[Federal Register Volume 61, Number 132 (Tuesday, July 9, 1996)]
[Rules and Regulations]
[Pages 35949-35958]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-17169]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 510 and 558


Animal Drugs, Feeds, and Related Products; Chlortetracycline

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is amending the animal 
drug regulations to reflect approval of five supplemental new animal 
drug applications (NADA's) filed by Hoffmann-LaRoche, Inc., Pfizer, 
Inc., ALPHARMA, Inc., ADM Animal Health & Nutrition Div., and PennField 
Oil Co. The supplemental NADA's provide for the safe and effective use 
of Type A medicated articles containing chlortetracycline (CTC) in the 
feed of chickens, turkeys, swine, sheep, and calves, beef and 
nonlactating dairy cattle for improved production efficiency and for 
control and treatment of certain bacterial diseases susceptible to CTC. 
The approvals reflect compliance with results of the National Academy 
of Sciences/National Research Council (NAS/NRC), Drug Efficacy Study 
Group's (DESI) evaluation of the drug's effectiveness, and FDA's 
conclusions concerning that evaluation.

EFFECTIVE DATE: July 9, 1996.

FOR FURTHER INFORMATION CONTACT: Dianne T. McRae, Center for Veterinary 
Medicine (HFV-102), Food and Drug Administration, 7500 Standish Pl., 
Rockville, MD 20855, 301-594-1623.

SUPPLEMENTARY INFORMATION: The following sponsors have submitted 
supplements to their approved NADA's:
    <bullet> Hoffmann-LaRoche, Inc., Nutley, NJ 07110 (formerly held by 
American Cyanamid Co.), to NADA 48-761, which covers the Type A 
medicated articles: Aureomix<Register> 293 (50 grams of 
chlortetracycline hydrochloride per pound (g CTC HCl/lb)) and 
Aureomycin<Register> 50, 70, 80, 90, and 100 (contain CTC calcium 
complex equivalent to the indicated g/lb concentrations of CTC HCl);
    <bullet> Pfizer, Inc., 235 East 42d St., New York, NY 10017, to 
NADA 92-286, which covers the Type A medicated articles CLTC<Register> 
10, 20, 30, 50, and 70 (contain CTC calcium complex equivalent to the 
indicated g/lb concentrations of CTC HCl) and to NADA 92-287, which 
covers the Type A medicated articles CLTC<Register> 50 MR and 100 MR 
(contain CTC calcium complex equivalent to the indicated g/lb 
concentrations of CTC HCl);
    <bullet> ALPHARMA, Inc. (formerly A. L. Laboratories), One 
Executive Dr., P.O. Box 1399, Fort Lee, NJ 07024, to NADA 46-699, which 
covers the Type A medicated articles: CTC 100 MR (100 g CTC HCl/lb) and 
CTC 10, CTC 50, CTC 65, CTC 70, and Micro CTC 100 (contains CTC calcium 
complex equivalent to the indicated g/lb concentrations of CTC HCl);
    <bullet> ADM Animal Health & Nutrition Div., P.O. Box 2508, Fort 
Wayne, IN 46801-2508 (formerly Feed Specialties Co., Inc.), to NADA 48-
480, which covers the Type A medicated article Chloratet<SUP>TM 50 
(contains CTC calcium complex equivalent to 50 g CTC HCI/lb); and
    <bullet> PennField Oil Co., 14040 Industrial Rd., Omaha, NE 68137, 
to NADA 138-935, which covers the Type A medicated articles: 
Chlortetracycline Premixes 50, 60, 70, 80, 100 (all contain CTC calcium 
complex equivalent to the indicated g/lb concentrations of CTC HCl), 
and 100 MR (100 g CTC HCl/lb).
    The drug products were the subject of a NAS/NRC DESI evaluation of 
effectiveness (DESI 0113NV). The findings were published in the Federal 
Register of July 21, 1970 (35 FR 11646). NAS/NRC evaluated the drug 
products as probably effective for growth promotion and feed efficiency 
and for the treatment of animal diseases caused by pathogens sensitive 
to chlortetracycline. NAS/NRC stated that:
    (1) Claims made regarding ``for prevention of'' or ``to 
prevent'' should be replaced with ``as an aid in the control of'' or 
``to aid in the control of'''; (2) claims for growth promotion or 
stimulation are disallowed and claims for faster gains and/or feed 
efficiency should be stated as ``may result in faster gains and/or 
improved feed efficiency under appropriate conditions''; (3) 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; (4) claims pertaining to egg production and hatchability 
should be changed to ``May aid in maintaining egg production and 
hatchability, under appropriate conditions, by controlling 
pathogenic microorganisms''; (5) the labels should warn that treated 
animals must actually be consuming enough medicated water or 
medicated feed to provide a therapeutic dosage under the conditions 
that prevail and, as a precaution, state the desired oral dose per 
unit of animal weight per day for each species as a guide to 
effective usage of the preparation in drinking water or feed; and 
(6) effective blood levels are required for each recommended dosage.

    FDA concurred with the NAS/NRC findings, interpreting the phrase 
``* * * cannot be so qualified * * *'' in above item (3) to mean ``* * 
* is not supported by adequate data * * *'' FDA reviewed all available 
effectiveness data of products subject to the evaluation and concluded 
that the data supported effectiveness for the control and treatment of 
certain bacterial diseases susceptible to CTC in chickens, turkeys, 
swine, sheep, calves, and cattle.

    The NAS/NRC DESI evaluation is concerned only with the drugs' 
effectiveness and safety to the treated animal. 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 the drugs or their metabolites 
in food products derived from treated animals.

    The five subject sponsors filed supplements that revised the 
labeling of their products to comply with the findings of the NAS/NRC 
review and FDA's conclusions concerning those findings. The 
supplemental NADA's were approved as of February 16, 1996. The 
revisions to Sec. 558.128 (21 CFR 558.128) list the NAS/NRC and FDA-
approved conditions of use for CTC-containing Type A medicated 
articles.

