[Federal Register Volume 71, Number 62 (Friday, March 31, 2006)]
[Rules and Regulations]
[Pages 16223-16227]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 06-3120]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 558

[Docket No. 2003N-0324]


New Animal Drugs for Use in Animal Feeds; Bacitracin; Nicarbazin; 
Oxytetracycline and Neomycin; Penicillin

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the animal 
drug regulations to reflect approval of four supplemental new animal 
drug applications (NADAs) filed by Phibro Animal Health. One 
supplemental NADA provides for the use of fixed-combination Type A 
medicated articles containing oxytetracycline and neomycin sulfate to 
formulate two-way fixed-combination drug Type B and Type C medicated 
feeds for chickens, turkeys, swine, cattle, and sheep. Two of the 
supplemental NADAs provide for the use of approved, single-ingredient 
Type A medicated articles containing nicarbazin and penicillin, with or 
without roxarsone, to formulate two-way or three-way combination drug 
Type C medicated feeds for broiler chickens. The fourth supplemental 
NADA provides for the use of approved, single-ingredient Type A 
medicated articles nicarbazin, bacitracin methylene disalicylate, and 
roxarsone to formulate three-way combination drug Type C

[[Page 16224]]

medicated feeds for broiler chickens. These approvals reflect FDA's 
effectiveness conclusions which relied on the National Academy of 
Sciences/National Research Council (NAS/NRC) Drug Efficacy Study 
Group's evaluation of the effectiveness of these drugs when used in 
animal feed as single ingredients.

DATES: This rule is effective March 31, 2006.

FOR FURTHER INFORMATION CONTACT: Andrew J. Beaulieu, Center for 
Veterinary Medicine (HFV-50), 7519 Standish Pl., Rockville, MD 20855, 
240-276-9090, e-mail: [email protected].

SUPPLEMENTARY INFORMATION: In the Federal Register of August 8, 2003 
(68 FR 47332), as corrected October 7, 2003 (68 FR 57919), as part of 
the Drug Efficacy Study Implementation (DESI) program, CVM announced 
the effective conditions of use for several drug products and use 
combinations listed in 21 CFR 558.15. CVM proposed to withdraw the new 
animal drug applications (NADAs) for those products or use combinations 
lacking substantial evidence of effectiveness following a 90-day 
opportunity to supplement the NADAs with labeling conforming to the 
relevant findings of effectiveness. Phibro Animal Health, 65 Challenger 
Rd., 3d Floor, Ridgefield Park, NJ 07660, filed supplements to four of 
its approved NADAs to revise the labeling of its products to comply 
with these findings of effectiveness.
    Phibro Animal Health filed a supplement to approved NADA 94-975 for 
NEO-TM 50/50D and NEO-TM 100/100D (oxytetracycline and neomycin 
sulfate) Type A medicated articles. The supplemental NADA provides for 
use of these fixed-combination Type A medicated articles to formulate 
two-way fixed-combination drug Type B and Type C medicated feeds 
containing oxytetracycline and neomycin sulfate, in a 1:1 ratio, for 
several production and therapeutic indications in chickens, turkeys, 
swine, cattle, and sheep.
    Phibro Animal Health also filed a supplement to approved NADA 98-
371 for use of nicarbazin, procaine penicillin, and roxarsone single-
ingredient Type A medicated articles to make three-way combination drug 
