[Federal Register Volume 68, Number 153 (Friday, August 8, 2003)]
[Notices]
[Pages 47332-47339]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-20241]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2003N-0324]
Certain Antibiotic New Animal Drug Products and Use Combinations
Subject to Listings in the New Animal Drug Regulations; Drug Efficacy
Study Implementation; Notice of Opportunity for Hearing
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of opportunity for hearing.
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SUMMARY: The Food and Drug Administration (FDA) is announcing the
effective conditions of use for certain drug products and use
combinations in the following four categories: Bacitracin methylene
disalicylate single-ingredient Type A medicated articles,
oxytetracycline and neomycin fixed-combination Type A medicated
articles, and combination drug Type B and Type C medicated feeds for
poultry containing bacitracin. The agency is also proposing 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. For applications proposed to be
withdrawn, the agency is providing an opportunity for hearing.
Elsewhere in this issue of the Federal Register, FDA is publishing a
proposed rule to remove certain obsolete or redundant sections of the
new animal
[[Page 47333]]
drug regulations where these subject drug products and use combinations
are listed. That proposed rule contains background information about
those regulations and also for this action.
DATES: Submit written appearances and a request for a hearing by
September 8, 2003. Submit all data and analysis upon which a request
for a hearing relies by October 7, 2003. Submit supplemental NADAs by
November 6, 2003.
ADDRESSES: Written requests for a hearing, data and analysis, and other
written appearances are to be identified with Docket No. 2003N-0324 and
submitted to the Division of Dockets Management (HFA-305), Food and
Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
Submit supplemental new animal drug applications to the Director,
Office of New Animal Drug Evaluation, c/o Document Control Unit (HFV-
199), Center for Veterinary Medicine, Food and Drug Administration,
7500 Standish Pl., Rockville, MD 20855.
FOR FURTHER INFORMATION CONTACT: Andrew J. Beaulieu, Center for
Veterinary Medicine (HFV-1), 7519 Standish Pl., Rockville, MD 20855,
301-827-2954, e-mail: [email protected].
SUPPLEMENTARY INFORMATION:
I. Background
In 1962, Congress amended the new drug provisions, which then
applied to new drugs intended for both man and other animals, to
require that a new drug be shown to be both safe and effective before
marketing (the Drug Amendments of 1962, Public Law 87-781, 76 Stat.
780). Before 1962, animal drug approvals did not require a
demonstration of effectiveness. Under the 1962 amendments, the
effectiveness requirement was made applicable, after a 2-year
transition period, to animal drugs approved before 1962. This pre-1962
drug evaluation is known as the Drug Efficacy Study Implementation
(DESI) program. In response to the need for an integrated approach, the
DESI program evaluated the efficacy of all animal drug products,
including antibiotic new animal drugs used in feed and antibiotic feed
use combinations (see, e.g., Sec. 558.15(b)(3) (21 CFR 558.15(b)(3))
and 37 FR 21279 (October 7, 1972)). Under the DESI program, a new
animal drug approved before October 10, 1962, could continue to be
approved if the sponsor submitted a supplemental NADA to revise the
indications for use to those for which the agency determined the drug
to be effective.
This document announces the effective indications for which certain
new animal drugs and drug combinations may be marketed, and provides an
opportunity for hearing on those indications for which products may not
be marketed because they lack substantial evidence of effectiveness.
There are nine products subject to this notice, and they fall into the
following four categories:
1. Bacitracin methylene disalicylate (BMD) single-ingredient Type A
medicated article,
2. Oxytetracycline and neomycin fixed-combination Type A medicated
articles,
3. Combination drug Type B and Type C medicated feeds for poultry
containing nicarbazin, and
4. Combination drug Type B and Type C medicated feeds for poultry
containing bacitracin.
Under section 108(b)(2) of Public Law 90-399 (82 Stat. 353), the
Animal Drug Amendments of 1968, any approval of a new animal drug
granted prior to the law's effective date, whether through approval of
a new drug application, master file, antibiotic regulation, or food
additive regulation, continues in effect and is subject to change in
accordance with the provisions of section 512 of the Federal Food,
Drug, and Cosmetic Act (the act) (21 U.S.C. 360b). The nine products
that are the subject of this notice are subject to this transitional
approval provision.
