"New Bulk Animal Drug Substances"

NADA - Imported bulk new animal drug substances labeled for further manufacturing and processing, or labeled as chemical substances, are frequently destined for veterinarians and to pharmaceutical processors that formulate animal drugs. These drug substances, consigned to individuals or processors who formulate and distribute animal drugs, may be adulterated under Section 501(a)(5) of the Act or misbranded under Section 502(f)(1). It is the responsibility of the distributor, whether the importer or some other firm, to assure that these drugs are only shipped to processors legally entitled to receive them.

INAD - Sponsors of investigational new animal drug (INAD) exemptions frequently import from foreign countries either the dosage form or bulk drug substances for use in laboratory research or clinical trials. However, some importers have found that they could obtain entry of large amounts of unapproved new animal drugs if they would merely advise the FDA that the entry was for investigational use and supply an INAD number as reference. The FDA has learned that some of these have not been legitimate. Internally, the Center for Veterinary Medicine has tightened its procedures for the issuance of INAD numbers.

The procedures in part implement the special notification requirements of 21 CFR 511.1(b)(9). This regulation pertains to the importation into the United States of a new animal drug for use in clinical trials. The regulation requires:

1. Prior notification to the FDA of the importer's intention to import the new animal drug for investigational use. This may be done by the INAD sponsor or his agent; or

2. The new animal drug for investigational use is shipped directly to an appropriate scientific institution which has submitted a statement to the FDA as sponsor of the clinical investigation.

Bulk new animal drug substances labeled for further manufacturing or processing, or as harmless chemicals, and bearing some indication for veterinary use, consigned to veterinarians, veterinary drug distributors or processors, may be detained since they are unapproved new animal drugs in violation of 501(a)(5) unless the recipient holds an approved NADA or an INAD exemption for preparation of a finished dosage form drug or medicated feed premix from that particular bulk drug source, or an approval is not required at this time either by regulation or policy.

Bulk new animal drug substances labeled for further manufacturing or processing, which do not bear any indications for veterinary use, may be misbranded under Section 502(f)(1) if they are intended for veterinary use or for further processing as animal drugs. Intended use may be established by showing the substances are consigned to veterinarians, veterinary drug distributors or processors, or by other evidence. Such drugs are in violation of Section 502(f)(1) because they do not bear adequate directions for use, except as specified in the following paragraph.

21 CFR 201.122 exempts a drug from adequate directions for use when labeled for further manufacturing and processing and when used to manufacture a new animal drug which is covered by an approved application or an investigational exemption under Part 511. 21 CFR 201.150 exempts a drug, which is intended to be further processed or manufactured, from adequate directions when it is shipped under the terms of a written agreement which, if followed, will assure the finished product is not adulterated or misbranded.

Therefore, bulk new animal drug substances labeled for further manufacturing and processing and shipped to pharmaceutical manufacturers or processors are exempted from applicable provisions of section 501 and 502 only if shipped in accord with 21 CFR 201.122 and/or 21 CFR 201.150.

*** Contact Division of Compliance (HFV-232) Center for Veterinary Medicine *** to determine the NADA approval status, the existence of a valid INAD (Investigational exemption) or to determine if the drugs are from approved foreign sources as specified in the approved NADA's. In addition, be alert to the importation of any new animal drug substance not consigned to an approved NADA holder which bears the trade name of an approved new animal drug.

A number of bulk new animal drugs, generally labeled or declared as "harmless chemicals" or "for ornamental fish use only," or similar wording, may be actually intended for direct use in commercial food-fish aquaculture, despite their labeling, and are frequently diverted for such food fish use. These drugs may be adulterated under Section 501(a)(5) or misbranded under Section 502(f)(1), because of such actual intended use in aquaculture. Importer's claims for intended sale only for manufacture of, or direct user as, drugs for ornamental fish use should be considered suspicious at best. When such drugs are encountered, contact ***Division of Compliance (HFV-235), Center for Veterinary Medicine*** for guidance.

COMMON NEW ANIMAL DRUG SUBSTANCES:

