71 FR 62 pgs. 16223-16227 - New Animal Drugs for Use in Animal Feeds; Bacitracin; Nicarbazin;Oxytetracycline and Neomycin; Penicillin
Type: RULEVolume: 71Number: 62Pages: 16223 - 16227
Docket number: [Docket No. 2003N-0324]
FR document: [FR Doc. 06-3120 Filed 3-30-06; 8:45 am]
Agency: Health and Human Services Department
Sub Agency: Food and Drug Administration
Official PDF Version: PDF Version
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.
SUMMARY:
The Food and Drug Administration (FDA) isamending the animal drug regulations to reflect approval of foursupplemental new animal drug applications (NADAs) filed by Phibro AnimalHealth. One supplemental NADA provides for the use of fixed-combinationType A medicated articles containing oxytetracycline and neomycin sulfateto formulate two-way fixed-combination drug Type B and Type C medicatedfeeds for chickens, turkeys, swine, cattle, and sheep. Two of thesupplemental NADAs provide for the use of approved, single-ingredient TypeA medicated articles containing nicarbazin and penicillin, with or withoutroxarsone, to formulate two-way or three-way combination drug Type Cmedicated feeds for broiler chickens. The fourth supplemental NADAprovides for the use of approved, single-ingredient Type A medicatedarticles nicarbazin, bacitracin methylene disalicylate, and roxarsone toformulate three-way combination drug Type C medicated feeds for broilerchickens. These approvals reflect FDA's effectiveness conclusions whichrelied on the National Academy of Sciences/National Research Council(NAS/NRC) Drug Efficacy Study Group's evaluation of the effectiveness ofthese 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: andrew.beaulieu@fda.hhs.gov .
SUPPLEMENTARY INFORMATION:
In the FederalRegister 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 drugproducts and use combinations listed in 21 CFR 558.15. CVM proposed towithdraw the new animal drug applications (NADAs) for those products or usecombinations lacking substantial evidence of effectiveness following a90-day opportunity to supplement the NADAs with labeling conforming to therelevant findings of effectiveness. Phibro Animal Health, 65 ChallengerRd., 3d Floor, Ridgefield Park, NJ 07660, filed supplements to four of itsapproved NADAs to revise the labeling of its products to comply with thesefindings of effectiveness.
Phibro Animal Health filed a supplement to approved NADA 94-975for NEO-TM 50/50D and NEO-TM 100/100D (oxytetracycline andneomycin sulfate) Type A medicated articles. The supplemental NADAprovides for use of these fixed-combination Type A medicated articles toformulate two-way fixed-combination drug Type B and Type C medicated feedscontaining oxytetracycline and neomycin sulfate, in a 1:1 ratio, forseveral production and therapeutic indications in chickens, turkeys, swine,cattle, and sheep.
Phibro Animal Health also filed a supplement to approved NADA98-371 for use of nicarbazin, procaine penicillin, and roxarsonesingle-ingredient Type A medicated articles to make three-way combinationdrug Type C medicated feeds. This supplemental NADA provides for the use ofcombination feeds containing NICARBAZIN (nicarbazin) at 90.8 to 181.6 gramsper ton (g/ton), PENICILLIN G PROCAINE (procaine penicillin) at 2.4 to 50g/ton, and 3-NITRO (roxarsone) at 22.7 to 45.4 g/ton of feed inbroiler 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 improvedfeed efficiency; and for improved pigmentation.
Phibro Animal Health also filed a supplement to approved NADA98-374 for use of nicarbazin and procaine penicillin G Type Amedicated articles to formulate two-way combination drug Type C medicatedfeeds. This supplemental NADA provides for the use of combination feedscontaining NICARBAZIN (nicarbazin) at 90.8 to 181.6 g/ton and PENICILLIN GPROCAINE (procaine penicillin) at 2.4 to 50 g/ton of feed in broilerchickens as an aid in preventing outbreaks of cecal ( Eimeriatenella ) and intestinal ( E. acervulina , E.maxima , E. necatrix , and E. brunetti )coccidiosis; and for increased rate of weight gain and improved feedefficiency.