    Products which comply with the NAS/NRC findings and FDA's 
conclusions regarding those findings are eligible for copying under the 
Generic Animal Drug and Patent Term Restoration Act (GADPTRA) (see the 
eighth in a series of policy letters issued to facilitate 
implementation of GADPTRA that published in the Federal Register of 
August 21, 1991 (56 FR 41561). Accordingly, sponsors may now

[[Page 35950]]

obtain approval of abbreviated new animal drug applications (ANADA's) 
for these CTC Type A medicated articles.
    FDA has incorporated within Sec. 558.128 a warning against use of 
CTC feed in veal calves as part of a general effort to distinguish 
between ruminating calves and preruminating calves based on information 
indicating that withdrawal periods established in ruminating calves may 
not be adequate for preruminating calves.
    Also, the agency has removed in Sec. 558.128 the use of the fixed 
combination for chlortetracycline and sulfamethazine to treat beef 
cattle. FDA has recodified this approval in a separate section 
(Sec. 558.140 (21 CFR 558.140)), as has been done for other fixed 
combinations. In addition, the agency is using this occasion, of the 
DESI finalization of the CTC Type A medicated articles, to amend those 
portions of the regulations containing CTC combination feeds (see list 
in Sec. 558.128(c)(5)) to revise the CTC claim language to make it 
consistent with the NAS/NRC and FDA-approved conditions of use.
    Furthermore, the agency is deleting the citations for CTC in 
Sec. 510.515 (21 CFR 510.515). Section 510.515 defines antibiotic drugs 
permitted in feed that were exempt from the requirement of 
certification. GADPTRA (Pub. L. 100-670) signed on November 16, 1988, 
removed the requirement for certification of antibiotic drugs for 
animal use. In fact, in a final rule published in the Federal Register 
of May 26, 1989 (54 FR 22741), the agency revoked the antibiotic 
procedural regulations. The published exemption constituted a sanction 
by the agency for use of the listed antibiotics. With the finalization 
of the DESI evaluation of the CTC products, the sanction is obsolete. 
Also, by deleting the CTC listing from Sec. 510.515, the agency is 
correcting an error introduced when the regulation was published. Our 
records indicate that concurrent cites to oxytetracycline in 
Sec. 510.515(b)(7)(i) and (b)(17)(i) were incorrect, as oxytetracycline 
was not considered a certifiable antibiotic animal drug; therefore, it 
was incorrectly listed in Sec. 510.515.
    In the Federal Register of October 21, 1977 (42 FR 56264), the then 
Bureau of Veterinary Medicine issued a notice of opportunity for a 
hearing (NOOH) on a proposal to withdraw approval of certain NADA's 
listed in Sec. 558.15, for most subtherapeutic uses of tetracycline 
(CTC and oxytetracycline) in animal feed. The NOOH was issued in 
response to scientific research suggesting that subtherapeutic use of 
such drugs has contributed to the pool of antibiotic-resistant 
pathogenic microorganisms in food animals. Furthermore, research 
indicated that the drug resistance could be transferred to pathogenic 
organisms in humans. The NOOH is still pending and approval of these 
supplements to finalize the DESI review process for CTC Type A 
medicated articles does not constitute a bar to subsequent action to 
withdraw approval on the grounds cited in the outstanding NOOH.
    In accordance with the freedom of information provisions of part 20 
(21 CFR part 20) and Sec. 514.11(e)(2)(ii) (21 CFR 514.11(e)(2)(ii)), a 
summary of safety and effectiveness data and information submitted to 
support approval of this application may be seen in the Dockets 
Management Branch (HFA-305), Food and Drug Administration, 12420 
Parklawn Dr., rm. 1-23, Rockville, MD 20857, between 9 a.m. and 4 p.m., 
Monday through Friday.
    Under section 512(c)(2)(F)(iii) of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 360b(c)(2)(F)(iii)), these approvals for food-
producing animals do not qualify for marketing exclusivity because the 
supplemental applications do not contain reports of new clinical or 
field investigations (other than bioequivalence or residue studies) and 
new human food safety studies (other than bioequivalence or residue 
studies) essential to the approvals and conducted or sponsored by the 
applicant.
    The agency has carefully considered the potential environmental 
effects of this action. FDA 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 and the evidence supporting that finding, 
contained in an environmental assessment, may be seen in the Dockets 
Management Branch (address above) between 9 a.m. and 4 p.m., Monday 
through Friday.

List of Subjects -

21 CFR Part 510

    Administrative practice and procedure, Animal drugs, Labeling, 
Reporting and recordkeeping requirements.

21 CFR Part 558

    Animal drugs, Animal feeds.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs and 
redelegated to the Center for Veterinary Medicine, 21 CFR parts 510 and 
558 are amended as follows:

PART 510--NEW ANIMAL DRUGS

    1. The authority citation for 21 CFR part 510 continues to read as 
follows:

    -Authority: Secs. 201, 301, 501, 502, 503, 512, 701, 721 of the 
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 351, 352, 
353, 360b, 371, 379e).

Sec. 510.515  [Amended]

    2. Section 510.515 Animal feeds bearing or containing new animal 
drugs subject to the provision of section 512(n) of the act is amended 
in paragraph (b) by removing and reserving paragraphs (b)(7), (b)(17), 
(b)(25), and (b)(29); by redesignating paragraphs (b)(10) and (b)(13) 
as paragraphs (b)(1) and (b)(2); and in the table in paragraph (c) by 
removing entries 6, 7, and 8 for ``Chlortetracycline.''

PART 558--NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS

    3. The authority citation for 21 CFR part 558 continues to read as 
follows:

    Authority: Secs. 512, 701 of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 360b, 371).

    4. Section 558.55 is amended in the table in paragraph (d)(2) under 
entries (i), (ii), and (iv) by revising the items for 
``Chlortetracycline 100 to 200'' and by adding new items for 
``Chlortetracycline 200 to 400'' to read as follows:


Sec. 558.55  Amprolium.

