Medicated Feeds Overview

1. Medicated Feeds Overview Dr. Dragan Momcilovic, Medicated Feeds Specialist Dr. Gabriel Davila, Staff Fellow Food and Drug Administration Center for Veterinary Medicine Division of Animal Feeds Medicated Feeds Team Rockville, MD June 2012

2. Agenda • Definitions and usages • Drug Categories • Types of Distribution • Medicated Products • Pre-approval activities • FDA’s new animal drug approval process (basics) • Label review • Labeling of medicated products • Post-approval activities • Current Good Manufacturing Practices (cGMP) • Program Monitoring • Licensing and Registration • Where to look for more information

3. Drug Categories

4. Drug Categories Category I Category II

5. Drug Categories Category I Category II Drugs with no withdrawal period required at the lowest use level for each species for which they are approved

6. Drug Categories Category I Category II Drugs with no withdrawal period required at the lowest use level for each species for which they are approved Drugs with a withdrawal period required at the lowest use level for at least one of the species for which they are approved

7. Drug Categories Category I Category II Drugs with no withdrawal period required at the lowest use level for each species for which they are approved Drugs with a withdrawal period required at the lowest use level for at least one of the species for which they are approved Drugs regulated on a “no-residue” basis or with a “zero” tolerance level because of a carcinogenic concern

8. Drug Categories Category I Category II Drugs with no withdrawal period required at the lowest use level for each species for which they are approved Drugs with a withdrawal period required at the lowest use level for at least one of the species for which they are approved Drugs regulated on a “no-residue” basis or with a “zero” tolerance level because of a carcinogenic concern Drugs that are veterinary feed directive

9. Drug Categories Category I Category II Drugs with no withdrawal period required at the lowest use level for each species for which they are approved Drugs with a withdrawal period required at the lowest use level for at least one of the species for which they are approved Drugs regulated on a “no-residue” basis or with a “zero” tolerance level because of a carcinogenic concern Drugs that are veterinary feed directive Level of risk

10. Drug Categories Category I Category II Drugs with no withdrawal period required at the lowest use level for each species for which they are approved Drugs with a withdrawal period required at the lowest use level for at least one of the species for which they are approved Drugs regulated on a “no-residue” basis or with a “zero” tolerance level because of a carcinogenic concern Drugs that are veterinary feed directive Level of risk

11. Drug Categories Category I Category II Drugs with no withdrawal period required at the lowest use level for each species for which they are approved Drugs with a withdrawal period required at the lowest use level for at least one of the species for which they are approved Drugs regulated on a “no-residue” basis or with a “zero” tolerance level because of a carcinogenic concern Drugs that are veterinary feed directive Less risky Level of risk

12. Drug Categories Category I Category II Drugs with no withdrawal period required at the lowest use level for each species for which they are approved Drugs with a withdrawal period required at the lowest use level for at least one of the species for which they are approved Drugs regulated on a “no-residue” basis or with a “zero” tolerance level because of a carcinogenic concern Drugs that are veterinary feed directive Less risky More risky Level of risk

13. Types of Distribution Medicated Feeds are distributed: - Over-The-Counter - Veterinary Feed Directive

14. Medicated ProductsType A medicated article Type B medicated feed Type C medicated feed

15. Medicated ProductsType A medicated articleis a new animal drug

16. A new animal drug is…. Section 201(v)*: - any drug intended for use for animals other than man, including any drug intended for use in animal feed - does not include animal feed *Federal Food, Drug, and Cosmetic Act

17. Medicated ProductsType A medicated articleis a new animal drug with or without inactive ingredients intended for use in animal feed intended solely for further manufacture

18. Medicated ProductsType A medicated article is used to makeanother Type A medicated article a Type B medicated feed a Type C medicated feed

19. Animal feed is... • Section 201(w)*: • an article intended for use for food for animals other than man • intended for use as a substantial source of nutrients in the diet of the animal • is not limited to a mixture intended to be the sole ration of the animal. *Federal Food, Drug, and Cosmetic Act

20. Medicated Products • Type A medicated article - DRUG • Type B medicated feed - FEED containing DRUG • Type C medicated feed - FEED containing DRUG

21. Type B Medicated Feed • contains a substantial quantity of nutrients • originates from: a) a Type A medicated article b) another Type B medicated feed c) an unstandardized drug component (bulk or “drum run”)