Phibro Animal Health also filed a supplement to approved NADA100-853 for use of nicarbazin, bacitracin methylene disalicylate, androxarsone single-ingredient Type A medicated articles to make three-waycombination drug Type C medicated feeds. This supplemental NADA providesfor the use of combination feeds containing NICARBAZIN (nicarbazin) at90.8 to 181.6 g/ton, BMD (bacitracin methylene disalicylate) at 4 to 50g/ton, and 3-NITRO (roxarsone) at 22.7 to 45.4 g/ton of feed inbroiler 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, improvedfeed efficiency, and improved pigmentation.
The DESI evaluation is concerned only with the effectiveness of the drugproducts and use combinations. Nothing in this document constitutes a barto further proceedings with respect to questions of safety of the subjectdrugs in treated animals or of the drugs or their metabolites in foodproducts derived from treated animals.
Products that comply with FDA's findings of effectiveness are eligiblefor copying, as described in the Generic Animal Drug and PatentTerm Restoration Act Policy Letter Eight , August 21, 1991 (56 FR41561). Accordingly, sponsors may now obtain approval of abbreviated NADAsfor this fixed combination Type A medicated article and three combinationdrug medicated feeds.
The supplemental NADAs are approved as of February 15, 2006, and theregulations are amended in 21 CFR 558.76, 558.460, and 558.366, and also in21 CFR part 558 by adding new § 558.455 to reflect theseapprovals. Approval of these supplemental NADAs did not require review ofany new safety or effectiveness data. Therefore, a freedom of informationsummary was not prepared.
The agency has determined under 21 CFR 25.33(a)(2) that these actionsare of a type that do not individually or cumulatively have a significanteffect on the human environment. Therefore, neither an environmentalassessment 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 5U.S.C. 801-808.
List of Subjects in 21 CFR Part 558
Animal drugs, Animal feeds.
Therefore, under the Federal Food, Drug, and Cosmetic Act and underauthority delegated to the Commissioner of Food and Drugs and redelegatedto the Center for Veterinary Medicine, 21 CFR part 558 is amended asfollows:
PART 558-NEW ANIMAL DRUGS FOR USE IN ANIMALFEEDS
1. The authority citation for 21 CFR part 558 continues to read asfollows:
Authority:
21 U.S.C. 360b, 371.
2. In § 558.76, revise paragraph (d)(3)(xiii) to readas follows:
§ 558.76 Bacitracinmethylene disalicylate.
(d) * * *
(3) * * *
(xiii) Nicarbazin alone or with narasin or roxarsone or with narasin androxarsone as in § 558.366.
3. In § 558.366, amend the table in paragraph (d) afterthe entry for "Narasin 27 to 45 and roxarsone 22.7 to 45.4" byadding three entries to read as follows:
§ 558.366 Nicarbazin.
(d) * * *
| Nicarbazin in grams per ton | Combination in grams per ton | Indications for use | Limitations | Sponsor |
|---|---|---|---|---|
| ******* | ||||
| 90.8 to 181.6 (0.01 to 0.02 pct) | Bacitracin methylene disalicylate 4 to 50 and roxarsone 22.7 to45.4 | 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 andimproved feed efficiency, and improved pigmentation | Feed continuously as sole ration from time chicks are placed on litteruntil past the time when coccidiosis is ordinarily a hazard; do not use asa treatment for outbreaks of coccidiosis. Feed as the sole source oforganic arsenic; drug overdose or lack of water may result in leg weakness;do not use in flushing mashes. Discontinue medication 5 days beforemarketing the birds for human consumption to allow for elimination of thedrug from edible tissue. Do not feed to laying hens in production.Nicarbazin as provided by No. 066104; bacitracin methylene disalicylate androxarsone by No. 046573 in § 510.600(c) of this chapter | 066104 |
| Penicillin 2.4 to 50 | 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 andimproved feed efficiency | Feed continuously as sole ration from time chicks are placed on litteruntil past the time when coccidiosis is ordinarily a hazard; do not use asa treatment for outbreaks of coccidiosis. Do not use in flushing mashes. Donot feed to chickens producing eggs for human consumption. Discontinuemedication 5 days before marketing the birds for human consumption to allowfor elimination of the drug from edible tissue. Penicillin as procainepenicillin G. Nicarbazin and penicillin as provided by No. 066104 in§ 510.600(c) of this chapter | 066104 | |
| Penicillin 2.4 to 50 and roxarsone 22.7 to 45.4 | 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 andimproved feed efficiency, and improved pigmentation | Feed continuously as sole ration from time chicks are placed on litteruntil past the time when coccidiosis is ordinarily a hazard; do not use asa treatment for outbreaks of coccidiosis. Feed as the sole source oforganic arsenic; drug overdose or lack of water may result in leg weakness;do not use in flushing mashes. Discontinue medication 5 days beforemarketing the birds for human consumption to allow for elimination of thedrug from edible tissue. Do not feed to laying hens in production.Penicillin as procaine penicillin G. Nicarbazin and penicillin as providedby No. 066104; roxarsone by No. 046573 in § 510.600(c) of thischapter | 066104 | |
| ******* | ||||
4. Add § 558.455 to read as follows:
§ 558.455 Oxytetracyclineand neomycin.