* * * * *
    (d) * * *
    (2) * * *

[[Page 35951]]



                                                                        
------------------------------------------------------------------------
  Amprolium in    Combination in   Indications                          
 grams per ton    grams per ton      for use      Limitations    Sponsor
------------------------------------------------------------------------
(i) * * *                                                               
  *                    *                    *                    *      
                   *                    *                    *          
                 Chlortetracycli  Chickens;      Do not feed            
                  ne 100 to 200.   development    to chickens           
                                   of active      producing             
                                   immunity to    eggs for              
                                   coccidiosis;   human                 
                                   control of     consumption.          
                                   infectious     Feed for 7            
                                   synovitis      to 14 d.              
                                   caused by                            
                                   Mycoplasma                           
                                   synoviae                             
                                   susceptible                          
                                   to                                   
                                   chlortetracy                         
                                   cline.                               
                 Chlortetracycli  Chickens;      Do not feed            
                  ne 200 to 400.   development    to chickens           
                                   of active      producing             
                                   immunity to    eggs for              
                                   coccidiosis;   human                 
                                   control of     consumption.          
                                   chronic        Feed for 7            
                                   respiratory    to 14 d.              
                                   disease                              
                                   (CRD) and                            
                                   air sac                              
                                   infection                            
                                   caused by M.                         
                                   gallisepticu                         
                                   m and E.                             
                                   coli                                 
                                   susceptible                          
                                   to                                   
                                   chlortetracy                         
                                   cline.                               
                                                                        
  *                    *                    *                    *      
                   *                    *                    *          
(ii) * * *                                                              
  *                    *                    *                    *      
                   *                    *                    *          
                 Chlortetracycli  Chickens;      Do not feed            
                  ne 100 to 200.   prevention     to chickens           
                                   of             producing             
                                   coccidiosis    eggs for              
                                   caused by E.   human                 
                                   tenella        consumption.          
                                   only;          Feed for 7            
                                   control of     to 14 d.              
                                   infectious                           
                                   synovitis                            
                                   caused by M.                         
                                   synoviae                             
                                   susceptible                          
                                   to                                   
                                   chlortetracy                         
                                   cline.                               
                 Chlortetracycli  Chickens;      Do not feed            
                  ne 200 to 400.   prevention     to chickens           
                                   of             producing             
                                   coccidiosis    eggs for              
                                   caused by E.   human                 
                                   tenella        consumption.          
                                   only;          Feed for 7            
                                   control of     to 14 d.              
                                   chronic                              
                                   respiratory                          
                                   disease                              
                                   (CRD) and                            
                                   air sac                              
                                   infection                            
                                   caused by M.                         
                                   gallisepticu                         
                                   m and E.                             
                                   coli                                 
                                   susceptible                          
                                   to                                   
                                   chlortetracy                         
                                   cline.                               
                                                                        
  *                    *                    *                    *      
                   *                    *                    *          
(iv) * * *                                                              
  *                    *                    *                    *      
                   *                    *                    *          
                 Chlortetracycli  Chickens       Do not feed            
                  ne 100 to 200.   where          to chickens           
                                   immunity to    producing             
                                   coccidiosis    eggs for              
                                   is not         human                 
                                   desired;       consumption.          
                                   prevention     Feed for 7            
                                   of             to 14 d.              
                                   coccidiosis;                         
                                   control of                           
                                   infectious                           
                                   synovitis                            
                                   caused by M.                         
                                   synoviae                             
                                   susceptible                          
                                   to                                   
                                   chlortetracy                         
                                   cline.                               
                 Chlortetracycli  Chickens       Do not feed            
                  ne 200 to 400.   where          to chickens           
                                   immunity to    producing             
                                   coccidiosis    eggs for              
                                   is not         human                 
                                   desired;       consumption.          
                                   control of     Feed for 7            
                                   chronic        to 14 d.              
                                   respiratory                          
                                   disease                              
                                   (CRD) and                            
                                   air sac                              
                                   infection                            
                                   caused by M.                         
                                   gallisepticu                         
                                   m and E.                             
                                   coli                                 
                                   susceptible                          
                                   to                                   
                                   chlortetracy                         
                                   cline.                               
  *                    *                    *                    *      
                   *                    *                    *          
------------------------------------------------------------------------

* * * * *
    5. Section 558.58 is amended in the table in paragraph (d)(1) by 
revising entry (iv) for the items ``Chlortetracycline 100 to 200'' and 
``Chlortetracycline 200'' to read as follows:


Sec. 558.58   Amprolium and ethopabate.

* * * * *
    (d) *  *  *
    (1) *  *  *

[[Page 35952]]



                                                                        
------------------------------------------------------------------------
 Amprolium and                                                          
 ethopabate in   Combination in   Indications   Limitations    Sponsor  
 grams per ton    grams per ton     for use                             
------------------------------------------------------------------------
  *                    *                    *                    *      
                   *                    *                    *          
(iv) * * *                                                              
  *                    *                    *                    *      
                   *                    *                    *          
                                                                        
                 Chlortetracycl  For chickens  Do not feed              
                  ine 100 to      where         to chickens             
                  200.            immunity to   producing               
                                  coccidiosis   eggs for                
                                  is not        human                   
                                  desired;      consumption             
                                  prevention    . Feed for              
                                  of            7 to 14 d.              
                                  coccidiosis                           
                                  ; control                             
                                  of                                    
                                  infectious                            
                                  synovitis                             
                                  caused by                             
                                  Mycoplasma                            
                                  synoviae                              
                                  susceptible                           
                                  to                                    
                                  chlortetrac                           
                                  ycline.                               
                 Chlortetracycl  For chickens  In low                   
                  ine 200 to      where         calcium                 
                  400.            immunity to   feed                    
                                  coccidiosis   containing              
                                  is not        0.8%                    
                                  desired;      dietary                 
                                  prevention    calcium and             
                                  of            1.5% sodium             
                                  coccidiosis   sulfate;                
                                  ; control     feed                    
                                  of chronic    continuousl             
                                  respiratory   y as sole               
                                  disease       ration for              
                                  (CRD) and     7 to 14 d;              
                                  air sac       do not feed             
                                  infection     to chickens             
                                  caused by     producing               
                                  M.            eggs for                
                                  galliseptic   human                   
                                  um and E.     consumption             
                                  coli          .                       
                                  susceptible                           
                                  to                                    
                                  chlortetrac                           
                                  ycline.                               
  *                    *                    *                    *      
                   *                    *                    *          
------------------------------------------------------------------------

    6. Section 558.128 is amended by revising paragraphs (a), (b), and 
(c)(1); by removing paragraphs (c)(2) and (c)(3); and by redesignating 
paragraphs (c)(4) and (c)(5) as paragraphs (c)(2) and (c)(3), to read 
as follows:


Sec. 558.128   Chlortetracycline.