22. Type B Medicated Feed • intended solely for the manufacture of: - other Type B medicated feed - Type C medicated feed

23. Type B Medicated Feed • the maximum concentration of drug(s) is: a) if a Category I drug - 200 X the highest continuous use level b) if a Category II drug - 100 X the highest continuous use level c) if a drug is not approved for continuous use - the highest level used for disease prevention/control

24. Components of a Type B Blue Bird Label • product name • purpose or indications for use • active ingredients • guaranteed analysis • ingredients • mixing directions • warning and caution sections (if any) • name and address of manufacturer • net weight statement

25. Type C Medicated Feed • Originates from: a) a Type A medicated article b) a Type B medicated feed c) another Type C medicated feed d) an unstandardized drug component (bulk or drum run)

26. Type C Medicated Feed • is intended for feeding as: a) the complete feed b) ‘top dressed’ c) ‘free choice’

27. Components of a Type C Blue Bird Label • product name • purpose or indications for use • active ingredients • guaranteed analysis • ingredients • feeding directions • warning and caution sections (if any) • name and address of manufacturer • net weight statement

28. Type C for feeding to be fed Labeling Feeding directions Type B for further mixing cannot be fed Labeling Mixing directions Major differences between Type B and Type C medicated feed labels

29. FDA’s animal drug approval process (basics)

30. New Animal Drug Application (NADA) • Required for: -the manufacture of all Type A medicated articles

31. The Federal Food, Drug, and Cosmetic Act • mandates that a new animal drug may not be sold in interstate commerce unless it is the subject of a New Animal Drug Application (NADA)

32. The Federal Food, Drug, and Cosmetic Act • What does an approved NADA mean?

33. The Federal Food, Drug, and Cosmetic Act • What does an approved NADA mean? • The product is safe and effective for its intended use

34. The Federal Food, Drug, and Cosmetic Act • What does an approved NADA mean? • The product is safe and effective for its intended use • The methods, facilities and controls used for the manufacturing, processing and packaging of the drug are adequate to preserve its identity, strength, quality and purity

35. The Federal Food, Drug, and Cosmetic Act • Effectiveness Based on substantial evidence consisting of one or more adequate and well controlled investigations, such as - a study in a target species - a study in laboratory animals - a bioequivalence study - an in vitro study

36. The Federal Food, Drug, and Cosmetic Act • Safety - Adequate tests by all methods reasonably applicable show that the drug is safe for use under the conditions prescribed, recommended, or suggested in the proposed labeling

37. The Federal Food, Drug, and Cosmetic Act • NADA - is a systematic approach to document evidence that drug products are safe and effective - consists of the drug, the packaging, and the labeling

38. Label review Division of Animal Feeds Office of Surveillance and Compliance (OSC), Center for Veterinary Medicine

39. Label review Division of Animal Feeds Office of Surveillance and Compliance (OSC), Center for Veterinary Medicine Pre-approval Post-approval

40. Label review Division of Animal Feeds Office of Surveillance and Compliance (OSC), Center for Veterinary Medicine Pre-approval Post-approval Office of New Animal Drug Evaluation (ONADE) Center for Veterinary Medicine

41. Label review Division of Animal Feeds Office of Surveillance and Compliance (OSC), Center for Veterinary Medicine Pre-approval Post-approval Office of New Animal Drug Evaluation (ONADE) Center for Veterinary Medicine Other units within the OSC Field personnel- FDA State Officials Drug Manufacturers

42. Labeling of Medicated Products

43. NADA Regulation • 21 CFR 514.1(b)(3)(v) • Labeling for new animal drugs intended for use in the manufacture of medicated feeds shall include: • ( a ) Specimens of labeling to be used for such new animal drug with adequate directions for the manufacture and use of finished feeds for all conditions for which the new animal drug is intended, recommended, or suggested in any of the labeling, including advertising, sponsored by the applicant. Ingredient labeling may utilize collective names as provided in §501.110 of this chapter. • ( b ) Representative labeling proposed to be used for Type B and Type C medicated feeds containing the new animal drug.