(a) Specifications . Type A medicated articles containingoxytetracycline equivalent to 50 grams per pound (g/lb) oxytetracyclinehydrochloride and 50 g/lb neomycin sulfate or oxytetracycline equivalent to100 g/lb oxytetracycline hydrochloride and 100 g/lb neomycin sulfate.
(b) Sponsors . See No. 066104 in § 510.600(c) ofthis chapter.
(c) Related tolerances . See §§ 556.430 and556.500 of this chapter.
(d) Indications for use -(1) Chickens .It is used in feed as follows:
| Oxytetracycline and neomycin sulfate amount in grams per ton offeed | Indications for use | Limitations | Sponsors |
|---|---|---|---|
| (i) 10 to 50 | Chickens: For increased rate of weight gain and improved feedefficiency | Feed continuously; do not feed to chickens producing eggs for humanconsumption | 066104 |
| (ii) 100 to 200 | Chickens: For control of infectious synovitis caused by Mycoplasma synoviae ; control of fowl cholera caused by Pasteurella multocida susceptible to oxytetracycline | Feed continuously for 7 to 14 days (d); do not feed to chickensproducing eggs for human consumption; in low calcium feed, withdraw 3 dbefore slaughter | 066104 |
| (iii) 400 | Chickens: For control of chronic respiratory disease (CRD) and airsac infection caused by M. gallisepticum and Escherichia coli susceptible to oxytetracycline | Feed continuously for 7 to 14 d; do not feed to chickens producingeggs for human consumption; in low calcium feeds, withdraw 3 d beforeslaughter | 066104 |
| (iv) 500 | Chickens: For reduction of mortality due to air sacculitis(air-sac-infection) caused by E. coli susceptible tooxytetracycline | Feed continuously for 5 d; do not feed to chickens producing eggs forhuman consumption; withdraw 24 hours before slaughter; in low calcium feedswithdraw 3 d before slaughter | 066104 |
(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 rate of weight gain and improved feedefficiency | Feed continuously; do not feed to turkeys producing eggs for humanconsumption | 066104 |
| (ii) 100 g/ton of feed | Turkeys: For control of hexamitiasis caused by Hexamitameleagridis susceptible to oxytetracycline | Feed continuously for 7 to 14 d; do not feed to turkeys producing eggsfor human consumption | 066104 |
| (iii) 200 g/ton of feed | Turkeys: For control of infectious synovitis caused by M.synoviae susceptible to oxytetracycline | Feed continuously for 7 to 14 d; withdraw 5 d before slaughter; do notfeed to turkeys producing eggs for human consumption | 066104 |
| (iv) To provide 25 mg/lb of body weight daily | Turkeys: For control of complicating bacterial organisms associatedwith bluecomb (transmissible enteritis; coronaviral enteritis) susceptibleto oxytetracycline | Feed continuously for 7 to 14 d; withdraw 5 d before slaughter; do notfeed to turkeys producing eggs for human consumption | 066104 |
(3) Swine . It is used in feed as follows:
| Oxytetracycline and neomycin sulfate amount | Indications for use | Limitations | Sponsor |
|---|---|---|---|
| (i) 10 to 50 g/ton of feed | Swine: For increased rate of weight gain and improved feedefficiency | 066104 | |
| (ii) To provide 10 mg/lb of body weight daily | 1. Swine: For treatment of bacterial enteritis caused by E.coli and Salmonella choleraesuis and treatment ofbacterial pneumonia caused by P. multocida susceptible tooxytetracycline; treatment and control of colibacillosis (bacterialenteritis) caused by E. coli susceptible to neomycin | Feed continuously for 7 to 14 d; withdraw 5 d before slaughter | 066104 |
| 2. Breeding swine: For control and treatment of leptospirosis(reducing the incidence of abortion and shedding of leptospirae) caused by Leptospira pomona susceptible to oxytetracycline | Feed continuously for not more than 14 d; withdraw 5 d beforeslaughter | 066104 |