    (a) Approvals. Type A medicated articles containing the following 
concentrations of either chlortetracycline calcium complex equivalent 
to chlortetracycline hydrochloride or, for products intended for use in 
milk replacer, chlortetracycline hydrochloride:
    (1) 50 to 100 grams per pound to 000004 in Sec. 510.600(c) of this 
chapter.
    (2) 50 to 100 grams per pound to 000069.
    (3) 50 to 100 grams per pound to 046573.
    (4) 50 grams per pound to 012286.
    (5) 50 to 100 grams per pound to 053389 .
    (b) Related tolerances. See Sec. 556.150 of this chapter.
    (c)(1) It is used in feeds as follows:

                                                                                                                
----------------------------------------------------------------------------------------------------------------
  Chlortetracycline amount        Combination         Indications for use          Limitations         Sponsor  
----------------------------------------------------------------------------------------------------------------
(i) 10 to 50 g/ton                                   1. Chickens; increased  Do not feed to              000004,
                                                     rate of weight gain      chickens producing         000069,
                                                     and improved feed        eggs for human             012286,
                                                     efficiency.              consumption.               046573,
                                                                                                          053389
                                                    2. Growing turkeys;      Do not feed to turkeys           do
                                                     increased rate of        producing eggs for                
                                                     weight gain and          human consumption.                
                                                     improved feed                                              
                                                     efficiency.                                                
                                                    3. Growing swine;                                         do
                                                     increased rate of                                          
                                                     weight gain and                                            
                                                     improved feed                                              
                                                     efficiency.                                                
(ii) 20 to 50 g/ton                                 Growing sheep;                                       000004,
                                                     increased rate of                                   000069,
                                                     weight gain and                                     046573,
                                                     improved feed                                       053389.
                                                     efficiency.                                                
                                                                                                                
(iii) 50 to 100 g/ton                               Swine; reducing the                                  000004,
                                                     incidence of cervical                               000069,
                                                     lymphadenitis (jowl                                 012286,
                                                     abscesses) caused by                                046573,
                                                     Group E. Streptococci                                053389
                                                     susceptible to                                             
                                                     chlortetracycline.                                         
(iv) 100 to 200 g/ton                               Chickens; control of     Feed continuously for            do
                                                     infectious synovitis     7 to 14 d; do not                 
                                                     caused by Mycoplasma     feed to chickens                  
                                                     synoviae susceptible     producing eggs for                
                                                     to chlortetracycline.    human consumption.                

[[Page 35953]]

                                                                                                                
(v) 200 g/ton                                       Turkeys; control of      Feed continuously for            do
                                                     infectious synovitis     7 to 14 d; do not                 
                                                     caused by M. synoviae    feed to turkeys                   
                                                     susceptible to           producing eggs for                
                                                     chlortetracycline.       human consumption.                
(vi) 200 to 400 g/ton                               1. Chickens; control of  Feed continuously for            do
                                                     chronic respiratory      7 to 14 d; do not                 
                                                     disease (CRD) and air    feed to chickens                  
                                                     sac infection caused     producing eggs for                
                                                     by M. gallisepticum      human consumption.                
                                                     and E. coli                                                
                                                     susceptible to                                             
                                                     chlortetracycline.                                         
                                                    2. Ducks; control and    Feed in complete             000004
                                                     treatment of fowl        ration to provide                 
                                                     cholera caused by        from 8 to 28                      
                                                     Pasteurella multocida    milligrams per pound              
                                                     susceptible to           of body weight per                
                                                     chlortetracycline.       day depending upon                
                                                                              age and severity of               
                                                                              disease, for not more             
                                                                              than 21 d.                        
(vii) 400 g/ton                                     1. Turkeys; control of   Feed continuously for       000004,
                                                     hexamitiasis caused by   7 to 14 d; do not          000069,
                                                     Hexamita meleagrides     feed to turkeys            012286,
                                                     susceptible to           producing eggs for         046573,
                                                     chlortetracycline.       human consumption.          053389
                                                    2. Turkey poults not                                      do
                                                     over 4 weeks of age;                                       
                                                     reduction of mortality                                     
                                                     due to paratyphoid                                         
                                                     caused by Salmonella                                       
                                                     typhimurium                                                
                                                     susceptible to                                             
                                                     chlortetracycline.                                         
                                                    3. Breeding swine;       Feed continuously for            do
                                                     control of               not more than 14 d.               
                                                     leptospirosis                                              
                                                     (reducing the                                              
                                                     incidence of abortion                                      
                                                     and shedding of                                            
                                                     leptospirae) caused by                                     
                                                     Leptospira pomona                                          
                                                     susceptible to                                             
                                                     chlortetracycline.                                         
(viii) 500 g/ton                                    Chickens; reduction of   Feed for 5 d; do not             do
                                                     mortality due to E.      feed to chickens                  
                                                     coli infections          producing eggs for                
                                                     susceptible to           human consumption;                
                                                     chlortetracycline.       withdraw 24 h prior               
                                                                              to slaughter.                     
(ix)10 mg/g of finished                             Psittacine birds         Feed continuously for         00004
 feed daily.                                         (cockatoos, macaws,      45 d; each bird                   
                                                     and parrots) suspected   should consume daily              
                                                     or known to be           an amount of                      
                                                     infected with            medicated feed equal              
                                                     psittacosis caused by    to one fifth of its               
                                                     Chlamydia psittaci       body weight. Warning:             
                                                     sensitive to             ``Psittacosis, avian              
                                                     chlortetracycline.       chlamydiosis, or                  
                                                                              ornithosis is a                   
                                                                              reportable                        
                                                                              communicable disease,             
                                                                              transmissible between             
                                                                              wild and domestic                 
                                                                              birds, other animals,             
                                                                              and man. Contact                  
                                                                              appropriate public                
                                                                              health and regulatory             
                                                                              officials.''                      
(x) 0.1 mg/lb of body                               Calves (up to 250 lb);   In milk replacers or        000004,
 weight daily.                                       for increased rate of    starter feed; include      000069,
                                                     weight gain and          on labeling the            012286,
                                                     improved feed            warning: ``A               046573,
                                                     efficiency.              withdrawal period has       053389
                                                                              not been established              
                                                                              for this product in               
                                                                              pre-ruminating                    
                                                                              calves. Do not use in             
                                                                              calves to be                      
                                                                              processed for veal.''             
(xi) 0.5 mg/lb of body                              Beef cattle (over 700    Withdraw 48 h prior to           do
 weight daily.                                       lb); control of active   slaughter.                        
                                                     infection of                                               
                                                     anaplasmosis caused by                                     
                                                     Anaplasma marginale                                        
                                                     susceptible to                                             
                                                     chlortetracycline.                                         
(xii) 10 mg/lb of body                              1. Calves, beef and      Treat for not more               do
 weight                                              nonlactating dairy       than 5 d; in feed                 
                                                     cattle; treatment of     excluding milk                    
                                                     bacterial enteritis      replacers; withdraw               
                                                     caused by E. coli and    10 d prior to                     
                                                     bacterial pneumonia      slaughter except for              
                                                     caused by P. multocida   24 h for sponsor                  
                                                     organisms susceptible    046573; include on                
                                                     to chlortetracycline.    labeling the warning:             
                                                                              ``A withdrawal period             
                                                                              has not been                      
                                                                              established for this              
                                                                              product in pre-                   
                                                                              ruminating calves. Do             
                                                                              not use in calves to              
                                                                              be processed for                  
                                                                              veal.''                           

