      Health Management Services.
      Tulare, CA 93275

    3. General Design:
      1. Purpose: To evaluate the effectiveness of sarafloxacin hydrochloride administered via in ovo injection to 18-day embryonated broiler eggs for the control of early chick mortality associated with E. coli susceptible to sarafloxacin.
      2. Animals: A total of 3600 18-day-old broiler chick eggs were used in this study. For each of three treatments (0, 0.05 or 0.1 mg sarafloxacin/egg) there were 10 trays of 120 eggs per tray. A total of 2700 chicks were placed (15 pens of 60 chicks per treatment). Males and females were included in each pen.
      3. Controls: Each egg in the negative control group received an in ovo injection of 0.1 mL saline (containing 0 mg sarafloxacin).
      4. Diagnosis: E. coli associated mortality was defined as having: a positive E. coli culture (from air sacs, liver or pericardia) and omphalitis; or a positive E. coli culture (from air sacs, liver or pericardia) and a moderate to severe lesion indicative of colibacillosis (score of 2).
      5. Dosage Form: A solution containing 50 mg sarafloxacin free-base per milliliter was used. This dosage form is the marketed form of SARAFLOX® INJECTION.
      6. Route of Administration: An in ovo injection was administered to each egg.
      7. Dose: A single 0.1 mL injection containing 0 mg, 0.05 mg, or 0.1 mg sarafloxacin per egg was administered.
      8. Test Duration: 17 days.
      9. Pertinent Variables Measured: The primary parameter for determining efficacy was a comparison of the number of E. coli associated mortalities that occurred during the 14-day growout period in the 0 mg sarafloxacin treatment group versus the 0.05 mg sarafloxacin treatment group. Other supportive data recorded were hatchability, morbidity observations, feed consumption and body weight by pen.
    4. Results: The mortality results are shown in Table 4.1.

      Table 4.1. Mean percent mortality from hatch to Day 14

                                      Mortality
           Dose          --------------------------------------                        
      sarafloxacin (mg)       Total          E. coli-associated
      ---------------------------------------------------------
           0              11.7 (105/900)        5.6 (50/900)             
           0.05            3.6  (32/900)        1.1 (10/900)             
           0.1             3.2  (29/900)        0.7  (6/900)      
      
    5. Statistical Analysis: The study used a randomized complete block design with 3 treatments in 15 blocks. A survival model and weighted least squares analysis were used to examine total and E. coli mortalities. Tests of significance were made at the P 0.05 level. Orthogonal contrasts were used to measure treatment differences.
    6. Conclusion: It was concluded that sarafloxacin was effective in controlling early chick mortality associated with E. coli susceptible to sarafloxacin when administered by in ovo injection to 18-day embryonated broiler eggs at a dose of 0.05 mg sarafloxacin/embryo.
    7. Adverse Reactions: No adverse reactions were observed.
  2. Dose Confirmation/Field Study
    1. Type of Study: A dose confirmation/clinical field study was conducted using sarafloxacin injection in broiler chick eggs from a breeder flock with a history of high early mortality due to E. coli in their progeny.
    2. Investigator:

