[Code of Federal Regulations] [Title 21, Volume 6] [Revised as of April 1, 2001] From the U.S. Government Printing Office via GPO Access [CITE: 21CFR558.15] [Page 361-367] TITLE 21--FOOD AND DRUGS CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES--(Continued) PART 558--NEW ANIMAL DRUGS FOR USE IN ANIMAL FEEDS--Table of Contents Subpart A--General Provisions Sec. 558.15 Antibiotic, nitrofuran, and sulfonamide drugs in the feed of animals. (a) The Commissioner of Food and Drugs will propose to revoke currently approved subtherapeutic (increased rate of gain, disease prevention. etc.) uses in animal feed of antibiotic and sulfonamide drugs whether granted by approval of new animal drug applications, master files and/or antibiotic or food additive regulations, by no later than April 20, 1975, or the nitrofuran drugs by no later than September 5, 1975, unless data are submitted which resolve conclusively the issues concerning their safety to man and animals and their effectiveness under specific criteria established by the Food and Drug Administration based on the guidelines included in the report of the FDA task force on the use of antibiotics in animal feeds. All persons or firms previously marketing identical, related, or similar products except the nitrofuran drugs not the subject of an approved new animal drug application must submit a new animal drug application by July 19, 1973, or by December 4, 1973, in the case of nitrofuran drugs, if marketing is to continue during the interim. New animal drug entities with antibacterial activity not previously marketed, now pending approval or submitted for approval prior to, on, or following the effective date of this publication, shall satisfy such criteria prior to approval. (b) Any person interested in developing data which will support retaining approval for such uses of such antibiotic, nitrofuran, and sulfonamide drugs pursuant to section 512(l) of the Federal Food, Drug, and Cosmetic Act shall submit to the Commissioner the following: (1) By July 19, 1973, records and reports of completed, ongoing, or planned studies, including protocols, on the tetracyclines, streptomycin, dihydrostreptomycin, penicillin, and the sulfonamides; for all other antibiotics by October 17, 1973; and for the nitrofuran drugs by March 4, 1974. The Food and Drug Administration encourages sponsors to consult with the Center for Veterinary Medicine on protocol design and plans for future studies. (2) By April 20, 1974, data from completed studies on the tetracyclines, streptomycin, dihydrostreptomycin, the sulfonamides, and penicillin assessing the effect of the subtherapeutic use of the drug in feed on the salmonella reservoir in the target animal as compared to that in nonmedicated controls. Failure to complete the salmonella studies for any of these drugs by that time will be grounds for proceeding to immediately withdraw approval. (3) By April 20, 1975, data satisfying all other specified criteria for safety and effectiveness, including the effect on the salmonella reservoir for any antibiotic or sulfonamide drugs and by September 5, 1975, for the nitrofuran drugs, approved for subtherapeutic use in animal feeds. Drug efficacy data shall be submitted for any feed-use combination product containing such drug and any feed-use single ingredient antibiotic, nitrofuran, or sulfonamide not reviewed by the National Academy of Sciences--National Research Council, Drug Efficacy Study covering drugs marketed between 1938 and 1962. (4) Progress reports on studies underway every January 1 and July 1 until completion. (c) Failure on the part of any sponsor to comply with any of the provisions of paragraph (b) of this section for any of the antibacterial drugs included in paragraph (b)(1) of this section, or interim results indicating a health hazard, will be considered as grounds for immediately proceeding to withdraw approval of that drug for use in animal feeds under section 512(l) of the act in the case of failure to submit required records and reports and under section 512(e) where new information shows that such drug is not shown to be safe. (d) Criteria based upon the guidelines laid down by the task force may be obtained from the Food and Drug Administration, Center for Veterinary Medicine, 7500 Standish Pl., Rockville, MD 20855. (e) Reports as specified in this section shall be submitted to: Food and Drug Administration, Center for Veterinary Medicine, Office of New Animal Drug Evaluation (HFV-100), 7500 Standish Pl., Rockville, MD 