[[Page 35954]]

                                                                                                                
                                                    2. Calves (up to 250     In milk replacers or               
                                                     lb); treatment of        starter feed; include             
                                                     bacterial enteritis      on labeling the                   
                                                     caused by E. coli        warning: ``A                      
                                                     susceptible to           withdrawal period has             
                                                     chlortetracycline.       not been established              
                                                                              for this product in               
                                                                              pre-ruminating                    
                                                                              calves. Do not use in             
                                                                              calves to be                      
                                                                              processed for veal.''             
                                                    3. Swine; treatment of   Feed for not more than      000004,
                                                     bacterial enteritis      14 d; withdraw 5 d         000069,
                                                     caused by E. coli and    prior to slaughter         012286,
                                                     S. choleraesuis and      for sponsor 012286.        046573,
                                                     bacterial pneumonia                                  053389
                                                     caused by P. multocida                                     
                                                     susceptible to                                             
                                                     chlortetracycline.                                         
(xiii) 25 mg/lb of body                             Turkeys; control of      Feed continuously for            do
 weight                                              complicating bacterial   7 to 14 d; do not                 
                                                     organisms associated     feed to turkeys                   
                                                     with bluecomb            producing eggs for                
                                                     (transmissible           human consumption.                
                                                     enteritis; coronaviral                                     
                                                     enteritis) susceptible                                     
                                                     to chlortetracycline.                                      
(xiv) 25 to 70 mg/head/day                          Calves (250 to 400 lb);  Include on labeling         000004,
                                                     increased rate of        the warning: ``A           000069,
                                                     weight gain and          withdrawal period has      012286,
                                                     improved feed            not been established       046573,
                                                     efficiency.              for this product in         053389
                                                                              pre-ruminating                    
                                                                              calves. Do not use in             
                                                                              calves to be                      
                                                                              processed for veal.''             
(xv) 70 mg/head/day                                 Growing cattle (over     do                               do
                                                     400 lb) increased rate                                     
                                                     of weight gain,                                            
                                                     improved feed                                              
                                                     efficiency, and                                            
                                                     reduction of liver                                         
                                                     condemnation due to                                        
                                                     liver abscesses.                                           
(xvi) 80 mg/head/day                                Breeding sheep;                                      000004,
                                                     reducing the incidence                              000069,
                                                     of (vibrionic)                                      046573,
                                                     abortion caused by                                   053389
                                                     Campylobacter fetus                                        
                                                     infection susceptible                                      
                                                     to chlortetracycline.                                      
(xvii) 350 mg/head/day                              1. Cattle (under 700     Withdraw 48 h prior to      000004,
                                                     lb); control of          slaughter.                 000069,
                                                     bacterial pneumonia                                 012286,
                                                     associated with                                     046573,
                                                     shipping fever complex                               053389
                                                     caused by Pasteurella                                      
                                                     spp. susceptible to                                        
                                                     chlortetracycline.                                         
                                                    2. Beef cattle (under    do                               do
                                                     700 lb); control of                                        
                                                     active infection of                                        
                                                     anaplasmosis caused by                                     
                                                     A. marginale                                               
                                                     susceptible to                                             
                                                     chlortetracycline.                                         
----------------------------------------------------------------------------------------------------------------



* * * * *
    7. New Sec. 558.140 is added to subpart B to read as follows:


Sec. 558.140   Chlortetracycline and sulfamethazine.

    (a) Approvals. Type A medicated articles: 35 grams of 
chlortetracycline per pound with 7.7 percent (35 grams) of 
sulfamethazine to 000004 in Sec. 510.600(c) of this chapter.
    (b) Related tolerances. See Secs. 556.150 and 556.670 of this 
chapter.
    (c) It is used in feed for beef cattle as follows:
    (1) Amount per head per day. Chlortetracycline, 350 milligrams plus 
sulfamethazine, 350 milligrams.
    (2) Indications for use. Aid in the maintenance of weight gains in 
the presence of respiratory disease such as shipping fever.
    (3) Limitations. Feed for 28 days; withdraw 7 days prior to 
slaughter.
    8. Section 558.175 is amended by revising paragraph (c)(2)(ii) to 
read as follows:


Sec. 558.175   Clopidol.