Type C medicated feeds. This supplemental NADA provides for the use of 
combination feeds containing NICARBAZIN (nicarbazin) at 90.8 to 181.6 
grams per ton (g/ton), PENICILLIN G PROCAINE (procaine penicillin) at 
2.4 to 50 g/ton, and 3-NITRO (roxarsone) at 22.7 to 45.4 g/ton of feed 
in broiler chickens as an aid in preventing outbreaks of cecal (Eimeria 
tenella) and intestinal (E. acervulina, E. maxima, E. necatrix, and E. 
brunetti) coccidiosis; for increased rate of weight gain and improved 
feed efficiency; and for improved pigmentation.
    Phibro Animal Health also filed a supplement to approved NADA 98-
374 for use of nicarbazin and procaine penicillin G Type A medicated 
articles to formulate two-way combination drug Type C medicated feeds. 
This supplemental NADA provides for the use of combination feeds 
containing NICARBAZIN (nicarbazin) at 90.8 to 181.6 g/ton and 
PENICILLIN G PROCAINE (procaine penicillin) at 2.4 to 50 g/ton of feed 
in broiler chickens as an aid in preventing outbreaks of cecal (Eimeria 
tenella) and intestinal (E. acervulina, E. maxima, E. necatrix, and E. 
brunetti) coccidiosis; and for increased rate of weight gain and 
improved feed efficiency.
    Phibro Animal Health also filed a supplement to approved NADA 100-
853 for use of nicarbazin, bacitracin methylene disalicylate, and 
roxarsone single-ingredient Type A medicated articles to make three-way 
combination drug Type C medicated feeds. This supplemental NADA 
provides for the use of combination feeds containing NICARBAZIN 
(nicarbazin) at 90.8 to 181.6 g/ton, BMD (bacitracin methylene 
disalicylate) at 4 to 50 g/ton, and 3-NITRO (roxarsone) at 22.7 to 45.4 
g/ton of feed in broiler chickens as an aid in preventing outbreaks of 
cecal (Eimeria tenella) and intestinal (E. acervulina, E. maxima, E. 
necatrix, and E. brunetti) coccidiosis, and for increased rate of 
weight gain, improved feed efficiency, and improved pigmentation.
    The DESI evaluation is concerned only with the effectiveness of the 
drug products and use combinations. Nothing in this document 
constitutes a bar to further proceedings with respect to questions of 
safety of the subject drugs in treated animals or of the drugs or their 
metabolites in food products derived from treated animals.
    Products that comply with FDA's findings of effectiveness are 
eligible for copying, as described in the Generic Animal Drug and 
Patent Term Restoration Act Policy Letter Eight, August 21, 1991 (56 FR 
41561). Accordingly, sponsors may now obtain approval of abbreviated 
NADAs for this fixed combination Type A medicated article and three 
combination drug medicated feeds.
    The supplemental NADAs are approved as of February 15, 2006, and 
the regulations are amended in 21 CFR 558.76, 558.460, and 558.366, and 
also in 21 CFR part 558 by adding new Sec.  558.455 to reflect these 
approvals. Approval of these supplemental NADAs did not require review 
of any new safety or effectiveness data. Therefore, a freedom of 
information summary was not prepared.
    The agency has determined under 21 CFR 25.33(a)(2) that these 
actions are of a type that do not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.
    This rule does not meet the definition of ``rule'' in 5 U.S.C. 
804(3)(A) because it is a rule of ``particular applicability.'' 
Therefore, it is not subject to the congressional review requirements 
in 5 U.S.C. 801-808.