In addition, they are all listed in the interim marketing
provisions of Sec. 558.15. A history of the interim marketing
provisions and the approval status of the products listed in them is
contained in a notice of proposed rulemaking published elsewhere in
this issue of the Federal Register. The agency has DESI finalized many
of the products subject to the listings in Sec. 558.15, codifying
their approvals in part 558 (21 CFR part 558) subpart B (see, e.g., 61
FR 35949, July 9, 1996). The nine products subject to this notice are
the only ones listed in Sec. 558.15 that are subject to DESI and that
have not yet been DESI finalized.
II. Findings of Effectiveness of Certain Drugs Listed in Sec. 558.15
A. Bacitracin Methylene Disalicylate Single-Ingredient Type A Medicated
Articles
The following drug is covered by the DESI findings of effectiveness
for BMD in animal feed:
[sbull] NADA 141-137, FORTRACIN MD 50 (BMD) Type A medicated
article used to make Type B and Type C medicated feeds. Pennfield Oil
Co., 14040 Industrial Rd., Omaha, NE 68137.
In 1970, FDA announced its DESI findings of effectiveness for feed
use of BMD (35 FR 11531, July 17, 1970, as corrected by 35 FR 15408,
October 2, 1970). Table 1 of this document summarizes FDA's
conclusions.
Table 1.--DESI Findings of Effectiveness For Use of Bacitracin Methylene
Disalicylate in Animal Feed
------------------------------------------------------------------------
Bacitracin methylene
disalicylate in grams per Indications for use Limitations
ton (g/ton)
------------------------------------------------------------------------
4 to 50 Chickens, turkeys, and ..............
pheasants: For increased
rate of weight gain and
improved feed efficiency.
------------------------------------------------------------------------
5 to 20 Quail not over 5 weeks of ..............
age: For increased rate of
weight gain and improved
feed efficiency.
------------------------------------------------------------------------
The agency notes that there are several potential sources of
confusion regarding NADA 141-137 and the interim marketing provision
for BMD in Sec. 558.15(g)(1) (further information about this provision
is contained in a notice of proposed rulemaking published elsewhere in
this issue of the Federal Register). Section 558.15(g)(1) contains a
table that lists antibacterial Type A medicated articles that are
eligible for interim marketing based on compliance with other
provisions of Sec. 558.15, and specifies the sponsors of these
articles and their approved species, use levels, and indications for
use. An example of the problems with this table is that the sponsors it
lists for BMD--A. L. Laboratories, Inc., and Fermenta Animal Health
Co.--are outdated. These companies are predecessors in interest
[[Page 47334]]
to the current sponsors, which are Alpharma, Inc., and Pennfield Oil
Co., respectively.
A second, more complicated example involves BMD's approved
conditions of use. Rather than listing the use levels and indications
for use for which interim marketing is permitted, the table in Sec.
558.15(g)(1) contains a reference to another section of the
regulations. When the table was first published in 1976, this reference
was to the uses and indications listed in 21 CFR 121.225 and 121.252
(see 41 FR 8282, February 25, 1976). These were the conditions of use
for which the BMD products were approved, under the transitional
approval provisions of the Animal Drug Amendments of 1968. Shortly
thereafter, these uses were recodified in Sec. 558.76 and the
reference in Sec. 558.15(g)(1) was adjusted accordingly (41 FR 10984,
March 15, 1976). Since that recodification, Sec. 558.76 has been
amended numerous times to reflect the approval of supplemental
applications, based on proprietary data, that were filed by sponsors
other than Pennfield Oil Co. or its predecessors in interest (see,
e.g., 63 FR 40824, July 31, 1998). At the time of these amendments to
Sec. 558.76, the table in Sec. 558.15(g)(1) was not updated by
removing the simple cross reference to Sec. 558.76 and by adding in
its place a correct reference or a correct listing of the uses for
which interim marketing was permitted. Thus, the table is misleading
unless the reader already knows the indications for which the sponsors
are approved or reviews the changes made over time to Sec. Sec. 558.15
and 558.76.
The confusion caused by the reference in Sec. 558.15(g)(1) to the
use levels and indications for use in Sec. 558.76 is illustrated by,
and perhaps exacerbated by, the administrative record for NADA 141-137.
As happened with several other products listed in Sec. 558.15, it
became apparent in the 1990s that the administrative record for this
NADA was incomplete, calling into question its approval status. This is
described in more detail in the proposed rule to remove Sec. 558.15
published elsewhere in this issue of the Federal Register. In 1998, to
help resolve the approval status, the company that owned the product at
the time, Boehringer Ingelheim Vetmedica, Inc. (BIVI), certified that
the product was approved pre-1968 and provided supporting information.