* * * * *
    (c) * * *
    (2) * * *
    (ii) Amount per ton. Clopidol, 113.5 grams (0.0125 percent) plus 
chlortetracycline 100 to 200 grams.
    (a) Indications for use. Aid in the prevention of coccidiosis 
caused by E. tenella, E. necatrix, E. acervulina, E. maxima, E. 
brunetti, and E. mivati; control of infectious synovitis caused by 
Mycoplasma synoviae susceptible to chlortetracycline.
    (b) Limitations. Feed continuously as sole ration from the time 
chicks are placed in floor pens for 7 to 14 days.
* * * * *
    9. Section 558.195 is amended in the table in paragraph (d) in the 
entry for ``27.2 (0.003pct)'' by removing the item for 
``Chlortetracycline 200'' and adding in its place an item for 
``Chlortetracycline 100 to 200'' and an item for ``Chlortetracycline 
200 and 400'' to read as follow:


Sec. 558.195   Decoquinate.

* * * * *
    (d) *  *  *

[[Page 35955]]



                                                                        
------------------------------------------------------------------------
                 Combination                                            
Decoquinate in   in grams per   Indications    Limitations     Sponsor  
 grams per ton       ton          for use                               
------------------------------------------------------------------------
27.2                                                                    
 (0.003pct)                                                             
  *                    *                    *                    *      
                   *                    *                    *          
                Chlortetracyc  Chickens; for  Do not feed         011526
                 line 100 to    the            to chickens              
                 200.           prevention     producing                
                                of             eggs for                 
                                coccidiosis    human                    
                                caused by      consumption;             
                                Eimeria        in low                   
                                tenella, E.    calcium feed             
                                necatrix, E.   containing               
                                mivati, E.     0.8 pct. of              
                                acervulina,    calcium;                 
                                E. maxima,     feed                     
                                and E.         continuously             
                                brunetti;      7 to 14                  
                                control of     days.                    
                                infectious                              
                                synovitis                               
                                caused by                               
                                Mycoplasma                              
                                synoviae                                
                                susceptible                             
                                to                                      
                                chlortetracy                            
                                cline.                                  
                Chlortetracyc  Chickens; for  do                  011526
                 line 200 to    the                                     
                 400.           prevention                              
                                of                                      
                                coccidiosis                             
                                caused by E.                            
                                tenella, E.                             
                                necatrix, E.                            
                                mivati , E.                             
                                acervulina,                             
                                E. maxima,                              
                                and E.                                  
                                brunetti;                               
                                control of                              
                                chronic                                 
                                respiratory                             
                                disease                                 
                                (CRD) and                               
                                air sac                                 
                                infection                               
                                caused by M.                            
                                gallisepticu                            
                                m and E.                                
                                coli                                    
                                susceptible                             
                                to                                      
                                chlortetracy                            
                                cline.                                  
  *                    *                    *                    *      
                   *                    *                    *          
------------------------------------------------------------------------

    10. Section 558.274 is amended in the table in paragraph (c)(1) 
under entry (i) by revising the item for ``Chlortetracycline 100 to 
200'' and by adding a new item for ``Chlortetracycline 200 to 400''; 
and under entry (ii) by removing the item for ``Chlortetracycline 100 
to 200'' and adding in its place an item for ``Chlortetracycline 400'' 
to read as follows:


Sec. 558.274  Hygromycin B.

* * * * *
    (c) * * *
    (1) * * *

                                                                        
------------------------------------------------------------------------
 Hygromycin B    Combination                                            
 in grams per    in grams per   Indications    Limitations     Sponsor  
      ton            ton          for use                               
------------------------------------------------------------------------
(i) * * *                                                               
  *                    *                    *                    *      
                   *                    *                    *          
                Chlortetracyc  Chickens;      Do not feed               
                 line 100 to    control of     to chickens              
                 200.           infestation    producing                
                                of large       eggs for                 
                                roundworms     human                    
                                (Ascaris       consumption;             
                                galli),        feed for 7               
                                cecal worms    to 14 days;              
                                (Heterakis     withdraw 3               
                                gallinae),     days before              
                                and            slaughter.               
                                capillary                               
                                worms                                   
                                (Capillaria                             
                                obsignata);                             
                                control of                              
                                infectious                              
                                synovitis                               
                                caused by                               
                                Mycoplasma                              
                                synoviae                                
                                susceptible                             
                                to                                      
                                chlortetracy                            
                                cline.                                  
                Chlortetracyc  Chickens;      do                        
                 line 200 to    control of                              
                 400.           infestation                             
                                of large                                
                                roundworms                              
                                (Ascaris                                
                                galli),                                 
                                cecal worms                             
                                (H.                                     
                                Gallinae),                              
                                and                                     
                                capillary                               
                                worms                                   
                                (Capillaria                             
                                obsignata);                             
                                control of                              
                                chronic                                 
                                respiratory                             
                                disease                                 
                                (CRD) and                               
                                air sac                                 
                                infection                               
                                caused by                               
                                Mycoplasma                              
                                gallisepticu                            
                                m and                                   
                                Escherichia                             
                                coli                                    
                                susceptible                             
                                to                                      
                                chlortetracy                            
                                cline.                                  
  *                    *                    *                    *      
                   *                    *                    *          
(ii) * * *                                                              

[[Page 35956]]

                                                                        
  *                    *                    *                    *      
                   *                    *                    *          
                Chlortetracyc  Swine;         Withdraw 15 d             
                 line 400.      control of     before                   
                                infestation    slaughter.               
                                of large                                
                                roundworms                              
                                (Ascaris                                
                                suis),                                  
                                nodular                                 
                                worms                                   
                                (Oesophagost                            
                                omum                                    
                                dentatum)                               
                                and                                     
                                whipworms                               
                                (Trichuris                              
                                suis);                                  
                                treatment of                            
                                bacterial                               
                                enteritis                               
                                caused by E.                            
                                coli and                                
                                Salmonella                              
                                choleraesuis                            
                                and                                     
                                bacterial                               
                                pneumonia                               
                                caused by P.                            
                                multocida                               
                                susceptible                             
                                to                                      
                                chlortetracy                            
                                cline.                                  
  *                    *                    *                    *      
                   *                    *                    *          
------------------------------------------------------------------------


* * * * *
    11. Section 558.515 is amended by revising paragraphs (d)(1)(iii), 
(d)(1)(iv), and (d)(1)(v)(b) to read as follows:


Sec. 558.515  Robenidine hydrochloride.

