IA #66-71, 1/23/07, "IMPORT ALERT #66-71, "DETENTION WITHOUT PHYSICAL
EXAMINATION OF HUMAN GROWTH HORMONE (HGH), ALSO KNOWN AS SOMATROPIN"
TYPE OF ALERT: Detention Without Physical Examination (DWPE)
NOTE: This import alert contains the Agency's current guidance to FDA field
personnel regarding the manufacturer(s) and/or product(s) at issue. It does
not create or confer any rights for or on any person and it does not operate
to bind FDA or the public.
PRODUCT: Human Growth Hormone (HGH); Somatropin
PRODUCT CODE: 64R[][]18 Human Growth Hormone (Hormone)
64R[][]20 Somatrem (Hormone)
64R[][]21 Somatropin (Hormone), Serostim, Nutropin,
Humatrope
64R[][]22 Somatropin (RDNA Origin) (Hormone)
64R[][]23 Somatropin, Biosynthetic (Hormone)
PROBLEM: Unapproved new drugs; Misbranded drugs
PAC: 56008H
PAF: AAP-Approval
COUNTRIES: All
MANUFACTURER/
SHIPPER: All. Please see guidance for exceptions.
CHARGES: 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)".]
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)]."
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; DRUGS DIRECTIONS
RECOMMENDING
OFFICE: CDER, OC, Division of New Drugs and Labeling Compliance
(HFD-310)
REASON FOR
ALERT: 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 reconstitution 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.
GUIDANCE: 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 Compliance at the number listed below 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 Import-Export
Team 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/OC/DNLC immediately.
Ada Irizarry 301-827-8967
PRIORITIZATION
GUIDANCE: N/A
FOI: No purging required
KEYWORDS: HGH, human growth hormone, somatropin; somatrem
PREPARED BY: Nawab A. Siddiqui, DIOP, 301-594-3871
William G. Nychis/CDER/OC/DNLC 301-827-8959
DATE LOADED
INTO FIARS: January 23, 2007
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