This certification was made by a letter dated September 18, 1998, as
amended by a letter dated November 17, 1998. It provided historical
information about the product, stated that the product had been
approved prior to 1968, and stated that it was subject to the
transitional approval provisions of the Animal Drug Amendments of 1968.
The company also provided information about the approved indications.
One piece of information, included with the September letter, is a
product label dated February 1969. BIVI stated that this label is
consistent with Sec. 558.15. This was probably intended to mean the
interim marketing table in Sec. 558.15 as it was originally issued in
1976 since the label's indications are generally consistent with,
albeit somewhat narrower than, BMD's indications listed in the table at
the time. Given this consistency and given that the date of the label
is just a few months before the effective date of the transitional
approval provision, the label provides good evidence that the product
was subject to transitional approval and the indications for which it
was transitionally approved.
However, two other pieces of information appear to be inconsistent
with the indications for which FDA believes Pennfield Oil Co.'s BMD
product is transitionally approved. The November 1998 letter from BIVI
states that the product was approved for ``the indications for use
itemized in 21 CFR Sec. 558.78,'' which was presumably meant to be
Sec. 558.76 since the other regulation (Sec. 558.78) concerns
bacitracin zinc. It is unclear whether BIVI meant the indications in
Sec. 558.76 in 1976 or 1998. Also unclear is the meaning of two labels
faxed by BIVI to FDA on December 9, 1998. These are in the product's
current NADA file, although without any cover page or other explanatory
notes. These labels, one a subset of the other, specify indications
that are much closer to those listed in Sec. 558.76 in 1998 than to
those that were transitionally-approved. It is possible that the labels
BIVI faxed to FDA on December 9, 1998, were based on Sec. 558.76 as it
existed at that time, given that the BMD listing in Sec. 558.15
contained the misleading cross-reference to Sec. 558.76.
On December 17, 1998, FDA sent BIVI a letter stating that the
agency received the company's November certification that amended the
September letter, that the certification would be used as part of the
administrative record of approval, and that the agency planned to
codify this approval as soon as possible given resource constraints and
public health priorities. FDA's letter also referred to the indications
``specified in the labeling attached to [BIVI's] letter.'' However,
FDA's letter does not state to which labeling it is referring.
We are not aware of any additional approved indications beyond
those listed in the original Sec. 558.76 from 1976 for Pennfield Oil
Co.'s product. If the sponsor has additional information on the other
approved indications, such information should be provided to FDA during
this administrative process.
B. Oxytetracycline and Neomycin Fixed-Combination Type A Medicated
Articles
The agency is making findings of effectiveness for oxytetracycline
and neomycin fixed-combination Type A medicated articles for use in
animal feed. These findings cover the following drugs:
[sbull] NADA 94-975, NEO-TERRAMYCIN (oxytetracycline and neomycin).
Phibro Animal Health, 710 Route 46 East, suite 401, Fairfield, NJ
07004.
[sbull] NADA 138-939, NEO-OXY (oxytetracycline and neomycin).
Pennfield Oil Co., 14040 Industrial Rd., Omaha, NE 68137.
Both of these products are two-way, fixed-combination Type A
medicated articles used to make two-way combination drug Type C
medicated feeds at use levels for the species and indications listed in
Sec. 558.15(g)(2). The drug sponsor information in this listing is
outdated, however, designating Pfizer, Inc., Pennfield Oil Co., and
VPO, Inc., instead of Phibro Animal Health and Pennfield Oil Co.
The National Academy of Sciences/National Research Council (NAS/
NRC) assisted FDA in its DESI program for numerous animal drug
products. While NAS/NRC did not evaluate the efficacy data relating to
these combinations, FDA has conducted such a review. This review was
based on the agency's findings of effectiveness for oxytetracycline and
neomycin single-ingredient feed use products, which in turn were based
on NAS/NRC's evaluation (see 35 FR 7089, May 5, 1970, and 36 FR 837,
January 19, 1971). FDA has determined that its previous findings of
effectiveness for the single ingredients are applicable to the
combinations in the absence of information indicating interference in
effectiveness between individual ingredients. The agency's review also
considered information about the effectiveness submitted to these two
NADAs, although this information did not alter the agency's conclusions
based on the single-ingredient findings. Tables 2, 3, 4, and 5 of this
document summarize FDA's findings of effectiveness for oxytetracycline
and neomycin fixed-combination Type A medicated articles for use in
animal feed.