* * * * *
    (d) * * *
    (1) * * *
    (iii) Amount per ton. Robenidine hydrochloride, 30 grams (0.0033 
percent) plus chlortetracycline, 100 to 200 grams.
    (a) Indications for use. As an aid in the prevention of coccidiosis 
caused by E. mivati, E. brunetti, E. tenella, E. acervulina, E. maxima, 
and E. necatrix; control of infectious synovitis caused by Mycoplasma 
synoviae susceptible to chlortetracycline.
    (b) Limitations. Withdraw 5 days prior to slaughter; do not feed to 
chickens producing eggs for human consumption; feed continuously as 
sole ration up to 14 days.
    (iv) Amount per ton. Robenidine hydrochloride, 30 grams (0.0033 
percent) plus chlortetracycline, 200 to 400 grams.
    (a) Indications for use. As an aid in the prevention of coccidiosis 
caused by E. mivati, E. brunetti, E. tenella, E. acervulina, E. maxima, 
and E. necatrix; control of chronic respiratory disease (CRD) and air 
sac infection caused by M. gallisepticum and E. coli susceptible to 
chlortetracycline.
    (b) Limitations. Withdraw 5 days prior to slaughter; do not feed to 
chickens producing eggs for human consumption; feed continuously as 
sole ration up to 14 days.
    (v) * * *
    (b) Limitations. Withdraw 5 days prior to slaughter; do not feed to 
chickens producing eggs for human consumption; feed continuously up to 
5 days.
 * * * * *
    12. Section 558.530 is amended by revising paragraph (a); by 
redesignating paragraphs (d)(2), (d)(3), and (d)(4) as paragraphs 
(d)(4), (d)(5), and (d)(6), by adding new paragraphs (d)(2) and (d)(3); 
and by revising newly redesignated paragraph (d)(4) to read as set 
forth below, and in newly redesignated paragraph (d)(6) by 
redesignating paragraphs (d)(6)(i)(a) through (d) as paragraphs 
(d)(6)(i)(A) through (D).:


Sec. 558.530  Roxarsone.

    (a) Approvals. Type A medicated articles: (1) 10, 20, and 50 
percent to 011526 in Sec. 510.600(c) of this chapter for use as in 
paragraph (d)(1) of this section.
    (2) 10, 20, 50, and 80 percent to 046573 in Sec. 510.600(c) of this 
chapter for use as in paragraphs (d)(1), (d)(2), (d)(3), and (d)(4) of 
this section.
* * * * *
    (d) * * *
    (2) Growing chickens--(i) Grams per ton. Roxarsone, 22.7 to 45.4 
(0.0025 to 0.005 percent) plus chlortetracycline, 10 to 50.
    (A) Indications for use. For increased rate of weight gain, 
improved feed efficiency, and improved pigmentation.
    (B) Limitations. Do not feed to chickens producing eggs for human 
consumption; withdraw 5 days before slaughter; as sole source of 
organic arsenic; drug overdose or lack of water may result in leg 
weakness; feed continuously throughout growing period.
    (ii) Grams per ton. Roxarsone 22.7 to 45.4 (0.0025 to 0.005 
percent) plus chlortetracycline, 100 to 200.
    (A) Indications for use. For increased rate of weight gain, 
improved feed efficiency, and improved pigmentation; control of 
infectious synovitis caused by Mycoplasma synoviae susceptible to 
chlortetracycline.
    (B) Limitations. See paragraph (d)(2)(i)(B) of this section except 
feed continuously for 7 to 14 days.
    (iii) Grams per ton. Roxarsone 22.7 to 45.4 (0.0025 to 0.005 
percent) plus chlortetracycline, 200 to 400.
    (A) Indications for use. For increased rate of weight gain, 
improved feed efficiency, and improved pigmentation; control of chronic 
respiratory disease (CRD) and air sac infection caused by M. 
gallisepticum and Escherichia coli susceptible to chlortetracycline.
    (B) Limitations. See paragraph (d)(2)(i)(B) of this section except 
feed continuously for 7 to 14 days.
    (iv) Grams per ton. Roxarsone 22.7 to 45.4 (0.0025 to 0.005 
percent) plus chlortetracycline, 500.
    (A) Indications for use. For increased rate of weight gain, 
improved feed efficiency, and improved pigmentation; reduction of 
mortality due to E. coli infections susceptible to chlortetracycline.
    (B) Limitations. See paragraph (d)(2)(i)(B) of this section except 
feed for 5 days.
    (3) Growing turkeys--(i) Grams per ton. Roxarsone 22.7 to 45.4 
(0.0025 to 0.005 percent) plus chlortetracycline, 10 to 50.
    (A) Indications for use. For increased rate of weight gain, 
improved feed efficiency, and improved pigmentation.
    (B) Limitations. Do not feed to turkeys producing eggs for human 
consumption; withdraw 5 days before slaughter; as sole source of 
organic arsenic; drug overdose or lack of water may result in leg 
weakness; feed continuously throughout growing season.
    (ii) Grams per ton. Roxarsone 22.7 to 45.4 (0.0025 to 0.005 
percent) plus chlortetracycline 200.
    (A) Indications for use. For increased rate of weight gain, 
improved feed efficiency, and improved pigmentation; control of 
infectious synovitis caused by

[[Page 35957]]