(4) Cattle and sheep . It is used in feed as follows:
| Oxytetracycline and neomycin sulfate amount | Indications for use | Limitations | Sponsor |
|---|---|---|---|
| (i) 10 to 20 grams per ton of feed | Sheep: For increased rate of weight gain and improved feedefficiency | 066104 | |
| (ii) To provide 0.05 to 0.1 mg/lb of body weight daily. | Calves (up to 250 lb): For increased rate of weight gain and improvedfeed efficiency | Feed continuously; in milk replacers or starter feed | 066104 |
| (iii) To provide 10 mg/lb of body weight daily | 1. Calves and beef and nonlactating dairy cattle: For treatment ofbacterial enteritis caused by E. coli and bacterial pneumonia(shipping fever complex) caused by P. multocida susceptibleto oxytetracycline; treatment and control of colibacillosis (bacterialenteritis) caused by E. coli susceptible to neomycin | Feed continuously for 7 to 14 d; in feed or milk replacers. Ifsymptoms persist after using for 2 or 3 d, consult a veterinarian.Treatment should continue 24 to 48 hours beyond remission of diseasesymptoms. A withdrawal period has not been established for use inpreruminating calves. Do not use in calves to be processed for veal. A milkdiscard time has not been established for use in lactating dairy cattle. Donot use in female dairy cattle 20 months of age or older. Withdraw 5 dbefore slaughter | 066104 |
| 2. Calves (up to 250 lb): For treatment of bacterial enteritis causedby E. coli susceptible to oxytetracycline; treatment andcontrol of colibacillosis (bacterial enteritis) caused by E.coli susceptible to neomycin | Feed continuously for 7 to 14 d; in milk replacers or starter feed. Ifsymptoms persist after using for 2 or 3 d, consult a veterinarian.Treatment should continue 24 to 48 hours beyond remission of diseasesymptoms. A withdrawal period has not been established for use inpreruminating calves. Do not use in calves to be processed for veal. A milkdiscard time has not been established for use in lactating dairy cattle. Donot use in female dairy cattle 20 months of age or older. Withdraw 5 dbefore slaughter | 066104 | |
| 3. Sheep: For treatment of bacterial enteritis caused by E.coli and bacterial pneumonia caused by P. multocida susceptible to oxytetracycline; treatment and control of colibacillosis(bacterial enteritis) caused by E. coli susceptible toneomycin | Feed continuously for 7 to 14 d. If symptoms persist after using for 2or 3 d, consult a veterinarian. Treatment should continue 24 to 48 hoursbeyond remission of disease symptoms. Withdraw 5 d before slaughter | 066104 | |
| (iv) To provide 25 mg/head/day | Calves (250 to 400 lb): For increased rate of weight gain andimproved feed efficiency | 066104 | |
| (v) To provide 75 mg/head/day | Growing cattle (over 400 lb): For increased rate of weight gain;improved feed efficiency, and reduction of liver condemnation due to liverabscesses | 066104 | |
| (vi) To provide 0.5 to 2.0 g/head/day | Cattle: For prevention and treatment of the early stages of shippingfever complex | Feed 3 to 5 d before and after arrival in feedlots. A withdrawalperiod has not been established for use in preruminating calves. Do not usein calves to be processed for veal. A milk discard time has not beenestablished for use in lactating dairy cattle. Do not use in female dairycattle 20 months of age or older | 066104 |
5. In § 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:
§ 558.460 Penicillin.
(d) * * *
(2) * * *
(iv) Nicarbazin alone or with roxarsone as in § 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