[[Page 47335]]
Table 2.--DESI Findings of Effectiveness for Use of Oxytetracycline and
Neomycin Administered in Chicken Feed in a 1:1 Ratio
------------------------------------------------------------------------
Oxytetracycline
and neomycin
amount in g/ton of Indications for use Limitations
feed
------------------------------------------------------------------------
10 to 50 Chickens: For increased Do not feed to chickens
rate of weight gain and producing eggs for human
improved feed consumption.
efficiency.
------------------------------------------------------------------------
100 to 200 Chickens: For control of Feed continuously for 7
infectious synovitis to 14 days (d); do not
caused by Mycoplasma feed to chickens
synoviae; control of producing eggs for human
fowl cholera caused by consumption; in low
Pasteurella multocida calcium feed, withdraw 3
susceptible to d before slaughter.
oxytetracycline.
------------------------------------------------------------------------
400 Chickens: For control of Feed continuously for 7
chronic respiratory to 14 d; do not feed to
disease (CRD) and air chickens producing eggs
sac infection caused by for human consumption;
M. gallisepticum and in low calcium feeds,
Escherichia coli withdraw 3 d before
susceptible to slaughter.
oxytetracycline.
------------------------------------------------------------------------
500 Chickens: For reduction Feed continuously for 5
of mortality due to air d; do not feed to
sacculitis (air-sac- chickens producing eggs
infection) caused by E. for human consumption;
coli susceptible to withdraw 24 hours before
oxytetracycline. slaughter; in low
calcium feeds withdraw 3
d before slaughter.
------------------------------------------------------------------------
Table 3.--DESI Findings of Effectiveness for Use of Oxytetracycline and
Neomycin Administered in Turkey Feed in a 1:1 Ratio
------------------------------------------------------------------------
Oxytetracycline
and neomycin Indications for use Limitations
amount
------------------------------------------------------------------------
10 to 50 g/ton of Growing turkeys: For Do not feed to turkeys
feed increased rate of weight producing eggs for human
and improved feed consumption.
efficiency.
------------------------------------------------------------------------
100 g/ton of feed Turkeys: For control of Feed continuously for 7
hexamitiasis caused by to 14 d; do not feed to
Hexamita meleagridis turkeys producing eggs
susceptible to for human consumption.
oxytetracycline.
------------------------------------------------------------------------
200 g/ton of feed Turkeys: For control of Feed continuously for 7
infectious synovitis to 14 d; withdraw 5 d
caused by M. synoviae before slaughter; do not
susceptible to feed to turkeys
oxytetracycline. producing eggs for human
consumption.
------------------------------------------------------------------------
25 milligrams per Turkeys: For control of Feed continuously for 7
pound (mg/lb) of complicating bacterial to 14 d; withdraw 5 d
body weight daily organisms associated before slaughter; do not
with bluecomb feed to turkeys
(transmissible producing eggs for human
enteritis; coronaviral consumption.
enteritis) susceptible
to oxytetracycline.
------------------------------------------------------------------------
Table 4.--DESI Findings of Effectiveness for Use of Oxytetracycline and
Neomycin Administered in Swine Feed in a 1:1 Ratio
------------------------------------------------------------------------
Oxytetracycline
and neomycin Indications for use Limitations
amount
------------------------------------------------------------------------
10 to 50 g/ton of Swine: For increased rate .........................
feed of weight and improved
feed efficiency
------------------------------------------------------------------------
10 mg/lb of body Swine: For treatment of Feed continuously for 7
weight daily bacterial enteritis to 14 d; withdraw 5 d
caused by E. coli and before slaughter.
Salmonella choleraesuis
and bacterial pneumonia
caused by P. multocida
susceptible to
oxytetracycline;
treatment and control of
colibacillosis
(bacterial enteritis)
caused by E. coli
susceptible to neomycin.
------------------------------------------------------------------------
10 mg/lb of body Breeding swine: For Feed continuously for not
weight daily control and treatment of more than 14 d; withdraw
leptospirosis (reducing 5 d before slaughter.
the incidence of
abortion and shedding of
leptospirae) caused by
Leptospira pomona
susceptible to
oxytetracycline.
------------------------------------------------------------------------
[[Page 47336]]
Table 5.--DESI Findings of Effectiveness for Use of Oxytetracycline and
Neomycin Administered in Cattle and Sheep Feed in a 1:1 Ratio
------------------------------------------------------------------------
Oxytetracycline
and neomycin Indications for use Limitations
amount
------------------------------------------------------------------------
10 to 20 g/ton of Sheep: For increased rate .........................
feed of weight gain and
improved feed
efficiency.