M. synoviae susceptible to chlortetracycline.
    (B) Limitations. See paragraph (d)(3)(i)(B) of this section except 
that the drug should only be fed continuously for 7 to 14 days.
    (iii) Grams per ton. Roxarsone 22.7 to 45.4 (0.0025 to 0.005 
percent) plus chlortetracycline, 400.
    (A) Indications for use. For increased rate of weight gain, 
improved feed efficiency, and improved pigmentation; control of 
hexamitiasis caused by Hexamita meleagrides susceptible to 
chlortetracycline. Turkey poults not over 4 weeks of age: Reduction of 
mortality due to paratyphoid caused by Salmonella typhimurium 
susceptible to chlortetracycline.
    (B) Limitations. See paragraph (d)(3)(i)(B) of this section except 
that the drug should only be fed continuously for 7 to 14 days.
    (iv) Amount. Roxarsone 22.7 to 45.4 grams per ton (0.0025 to 0.005 
percent) plus chlortetracycline, 25 milligrams per pound of body weight 
daily.
    (A) Indications for use. For increased rate of weight gain, 
improved feed efficiency, and improved pigmentation; control of 
complicating bacterial organisms associated with bluecomb 
(transmissible enteritis, coronaviral enteritis) susceptible to 
chlortetracycline.
    (B) Limitations. See paragraph (d)(3)(i)(B) of this section except 
that the drug should only be fed continuously for 7 to 14 days.
    (4) Growing-finishing swine--(i) Grams per ton. Roxarsone 22.7 to 
34.1 (0.0025 to 0.00375 percent).
    (A) Indications for use. For increased rate of weight gain and 
improved feed efficiency.
    (B) Limitations. Withdraw 5 days before slaughter; as sole source 
of organic arsenic; feed continuously throughout growing season.
    (ii) Grams per ton. Roxarsone 22.7 to 34.1 (0.0025 to 0.00375 
percent) plus chlortetracycline, 400 (to administer 10 milligrams per 
pound of body weight).
    (A) Indications for use. For increased rate of weight gain and 
improved feed efficiency; treatment of bacterial enteritis caused by E. 
coli and S. choleraesuis and bacterial pneumonia caused by P. multocida 
susceptible to chlortetracycline.
    (B) Limitations. Withdraw 5 days before slaughter; as sole source 
of organic arsenic; feed for not more than 14 days.
    (iii) Grams per ton. Roxarsone 181.5 (0.02 percent).
    (A) Indications for use. For the treatment of swine dysentery.
    (B) Limitations. Feed for not more than 6 consecutive days; if 
improvement is not observed, consult a veterinarian; withdraw 5 days 
before slaughter; as a sole source or organic arsenic; animals must 
consume enough medicated feed to provide a therapeutic dose.
    (iv) Grams per ton. Roxarsone, 181.5 (0.02 percent) plus 
chlortetracycline, 10 to 50.
    (A) Indications for use. For the treatment of swine dysentery; 
increased rate of weight gain and improved feed efficiency.
    (B) Limitations. See paragraph (d)(4)(iii)(B) of this section.
    (v) Grams per ton. Roxarsone, 181.5 (0.02 percent) plus 
chlortetracycline, 400.
    (A) Indications for use. For the treatment of swine dysentery; 
treatment of bacterial enteritis caused by E. coli and S. choleraesuis 
and bacterial pneumonia caused by P. multocida susceptible to 
chlortetracycline.
    (B) Limitations. See paragraph (d)(4)(iii)(B) of this section.
* * * * *
    13. Section 558.680 is amended in the table in paragraph (c)(1) 
under entries (i) and (ii) by revising the item for ``Chlortetracycline 
100 to 200''; by removing the item for ``Chlortetracycline 200'' and 
adding in its place an item for ``Chlortetracycline 200 to 400'' to 
read as follows:


Sec. 558.680  Zoalene.

* * * * *
    (c) * * *
    (1) * * *

                                                                        
------------------------------------------------------------------------
   Zoalene in     Combination in    Indications for                     
   grams/ton        grams/ton             use             Limitations   
------------------------------------------------------------------------
(i) * * *                                                               
  *                    *                    *                    *      
                   *                    *                    *          
                 Chlortetracycli  Replacement         Do not feed to    
                  ne 100 to 200.   chickens;           chickens         
                                   development of      producing eggs   
                                   active immunity     for human        
                                   to coccidiosis;     consumption;     
                                   control of          grower ration not
                                   infectious          to be fed to     
                                   synovitis caused    birds over 14    
                                   by Mycoplasma       weeks of age;    
                                   synoviae            feed as in       
                                   susceptible to      subtable in item 
                                   chlortetracycline   (i).             
                                   .                                    
                 Chlortetracycli  Replacement         Do not feed to    
                  ne 200 to 400.   chickens;           chickens         
                                   development of      producing eggs   
                                   active immunity     for human        
                                   to coccidiosis;     consumption;     
                                   control of          grower ration not
                                   chronic             to be fed to     
                                   respiratory         birds over 14    
                                   disease (CRD) and   weeks of age;    
                                   air sac infection   feed as in       
                                   caused by M.        subtable in item 
                                   gallisepticum and   (i).             
                                   Escherichia coli                     
                                   susceptible to                       
                                   chlortetracycline                    
                                   .                                    
  *                    *                    *                    *      
                   *                    *                    *          
(ii) * * *                                                              
  *                    *                    *                    *      
                   *                    *                    *          
                 Chlortetracycli  Broiler chickens;   Do not feed to    
                  ne 100 to 200    prevention and      chickens         
                                   control of          producing eggs   
                                   coccidiosis;        for human        
                                   control of          consumption; feed
                                   infectious          continuously for 
                                   synovitis caused    7 to 14 d.       
                                   by M. synoviae                       
                                   susceptible to                       
                                   chlortetracycline                    
                                   .                                    

[[Page 35958]]

                                                                        
                 Chlortetracycli  Broiler chickens;   Do not feed to    
                  ne 200 to 400    prevention and      chickens         
                                   control of          producing eggs   
                                   coccidiosis;        for human        
                                   control of          consumption; feed
                                   chronic             continuously for 
                                   respiratory         7 to 14 d.       
                                   disease (CRD) and                    
                                   air sac infection                    
                                   caused by M.                         
                                   gallisepticum and                    
                                   E. coli                              
                                   susceptible to                       
                                   chlortetracycline                    
                                   .                                    
  *                    *                    *                    *      
                   *                    *                    *          
------------------------------------------------------------------------


* * * * *

    Dated: June 13, 1996.
Andrew J. Beaulieau,
Acting Director, Office of New Animal Drug Evaluation, Center for 
Veterinary Medicine.
[FR Doc. 96-17169 Filed 7-8-96; 8:45 am]
BILLING CODE 4160-01-F