Import Alert 68-09

Import Alert # 68-09

Published Date: 02/15/2024

Type: DWPE

"Detention Without Physical Examination of New Bulk Animal Drug Substances"

Note: The revision to this import alert dated 10/26/2022 updates reason for the alert section, updates program contacts, and updates product description and PAF. Changes are noted and bracketed by three asterisks (***).

***Imported bulk active pharmaceutical ingredients (APIs) labeled for further manufacturing and processing or labeled as chemical substances, are frequently destined for veterinarians and to pharmaceutical processors that formulate unapproved new animal drugs from these APIs.

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.

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. ***

Divisions may detain, without physical examination, the shipments of the products identified on the Red List of this Alert.

***Divisions may also detain:

1. Bulk new animal drug substances labeled as harmless chemicals for further manufacturing or processing 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 New Animal Drug Application (NADA) or an Investigational New Animal Drug (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.

2. 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 Drug Compliance, Process and Program Team (HFV-217) Animal Drug Program Team (HFV-233) determine the NADA approval status, the existence of a valid INAD, or to determine if the drug is from approved foreign source as specified in the approved NADA. 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.

3. A number of bulk new animal drugs, generally labeled or declared as "harmless chemicals" or "for ornamental fish use only," or similar wording, may actually be 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 Animal Drug Program Team (HFV-233), Center for Veterinary Medicine for guidance.

For any drugs being imported for fish, contact, CVM, Division of Compliance Animal Drug Program Team (HFV-233). 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.***

Recommendations for additions to the Red List should be forwarded to the Division of Import Operations (DIO). DIO will coordinate a review of all recommendations for addition to DWPE with FDA's Center for Veterinary Medicine (CVM).

*** Release of Articles subject to Detention without physical examination:

In order to secure release of an individual entry that has been detained for being subject to the Red List or for any of the reasons noted above, the importer should provide documentation which verifies the product has a valid New Animal Drug Application (NADA) or abbreviated NADA (ANADA), conditionally approved NADA (CNADA), index listing, or Investigational New Animal Drug exemption (INAD). ***

Removal from Detention without Physical Examination (REMOVE FROM RED LIST):

***In order to remove a firm's product from the Red List, information should be provided to the Agency to adequately demonstrate that the firm has resolved the conditions that gave rise to the appearance of the violation. The purpose of this is so that the Agency will have confidence that future shipments/entries will be in compliance with the Federal Food Drug and Cosmetic Act (FD&C Act). For further guidance on removal from detention without physical examination, refer to FDAs Regulatory Procedures Manual (RPM), Chapter 9-8, "Detention without Physical Examination (DWPE)."***

If a firm and/or a representative thereof would like to petition for removal from detention without physical examination under this Import Alert, all relevant information supporting the request should be forwarded to the following address:

Food and Drug Administration
Division of Import Operations
12420 Parklawn Drive, ELEM-3109
Rockville, MD 20857

Or, be sent via email to: Importalerts2@fda.hhs.gov

*** Questions or issues involving import operations should be addressed to ORA/DIO at (301)796-0356 or FDAImportsInquiry@fda.hhs.gov

Questions or issues involving science policy, analysis, preparation, or analytical methodology, should be addressed to ORA/Office of Regulatory Science at oraorsprivatelabimportalerts@fda.hhs.gov

Questions or issues on policy, sample collection recommendations, or any other additional questions, should be addressed to Center for Veterinary Medicine (CVM), Division of Compliance, Animal Drug Program Team (HFV-233) at CVMImportRequests@fda.hhs.gov

                                                                                                                                                                        ***

***NEW ANIMAL DRUG SUBSTANCES & DRUGS LIKELY INTENDED FOR USE IN AQUACULTURE ***

The article is subject to refusal of admission pursuant to Section 801(a)(3) of the Federal Food, Drug, and Cosmetic Act in that it appears to be a new animal drug that is unsafe within the meaning of Section 512(a) of the Federal Food, Drug, and Cosmetic Act as it is not the subject of an approved new animal drug application, conditionally approved new animal drug application, or index listing, and no investigational new animal drug exemption applies. [Adulteration, Section 501(a)(5)]

OASIS Charge Code: NEW VET DR

If the bulk new animal drug substance does not bear any indications for animal use the below charge applies:

***"The article is subject to refusal of admission pursuant to Section 801(a)(3) in that it appears to be a drug within the meaning of Section 201(g) and it lacks adequate directions for use. [Misbranding, Section 502(f)(1)].

OASIS Charge Code: DIRSEXMPT***

Desc: AGMATINE SULFATE

Desc: Enrofloxacin (Fluoroquinolone)

Desc: Climbazole

Desc: Radix Dichroae Extract

Desc: Radix Dichroae Extract

Desc: Amoxicillin Trihydrate

Desc: Praziquantel

Desc: Praziquantel

Desc: Cantharidin Powder