      Jon L. Schaeffer, D.V.M., Ph.D.
      JLS Research
      Mount Olive, NC

    3. General Design:
      1. Purpose: To evaluate the effectiveness of sarafloxacin hydrochloride administered via in ovo injection to 18-day embryonated broiler eggs for the control of early chick mortality associated with E. coli susceptible to sarafloxacin.
      2. Animals: A total of 3240 18-day-old broiler chick eggs were used in this study. For each of three treatments there were 10 trays of 108 eggs per tray. A total of 2880 chicks were placed (16 pens of 60 chicks per treatment). Males and females were included in each pen.
      3. Controls: Each egg in the negative control group received an in ovo injection of 0.1 mL saline (containing 0 mg sarafloxacin).
      4. Diagnosis: E. coli associated mortality was defined as having: a positive E. coli culture (from air sacs, liver or pericardia) and omphalitis; or a positive E. coli culture (from air sacs, liver or pericardia) and a moderate to severe lesion indicative of colibacillosis (score of 2)
      5. Dosage Form: A solution containing 50 mg sarafloxacin free-base per milliliter was used. This dosage form is the marketed form of SARAFLOX® INJECTION.
      6. Route of Administration: An in ovo injection was administered to each egg.
      7. Dose: A single 0.1 mL injection containing 0 mg, 0.05 mg, or 0.1 mg sarafloxacin per egg was administered.
      8. Test Duration: 17 days
      9. Pertinent Variables Measured: The primary parameter for determining efficacy was a comparison of the number of E. coli associated mortalities that occurred during the 14-day growout period in the 0 mg sarafloxacin treatment group versus the 0.05 mg sarafloxacin treatment group. Other supportive data recorded were hatchability, morbidity observations, feed consumption and body weight by pen.
    4. Results: The mortality results are shown in Table 4.2.

      Table 4.2. Mean percent mortality from hatch to Day 14

                                      Mortality
           Dose          --------------------------------------                        
      sarafloxacin (mg)       Total          E. coli-associated
      ---------------------------------------------------------    
           0              13.9 (133/960)        8.8 (84/960)             
           0.05            5.5  (53/960)        2.3 (22/960)             
           0.1             5.7  (55/960)        2.3 (22/960)     
      
    5. Statistical Analysis: The study used a randomized complete block design with 3 treatments in 16 blocks. A survival model and weighted least squares analysis were used to examine total and E. coli mortalities. Tests of significance were made at the P < or = 0.05 level. Orthogonal contrasts were used to measure treatment differences. f. Conclusion: It was concluded that sarafloxacin was effective in controlling early chick mortality associated with E. coli susceptible to sarafloxacin when administered in ovo to 18-day embryonated broiler eggs at a dose of 0.05 mg sarafloxacin/embryo.
    6. Adverse Reactions: No adverse reactions were observed.
  3. Dose Confirmation/Field Study
    1. Type of Study: A dose confirmation/clinical field study was conducted using sarafloxacin injection in broiler chick eggs from a breeder flock with a history of high early mortality due to E. coli in their progeny.
    2. Investigator:

      Jon L. Schaeffer, D.V.M., Ph.D.
      JLS Research
      Mount Olive, NC

    3. General Design:
      1. Purpose: To evaluate the effectiveness of sarafloxacin hydrochloride administered via in ovo injection to 18-day embryonated broiler eggs for the control of early chick mortality associated with E. coli susceptible to sarafloxacin.
      2. Animals: A total of 3240 18-day-old broiler chick eggs were used in this study. For each of three treatments there were 10 trays of 108 eggs per tray. A total of 2880 chicks were placed (16 pens of 60 chicks per treatment). Males and females were included in each pen.
      3. Controls: Each egg in the negative control group received an in ovo injection of 0.05 mL saline (containing 0 mg sarafloxacin).
      4. Diagnosis: E. coli associated mortality was defined as having: a positive E. coli culture (from air sacs, liver or pericardia) and omphalitis; or a positive E. coli culture (from air sacs, liver or pericardia) and a moderate to severe lesion indicative of colibacillosis (score of 2)
      5. Dosage Form: A solution containing 50 mg sarafloxacin free-base per milliliter was used. This dosage form is the marketed form of SARAFLOX® INJECTION.
      6. Route of Administration: An in ovo injection was administered to each egg.
      7. Dose: A single 0.05 mL injection containing 0 mg, 0.05 mg, or 0.1 mg sarafloxacin per egg was administered by automated machine.
      8. Test Duration: 17 days
      9. Pertinent Variables Measured: The primary parameter for determining efficacy was a comparison of the number of E. coli associated mortalities that occurred during the 14-day growout period in the 0 mg sarafloxacin treatment group versus the 0.05 mg sarafloxacin treatment group. Other supportive data recorded were hatchability, morbidity observations, feed consumption and body weight by pen.
    4. Results: The mortality results are shown in Table 4.3.