List of Subjects in 21 CFR Part 558

    Animal drugs, Animal feeds.

0
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 part 558 is 
amended as follows:

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

0
1. The authority citation for 21 CFR part 558 continues to read as 
follows:

    Authority: 21 U.S.C. 360b, 371.

0
2. In Sec.  558.76, revise paragraph (d)(3)(xiii) to read as follows:


Sec.  558.76  Bacitracin methylene disalicylate.

* * * * *
    (d) * * *
    (3) * * *
    (xiii) Nicarbazin alone or with narasin or roxarsone or with 
narasin and roxarsone as in Sec.  558.366.
* * * * *

0
3. In Sec.  558.366, amend the table in paragraph (d) after the entry 
for ``Narasin 27 to 45 and roxarsone 22.7 to 45.4'' by adding three 
entries to read as follows:


Sec.  558.366  Nicarbazin.

* * * * *
    (d) * * *

[[Page 16225]]



----------------------------------------------------------------------------------------------------------------
Nicarbazin in grams  Combination in grams
      per ton               per ton            Indications for use              Limitations            Sponsor
----------------------------------------------------------------------------------------------------------------
                                                  * * * * * * *
----------------------------------------------------------------------------------------------------------------
90.8 to 181.6 (0.01  Bacitracin methylene  Broiler chickens: As an aid  Feed continuously as sole         066104
 to 0.02 pct)         disalicylate 4 to     in preventing outbreaks of   ration from time chicks
                      50 and roxarsone      cecal (Eimeria tenella)      are placed on litter until
                      22.7 to 45.4          and intestinal (E.           past the time when
                                            acervulina, E. maxima, E.    coccidiosis is ordinarily
                                            necatrix, and E. brunetti)   a hazard; do not use as a
                                            coccidiosis, and for         treatment for outbreaks of
                                            increased rate of weight     coccidiosis. Feed as the
                                            gain and improved feed       sole source of organic
                                            efficiency, and improved     arsenic; drug overdose or
                                            pigmentation                 lack of water may result
                                                                         in leg weakness; do not
                                                                         use in flushing mashes.
                                                                         Discontinue medication 5
                                                                         days before marketing the
                                                                         birds for human
                                                                         consumption to allow for
                                                                         elimination of the drug
                                                                         from edible tissue. Do not
                                                                         feed to laying hens in
                                                                         production. Nicarbazin as
                                                                         provided by No. 066104;
                                                                         bacitracin methylene
                                                                         disalicylate and roxarsone
                                                                         by No. 046573 in Sec.
                                                                         510.600(c) of this chapter
----------------------------------------------------------------------------------------------------------------
                     Penicillin 2.4 to 50  Broiler chickens: As an aid  Feed continuously as sole         066104
                                            in preventing outbreaks of   ration from time chicks
                                            cecal (Eimeria tenella)      are placed on litter until
                                            and intestinal (E.           past the time when
                                            acervulina, E. maxima, E.    coccidiosis is ordinarily
                                            necatrix, and E. brunetti)   a hazard; do not use as a
                                            coccidiosis, and for         treatment for outbreaks of
                                            increased rate of weight     coccidiosis. Do not use in
                                            gain and improved feed       flushing mashes. Do not
                                            efficiency                   feed to chickens producing
                                                                         eggs for human
                                                                         consumption. Discontinue
                                                                         medication 5 days before
                                                                         marketing the birds for
                                                                         human consumption to allow
                                                                         for elimination of the
                                                                         drug from edible tissue.
                                                                         Penicillin as procaine
                                                                         penicillin G. Nicarbazin
                                                                         and penicillin as provided
                                                                         by No. 066104 in Sec.
                                                                         510.600(c) of this chapter
----------------------------------------------------------------------------------------------------------------
                     Penicillin 2.4 to 50  Broiler chickens: As an aid  Feed continuously as sole         066104
                      and roxarsone 22.7    in preventing outbreaks of   ration from time chicks
                      to 45.4               cecal (Eimeria tenella)      are placed on litter until
                                            and intestinal (E.           past the time when
                                            acervulina, E. maxima, E.    coccidiosis is ordinarily
                                            necatrix, and E. brunetti)   a hazard; do not use as a
                                            coccidiosis, and for         treatment for outbreaks of
                                            increased rate of weight     coccidiosis. Feed as the
                                            gain and improved feed       sole source of organic
                                            efficiency, and improved     arsenic; drug overdose or
                                            pigmentation                 lack of water may result
                                                                         in leg weakness; do not
                                                                         use in flushing mashes.
                                                                         Discontinue medication 5
                                                                         days before marketing the
                                                                         birds for human
                                                                         consumption to allow for
                                                                         elimination of the drug
                                                                         from edible tissue. Do not
                                                                         feed to laying hens in
                                                                         production. Penicillin as
                                                                         procaine penicillin G.
                                                                         Nicarbazin and penicillin
                                                                         as provided by No. 066104;
                                                                         roxarsone by No. 046573 in
                                                                         Sec.   510.600(c) of this
                                                                         chapter
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                                                  * * * * * * *
----------------------------------------------------------------------------------------------------------------


0
4. Add Sec.  558.455 to read as follows:


Sec.  558.455  Oxytetracycline and neomycin.

    (a) Specifications. Type A medicated articles containing 
oxytetracycline equivalent to 50 grams per pound (g/lb) oxytetracycline 
hydrochloride and 50 g/lb neomycin sulfate or oxytetracycline 
equivalent to 100 g/lb oxytetracycline hydrochloride and 100 g/lb 
neomycin sulfate.
    (b) Sponsors. See No. 066104 in Sec.  510.600(c) of this chapter.
    (c) Related tolerances. See Sec. Sec.  556.430 and 556.500 of this 
chapter.
    (d) Indications for use--(1) Chickens. It is used in feed as 
follows:

[[Page 16226]]



