medicated feeds overview

Rockville, MD June 2012

Dr. Dragan Momcilovic, Medicated Feeds SpecialistDr. Gabriel Davila, Staff Fellow

Food and Drug AdministrationCenter for Veterinary MedicineDivision of Animal FeedsMedicated Feeds Team

Medicated Feeds Overview

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

Agenda

Drug Categories

Drug Categories

Category IICategory I

Drug Categories

Category IICategory I

Drugs with no withdrawal period required at the lowest use level for each species for which they are approved

Drug Categories

Category IICategory I

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

Drug Categories

Category IICategory I

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

Drug Categories

Category IICategory I

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 concernDrugs that are veterinary feed directive

Drug Categories

Category IICategory I

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 concernDrugs that are veterinary feed directive

Level of risk

Drug Categories

Category IICategory I

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 concernDrugs that are veterinary feed directive

Level of risk

Less risky

Drug Categories

Category IICategory I

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 concernDrugs that are veterinary feed directive

Level of risk

Drug Categories

Category IICategory I

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 concernDrugs that are veterinary feed directive

Level of risk

Less risky More risky

Medicated Feeds are distributed:

- Over-The-Counter

- Veterinary Feed Directive

Types of Distribution

Medicated Products

Type A medicated article

Type B medicated feed

Type C medicated feed

Medicated Products

Type A medicated article is a new animal drug

*Federal Food, Drug, and Cosmetic Act

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

A new animal drug is….

Medicated Products

Type A medicated article

is a new animal drug with or without inactive ingredients

intended for use in animal feed intended solely for further

manufacture

Medicated Products

Type A medicated article is used to make another Type A medicated article

a Type B medicated feed a Type C medicated feed

*Federal Food, Drug, and Cosmetic Act

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.

Animal feed is...

• Type A medicated article - DRUG

• Type B medicated feed - FEED containing DRUG

• Type C medicated feed - FEED containing DRUG

Medicated Products

• 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”)

Type B Medicated Feed

• intended solely for the manufacture of:

- other Type B medicated feed

- Type C medicated feed

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

Type B Medicated Feed

• 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

Components of a Type B Blue Bird Label

• Originates from:

a) a Type A medicated articleb) a Type B medicated feedc) another Type C medicated feed d) an unstandardized drug component (bulk or drum run)

Type C Medicated Feed

•is intended for feeding as:

a) the complete feed

b) ‘top dressed’

c) ‘free choice’

Type C Medicated Feed

• 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

Components of a Type C Blue Bird Label

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

FDA’s animal drug approval process (basics)

- Required for:

- the manufacture of all Type A medicated articles

New Animal Drug Application (NADA)

• 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)

The Federal Food, Drug, and Cosmetic Act

• What does an approved NADA mean?

The Federal Food, Drug, and Cosmetic Act

• What does an approved NADA mean?• The product is safe and effective for its

intended use

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

The Federal Food, Drug, and Cosmetic Act

• EffectivenessBased 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

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

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

The Federal Food, Drug, and Cosmetic Act

Division of Animal FeedsOffice of Surveillance and Compliance (OSC),

Center for Veterinary Medicine

Label review

Division of Animal FeedsOffice of Surveillance and Compliance (OSC),

Center for Veterinary Medicine

Pre-approval Post-approval

Label review

Division of Animal FeedsOffice of Surveillance and Compliance (OSC),

Center for Veterinary Medicine

Office of New Animal Drug Evaluation

(ONADE)Center for Veterinary Medicine

Pre-approval Post-approval

Label review

Division of Animal FeedsOffice of Surveillance and Compliance (OSC),

Center for Veterinary Medicine

Office of New Animal Drug Evaluation

(ONADE)Center for Veterinary Medicine

Other units within the OSCField personnel- FDA

State OfficialsDrug Manufacturers

Pre-approval Post-approval

Label review

Labeling of Medicated Products

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.