------------------------------------------------------------------------
0.05 to 0.1 mg/lb Calves (up to 250 lb): Feed continuously; in
of body weight For increased rate of milk replacers or
daily weight gain and improved starter feed.
feed efficiency.
------------------------------------------------------------------------
10 mg/lb of body Calves and beef and Feed continuously for 7
weight daily nonlactating dairy to 14 d in feed or milk
cattle: For treatment of replacers. If symptoms
bacterial enteritis persist after using for
caused by E. coli and 2 or 3 d, consult a
bacterial pneumonia veterinarian. Treatment
(shipping fever complex) should continue 24 to 48
caused by P. multocida hours beyond remission
susceptible to of disease symptoms. A
oxytetracycline; withdrawal period has
treatment and control of not been established for
colibacillosis use in preruminating
(bacterial enteritis) calves. Do not use in
caused by E. coli calves to be processed
susceptible to neomycin. 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.
------------------------------------------------------------------------
10 mg/lb of body Calves (up to 250 lb): Feed continuously for 7
weight daily For the treatment of to 14 d in milk
bacterial enteritis replacers or starter
caused by E. coli feed. If symptoms
susceptible to persist after using for
oxytetracycline; 2 or 3 d, consult a
treatment and control of veterinarian. Treatment
colibacillosis should continue 24 to 48
(bacterial enteritis) hours beyond remission
caused by E. coli of disease symptoms. A
susceptible to neomycin. withdrawal period has
not been 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.
Withdraw 5 d before
slaughter.
------------------------------------------------------------------------
10 mg/lb of body Sheep: For the treatment Feed continuously for 7
weight daily of bacterial enteritis to 14 d. If symptoms
caused by E. coli and persist after using for
bacterial pneumonia 2 or 3 d, consult a
caused by P. multocida veterinarian. Treatment
susceptible to should continue 24 to 48
oxytetracycline; hours beyond remission
treatment and control of of disease symptoms.
colibacillosis Withdraw 5 d before
(bacterial enteritis) slaughter.
caused by E. coli
susceptible to neomycin.
------------------------------------------------------------------------
25 mg/head/d Calves (250 to 400 lb): .........................
For increased rate of
weight gain and improved
feed efficiency.
------------------------------------------------------------------------
75 mg/head/d Growing cattle (over 400 .........................
lb): For increased rate
of weight gain, improved
feed efficiency, and
reduction of liver
condemnation due to
liver abscesses.
------------------------------------------------------------------------
0.5 to 2.0 g/head/ Cattle: For prevention Feed 3 to 5 d before and
d and treatment of the after arrival in
early stages of shipping feedlots. A withdrawal
fever complex. period has not been
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.
------------------------------------------------------------------------
C. Combination Drug Type B and Type C Medicated Feeds for Poultry
Containing Nicarbazin
The agency is making findings of effectiveness for combination drug
Type B and Type C medicated feeds containing nicarbazin. These findings
cover the following drugs:
[sbull] NADA 98-371, for the combination use of NICARBAZIN
(nicarbazin), PENICILLIN G PROCAINE (procaine penicillin), and 3-NITRO
(roxarsone). Phibro Animal Health.
[sbull] NADA 98-374, for the combination use of NICARBAZIN
(nicarbazin) and PENICILLIN G PROCAINE (procaine penicillin). Phibro
Animal Health.
[sbull] NADA 100-853, for the combination use of NICARBAZIN
(nicarbazin), BACIFERM (BMD), and 3-NITRO (roxarsone). Phibro Animal
Health.
These three combination drugs are for uses listed in Sec.
558.15(g)(2). The drug sponsor information in the listing is outdated,
designating The Upjohn Co. instead of Phibro Animal Health. In
addition, rather than itemizing the indications for use, the listing
gives references to the indications itemized in Sec. Sec. 558.325,
558.355, and 558.530. These references are not accurate since they are
for lincomycin, monensin, and roxarsone.
While NAS/NRC did not evaluate the efficacy data relating to these
combinations, FDA has conducted such a review. This review was based on
the agency's findings of effectiveness for bacitracin zinc, nicarbazin,
procaine penicillin, and roxarsone single-ingredient feed use products,
which in turn were based on NAS/NRC's evaluation (see 35 FR 12490,
August 5, 1970 (bacitracin zinc); 34 FR 6495, April 15, 1969
(nicarbazin); 35 FR 11534, July 17, 1970 (procaine penicillin); and 35
FR 14273, September 10, 1970 (roxarsone)). FDA has determined that its
previous findings of effectiveness are applicable to the combinations
in the absence of information indicating interference in effectiveness
between individual ingredients. Table 6 of this
[[Page 47337]]
document summarizes FDA's findings of effectiveness for certain
combination drug Type B and Type C medicated feeds containing
nicarbazin.