      Table 4.3 Mean percent mortality from hatch to Day 14

                                      Mortality
           Dose          --------------------------------------                        
      sarafloxacin (mg)       Total          E. coli-associated
      ---------------------------------------------------------    
           0              22.5 (216/960)       17.8 (171/960)          
           0.05            8.4  (81/960)        6.3  (60/960)            
           0.1             6.1  (59/960)        3.8  (36/960)    
      
    5. Statistical Analysis: The study used a randomized complete block design with 3 treatments in 16 blocks. A survival model and weighted least squares analysis were used to examine total and E. coli mortalities. Tests of significance were made at the P 0.05 level. Orthogonal contrasts were used to measure treatment differences.
    6. Conclusion: It was concluded that sarafloxacin was effective in controlling early chick mortality associated with E. coli susceptible to sarafloxacin when administered in ovo to 18-day embryonated broiler eggs at a dose of 0.05 mg sarafloxacin/embryo.
    7. Adverse Reactions: No adverse reactions were observed.
  4. Dose Confirmation/Field Studies - Combined
    1. Results: The pooled mortality results are shown in Table 4.4.

      Table 4.4 Mean percent chick mortality from hatch to Day 14

                                      Mortality
           Dose          --------------------------------------                        
      sarafloxacin (mg)       Total          E. coli-associated
      --------------------------------------------------------- 
            0              16.1 (454/2820)     10.8 (305/2820)         
            0.05            5.9 (166/2820)      3.3  (92/2820)           
            0.1             5.1 (143/2820)      2.3  (64/2820)   
      
    2. Statistical Analysis: A weighted least squares analysis was used to examine total and E. coli mortalities. Both procedures included trial, treatment and the interaction in the model. Tests of significance were made at the P 0.05 level. c. Conclusion: It was concluded that sarafloxacin was effective in controlling early chick mortality associated with E. coli susceptible to sarafloxacin when administered in ovo to 18-day embryonated broiler eggs at a dose of 0.05 mg sarafloxacin/embryo.

B. Pharmacokinetic Study Supporting Labeling

  1. Type of Study: This was a study to determine the serum concentration profile for sarafloxacin injected into embryonated broiler eggs on Day 18 of incubation.
  2. Investigator:

    Terry N. TerHune, D.V.M., Ph.D.
    Health Management Services
    Tulare, CA

  3. General Design:
    1. Purpose: The purpose of this study was to determine the effect of a single in ovo injection of 0.05 mg of sarafloxacin on blood (serum) levels of the fluoroquinolone in Day 18 embryonated eggs.
    2. Animals: One hundred twenty Peterson X Arbor Acres eggs were used in this study. Eggs were randomly selected from a group of 200 without regard to sex. Eggs were at Day 18 of incubation at the start of the trial.
    3. Route of Administration: An in ovo injection was administered to each egg.
    4. Dosage Form: A solution containing 50 mg sarafloxacin free-base per milliliter was used. This dosage form is the marketed form of SARAFLOX® INJECTION.
    5. Dose: A single 0.1 mL injection containing 0.05 mg sarafloxacin per egg was administered.
    6. Test Duration: The study spanned three days.
    7. Pertinent Variables Measured: Blood samples were taken by cardiac puncture from 10 preselected embryos at each time point. Samples were collected at 1, 2, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dosing. Sarafloxacin levels were measured in serum samples. The injection solution was also analyzed to determine sarafloxacin levels.
  4. Results: The data indicated that there is a wide variation in the serum concentration among birds during the first 8 hours post-injection, the coefficient of variation about the concentration means ranging from 64% to 101%. Mean levels of sarafloxacin tended to be highest at approximately 2 hours post-injection with an average of 1329 ± 1206 ng/mL for nine birds. The terminal depletion half-life, based upon a linear regression of the average terminal concentrations, was approximately 15 hours.
  5. Statistical Analysis: Means and standard deviations were calculated for each timepoint.
  6. Conclusion: The average serum concentration exceeded the MIC90 for E. coli (60 ng/mL) by the first hour post-injection. Sarafloxacin concentrations exceeded 10X MIC90 in seven out of 9 birds at 2 hours pos-injection, and exceeded 2X MIC90 in 50 out of 58 birds through 12 hours post-injection.

