"Detention Without Physical Examination of Human Growth Hormone (HGH), Also Known As Somatropin"

Human Growth Hormone (HGH) is the active ingredient in a number of human prescription drugs approved for marketing in the U.S. under new drug applications (NDAs). FDA-approved HGH can be legally prescribed for a limited number of conditions including:

* hormonal deficiency that causes short stature in children;

* long-term treatment of growth failure due to lack of exogenous GH secretion;

* long-term treatment of short stature associated with Turner syndrome;

* adult short bowel syndrome;

* adult deficiency due to rare pituitary tumors or their treatment; and

* muscle-wasting disease associated with HIV/AIDS.

HGH has important benefits, but also serious, known risks. Among the possible long-term side effects of HGH is an increased risk of cancer, and other dangerous side effects have been reported, including nerve pain and elevated cholesterol and glucose levels. For this reason, HGH is carefully regulated in the U.S.

The cost of approved HGH products is high, averaging several hundred dollars per dose. Because of this high cost, HGH drugs have been counterfeited and unapproved HGH products are offered for sale to U.S. consumers. For example, we have encountered HGH products imported as a lyophilized powder and declared as an active pharmaceutical ingredient (API) for pharmacy compounding. Some pharmacies promote compounded HGH for anti-aging purposes. It is sold as a "fountain of youth" in longevity clinics and to build body mass, weight loss, increase libido, and gain stamina. None of these indications are in the labeling of the FDA approved products.

The agency is aware of unapproved HGH finished dosage form products being imported into the U.S. and recently noted a large increase of HGH being offered for import for pharmacy compounding. If the drug is bought from foreign sources or over the Internet, safeguards built into the U.S. drug distribution system may be bypassed, placing consumers who
use HGH at higher risk.

Section 303(e)(1) of the FDCA, 21 U.S.C. 333(e) (1), prohibits knowingly distributing, or possessing with the intent to distribute, HGH for any use in humans other than the treatment of a disease or other recognized medical condition, where such use has been authorized by the Secretary of Health and Human Services (HHS) under section 505 of the FDCA (21 U.S.C. 355) and pursuant to the order of a physician. The Secretary of HHS has not authorized, for example, any HGH use for anti-aging, bodybuilding, or athletic enhancement. Thus, distributing, or possessing with the intent to distribute, HGH for these uses or any other unapproved use violates section 303(e)(1) of the FDCA. A violation of section 303(e)(1) carries up to 5 years imprisonment and fines and, if the offense involves an individual under the age of 18 years of age, up to 10 years imprisonment and fines.

HGH products are new drugs and cannot be legally marketed in the U.S. without an approved application. The few HGH products that have been approved for sale by FDA are sold either in liquid form or as lyophilized powders that are labeled for constitution by the health care professionals who dispense them. Accordingly, FDA considers both imported HGH lyophilized powder products and liquid HGH products to be finished dosage form drugs, not APIs. Unless these products are the subject of approved new drug applications, they violate section 505 of the FDCA, 21 U.S.C. 355, and may not be legally imported into the U.S. Some HGH marketers may claim that their HGH drug products are intended for use in pharmaceutical compounding. These drugs should be evaluated on a case-by-case basis considering the factors in FDA Compliance Policy Guide, section 460.200, and the specific prohibitions set forth in section 303(e) of the FDCA, 21 U.S.C. 333(e). The use of
HGH in pharmacy compounding is addressed in more detail, below.

Some HGH marketers may claim that their HGH products are dietary supplements. FDA first approved HGH as a new drug in 1940, and HGH was not marketed as a dietary supplement, or as a food, before then. Accordingly, HGH is excluded from the definition of a dietary supplement under section 201(ff) (1) of the FDCA (21 U.S.C. 321(ff)(3)(A)) because growth hormone was an article approved as a new drug
under section 505 of the FDCA (21 U.S.C. 355) before its introduction as a dietary supplement.

Districts may detain without physical examination all shipments of HGH finished drug products and all shipments of HGH APIs intended for the manufacture of a drug that is not subject to an approved new drug application (NDA). If field personnel are unsure of whether the HGH product at issue is an API or finished drug product, those personnel should contact CDER ***Office of Compliance Import Exports Compliance Branch***for further guidance.

Exceptions include:

(1) Finished drug products that are covered by approved NDAs;

Note: Shipments should be intended for persons who can lawfully possess and/or distribute HGH;

(2) APIs that are intended for use in the manufacture of finished drug products subject to approved or pending applications and where the approved/pending application covers the production and delivery of the
API to the application holder by persons named in the application;

Note: Districts should contact the CDER ***Office of Compliance/Import Exports Compliance Branch*** if they cannot confirm in CDER's databases that an HGH finished drug product is covered by an approved application or if an API is covered by an approved or pending application.

(3) APIs that are intended solely for tests in vitro or in animals used only for laboratory research, and are labeled in accordance with 21 CFR 312.160(a)(1)(i);

(4) APIs that will be used for non-clinical research and development, under the conditions set forth in 21 CFR 201.125;

Note: Importers of HGH API that claim to fall within exceptions (3) or (4) may obtain release of the detained substance only by providing documentation establishing that the substance meets the conditions
set forth in 21 CFR 312.160 or 201.125.

(5) HGH intended for pharmacy compounding should be reviewed on a case-by-case basis. Consistent with its Compliance Policy Guide on human drug compounding and the prohibitions set forth in section 303(e) of the
Act, 21 U.S.C. 333(e), FDA may exercise its enforcement discretion in certain instances to allow the importation of HGH for use in traditional pharmacy compounding.

In general, FDA should exercise its enforcement discretion only in those instances where (1) the compounded product is intended for a use that has been authorized by FDA for HGH under section 505 of the FDCA; and (2) the drug will be compounded to meet the individual medical needs of a specific patient who cannot be treated with an FDA-approved HGH drug product (e.g., the patient is allergic to the commercially available FDA-approved HGH product.

To this end, FDA should consider the following factors when making a determination about whether it is appropriate to exercise enforcement discretion to allow entry of a shipment:

* the indication for which the HGH is being compounded;

* information indicating the individual medical need for a specific patient; e.g., letter from physician or prescription;

* the volume of HGH imported and the appropriateness of the volume, based on considerations such as the amount of HGH used to compound a typical prescription;

* the medical need for the compounded product;

* the identity of the firms that will receive HGH from the shipment;

* the identity of the firms that have received the HGH in the past;

* the presence of statements on the HGH label, at the time that it is imported or offered for import, that the HGH is "For Prescription Compounding" and "Rx only";

* whether the HGH meets official compendia requirements where applicable (for example, as shown on a certificate of analysis), and

* whether the HGH comes from a firm that complies with drug registration and listing requirements

Additionally, the importer should affirm in writing that the HGH will be used solely for human drug compounding.

In order to facilitate FDA's case-by-case review, the information identified in points (1)-(5) above should be made available to FDA at the time the offer to import is made.

Discretionary release of these products under the Personal Importation guidance of Chapter 9 of the Regulatory Procedures Manual (RPM) is not appropriate.

If the District Offices have questions concerning the importation of Human Growth Hormone (HGH) they should contact *** CDER/Office of Compliance (OC), Imports Exports Compliance Branch. The CDER/OC/Imports Exports Compliance Branch can be contacted at cderimportsexports@fda.hhs.gov***

Human Growth Hormone (HGH); Somatropin

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)".] "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 and it is not exempt from this requirement. (Misbranding, section 502(f)(1) of the FDCA)"

OASIS charge code - UNAPPROVED