Approval Date: June 22, 1998

Freedom of Information Summary
NADA 046-592

I. GENERAL INFORMATION:

NADA	046-592
Sponsor:	Alpharma, Inc. One Executive Drive Fort Lee, New Jersey 07024
Generic Name:	bacitracin methylene disalicylate
Trade Name:	BMDâ
Marketing Status:	Over The Counter
Effect of Supplement:	This supplement provides for the addition of a class, replacement chickens, to be added to the previously approved product, BMDâ Type A medicated article.

II. INDICATIONS FOR USE

Replacement chickens: as an aid in the prevention and control of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin methylene disalicylate.

III. DOSAGE:

A.	DOSAGE FORM	Bacitracin methylene disalicylate is supplied as a Type A medicated article in concentrations of 10, 25, 30, 40, 50, 60, and 75 grams bacitracin activity per pound.
B.	ROUTE OF ADMINISTRATION	Oral, via the feed
C.	RECOMMENDED DOSAGES:	As an aid in the prevention of necrotic enteritis: BMD should be fed to replacement chickens at a concentration of 50 grams per ton of feed. As an aid in the control of necrotic enteritis: BMD should be fed to replacement chickens at a concentration of 100 to 200grams per ton of feed for 5 to 7 days or as long as clinical signs persist, and then the concentration should be reduced to prevention level (50 grams/ton).

IV. EFFECTIVENESS:

Bacitracin methylene disalicylate is approved under this NADA for use in laying chickens, turkeys, pheasants, quail, swine, broiler chickens, growing/finishing swine, pregnant sows, and feedlot beef cattle. Approvals relevant to the present supplement include: bacitracin MD from 10 to 25 grams per ton for use in chickens for increased egg production and improved feed efficiency for egg production [21 CFR 558.76 (d)(1)(iii)]; BMD at 50 grams per ton for use in broiler chickens as an aid in the prevention of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin [21 CFR 558.76 (d)(1)(vi)]; and BMD from 100 to 200 grams per ton for use in broiler chickens as an aid in the control of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin [21 CFR 558.76 (d)(1)(ix)]. Since the effectiveness of bacitracin methylene disalicylate for the prevention (50 g/ton) and control (100 to 200 g/ton) of necrotic enteritis in broiler chickens has previously been established under this NADA, and because the agency believes that broiler chickens and replacement chickens are similar enough physiologically that a drug that is effective for this indication in broiler chickens will be equally effective in replacement chickens, additional effectiveness studies were not required for this supplemental application.

V. ANIMAL SAFETY:

The safety of administering up to 4000 g/ton of BMD in the feed of broiler chickens for up to 8 weeks has previously been demonstrated under this NADA. Similarly, the safety of administering up to 1000 g/ton of BMD in the feed of laying hens for 5months has also previously been demonstrated under this NADA. For additional information refer to the FOI summaries for the supplemental approvals of bacitracin methylene disalicylate for use in laying chickens for increased egg production and improved feed efficiency for egg production, and for use in broiler chickens as an aid in the prevention and control of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin.

Based on the margin of safety previously documented in the safety studies summarized for use of this drug in broiler chickens and laying hens, additional safety studies were not required for this supplemental application.

VI. HUMAN FOOD SAFETY:

The human food safety of this product has been previously established under this NADA. For additional information refer to the FOI summaries for the supplemental approvals of bacitracin methylene disalicylate for use in chickens for increased egg production and improved feed efficiency for egg production, for use in broiler chickens as an aid in the prevention of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin, and for use in broiler chickens as an aid in the control of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin.

Tolerances for residues of bacitracin from bacitracin methylene disalicylate in the uncooked edible tissue of chickens and turkeys have been established at 0.5 ppm (0.02unit per gram), negligible residue (21 CFR 556.70).

Earlier FOI Summaries under this NADA highlight two studies in which chickens were fed 1000 g/ton BMD for 8 weeks with no detection of residues in target tissue at zero withdrawal; and laying hens were fed 1000 g/ton for 5 months with no detection of residues either in tissues or egg yolk and egg whites. These two studies are sufficient to support a zero withdrawal period for replacement (breeder and layer) chickens that will be treated with BMD at levels up to 200 g/ton.

A microbiological assay method is used to assay tissues for bacitracin residues. The method entitled "Modified Microbiological Method for Determination of Bacitracin in Tissues" is on file at the Center for Veterinary Medicine, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20855.

VII. AGENCY CONCLUSIONS:

The data submitted in support of this NADA supplement satisfy the requirements of Section 512 of the Federal Food, Drug and Cosmetic Act and 21 CFR Part 514 of the implementing regulations. The data demonstrate that bacitracin methylene disalicylate, when administered in the feed of replacement chickens at a concentration of 50 g/ton (for prevention) or 100 to 200 g/ton (for control), is safe and effective as an aid in the prevention and control of necrotic enteritis caused or complicated by Clostridium spp. or other organisms susceptible to bacitracin methylene disalicylate.

The tolerance for residues of bacitracin in edible uncooked tissues of chickens has been established as 0.5 ppm under 21 CFR 556.70. Earlier FOI Summaries under this NADA highlight two studies in which chickens were fed 1000 g/ton BMD for 8 weeks with no detection of residues in target tissue at zero withdrawal; and laying hens were fed 1000 g/ton for 5 months with no detection of residues either in tissues or egg yolk and egg whites. These two studies are sufficient to support a zero withdrawal period for replacement (breeder and layer) chickens that will be treated with BMD at levels up to 200 g/ton.

Proper use by lay persons can be expected because the directions are clearly written and there is reasonable certainty that the conditions of use can and will be followed by the producer. The agency has concluded that this product can be approved for over-the-counter use.

The agency has determined under 21 CFR 25.33(a)(1) that this action is of a type that does not individually or cumulatively have a significant impact on the human environment. Therefore, neither an environmental assessment nor an environmental impact statement is required.

Under the Center's supplemental approval policy (21 CFR 514.106(b)(2)), these are Category II changes. The approval of these changes is not expected to have any adverse effect on the safety or effectiveness of this new animal drug and, therefore, did not require a reevaluation of the human food or target animal safety data in the parent application.

VIII. LABELING (Attached)

A copy of the draft facsimile labeling is attached to this document.

A. BMDâ 30 Type A Medicated Article Bag Label
B. BMDâ 50 Type A Medicated Article Bag Label
C. BMDâ 60 Type A Medicated Article Bag Label
D. BMDâ Bluebird Label for Type C Medicated Feed (100 to 200 g/ton)
E. BMDâ Bluebird Label for Type C Medicated Feed (50 g/ton)5-20 grams/ton

Copies of applicable labels may be obtained by writing to the:

Food and Drug Administration
Freedom of Information Staff (HFI-35)
5600 Fishers Lane
Rockville, MD 20857

Or requests may be sent via fax to: (301) 443-1726. If there are problems sending a fax, call (301) 443-2414.