 

V. ANIMAL SAFETY

A. Overview

SaraFlox Injection (sarafloxacin hydrochloride) was approved on November 22, 1995, (NADA 141-018) for use in day-old chicks for the control of early chick mortality associated with E. coli susceptible to sarafloxacin.

Based on the physiologic similarities between the 18-day embryo and the day-old chick, and because the safety of the drug had already been demonstrated at 20X the label in ovo dose for the day-old chick approval, additional pivotal target animal safety studies were not required for this supplemental application. A non-GLP safety study that further supports the safety of in ovo administration of this drug is summarized below.

B. Target Animal Safety Study Supporting Labeling

A specifically designed target animal safety study in 18-day embryonated broiler eggs was conducted to address the tolerance to and safety of a single in ovo injection of sarafloxacin.

  1. Type of Study: This was a 17 day study in which a single injection of 0, 0.5, or 1.0 mg of sarafloxacin was administered to 18-day embryonated broiler eggs followed by a 14-day growout period.
  2. Investigator:

    Jon L. Schaeffer, D.V.M., Ph.D.
    JLS Research
    Mount Olive, NC

  3. General Design:
    1. Purpose: This study was designed to determine the toxicologic effects of sarafloxacin administered by in ovo injection to 18-day embryonated broiler eggs. Potential target organs and tissues were to be identified through clinical observations and gross necropsy. Hatchability, mortality, body weight, and feed consumption were other variables of interest.
    2. Animals: A total of 1296 18-day Hubbard x Arbor Acres embryonated eggs were used in this study. For each of 4 treatments, there were three trays of 108 eggs each; 60 to 62 chicks per pen were placed for a 14-day growout (15 pens of about 324 chicks per treatment).
    3. Controls: Sterile saline (0.1 mL) was administered by a single in ovo injection to one group while another group was uninjected.
    4. Dosage form: An aqueous formulation containing 50 mg sarafloxacin base per milliliter was used. This dosage form is the marketed form of SARAFLOX® INJECTION.
    5. Dose: 0, 0.5, or 1.0 mg/egg in 0.1 mL sterile saline.
    6. Route of Administration: The drug was administered by in ovo injection.
    7. Study Duration: The study spanned 17 days beginning with 18-day embryonated eggs.
    8. Pertinent measurements/observations: Hatchability, daily clinical observations, mortality, body weight (at placement and Day 14 by pen), feed consumption (pen basis) and gross necropsy of mortalities were evaluated to assess potential toxicity in broilers.
  4. Results:
    1. Hatchability

      Total hatchability (% live chicks hatched from candled eggs set) and hatchability of embryos alive at injection (% live chicks hatched of embryos alive at injection, as determined by egg necropsy on day of hatch) were determined for each treatment group at Day 21 of incubation (Table 5.1).

      Table 5.1 Effect of sarafloxacin on hatchability

           Dose            Total         Embryos alive at   Culled   
        Sarafloxacin    hatchability      injection that    chicks   
        (mg/embryo)         (%)             hatch (%)
       -----------------------------------------------------------
        non-injected     93.8 ± 1.4        98.4 ± 0.3         1      
            0            93.8 ± 1.1        98.7 ± 0.5         2      
            0.5          95.1 ± 0.5        98.4 ± 0.3         2      
            1.0          94.4 ± 0.4        98.1 ± 0.5         1
      

      Total hatchability was similar among treatments, although a small numerical improvement was seen in sarafloxacin treated groups as compared to injected and non-injected control groups.