NADA Regulation

•Type A medicated article

• Type B medicated feed

• Type C medicated feed

Medicated Products

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

Label Review

Drug X/Drug YGrowing 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 INGREDIENTSDrug X ...........................................................................…….…………….……….....80,000 g/tonDrug 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

YOUR NAME FEEDS

Breeding Swine RationMedicated

For control and treatment of leptospirosis (reducing the incidence of abortion and shedding of leptospirae) caused by Leptospira pomona susceptible to Drug Y

Active drug ingredientDrug X…………………….................................400 grams/tonDrug Y……………………….............................400 grams/ton

Guaranteed AnalysisCrude Protein, minimum ............................18.0%Lysine…………………………………………..1.27%Crude Fat, minimum .....................................7.0%Crude Fiber, maximum .................................3.5%Calcium, minimum ........................................0.7%Calcium, maximum .......................................1.2%Phosphorus, minimum ..................................0.65%Selenium, minimum ......................................0.29 ppmZinc, minimum…………………… ……….2000 ppm

Ingredient StatementGrain Products, Plant Protein Products, Whey, Animal Fat (preserved with Ethoxyquin), Vitamin A Supplement, D-Activated Animal Sterol (source of Vitamin D3), Vitamin E Supplement, Folic Acid, Biotin, Ascorbic Acid, Copper Sulfate, Manganous Oxide, Zinc Oxide, Ferrous Sulfate, Cobalt Carbonate, Calcium Iodate, Sodium Selenite, Sodium Silico Aluminate, Natural and Artificial Flavors.

FEEDING DIRECTIONSFeed continuously for not more than 14 days as the sole ration to provide 10 mg/lb body weight per day of each of the two drugs.

CAUTION: Consult your veterinarian if abortions continue to occur at an unacceptable level.

WARNING: Withdraw 5 days before slaughter.

YOUR NAME FEEDSCity, State Zip

NET WT 50 LB (22.67 kg)

Brand Label

YOUR NAME FEEDS

Breeding Swine RationMedicated

For control and treatment of leptospirosis (reducing the incidence of abortion and shedding of leptospirae) caused by Leptospira pomona susceptible to Drug Y

Active drug ingredientDrug X…………………….................................400 grams/tonDrug Y……………………….............................400 grams/ton

Guaranteed AnalysisCrude Protein, minimum ............................18.0%Lysine…………………………………………..1.27%Crude Fat, minimum .....................................7.0%Crude Fiber, maximum .................................3.5%Calcium, minimum ........................................0.7%Calcium, maximum .......................................1.2%Phosphorus, minimum ..................................0.65%Selenium, minimum ......................................0.29 ppmZinc, minimum…………………… ……….2000 ppm

Ingredient StatementGrain Products, Plant Protein Products, Whey, Animal Fat (preserved with Ethoxyquin), Vitamin A Supplement, D-Activated Animal Sterol (source of Vitamin D3), Vitamin E Supplement, Folic Acid, Biotin, Ascorbic Acid, Copper Sulfate, Manganous Oxide, Zinc Oxide, Ferrous Sulfate, Cobalt Carbonate, Calcium Iodate, Sodium Selenite, Sodium Silico Aluminate, Natural and Artificial Flavors.

FEEDING DIRECTIONSFeed continuously for not more than 14 days as the sole ration to provide 10 mg/lb body weight per day of each of the two drugs.

CAUTION: Consult your veterinarian if abortions occur at an unacceptable level.

WARNING: Withdraw 5 days before slaughter.

YOUR NAME FEEDSCity, State Zip

NET WT 50 LB (22.67 kg)

Drug X/Drug YGrowing 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 INGREDIENTSDrug X ....................................................................…….…………….……….....80,000 g/tonDrug 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 v Brand label

Section Blue Bird Brand

Product name Generic BrandIndications for use As regulation says SameActive ingredients As regulation says SameGuaranteed analysis Blank levels Specific levelsIngredients AAFCO statement List ingredientsDirections for use As regulation says Mostly sameWarning section As regulation says SameCaution section As regulation says SameManufacturer information Generic Exact informationNet weight statement Generic Exact

Comparison between Blue Bird and Brand labels