[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]



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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