    2. Egg Necropsy

      Egg necropsies were performed on all unhatched eggs at the time normal, live chicks were removed from the hatching baskets to determine the stage of embryonic death. Necropsy categories were divided into two groups: 1) embryos that died prior to Day 18 injection (early and middle deads, malformed and malpositioned) and, 2) unhatched embryos that died after Day 18 injection (late deads, live and dead pips). Results of the egg necropsies indicate injection with sarafloxacin at 0.5 or 1.0 mg per embryo at Day 18 of incubation did not adversely affect late stage embryonic development.

    3. Clinical Observations

      There were no clinical signs indicative of toxicity noted in birds from any of the treatment groups.

    4. Mortality

      A total of 1222 chicks were placed of which nine (excluding four cull birds) subsequently died during the study (Table 5.2).

      Table 5.2. Chick Mortality Days 1 through 14

      Dose sarafloxacin (mg)        Mortality
      -----------------------------------------
         non-injected              2/304 (0.7%)       
             0                     3/304 (1.0%)       
             0.5                   3/308 (1.0%)       
             1.0                   1/306 (0.3%)
      
    5. Necropsy

      A gross necropsy was performed on all birds that died during the study to determine probable cause of death. A majority of the lesions in the dead birds were a result of an infection (omphalitis or pericarditis/colibacillosis), while two birds in the 0.5 mg sarafloxacin group did not reveal any gross lesions. None of the mortalities was thought to be drug-related.

    6. Body Weight and Feed Consumption

      Average body weight at hatch and Day 14, and feed consumption during the 14-day study were similar for all treatment groups.

  5. Conclusions: The in ovo injection of sarafloxacin to 18-day embryonated broiler eggs at 0.5 and 1.0 mg per embryo [ten times (10X) and twenty times (20X) the label in ovo dose] caused no adverse effects that were believed to be drug-related in this study.

 

VI. HUMAN SAFETY

A. Toxicity Studies:

All issues concerning toxicity testing of sarafloxacin are addressed in the previous Freedom of Information Summary for NADA 141-018, approved on October 12, 1995.

B. Safe Concentration of Total Residues:

This section is unchanged from NADA 141-018 approved October 12, 1995. The safe concentrations as total sarafloxacin hydrochloride (ppm) in edible chicken tissues are summarized in Table 6.1.

Table 6.1. Safe Concentrations (SC) for total residues of sarafloxacin hydrochloride in edible chicken tissues using the revised food consumption factors

  Edible Tissue     Amount Consumed/Day    Safe Concentration (SC)
------------------------------------------------------------------
     Muscle                300 g                   1.75 ppm  
     Liver                 100 g                   5.25 ppm  
    Fat/Skin                50 g                  10.50 ppm

C. Total Residue Depletion and Metabolism Studies:

Based on the physiologic similarities between the 18-day embryo and the day-old chick and the low dose in the embryo (0.05 mg vs 0.1 mg in the day-old chick), no residue depletion and metabolism studies were conducted for this use. Data in the application of the day-old chick indicate that the residues in edible tissues are well below the safe concentration at 14 days after treatment.

D. Comparative Metabolism:

This section is unchanged from NADA 141-018 approved October 12, 1995.

E. Withdrawal Time:

In the approved application for day-old chicks, the total residue data showed that the mean concentrations of total sarafloxacin residues at 14 days after injection were well below the permitted safe concentration in the edible tissues of growing broiler chickens. Based on the physiologic similarities between 18-day embryos and day-old chicks, concentrations in the edible tissues as a result of in ovo treatment are expected to be less than those found following treatment of the day-old chick, since the dose in the embryo is only one-half that in the day-old chick and the administration is 3 days earlier. Husbandry practices for broilers are such that they will only be handled in ovo or at one day of age for injection with sarafloxacin HCl; they will not enter the human food chain until at least 28 days of age in the case of Cornish hens, or, more likely, not until 42 or more days of age. Therefore, a withdrawal period will not be required for this use of sarafloxacin HCl in 18-day embryonated broiler eggs, and a target tissue, marker residue and tolerance have not been assigned.