----------------------------------------------------------------------------------------------------------------
Oxytetracycline and neomycin
 sulfate amount in grams per        Indications for use                  Limitations                Sponsors
         ton of feed
----------------------------------------------------------------------------------------------------------------
(i) 10 to 50                  Chickens: For increased rate of  Feed continuously; do not feed             066104
                               weight gain and improved feed    to chickens producing eggs
                               efficiency                       for human consumption
----------------------------------------------------------------------------------------------------------------
(ii) 100 to 200               Chickens: For control of         Feed continuously for 7 to 14              066104
                               infectious synovitis caused by   days (d); do not feed to
                               Mycoplasma synoviae; control     chickens producing eggs for
                               of fowl cholera caused by        human consumption; in low
                               Pasteurella multocida            calcium feed, withdraw 3 d
                               susceptible to oxytetracycline   before slaughter
----------------------------------------------------------------------------------------------------------------
(iii) 400                     Chickens: For control of         Feed continuously for 7 to 14              066104
                               chronic respiratory disease      d; do not feed to chickens
                               (CRD) and air sac infection      producing eggs for human
                               caused by M. gallisepticum and   consumption; in low calcium
                               Escherichia coli susceptible     feeds, withdraw 3 d before
                               to oxytetracycline               slaughter
----------------------------------------------------------------------------------------------------------------
(iv) 500                      Chickens: For reduction of       Feed continuously for 5 d; do              066104
                               mortality due to air             not feed to chickens
                               sacculitis (air-sac-infection)   producing eggs for human
                               caused by E. coli susceptible    consumption; withdraw 24
                               to oxytetracycline               hours before slaughter; in
                                                                low calcium feeds withdraw 3
                                                                d before slaughter
----------------------------------------------------------------------------------------------------------------

    (2) Turkeys. It is used in feed as follows:

----------------------------------------------------------------------------------------------------------------
Oxytetracycline and neomycin
       sulfate amount               Indications for use                  Limitations                Sponsors
----------------------------------------------------------------------------------------------------------------
(i) 10 to 50 g/ton of feed    Growing turkeys: For increased   Feed continuously; do not feed             066104
                               rate of weight gain and          to turkeys producing eggs for
                               improved feed efficiency         human consumption
----------------------------------------------------------------------------------------------------------------
(ii) 100 g/ton of feed        Turkeys: For control of          Feed continuously for 7 to 14              066104
                               hexamitiasis caused by           d; do not feed to turkeys
                               Hexamita meleagridis             producing eggs for human
                               susceptible to oxytetracycline   consumption
----------------------------------------------------------------------------------------------------------------
(iii) 200 g/ton of feed       Turkeys: For control of          Feed continuously for 7 to 14              066104
                               infectious synovitis caused by   d; withdraw 5 d before
                               M. synoviae susceptible to       slaughter; do not feed to
                               oxytetracycline                  turkeys producing eggs for
                                                                human consumption
----------------------------------------------------------------------------------------------------------------
(iv) To provide 25 mg/lb of   Turkeys: For control of          Feed continuously for 7 to 14              066104
 body weight daily             complicating bacterial           d; withdraw 5 d before
                               organisms associated with        slaughter; do not feed to
                               bluecomb (transmissible          turkeys producing eggs for
                               enteritis; coronaviral           human consumption
                               enteritis) susceptible to
                               oxytetracycline
----------------------------------------------------------------------------------------------------------------

    (3) Swine. It is used in feed as follows:

------------------------------------------------------------------------
 Oxytetracycline
  and neomycin      Indications for use   Limitations       Sponsor
 sulfate amount
------------------------------------------------------------------------
(i) 10 to 50 g/   Swine: For increased    ...........             066104
 ton of feed       rate of weight gain
                   and improved feed
                   efficiency
------------------------------------------------------------------------
(ii) To provide   1. Swine: For           Feed                    066104
 10 mg/lb of       treatment of            continuous
 body weight       bacterial enteritis     ly for 7
 daily             caused by E. coli and   to 14 d;
                   Salmonella              withdraw 5
                   choleraesuis and        d before
                   treatment of            slaughter
                   bacterial pneumonia
                   caused by P.
                   multocida susceptible
                   to oxytetracycline;
                   treatment and control
                   of colibacillosis
                   (bacterial enteritis)
                   caused by E. coli
                   susceptible to
                   neomycin
                  2. Breeding swine: For  Feed                    066104
                   control and treatment   continuous
                   of leptospirosis        ly for not
                   (reducing the           more than
                   incidence of abortion   14 d;
                   and shedding of         withdraw 5
                   leptospirae) caused     d before
                   by Leptospira pomona    slaughter
                   susceptible to
                   oxytetracycline
------------------------------------------------------------------------

    (4) Cattle and sheep. It is used in feed as follows:

[[Page 16227]]