20855. [[Page 362]] (f) Following the completion of the requirements of paragraphs (a) and (b) of this section and the studies provided for therein: (1) Those antibiotic, nitrofuran, and sulfonamide drugs which fail to meet the prescribed criteria for subtherapeutic uses but which are found to be effective for the therapeutic purposes will be permitted in feed only for high-level, short-term therapeutic use and only by or on the order of a licensed veterinarian. (2) Animal feeds containing antibacterial drugs permitted to remain in use for subtherapeutic purposes shall be labeled to include a statement of the quantity of such drugs. (g) The submission of applications and data required by paragraphs (a) and (b) of this section is not required for the continued manufacture of any Type A medicated article which is produced solely from a Type A article that is in compliance with the requirements of this section: Provided, That the Type A medicated article contains no drug ingredient whose use in or on animal feed requires an approved application pursuant to section 512(m) of the act and/or where the Type A article is approved by regulation in this part. (1) The following antibacterial Type A articles manufactured by the designated sponsors are eligible for interim marketing based on their compliance with the requirements of this section: ---------------------------------------------------------------------------------------------------------------- Indications for Drug sponsor Type A article Species Use levels use ---------------------------------------------------------------------------------------------------------------- Pitman-Moore, Inc.............. Bacitracin zinc.... Chickens, turkeys, Sec. 558.78....... Sec. 558.78. swine, pheasants, quail, and cattle. A. L. Laboratories, Inc........ ......do........... Chickens, turkeys, ......do.......... Do. pheasants, and quail. A.L. Laboratories, Inc., Bacitracin Chicken turkeys, Sec. 558.76....... Sec. 558.76. Fermenta Animal Health Co.. methylene swine, and cattle. disalicylate. Elanco Products Co............. Hygromycin B....... Chickens and swine. Sec. 558.274...... Sec. 558.274. Do......................... Tylosin............ Chickens, swine, Sec. 558.625...... Sec. 558.625. and beef cattle. Sanofi Animal Health, Inc...... Erythromycin....... Chickens, turkeys, Sec. 558.248...... Sec. 558.248. and swine. The Upjohn Co.................. Lincomycin......... Chickens........... Sec. 558.325...... Sec. 558.325. Pfizer, Inc.................... Oleandomycin....... Chickens, turkeys, Sec. 558.435...... Sec. 558.435. and swine. Hoechst-Roussel Agri-Vet, Inc.. Bambermycins....... Chickens........... Sec. 558.95....... Sec. 558.95. Elanco Products Co............. Tylosin and Swine.............. Sec. 558.630...... Sec. 558.630. sulfamethazine. American Cyanamid Co., Fermenta Chlortetracycline.. Chickens, turkeys, Sec. 558.128...... Sec. 558.128. Animal Health Co., Feed swine, and cattle. Specialties Co., Inc., Pfizer, Inc., PennField Oil Co., and VPO, Inc.. Merck Sharp & Dohme Research Procaine Penicillin Chickens, turkeys, Sec. 558.460...... Sec. 558.460. Labs., and Solvay Veterinary, swine, pheasants, Inc. and quail. Pfizer, Inc., PennField Oil Co. Oxytetracycline.... Sec. 558.450....... Sec. 558.450...... Sec. 558.450. American Cyanamid Co........... Chlortetracycline Cattle............. Sec. 558.128...... Sec. 558.128. and sulfamethazine. Sanofi Animal Health, Inc...... Erythromycin....... Cattle............. 37 mg per head per Sec. 558.248. day. Hoffman-La Roche, Inc.......... Sulfadimethoxine Chickens and Sec. 558.575...... Sec. 558.575. and ormetoprim. turkeys.. Pfizer, Inc.................... Oxytetracycline and Chickens, turkeys, As provided in As provided in neomycin. swine, and calves. paragraph (g)(2) paragraph (g)(2) of this section. of this section. American Cyanamid Co. and Chlortetracycline, Swine.............. ......do.......... Do. Pfizer, Inc. sulfamethazine, and penicillin. Boehringer Ingelheim Vetmedica, Chlortetracycline, ......do........... ......do.......... Do. Inc.. sulfathiazole, and penicillin. ---------------------------------------------------------------------------------------------------------------- [[Page 363]] (2) The following is a list of drug combinations permitted when prepared from antibacterial Type A articles listed in paragraph (g)(1) of this section. Drug combinations listed in subpart B of this part name their sponsors and are incorporated herein by reference since they are safe and effective by contemporary standards, or such sponsors have been notified of any additional safety or efficacy data required on an individual basis: ---------------------------------------------------------------------------------------------------------------- Indications for Drug sponsor Type A article Species Use levels use ---------------------------------------------------------------------------------------------------------------- Boehringer Ingelheim Vetmedica, Chlortetracycline Swine.............. 