Table 6.--Findings of Effectiveness for Use of Certain Drug Combinations
Containing Nicarbazin in Poultry Feed
------------------------------------------------------------------------
Type A Type A Type A
article in g/ article in g/ article in g/ Indications Limitations
ton ton ton for use
------------------------------------------------------------------------
Nicarbazin Bacitracin Roxarsone Growing Feed
90.8 to methylene 22.7 to chickens: As continuously
181.6 (0.01 disalicylate 45.4 an aid in as sole
to 0.02 4 to 50 preventing ration from
percent outbreaks of time chicks
(pct) cecal are placed
(Eimeria on litter
tenella) and until past
intestinal the time
(E. when
acervulina, coccidiosis
E. maxima, is
E. necatrix, ordinarily a
and E. hazard; do
brunetti) not use as a
coccidiosis, treatment
and for for
increased outbreaks of
rate of coccidiosis.
weight gain, As a sole
improved source of
feed organic
efficiency, arsenic;
and improved drug
pigmentation overdose or
. lack of
water may
result in
leg
weakness. Do
not use in
flushing
mashes. Do
not feed to
laying hens
in
production.
Discontinue
medication 5
d before
marketing
the birds
for human
consumption
to allow for
elimination
of the drug
from edible
tissue.
------------------------------------------------------------------------
Nicarbazin Procaine ............ Growing Feed
90.8 to penicillin chickens: As continuously
181.6 (0.01 2.4 to 50 an aid in as sole
to 0.02 pct) preventing ration from
outbreaks of time chicks
cecal are placed
(Eimeria on litter
tenella) and until past
intestinal the time
(E. when
acervulina, coccidiosis
E. maxima, is
E. necatrix, ordinarily a
and E. hazard; do
brunetti) not use as a
coccidiosis, treatment
and for for
increased outbreaks of
rate of coccidiosis.
weight gain Do not use
and improved in flushing
feed mashes. Do
efficiency. not feed to
chickens
producing
eggs for
human
consumption.
Discontinue
medication 4
d before
marketing
the birds
for human
consumption
to allow for
elimination
of the drug
from edible
tissue.
------------------------------------------------------------------------
Nicarbazin Procaine Roxarsone Growing Feed
90.8 to penicillin 22.7 to chickens: As continuously
181.6 (0.01 2.4 to 50 45.4 an aid in as sole
to 0.02 pct) preventing ration from
outbreaks of time chicks
cecal are placed
(Eimeria on litter
tenella) and until past
intestinal the time
(E. when
acervulina, coccidiosis
E. maxima, is
E. necatrix, ordinarily a
and E. hazard; do
brunetti) not use as a
coccidiosis, treatment
and for for
increased outbreaks of
rate of coccidiosis.
weight gain, As a sole
improved source of
feed organic
efficiency, arsenic;
and improved drug
pigmentation overdose or
. lack of
water may
result in
leg
weakness. Do
not use in
flushing
mashes. Do
not feed to
chickens
producing
eggs for
human
consumption.
Discontinue
medication 5
d before
marketing
the birds
for human
consumption
to allow for
elimination
of the drug
from edible
tissue.
------------------------------------------------------------------------
[[Page 47338]]
D. Combination Drug Type B and Type C Medicated Feeds for Poultry
Containing Bacitracin
The agency is making findings of effectiveness for combination drug
Type B and Type C medicated feeds containing bacitracin. These findings
cover the following drugs:
[sbull] NADA 141-130, for the combination use of BMD and zoalene.
Alpharma, Inc., One Executive Dr., P.O. Box 1399, Fort Lee, NJ 07024.
[sbull] NADA 141-131, for the combination use of BMD, zoalene, and
roxarsone. Alpharma, Inc.
[sbull] NADA 141-132, for the combination use of zinc bacitracin
and nitarsone. Alpharma, Inc.
These three combination drugs are for uses listed in Sec.
558.15(g)(2). The drug sponsor information in the listing is outdated,
designating A. L. Laboratories, Inc., instead of Alpharma, Inc.
