"Detention Without Physical Examination Of Misbranded Drugs And Marketed New Drugs Without Approved Applications"

As part of its ongoing drug safety initiative, FDA issued a final guidance document, announced in the Federal Register at 71 FR 33466 33467 (June 9, 2006), outlining its enforcement approach to drugs that are marketed without required FDA approval. The guidance may be found at http://www.fda.gov/ICECI/ComplianceManuals/CompliancePolicyGuidanceManual/ucm074382.htm

Background:

For a variety of historical reasons, some drugs, mostly older products, continue to be marketed illegally in the United States without required FDA approval. FDA's guidance document on marketed unapproved drugs clearly articulates the agency's expectation that manufacturers of products requiring FDA approval submit applications showing that their products are safe and effective. The guidance also outlines the agency's enforcement policies aimed at efficiently and rationally bringing these drugs into the approval process. This approach includes efforts to identify illegally marketed drugs, prioritization of those drugs according to potential public health concerns or other impacts on the public health, and subsequent regulatory follow up.

Many marketed unapproved new drugs are imported into the U.S. Others are manufactured domestically using imported APIs. As unapproved new drug products are identified and selected for enforcement action, the finished unapproved products and/or the APIs used in their manufacture may be included in this alert. The finished products and APIs listed in the alert should not be allowed entry into the U.S. unless they comply with the exceptions listed below. The products subject to this import alert will be identified and covered by separate attachments to this alert.

Districts may detain without physical examination all shipments of unapproved finished drug products and all shipments of APIs intended for the manufacture of unapproved finished drug products that are identified in the Red List to this alert.

Exceptions include:

(1) Finished drug products that are covered by approved applications (NDA or ANDA);

(2) Finished drug products that are covered by an Investigational New Drug Application (IND);

(3) APIs that are intended for use in the manufacture of finished drug products that are subject to approved applications, under the conditions set forth in 21 CFR 201.122(a);

(4) APIs that are intended for use in the manufacture of an investigational new drug, under the conditions set forth in 21 CFR 201.122(b);

(5) APIs that are intended for use in the manufacture of finished drug products subject to a pending application, under the conditions set forth in 21 CFR 201.122(c);

Note: Districts should contact ***the CDER Office of Compliance/CDER Imports Exports Compliance Branch at cderimportsexports@fda.hhs.gov*** if they cannot confirm in CDER's databases that an approved application or an IND covers the shipment of a finished drug product, or that an approved or pending application, or an IND covers the shipment of an API.

(6) APIs that are intended solely for tests in vitro or in animals used only for laboratory research, under the conditions set forth in 21 CFR 312.160, and

(7) APIs that will be used in teaching, law enforcement, research, and analysis under the conditions set forth in 21 CFR 201.125;

Note: Importers of APIs that claim to fall within exceptions (6) or (7) should provide documentation establishing that the product meets the conditions set forth in 21 CFR 312.160 or 201.125.

Other

(1) APIs intended for pharmacy compounding: Districts should contact ***the CDER Office of Compliance/CDER Imports Exports Compliance Branch at cderimportsexports@fda.hhs.gov*** for further instructions when reviewing entries of APIs identified in the attachments to this alert that are intended for pharmacy compounding.

(2) APIs for use in the manufacture of drugs intended to generate data for the submission of an application (pre submission batches): Districts should contact
***the CDER Office of Compliance/CDER Imports Exports Compliance Branch at cderimportsexports@fda.hhs.gov*** when reviewing entries of APIs identified in the attachments to this alert that are intended for pre submission batches.

If the District Offices have questions concerning this alert they should contact CDER/OC/***ODSIR/DIOR/Imports Exports Compliance Branch*** or ORA/ORO/DIOP/immediately.

Note: Importers of APIs that claim to fall within exceptions (6) or (7) should provide documentation establishing that the product meets the conditions set forth in 21 CFR 312.160 or 201.125.

Other

(1) APIs intended for pharmacy compounding: Districts should contact ***the CDER Office of Compliance/CDER Imports Exports Compliance Branch at cderimportsexports@fda.hhs.gov*** for further instructions when reviewing entries of APIs identified in the attachments to this alert that are intended for pharmacy compounding.

(2) APIs for use in the manufacture of drugs intended to generate data for the submission of an application (pre-submission batches): Districts should contact ***the CDER Office of Compliance/CDER Imports Exports Compliance Branch at cderimportsexports@fda.hhs.gov*** when reviewing entries of APIs identified in the attachments to this alert that are intended for pre-submission batches.

If the District Offices have questions concerning this alert they should contact CDER/OC/***ODSIR/DIOR/Imports Exports Compliance Branch***or
ORA/ORO/DIOP/immediately.

Bulk and finished dosage drug products

For finished drug products: "The article is subject to refusal of admission pursuant to Section 801(a)(3) in that it appears to be a new drug within the meaning of Section 201(p) without an effective new drug application (NDA). [Unapproved New Drug, Section 505(a)]"

OASIS Charge Code - UNAPPROVED

and/or

"The article is subject to refusal of admission pursuant to section 801(a)(3) in that it appears to be misbranded in that it lacks adequate directions for its intended use. [Misbranding, Section 502(f)(1)]"

OASIS Charge Code - DIRECTIONS

For all active pharmaceutical ingredients (APIs), including those APIs intended for use in pharmaceutical compounding "The article is subject to refusal of admission pursuant to section 801(a)(3) of the FDCA because it appears to be misbranded in that it lacks adequate directions for its intended use. [Misbranding, Section 502(f) (1)]"

OASIS Charge Code - DIRECTIONS