44. Medicated Products • Type A medicated article • Type B medicated feed • Type C medicated feed

45. Label Review • Types of labels Type A medicated article Brand Brand Type B medicated feed Blue Bird Brand Type C medicated feed Blue Bird Brand Medicated Product Pre-approval Post-approval

46. Drug X/Drug Y • Growing Turkey Ration • Type B MEDICATED FEED • For the prevention of coccidiosis caused by Eimeriameleagrimitis, E gallopavonis, and E. adenoeidesand for increased rate of weight gain and improved feed efficiency in growing turkeys. • ACTIVE DRUG INGREDIENTS • Drug X ...........................................................................…….…………….……….....80,000 g/ton • Drug Y…………………………………………….……………………….........……………6,000 g/ton • GUARANTEED ANALYSIS • Crude Protein (min)……………………………………………….........................................…..……….…..______% • Lysine (min)………………………………………………………...........................................….….….……..______% • Methionine (min)…………………………………………………...........................................….….….……..______% • Crude Fat (min)……………………………………………………...........................................………..……..______% • Crude Fiber (max)………………………………………………………............................................………..______% • Calcium (min)…………...………………………………………………………………………..……..….……..______% • Calcium (max)………..…………………………………………………………………………..……..….……..______% • Phosphorus (min)…..………………………………………………………………………….……….………..______% • Salt (min)1……………..…………………………………………............................................………………..______% • Salt (max)1……………..……………………………………...........................................….………...………..______% • Sodium (min)2…..……..…………………………………….........................................………….. ......……..______% • Sodium (max)2….……..…………………………………..........................................………………....……..______% • 1If added. • 2Shall be guaranteed only when total Sodium exceeds that furnished by the maximum salt guarantee. • INGREDIENTS: Ingredients as defined by AAFCO. • MIXING DIRECTIONS: Mix 10 pounds of this Type B medicated feed with 1990 lb non‑medicated feed ingredients to manufacture one ton of complete turkey feed containing 400 grams of Drug X and 30 grams of Drug Y. • CAUTION: Do not feed to breeding turkeys. • WARNING: Do not feed five days before slaughter. • MANUFACTURED BY: • BLUE BIRD FEED MILL • Robin, IN 00000 • Net Weight____lbs (______kg) • Bag or Bulk Blue Bird Label

47. Brand Label

48. Blue Bird v Brand label • Drug X/Drug Y • Growing Turkey Ration • Type B MEDICATED FEED • For the prevention of coccidiosis caused by Eimeria meleagrimitis, E gallopavonis, and E. adenoeides and for increased rate of weight gain and improved feed efficiency in growing turkeys. • ACTIVE DRUG INGREDIENTS • Drug X ....................................................................…….…………….……….....80,000 g/ton • Drug Y……………………………………….……………………….........……………6,000 g/ton • GUARANTEED ANALYSIS • Crude Protein (min)……………………………………………….........................................…..……….…..______% • Lysine (min)………………………………………………………...........................................….….….……..______% • Methionine (min)…………………………………………………...........................................….….….……..______% • Crude Fat (min)……………………………………………………...........................................………..……..______% • Crude Fiber (max)………………………………………………………............................................………..______% • Calcium (min)…………...………………………………………………………………………..……..….……..______% • Calcium (max)………..…………………………………………………………………………..……..….……..______% • Phosphorus (min)…..………………………………………………………………………….……….………..______% • Salt (min)1……………..…………………………………………............................................………………..______% • Salt (max)1……………..……………………………………...........................................….………...………..______% • Sodium (min)2…..……..…………………………………….........................................………….. ......……..______% • Sodium (max)2….……..…………………………………..........................................………………....……..______% • 1If added. • 2Shall be guaranteed only when total Sodium exceeds that furnished by the maximum salt guarantee. • INGREDIENTS: Ingredients as defined by AAFCO. • MIXING DIRECTIONS: Mix 10 pounds of this Type B medicated feed with 1990 lb non‑medicated feed ingredients to manufacture one ton of complete turkey feed containing 400 grams of Drug X and 30 grams of Drug Y. • CAUTION: Do not feed to breeding turkeys. • WARNING: Do not feed five days before slaughter. • MANUFACTURED BY: • BLUE BIRD FEED MILL • Robin, IN 00000 • Net Weight____lbs (______kg) • Bag or Bulk

49. Comparison between Blue Bird and Brand labels Section Blue Bird Brand Product name Generic Brand Indications for use As regulation says Same Active ingredients As regulation says Same Guaranteed analysis Blank levels Specific levels Ingredients AAFCO statement List ingredients Directions for use As regulation says Mostly same Warning section As regulation says Same Caution section As regulation says Same Manufacturer information Generic Exact information Net weight statement Generic Exact