While NAS/NRC did not evaluate the efficacy data relating to these
combinations, FDA has conducted such a review. This review was based on
the agency's findings of effectiveness for BMD, bacitracin zinc,
nitarsone, roxarsone, and zoalene single-ingredient feed use products.
Most of these were based on NAS/NRC's evaluation (see 35 FR 11531, July
17, 1970 (BMD); 35 FR 12490, August 5, 1970 (bacitracin zinc); 34 FR
6494, April 15, 1969 (nitarsone); and 35 FR 14273, September 10, 1970
(roxarsone)). The effectiveness of zoalene in these combinations was
based on FDA's review of a food additive petition containing
effectiveness data (see 27 FR 11546, November 24, 1962). FDA has
determined that its previous findings of effectiveness are applicable
to the combinations in the absence of information indicating
interference in effectiveness between individual ingredients. Table 7
of this document summarizes FDA's findings of effectiveness for certain
combination drug Type B and Type C medicated feeds containing
bacitracin.
Table 7.--Findings of Effectiveness for Use of Certain Drug Combinations
Containing Bacitracin in Poultry Feed
------------------------------------------------------------------------
Type A Type A Type A
article in g/ article in g/ article in g/ Indications Limitations
ton ton ton for use
------------------------------------------------------------------------
Bacitracin 4 Zoalene 36.3 ............ Replacement As bacitracin
to 50 to 113.5. chickens: methylene
For disalicylate
increased . Grower
rate of ration not
weight gain to be fed to
and improved birds over
feed 14 weeks of
efficiency; age; feed as
and for in Sec.
development 558.680(d)(1
of active )(i).
immunity to
coccidiosis.
------------------------------------------------------------------------
Bacitracin 4 Zoalene 36.3 Roxarsone Replacement As bacitracin
to 50 to 113.5. 22.7 to chickens: methylene
45.4 For disalicylate
increased ;
rate of discontinue
weight gain use 5 d
and improved before
feed slaughter;
efficiency; as sole
for source of
development organic
of active arsenic;
immunity to drug
coccidiosis; overdose or
and for lack of
improved water may
pigmentation result in
. leg
weakness.
Grower
ration not
to be fed to
birds over
14 weeks of
age; feed as
in Sec.
558.680(d)(1
)(i).
------------------------------------------------------------------------
Bacitracin 4 Nitarsone 170 ............ Growing As bacitracin
to 50 (0.01875 turkeys: For zinc;
pct) increased discontinue
rate of use 5 d
weight gain before
and improved slaughter.
feed Early
efficiency; medication
and as an is essential
aid in the to prevent
prevention spread of
of disease.
blackhead. Adequate
drinking
water must
be provided
near feeder
at all
times. The
drug is not
effective in
preventing
blackhead in
birds
infected
more than 4
or 5 d. The
drug is
dangerous
for ducks,
geese, and
dogs.
Overdosage
or lack of
water may
result in
leg weakness
or
paralysis.
Use as sole
source of
arsenic.
------------------------------------------------------------------------
E. Applicability of Findings of Effectiveness
The findings of effectiveness as described previously in this
document are concerned only with a drug's effectiveness for the stated
conditions in the treated animals. Nothing in this document constitutes
a bar to further proceedings with respect to questions of the safety of
the subject drugs in treated animals or of the drugs or their
metabolites in food products derived from treated animals.
F. Applicability of Pending Notices of Opportunity for Hearing
In the Federal Registers of August 30, 1977 (42 FR 43772), and
October 21, 1977 (42 FR 56264), the Director of the Center for
Veterinary Medicine (CVM) issued notices of opportunity for
[[Page 47339]]
hearing (NOOHs) on proposals to withdraw approval of NADAs for all
penicillin-containing premix products intended for use in animal feed
and for certain subtherapeutic uses of tetracyclines (chlortetracycline
and oxytetracycline) in animal feed. Some of these products are listed
in Sec. 558.15. These NOOHs are still pending and nothing in this
document constitutes a bar to subsequent action to withdraw approval on
the grounds cited in the outstanding NOOHs.
G. Marketing
Marketing of the products that are the subject of this document,
and which are approved, may be continued, provided that, on or before
(see DATES), the holder of the application submits a signed Form FDA
356v New Animal Drug Application and complete product labeling
(including specimen labeling for Type B and Type C medicated feeds)
conforming to the applicable findings of effectiveness.
Supplemental NADAs that are filed in response to this document and
comply with the requirements set forth will be approved, and documents
will be published in the Federal Register amending the approval
regulations in accordance with the approval and identifying the sponsor
under section 512(i) of the act.