****Acriflavin (Acriflavine)
------Albendzaole
****Amoxicillin
-----Atorvastin Calcium
-----Benzathine penicillin G with or without procaine penicillin G
....Benzocaine
-----Carbadox 1 2 (2 Quinoxalinylmethylene) hydrazinecarboxylic acid methyl ester N,N4 dioxide
****Carp Pituitary Extract (CPE)
-----Chloramphenicol D( )threo 2,2 dichloro N [B hydroxy 2 (hydroxymethyl) p nitrophenethyl]acetamide
-----Chlortetracycline
****Crystal Violet (gentian violet)
****Cytochalasin B
-----Diethylstilbestrol (DES) (E) 4,4 (1,2, Diethyl 1,2 ethenediyl) bisphenol
****Difloxacin
-----Dihydrostreptomycin
-----Dimethylsufoxide (DMSO)- Sulfinylbis [methane], methyl sulfoxide
-----Dimetridazole 1,2 Dimethyl 5nitro 1H imidazole
****Enrofloxacin
****Erythromyocin Phosphate
****Flumequine
****Formaldehyde (Formalin)
-----Furosemide 5 (aminosulfonyl) 4 chloro 2[(2 furanylmethyl)amino] benzoic acid
****GNRHa Gentamicin and Salts
-----Hexachloroethane
****Human Chorionic Gonadotropin (HCG)
-----Ipronidazole 1 Methyl 2 (1 methylethyl) 5 nitro 1H imidazole
-----Iron polysaccharides (dextran & destrin)
****Isoxsuprine HCL
-----Ivermectin
****Kanamycin (Kanamycin Sulfate)
-----Ketamine 2 (o Chlorophenyl) 2 (methylamino cyclohexanone
----Lasaloid sodium Levamisole (L tetramisole)
-----L-(-)2,3,5,6, Tetrahydro-6-phenyl-imidazo-[2,1-b] thiazole
****LHRHa
-----Linocomycin
****Malachite Green (crystal and solution) (AKA victoria green)
-----Melengestrol acetate-17a-hydroxy-6-16-methyl-16-methylenepregna-4, 6-diene-3,2-dione
****Methylene Blue
****Metronidazole Monensin
****Nalixidic Acid
****Neomycin Sulfate
****Nifurpirinol
-----Nitrofurans (furazolidone, nitrofurazone, furaltadone, nihydrazone, furacin) Novobiocin sodium
****Oxolinic Acid
-----Oxytetracyline (Oxytetracycline HCL)
-----Parbendazole (5 Butyl 1H benzimidazol 2 yl) carbamic acid methyl ester
-----Pergolide mesylate
-----Phenylbutazone - 4-butyl,1,2-diphenyl-3,5-pyrazolidinedione
-----Phenylpropanolamine (PPA)
-----Pravastatin Sodium
-----Prostaglandins
****Quinaldine Sulfate
****Sarafloxacin
****Salmonid Pituitary Extract (SPE)
-----Streptomycin
****Streptomycin Sulfate
-----Sulfachloropyridazine-4-animo-N-(6-chloro-3-pyridazinyl) benzenesulfonamide
-----Sulfaethoxypyradizine -N-(6-ethoxy-3-pyridazinyl)-Sylfanilamide
-----Sulfadiazine - 4-amino-N-2-(2,6-dimethoxy-4-pyrimidinyl) benzenesulfonamide
-----Sulfaethoxypyradizine -N-(6-ethoxy-3-pyridazinyl) Sulfanilamide
-----Sulfadiazine - 4-amino-N-2-pyrimidinyl-benzenesulfonamide
****Sulfamerazine 4 amino N (4 methyl 4 2 pyrimidinyl) Sulfanilamide ****Sulfamethazine -(sulfadimidine-4-amino-N(4,6-Dimethyl-2-pyrimidinyl)
-----Sulfathiazole - 4-amino-N-(5-methyl-3-isoxazoly) benzenesulfonamide)
-----Sulfathiazole - 4-amino-N-2-thiazolylbenzenesulfonamide
-----Tetracycline
-----Tetramisole - (+)-2,3,5,6,-tetrahydro-6-phenyl-imidazo[2,1-b]thiazole
-----Trilostane
-----Virginiamycin
-----Xylazine- N-(2,6-Dimethylphenyl)5,6-dihydro-4H-1,3-thiazin-2-imine
-----Zinc Bacitracin
-----Zoalene (Dinitolmide)- 2-Methyl-3,5-dinitrobenzamide
****Drugs likely intended for use in aquaculture

"The article is subject to refusal of admission within the meaning of Section 801(a)(3) in that it appears to be a new animal drug and no new animal drug application (NADA) has been approved and no notice of claimed investigational exemption is on file for this drug or the drug is not from an approved foreign source as specified in the approved NADA, (Adulteration, Section 501(a)(5))."

***(OASIS CHARGE CODE: NEW VET DR)

***Detain if the bulk new animal drug substance does not bear any indications for animal use; charging: "The article is subject to refusal of admission within the meaning of Section 801(a)(3) in that it does not bear adequate directions for use (Misbranding, Section 502(f)(1))."

***(OASIS CHARGE CODE: DIRECTIONS)*** INAD:

When bulk new animal drugs are offered for entry for investigational (INAD) use, contact *** Division of Compliance (HFV-232), Center for Veterinary Medicine *** to determine whether the requirements of 21 CFR 511.1(b)(9) have been met. ***

For any drugs being imported for fish, contact, CVM, Division of Compliance (HFV-235)

*** If prior notification (or statement from a scientific institution) has not been given and CVM cannot make an immediate determination that the import is to a legitimate sponsor, detain the entry, charging: "The article is subject to refusal of admission within the meaning of Section 801(a)(3) in that it appears to be a new animal drug and no new animal drug application has been approved and no notice of claimed investigational exemption is on file for this drug."

***(OASIS CHARGE CODE: NEW VET DR)***