[Federal Register Volume 62, Number 87 (Tuesday, May 6, 1997)]
[Proposed Rules]
[Pages 24620-24622]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-11689]
[[Page 24620]]
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DEPARTMENT OF JUSTICE
Drug Enforcement Administration
21 CFR Part 1308
[DEA Number 162P]
Schedules of Controlled Substances: Proposed Removal of
Fenfluramine From the Controlled Substances Act
AGENCY: Drug Enforcement Administration (DEA), Justice.
ACTION: Notice of proposed rulemaking.
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SUMMARY: This proposed rule is issued by the Acting Deputy
Administrator of the DEA to remove the anorectic drug, fenfluramine,
including its salts, isomers and salts of isomers from control under
the Controlled Substances Act (CSA). This proposed action is based upon
a finding by the Acting Deputy Administrator of the DEA that the data
collected and reviewed to date are insufficient to establish that
fenfluramine has sufficient potential for abuse and dependence to
justify its continued control in any schedule at this time. This rule,
if finalized, would remove all regulatory controls and criminal
sanctions of the CSA from activities involving fenfluramine.
DATES: Comments, objections, and requests for a hearing must be
received on or before July 7, 1997.
ADDRESSES: Comments, objections and requests for a hearing should be
submitted in quintuplicate to the Acting Deputy Administrator, Drug
Enforcement Administration, Washington, DC 20537, Attn: DEA Federal
Register Representative/CCR.
FOR FURTHER INFORMATION CONTACT:
Frank Sapienza, Chief, Drug and Chemical Evaluation Section, Drug
Enforcement Administration, Washington, D.C. 20537, (202) 307-7183.
SUPPLEMENTARY INFORMATION: Fenfluramine is an anorectic indicated for
the management of exogenous obesity that was first approved for
marketing in the United States under the trade name of Pondimin in
1973. Fenfluramine, its salts, isomers and salts of isomers, were
placed into Schedule IV of the CSA effective on June 15, 1973 because
fenfluramine was determined to be chemically and pharmacologically
similar to amphetamine and other anorectic drugs controlled under the
CSA. This action was based on a recommendation by the Acting Assistant
Secretary for Health. Interneuron Pharmaceuticals, Inc., the
manufacturer of a new fenfluramine product (Redux, approved by the Food
and Drug Administration for marketing in the United States in April
1996) petitioned the DEA on March 18, 1991 to decontrol fenfluramine,
citing a lack of actual or potential for abuse. The DEA Administrator,
after gathering available data and conducting an initial review of that
data, requested a scientific and medical evaluation and scheduling
recommendation from the Assistant Secretary for Health, Department of
Health and Human Services (DHHS) by letter dated December 2, 1991 in
accordance with 21 U.S.C. 811(b). DHHS provided its medical and
scientific evaluation and scheduling recommendation on fenfluramine to
the DEA by letter dated June 3, 1996. The Assistant Secretary for
Health concluded that fenfluramine does not warrant control under the
CSA and recommended to the DEA that fenfluramine be decontrolled. The
Assistant Secretary for Health provided a written scientific and
medical evaluation which formed the basis for the recommendation.
The DHHS evaluation considered reports in the scientific and
medical literature (1968-1995), adverse reaction reports (1973-1995),
data from the Drug Abuse Warning Network (DAWN) (1985-1993), the System
to Retrieve Information from Drug Evidence (STRIDE) (1973-1991),
marketing data (1990-1993) and other sources of information. Data from
the scientific and medical literature demonstrate that fenfluramine is
not an amphetamine-like stimulant. Fenfluramine does not maintain self-
administration as evidenced by studies in several species (rhesus
monkeys, baboons, dogs or rodents). In drug discrimination studies in
humans and laboratory animals, the effects of fenfluramine differed
from those of amphetamine and cocaine. In human studies, the subjective
effects of fenfluramine were found to differ from those of other
amphetamine-like anorectics. Fenfluramine however, at high doses,
displays complete generalization to MDMA in rodents. Subjective
evaluation studies of high doses of fenfluramine in humans shows that
in some cases it produces euphoria alternating with dysphoria. The DHHS
reported that although high doses of fenfluramine may result in LSD-
like responses, these have been characterized by dysphoric. Clinical
data does not show that the use of fenfluramine or dexfenfluramine at
high doses leads to dependence to the same extend as other substances
in Schedules IV or V. The DHHS found the risks to the public health
resulting from the abuse of fenfluramine to be similar to the abuse or
misuse of any other agent that is taken outside of appropriate medical
direction. However, the DHHS did cite neurotoxic consequences and
primary pulmonary hypertension in humans as possible safety risks
associated with fenfluramine use. The DHHS review also indicates that
based upon over 20 years of marketing of fenfluramine in the United
States and elsewhere, abuse of fenfluramine has not been demonstrated
to result in either physical or psychic dependence that would lead to
craving of the desire to re-initiate the drug upon discontinuation of
use. The document indicates that reports of actual abuse, diversion and
withdrawal syndrome have been collected but are considered isolated.