10 to 50 g/ton and Enhancement of Inc.. and arsanilic acid. 0.005 to 0.01 growth and feed percent. efficiency. American Cyanamid Co........... Chlortetracycline Cattle............. Sec. 558.128...... Sec. 558.128. and sulfamethazine. Pfizer, Inc., PennField Oil Oxytetracycline and Chickens........... 50 g/ton and 35 to Prevention of Co., and VPO, Inc. neomycin base. 140 g/ton. diseases from oxytetracycline susceptible organisms during periods of stress. As an aid in the prevention of bacterial enteritis and in the control of neomycin- sensitive organisms associated with bluecomb (mud fever or nonspecific enteritis). Do......................... ......do........... Chickens (first 2 50 to 100 g/ton Prevention of weeks). and 35 to 140 g/ early chick ton. mortality due to oxytetracycline- susceptible organisms. As an aid in the prevention of bacterial enteritis and in the control of neomycin- sensitive organisms associated with bluecomb (mud fever or nonspecific enteritis). Do......................... ......do........... Chickens........... ......do.......... To extend period of high egg production, to improve feed efficiency, to improve egg production and feed efficiency in presence of disease and at time of stress. As an aid in maintaining and improving hatchability where birds are suffering stress from moving, vaccinations, culling, extreme temperature changes, and worming; to improve livability of progeny when losses are due to oxytetracycline- susceptible organisms, to improve egg shell quality, prevention of bluecomb (mud fever or nonspecific enteritis). As an aid in the prevention of bacterial enteritis and in the control of nermycon- sensitive organisms associated with bluecomb (mud fever or nonspecific enteritis). Do......................... ......do........... ......do........... 100 to 200 g/ton Prevention of and 35 to 140 g/ complicated ton. chronic respiratory disease (air-sac infection) and control of complicated chronic respiratory disease by lowering mortality and severity during outbreaks. As an aid in the prevention of bacterial enteritis and in the control of neomycin- sensitive organisms associated with bluecomb (mud fever or nonspecific enteritis). [[Page 364]] Do......................... ......do........... Turkeys............ 50 g/ton and 35 to As an aid in the 140 g/ton. prevention of disease from oxytetracycline susceptible organisms during periods of stress. As an aid in the prevention of bacterial enteritis and in the control of neomycin- sensitive organisms associated with bluecomb (mud fever or nonspecific enteritis). Do......................... ......do........... ......do........... 50 to 100 g/ton To extend periord and 35 to 140 g/ of high egg ton. production, to improve egg production, to improve feed efficiency, to improve fertility, to improve egg production and feed efficiency in presence of disease and time of stress; as an aid in maintaining and improving hatchability where birds are suffering from stress, exposure, moving, vaccination, culling, extreme losses due to oxytetracycline- susceptible organisms, and to improve egg shell quality prevention of hexamitiasis. As an aid in the prevention of bacterial enteritis and in the control of neomycin- sensitive organisms associated with bluecomb (mud fever or nonspecific enteritis). Do......................... ......do........... Turkeys (first 4 ......do.......... As an aid in the weeks). prevention of early poult mortality due to oxytetracycline- susceptible organisms. As an aid in the prevention of bacterial enteritis and in the control of neomycin- sensitive organisms associated with bluecomb (mud fever or nonspecific enteritis). Do......................... ......do........... ......do........... 100 to 150 g/ton As an aid in and 35 to 105 g/ reducing ton. mortality in birds which have suffered an attack of air- sacculitis (it is recommended, wherever possible, to feed from time of attack to marketing). Do......................... ......do........... Turkeys............ ......do.......... As an aid in the prevention of bacterial enteritis and in the control of neomycin- sensitive organisms associated with bluecomb (mud fever or nonspecific enteritis). Do......................... ......do........... ......do........... 100 to 200 g/ton Control of and 35 to 140 g/ bluecomb (mud ton. fever or nonspecific enteritis), infectious sinusitis and hexamitiasis, prevention of infectious synovitis. As an aid in the prevention of bacterial enteritis and in the control of neomycin- sensitive organisms associated with bluecomb (mud fever or nonspecific enteritis). Do......................... ......do........... ......do........... 200 g/ton and 70 Control of to 140 g/ton. infectious synovitis. For the treatment of bacterial enteritis and bluecomb (mud fever or nonspecific enteritis). [[Page 365]] Do......................... ......do........... Swine.............. 50 g/ton and 35 to As an aid in the 140 g/ton. prevention of bacterial enteritis (scours), baby pig diarrhea (in baby pigs only), vibrionic dysentery, bloody dysentery, and salmonellosis (necro or necrotic enteritis). Do......................... ......do........... ......do........... 50 to 150 g/ton As an aid in the and 70 to 140 g/ maintenance of ton. weight gains and feed consumption in the presence of atrophic rhinitis. As an aid in the treatment of bacterial enteritis. Do......................... ......do........... Calves............. 50 g/ton and 35 to As an aid in the 140 g/ton. prevention of bacterial enteritis (scours). Do......................... ......do........... ......do........... 100 g/ton and 70 As an aid in the to 140 g/ton. treatment of bacterial enteritis (scours). Do......................... ......do........... ......do........... 8 to 100 mg/gal As an aid in the and 100 to 200 mg/ prevention of gal reconstituted bacterial milk replacer. diarrhea (scours). Do......................... ......do........... ......do........... 40 to 200 mg/gal As an aid in the and 200 to 400 mg/ treatment of gal reconstituted bacterial milk replacer. diarrhea (scours). The Upjohn Co.................. Lincomycin, Chickens........... Secs. 558.58 and Secs. 558.58 and amprolium, and 558.325. 558.325. ethopabate. Do......................... Lincomycin and ......do........... Secs. 558.325 and Secs. 558.325 and zoalene. 558.680. 558.680. Do......................... Lincomycin, ......do........... Secs. 558.58, Secs. 558.58, amprolium, 558.325, and 558.325, and ethopabate, and 558.530. 558.530. roxarsone. Do......................... Lincomycin, ......do........... Secs. 558.325, Secs. 558.325, monensin, and 558.355, and 558.355, and roxarsone. 558.530. 558.530. Do......................... Nicarbazin and Chickens........... 0.01 to 0.02 Do. procaine percent and 2.4 penicillin. to 50 g/ton. Do......................... Nicarbazin and .....do............ 0.01 to 0.02 Do. bacitracin percent and 4 to methylene 50 g/ton. disalicylate. Do......................... Nicarbazin, .....do............ 0.01 to 0.02 Do. bacitracin percent, 4 to 50 methylene g/ton, and 0.0025 disalicylate, and to 0.005 percent. roxarsone. Do......................... Nicarbazin, .....do............ 0.01 to 0.02 Do. procaine percent, 2.4 to penicillin, and 50 g/ton, and roxarsone. 0.0025 to 0.025 percent. Do......................... Amprolium and Chickens and 0.0125 to 0.025 Secs. 558.55 and bacitracin turkeys. percent and 4 to 558.76. methylene 50 g/ton. disalicylate. Do......................... Amprolium, Chickens........... 0.0125 to 0.025 Secs. 558.58 and ethopabate, and percent, 0.0004 558.76. bacitracin percent, and 4 to methylene 50 g/ton. disalicylate. Do......................... Amprolium, .....do............ 0.0125 to 0.025 Secs. 558.58, ethopabate, percent, 0.0004 558.76, and bacitracin percent, 4 to 50 558.530. methylene g/ton, and 0.0025 disalicylate, and to 0.005 percent. roxarsone. Do......................... Amprolium and Chickens and 0.004 to 0.025 Secs. 558.55 and procaine turkeys. percent and 2.4 558.460. penicillin. to 50 g/ton. [[Page 366]] Do......................... Amprolium, procaine Chickens........... 0.004 to 0.025 Secs. 558.55, penicillin, and percent, 2.4 to 558.460, and roxarsone. 50 g/ton, and 558.530. 