----------------------------------------------------------------------------------------------------------------
Oxytetracycline and neomycin
       sulfate amount              Indications for use                 Limitations                  Sponsor
----------------------------------------------------------------------------------------------------------------
(i) 10 to 20 grams per ton    Sheep: For increased rate of  .................................             066104
 of feed                       weight gain and improved
                               feed efficiency
----------------------------------------------------------------------------------------------------------------
(ii) To provide 0.05 to 0.1   Calves (up to 250 lb): For    Feed continuously; in milk                    066104
 mg/lb of body weight daily.   increased rate of weight      replacers or starter feed
                               gain and improved feed
                               efficiency
----------------------------------------------------------------------------------------------------------------
(iii) To provide 10 mg/lb of  1. Calves and beef and        Feed continuously for 7 to 14 d;              066104
 body weight daily             nonlactating dairy cattle:    in feed or milk replacers. If
                               For treatment of bacterial    symptoms persist after using for
                               enteritis caused by E. coli   2 or 3 d, consult a
                               and bacterial pneumonia       veterinarian. Treatment should
                               (shipping fever complex)      continue 24 to 48 hours beyond
                               caused by P. multocida        remission of disease symptoms. A
                               susceptible to                withdrawal period has not been
                               oxytetracycline; treatment    established for use in
                               and control of                preruminating calves. Do not use
                               colibacillosis (bacterial     in calves to be processed for
                               enteritis) caused by E.       veal. A milk discard time has
                               coli susceptible to           not been established for use in
                               neomycin                      lactating dairy cattle. Do not
                                                             use in female dairy cattle 20
                                                             months of age or older. Withdraw
                                                             5 d before slaughter
                              2. Calves (up to 250 lb):     Feed continuously for 7 to 14 d;              066104
                               For treatment of bacterial    in milk replacers or starter
                               enteritis caused by E. coli   feed. If symptoms persist after
                               susceptible to                using for 2 or 3 d, consult a
                               oxytetracycline; treatment    veterinarian. Treatment should
                               and control of                continue 24 to 48 hours beyond
                               colibacillosis (bacterial     remission of disease symptoms. A
                               enteritis) caused by E.       withdrawal period has not been
                               coli susceptible to           established for use in
                               neomycin                      preruminating calves. Do not use
                                                             in calves to be processed for
                                                             veal. A milk discard time has
                                                             not been established for use in
                                                             lactating dairy cattle. Do not
                                                             use in female dairy cattle 20
                                                             months of age or older. Withdraw
                                                             5 d before slaughter
                              3. Sheep: For treatment of    Feed continuously for 7 to 14 d.              066104
                               bacterial enteritis caused    If symptoms persist after using
                               by E. coli and bacterial      for 2 or 3 d, consult a
                               pneumonia caused by P.        veterinarian. Treatment should
                               multocida susceptible to      continue 24 to 48 hours beyond
                               oxytetracycline; treatment    remission of disease symptoms.
                               and control of                Withdraw 5 d before slaughter
                               colibacillosis (bacterial
                               enteritis) caused by E.
                               coli susceptible to
                               neomycin
----------------------------------------------------------------------------------------------------------------
(iv) To provide 25 mg/head/   Calves (250 to 400 lb): For   .................................             066104
 day                           increased rate of weight
                               gain and improved feed
                               efficiency
----------------------------------------------------------------------------------------------------------------
(v) To provide 75 mg/head/    Growing cattle (over 400      .................................             066104
 day                           lb): For increased rate of
                               weight gain; improved feed
                               efficiency, and reduction
                               of liver condemnation due
                               to liver abscesses
----------------------------------------------------------------------------------------------------------------
(vi) To provide 0.5 to 2.0 g/ Cattle: For prevention and    Feed 3 to 5 d before and after                066104
 head/day                      treatment of the early        arrival in feedlots. A
                               stages of shipping fever      withdrawal period has not been
                               complex                       established for use in
                                                             preruminating calves. Do not use
                                                             in calves to be processed for
                                                             veal. A milk discard time has
                                                             not been established for use in
                                                             lactating dairy cattle. Do not
                                                             use in female dairy cattle 20
                                                             months of age or older
----------------------------------------------------------------------------------------------------------------


0
5. In Sec.  558.460, redesignate paragraphs (d)(2)(vi), (d)(2)(vii), 
and (d)(2)(viii) as paragraphs (d)(2)(iii), (d)(2)(v), and (d)(2)(vi); 
and add new paragraph (d)(2)(iv) to read as follows:


Sec.  558.460  Penicillin.

* * * * *
    (d) * * *
    (2) * * *
    (iv) Nicarbazin alone or with roxarsone as in Sec.  558.366.
* * * * *

    Dated: March 22, 2006.
Stephen F. Sundlof,
Director, Center for Veterinary Medicine.
[FR Doc. 06-3120 Filed 3-30-06; 8:45 am]
BILLING CODE 4160-01-S