The significance of these reports, relative to the production of
dependence to the same extend as other substances in Schedules IV or V,
has not been established.
The DHHS, in its evaluation, however, noted that there had been
limited sales and prescribing of fenfluramine from 1973 to 1992, thus
data on abuse, diversion and trafficking of fenfluramine would be
expected to be minimal. DHHS reported a recent dramatic increase in
usage of fenfluramine, particularly in combination with phentermine, a
Schedule IV controlled substance. DHHS noted that this could be reason
for concern because the long-term use could significantly impact the
public health.
While the recommendations of DHHS are binding on DEA regarding
scientific and medical matters, the recommendation to decontrol
fenfluramine is not binding on the DEA because fenfluramine is
currently controlled under the CSA. The DEA must consider the DHHS
recommendation and all other relevant data prior to making a
determination as to whether substantial evidence of potential for abuse
exists so as to warrant continued control of fenfluramine under the
CSA. Thus, the DEA examined the DHHS recommendation, supplemented by
more recent abuse, diversion, and trafficking data in light of the
following factors determinative of control or removal of a drug or
other substance from the schedules [21 U.S.C. 811(c)]:
(1) Its actual or relative potential for abuse.
(2) Scientific evidence of its pharmacological effect, if known.
(3) The state of current scientific knowledge regarding the drug or
other substance.
(4) Its history and current pattern of abuse.
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(5) The scope, duration, and significance of abuse.
(6) What, if any, risk there is to the public health.
(7) Its psychic or physiological dependence liability.
(8) Whether the substance is an immediate precursor of a substance
already controlled under the CSA.
In addition to the DHHS data, the DEA review shows that:
(1) DAWN, forensic laboratory data and associated federal
investigative files show very little abuse, trafficking and diversion
of fenfluramine. A few DEA Field Offices have reported increases in
fenfluramine purchases by physicians and pharmacies accompanied by
indiscriminate prescribing of fenfluramine, often in combination with
phentermine. The U.S. Customs Service has documented seizures of
illegally imported fenfluramine tablets into the United States, that
were repackaged and shipped to Mexican pharmacies. The significance of
these reports in terms of fenfluramine's abuse potential is unknown as
of this time. The levels of abuse, trafficking and diversion identified
thus far for fenfluramine are less than those of similarly controlled
substances.
(2) State authorities including Boards of Pharmacy, Boards of
Medical Examiners, Departments of Health, and police crime laboratories
were queried and reported little or no documented actual abuse,
trafficking and diversion at this time. DEA received input from 36
state agencies and the District of Columbia. The majority of state drug
regulatory agencies reported that they had no evidence that
fenfluramine is trafficked or abused. There were a few cases reported
where patients had obtained fenfluramine through unauthorized
prescription refills, fraudulent prescriptions, doctor shopping,
illegal sales, mail order schemes and thefts. However, these reports
generally include phentermine and their association with fenfluramine
abuse has not been established. Very few state police crime
laboratories reported cases involving fenfluramine.
(3) Fenfluramine has been marketed in the U.S. since 1973, with
little therapeutic use until recently when the combination of
phentermine and fenfluramine emerged. The number of prescriptions for
fenfluramine has increased dramatically since 1992 and has more than
doubled each year since 1994. Total prescriptions dispensed in the
United States in 1992 for fenfluramine were less than 100,000. In 1996,
total prescriptions dispensed in the United States totalled over 5.1
million, an increase of 6100 percent in four years.