0.0025 to 0.005 percent. Do......................... Amprolium, ......do........... 0.0125 to 0.025 Secs. 558.58 and ethopabate, percent, 0.0004 558.460. procaine percent, 2.4 to penicillin, and 50 g/ton, and 4.6 erythromycin. to 18.5 g/ton. Do......................... Amprolium and ......do........... 0.0125 to 0.025 Sec. 558.55. erythromycin. percent and 4.6 to 18.5 g/ton. Do......................... Amprolium and ......do........... 0.0125 to 0.025 Sec. 558.58. ethopabate. percent and 0.0004 percent. Do......................... Amprolium, ......do........... 0.0125 to 0.025 Sec. 558.55. arsanilic acid, percent, 0.01 and erythromycin. percent, and 4.6 to 18.5 g/ton. Do......................... Amprolium, ......do........... 0.0125 to 0.025 Sec. 558.58. arsanilic acid, percent, 0.01 and ethopabate. percent, and 0.0004 percent. Do......................... Amprolium, ......do........... 0.0125 percent, Do. ethopabate, and 0.004 percent, bacitracin and 4 to 50 g/ton. methylene disalicylate. Do......................... Amprolium, ......do........... 0.0125 percent, Do. ethopabate, 0.004 percent, 5 bacitracin to 35 g/ton, and methylene 0.00375 percent. disalicylate, and roxarsone. Pitman-Moore, Inc.............. Bacitracin zinc, ......do........... 4 to 50 g/ton, Prevention of amprolium, and 0.0125 to 0.025 coccidiosis. ethopabate. percent, and Growth promotion 0.0004 percent. and feed efficiency. Sec.558.78. Do......................... Bacitracin zinc, ......do........... 4 to 50 g/ton, Prevention of amprolium, 0.0125 to 0.025 coccidiosis. ethopabate, and percent, 0.0004 Growth promotion roxarsone. percent, and and feed 0.0025 to 0.005 efficiency. percent. Improving pigmentation. Sec. 558.78. Do......................... Bacitracin zinc and Swine.............. 10 to 50 g/ton and Increased rate of arsanilic acid. 0.005 to 0.01 weight gain and percent. improved feed efficiency. Merck Sharp & Dohme Research Amprolium, Chickens........... 0.125 to 0.025 Secs. 558.58, Labs. ethopabate, percent, 0.0004 558.460 and procaine percent, 2.4 to 558.530. penicillin, and 50 g/ton, and roxarsone. 0.0025 to 0.005 percent. A. L. Laboratories, Inc........ Zoalene and Chickens........... 0.0125 percent and Sec. 558.680. bacitracin 4 to 50 g/ton. methylene disalicylate. Do......................... Zoalene, roxarsone, ......do........... 0.0125 percent, Do. and bacitracin 0.005 percent, methylene and 4 to 50 g/ton. disalicylate. Do......................... Zoalene and ......do........... 0.0125 percent and Do. bacitracin zinc. 4 to 50 g/ton. Do......................... Zoalene, roxarsone, ......do........... 0.0125 percent, Do. and bacitracin 0.0025 to 0.005 zinc. percent, and 4 to 50 g/ton. Do......................... Zoalene and ......do........... 0.0125 percent and Do. penicillin. 2.4 to 50 g/ton. [[Page 367]] Do......................... Zoalene, roxarsone, ......do........... 0.0125 percent, Do. and penicillin. 0.0025 to 0.005 percent, and 2.4 to 50 g/ton. Do......................... Zoalene, arsanilic ......do........... 0.0125 percent, Do. acid, and 0.01 percent, and bacitracin 4 to 50 g/ton. methylene disalicylate or bacitracin zinc. Do......................... Zoalene, arsanilic ......do........... 0.0125 percent, Do. acid, and 0.01 percent, and penicillin. 2.4 to 50 g/ton. Do......................... Zoalene, and ......do........... 0.004 to 0.0125 Do. bacitracin percent and 4 to methylene 50 g/ton. disalicylate. Do......................... Zoalene, roxarsone, ......do........... 0.004 to 0.0125 Do. and bacitracin percent, 0.0025 methylene to 0.005 percent, disalicylate. and 4 to 50 g/ton. Whitmoyer Labs, Inc............ Carbarsone and Turkeys............ Sec. 558.120...... Sec. 558.120. bacitracin. Elanco Products Co............. Hygromycin B and Chickens........... 8 to 12 g/ton and Sec. 558.274. tylosin. 4 to 50 g/ton. Do......................... ......do........... Swine.............. 12 g/ton and 10 to Do. 100 g/ton. A. L. Laboratories, Inc........ Nitarsone and Turkeys............ 0.01875 percent, 4 As an aid in the bacitracin zinc. to 50 g/ton. prevention of blackhead. To increase rate of weight gain and improve feed efficiency. ---------------------------------------------------------------------------------------------------------------- [51 FR 8811, Mar. 14, 1986; 51 FR 11014, Apr. 1, 1986, as amended at 51 FR 28547, Aug. 8, 1986; 53 FR 20843, June 7, 1988; 54 FR 37098, Sept. 7, 1989; 54 FR 51386, Dec. 15, 1989; 55 FR 8460, 8462, Mar. 8, 1990; 56 FR 41912, Aug. 23, 1991; 56 FR 64702, Dec. 12, 1991; 57 FR 6476, Feb. 25, 1992; 57 FR 8577, Mar. 11, 1992; 57 FR 14639, Apr. 22, 1992; 58 FR 17515, Apr. 5, 1993; 58 FR 30119, May 26, 1993; 61 FR 51589, Oct. 3, 1996; 64 FR 992, Jan. 7, 1999; 64 FR 37673, July 13, 1999]