III. Notice of Opportunity for Hearing
On the basis of all available data and information, the Director of
CVM is unaware of any adequate and well-controlled clinical
investigation, conducted by experts qualified by scientific training
and experience, meeting the requirements of section 512 of the act that
demonstrates effectiveness of the drugs listed in section II of this
document, for their labeled indications of use other than the effective
claims as stated in this document.
Therefore, notice is given to the sponsors of the NADAs for the
nine animal drug products or combination uses described in section II
of this document, and to all other interested persons, that the
Director of CVM proposes to issue an order under section 512(e) of the
act withdrawing approval of the NADAs providing for any claims other
than those classified in this document as effective. The ground for the
proposed withdrawal is that new information about the drug products,
such as that provided by the NAS/NRC reviews, evaluated together with
the evidence available at the time of approval, show there is a lack of
substantial evidence that the drug will have the effect it purports or
is represented to have under the conditions of use prescribed,
recommended, or suggested in the labeling. An order withdrawing
approval will not issue with respect to any application supplemented in
accordance with this document to delete any indication for use lacking
substantial evidence of effectiveness.
This notice of opportunity for hearing encompasses, in addition to
the ground for the proposed withdrawal of the approvals, all issues
relating to the legal status of the drug products subject to it, e.g.,
any contention that any such product is not a new animal drug within
the meaning of section 201(w) of the act (21 U.S.C. 321(w)).
In accordance with section 512 of the act and part 514 (21 CFR part
514) and under the authority delegated to the Director of CVM (21 CFR
5.502), a sponsor and all other persons subject to this document are
hereby given an opportunity for hearing to show why approval of the
applications should not be withdrawn.
A sponsor or any other person subject to this document who wishes
to request a hearing must file: (1) On or before (see DATES), a written
notice of appearance and request for a hearing, and (2) on or before
(see DATES), the data, information, and analyses relied on to
demonstrate that there is a genuine and substantial issue of fact to
justify a hearing as specified in Sec. 514.200. Any other interested
person may also submit comments on this document. Procedures and
requirements governing this notice of opportunity for hearing, a notice
of appearance and request for a hearing, submission of data,
information, and analyses to justify a hearing, other comments, and a
grant or denial of a hearing, are contained in Sec. 514.200 and 21 CFR
part 12.
The failure of a holder of an approval, or any other party subject
to this document, to file a timely written appearance and request for
hearing as required by Sec. 514.200 constitutes an election not to
avail itself of the opportunity for hearing and a waiver of any
contentions concerning the legal status of any such drug product, and
the Director of CVM will summarily enter a final order withdrawing the
approval. Any such drug product labeled other than for the effective
claims identified in this document may not thereafter be marketed
lawfully, and FDA will initiate appropriate regulatory action to remove
any such drug product from the market. Any new animal drug product
marketed without an approved NADA is subject to regulatory action at
any time.
A request for hearing may not rest upon mere allegations or
denials, but must set forth specific facts showing that there is a
genuine and substantial issue of fact that requires a hearing. If it
conclusively appears from the face of the data, information, and
factual analyses in the request for hearing that there is no genuine
and substantial issue of fact that precludes the withdrawal of approval
of the application, or when a request for hearing is not made in the
required format or with the required analyses, the Commissioner of Food
and Drugs will enter summary judgment against the person who requests a
hearing, making findings and conclusions, and denying a hearing.
If a hearing is requested and is justified by the sponsor's
response to this notice of opportunity for hearing, the issues will be
defined, an administrative law judge will be assigned, and a written
notice of the time and place at which the hearing will commence will be
issued as soon as practicable.
All submissions under this document must be filed in four copies.
Except for data and information prohibited from public disclosure by
law, the submissions may be seen in the Division of Dockets Management
(see ADDRESSES) between 9 a.m. and 4 p.m. Monday through Friday. This
document is issued under section 512 of the act and under the authority
delegated to the Director of CVM (21 CFR 5.502).
IV. Environmental Impact
The agency has determined under 21 CFR 25.33(g) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
V. Paperwork Reduction Act of 1995
The collections of information requirements for this document are
covered under OMB control numbers 0910-0032 and 0910-0184.
Dated: August 1, 2003.
Stephen F. Sundlof,
Director, Center for Veterinary Medicine.
[FR Doc. 03-20241 Filed 8-5-03; 4:09 pm]
BILLING CODE 4160-01-S