F. Regulatory Method:

A regulatory method is unnecessary because a withdrawal period is not required for this use of sarafloxacin HCl in 18-day embryonated broiler eggs.

G. User Safety Concerns:

This section is unchanged from NADA 141-018, approved October 12, 1995.

 

VII. AGENCY CONCLUSIONS

The data submitted in support of this NADA supplement satisfy the requirements of Section 512 of the Federal Food, Drug, and Cosmetic Act and 21 CFR Part 514 of the implementing regulations. The data demonstrate that SARAFLOX® INJECTION (sarafloxacin hydrochloride), when administered as a single in ovo injection to 18-day embryonated broiler eggs, is safe and effective for the control of early chick mortality associated with E. coli organisms susceptible to sarafloxacin.

Based on a battery of toxicology tests, the safe concentrations for total residues of sarafloxacin hydrochloride are 1.75 ppm in muscle, 5.25 ppm in liver, and 10.5 ppm in fat/skin. The total residue data showed that the mean concentrations of total sarafloxacin hydrochloride residues at 14 days after injection were well below the permitted safe concentration in the edible tissues of growing broiler chickens. Husbandry practices for broilers are such that they will only be handled in ovo or at one day of age for injection with sarafloxacin HCl; they will not enter the human food chain until at least 28 days of age in the case of Cornish hens, or, more likely, not until 42 or more days of age. Therefore, a withdrawal period will not be required for this use of sarafloxacin HCl in 18-day embryonated broiler eggs, and a target tissue, marker residue, and tolerance have not been assigned. An official regulatory method is not required because the residue and toxicology data support a zero-day withdrawal.

Labeling restricts this drug to use by or on order of a licensed veterinarian. This decision was based on the following factors: (a) adequate directions cannot be written to enable lay persons to appropriately diagnose and subsequently use this product to control early chick mortality associated with E. coli organisms, and (b) the rate of emergence of sarafloxacin-resistant organisms may be reduced by the involvement of veterinarians in product use.

Public health concerns associated with potential increases in antimicrobial resistance have been satisfactorily addressed by establishing conditions of use intended to minimize inappropriate use of this product, and excretion of sarafloxacin and sarafloxacin-resistant zoonotic pathogens into the environment. In addition, the sponsor is participating in an antimicrobial resistance surveillance program.

The agency has carefully considered the potential environmental effects of this action and has concluded that the action will not have a significant impact on the human environment and that an environmental impact statement is not required. The agency's finding of no significant impact (FONSI) and the evidence supporting that finding are contained in an environmental assessment, which may be seen in the Dockets Management Branch (HFA-305), Parklawn Building (Room 1-23), 12420 Parklawn Dr., Rockville, Maryland 20857.

Under the Center's supplemental approval policy (21 CFR 514.106(b)(2)), these are Category II changes. The approval of these changes is 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 Section 512(c)(2)(F)(iii) of the FFDCA, this approval for food-producing animals qualifies for THREE (3) years of marketing exclusivity beginning on the date of approval because the supplemental application contains substantial evidence of the effectiveness of the drug involved, any studies of animal safety, or in the case of food producing animals, human food safety studies (other than bioequivalence or residue studies) required for the approval of the application and conducted or sponsored by the applicant. The three years of marketing exclusivity applies only to the addition of a new dose for in ovo administration into 18-day embryonated broiler eggs for which the supplemental application was approved.

SARAFLOX® INJECTION is under patent number U.S. 4,730,000, expiring March 18, 2005.

 

VIII. APPROVED LABELING

A copy of the draft facsimile labeling is attached to this document.

  1. SARAFLOX INJECTION Carton Label
  2. SARAFLOX INJECTION Bottle Label
  3. SARAFLOX INJECTION Package Insert

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