The Acting Deputy Administrator of the DEA, based on the DHHS
evaluation and the DEA review, has concluded that there is insufficient
data available at this time to establish that fenfluramine has a
potential for abuse which warrants control under the CSA. Nevertheless,
it is unclear whether the low levels of abuse, trafficking and
diversion are due to the fact that only recently fenfluramine became
available in significant quantities or if the low levels of data are an
indication that fenfluramine lacks abuse potential. Therefore, in light
of the increasing availability and use of fenfluramine, particularly in
combination with phentermine, and possible public health and safety
risks including neurotoxicity, primary pulmonary hypertension and
reports that fenfluramine may have pharmacological similarity to some
hallucinogenic substances, the DEA will carefully monitor the abuse,
trafficking and diversion indicators regarding this substance. If this
data indicates the need for a reexamination of the control status of
fenfluramine, the DEA will re-initiate the evaluation process as set
forth in the CSA [21 U.S.C. 811(b)].
Relying on the scientific and medical evaluation and the
recommendation of the Assistant Secretary of Health received in
accordance with 21 U.S.C. 811(b), and the independent review of the
DEA, the Acting Deputy Administrator of the DEA, pursuant to Section
201(b) of the Act [21 U.S.C. 811(b)], has determined that these facts
and all other relevant data constitute substantial evidence that
fenfluramine should be removed entirely from the schedules.
Interested persons are invited to submit their comments, objections
or requests for a hearing, in writing, with regard to this proposal.
Requests for a hearing should state, with particularity, the issues
concerning which the person desires to be heard. All correspondence
regarding this matter should be submitted to the Acting Deputy
Administrator, Drug Enforcement Administration, Washington, D.C. 20537.
Attention: DEA Federal Register Representative. In the event that
comments, objections or requests for a hearing raise one or more issues
which the Acting Deputy Administrator finds warrants a hearing, the
Acting Deputy Administrator shall order a public hearing by notice in
the Federal Register, summarizing the issues to be heard and setting
the time for the hearing.
In accordance with the provisions of the CSA [21 U.S.C. 811(a)],
this action is a formal rulemaking ``on the record after opportunity
for a hearing.'' Such proceedings are conducted pursuant to the
provisions of 5 U.S.C. 556 and 557 and, as such, are exempt from review
by the Office of Management and Budget pursuant to Executive Order
(E.O.) 12866, Section 3(d)(1).
The Acting Deputy Administrator, in accordance with the Regulatory
Flexibility Act [5 U.S.C. 605(b)], has reviewed this proposed rule and
by approving it certifies that it will not have a significant economic
impact on a substantial number of small-business entities. Fenfluramine
is available in drug products for the treatment of obesity, some of
which have been marketed in the United States for a number of years.
This proposed rule, if finalized, will allow persons to handle
fenfluramine without being subject to the regulatory controls of the
CSA. Fenfluramine will continue to be a prescription drug.
This rule will not have substantial direct effects on the States,
on the relationship between the national government and the States, or
the distribution of power and responsibilities among their various
levels of government. States may choose to decontrol fenfluramine or
continue to control it under their respective CSA. Therefore, in
accordance with E.O. 12612, it is determined that this rule, if
finalized, does not have sufficient federalism implications to warrant
the preparation of a Federalism Assessment.
List of Subjects in 21 CFR Part 1308
Administrative practice and procedure, drug traffic control,
narcotics, prescription drugs.
Under the authority vested in the Attorney General by section
201(a) of the CSA [21 U.S.C. 811(a)], and delegated to the
Administrator of the DEA by the Department of Justice regulations (28
CFR 0.100) and redelegate to the Acting Deputy Administrator pursuant
to 28 CFR 0.104, the Acting Deputy Administrator hereby proposes that
21 CFR part 1308 be amended as follows:
PART 1308--[AMENDED]
1. The authority citation for 21 CFR part 1308 continues to read as
follows:
Authority: 21 U.S.C. 811, 812, 871(b) unless otherwise noted.
Sec. 1308.14 [Amended]
2. Section 1308.14 is proposed to be amended by removing the
existing paragraph (d) and by redesignating the existing paragraphs (e)
and (f) as (d) and (e), respectively.
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Dated: April 29, 1997.
James S. Milford,
Acting Deputy Administrator.
[FR Doc. 97-11689 Filed 5-5-97; 8:45 am]
BILLING CODE 4410-09-M