82 FR 14815 - Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] in Schedule II

DEPARTMENT OF JUSTICE
Drug Enforcement Administration

Federal Register Volume 82, Issue 55 (March 23, 2017)

Page Range		14815-14820
FR Document		2017-05809

On July 1, 2016, the U.S. Food and Drug Administration (FDA) approved a new drug application for Syndros, a drug product consisting of dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] oral solution. Thereafter, the Department of Health and Human Services (HHS) provided the Drug Enforcement Administration (DEA) with a scheduling recommendation that would result in Syndros (and other oral solutions containing dronabinol) being placed in schedule II of the Controlled Substances Act (CSA). In accordance with the CSA, as revised by the Improving Regulatory Transparency for New Medical Therapies Act, DEA is hereby issuing an interim final rule placing FDA-approved products of oral solutions containing dronabinol in schedule II of the CSA.

Federal Register, Volume 82 Issue 55 (Thursday, March 23, 2017)

[Federal Register Volume 82, Number 55 (Thursday, March 23, 2017)]
[Rules and Regulations]
[Pages 14815-14820]
From the Federal Register Online [www.thefederalregister.org]
[FR Doc No: 2017-05809]

[[Page 14815]]

=======================================================================
-----------------------------------------------------------------------

DEPARTMENT OF JUSTICE

Drug Enforcement Administration

21 CFR Part 1308

[Docket No. DEA-344]

Schedules of Controlled Substances: Placement of FDA-Approved
Products of Oral Solutions Containing Dronabinol [(-)-delta-9-trans-
tetrahydrocannabinol (delta-9-THC)] in Schedule II

AGENCY: Drug Enforcement Administration, Department of Justice.

ACTION: Interim final rule, with request for comments.

-----------------------------------------------------------------------

SUMMARY: On July 1, 2016, the U.S. Food and Drug Administration (FDA)
approved a new drug application for Syndros, a drug product consisting
of dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)]
oral solution. Thereafter, the Department of Health and Human Services
(HHS) provided the Drug Enforcement Administration (DEA) with a
scheduling recommendation that would result in Syndros (and other oral
solutions containing dronabinol) being placed in schedule II of the
Controlled Substances Act (CSA). In accordance with the CSA, as revised
by the Improving Regulatory Transparency for New Medical Therapies Act,
DEA is hereby issuing an interim final rule placing FDA-approved
products of oral solutions containing dronabinol in schedule II of the
CSA.

DATES: The effective date of this rulemaking is March 23, 2017.
Interested persons may file written comments on this rulemaking in
accordance with 21 CFR 1308.43(g). Electronic comments must be
submitted, and written comments must be postmarked, on or before April
24, 2017. Commenters should be aware that the electronic Federal Docket
Management System will not accept comments after 11:59 p.m. Eastern
Time on the last day of the comment period.
Interested persons, defined at 21 CFR 1300.01 as those ``adversely
affected or aggrieved by any rule or proposed rule issuable pursuant to
section 201 of the Act (21 U.S.C. 811),'' may file a request for
hearing or waiver of hearing pursuant to 21 CFR 1308.44. Requests for
hearing and waivers of an opportunity for a hearing or to participate
in a hearing must be received on or before April 24, 2017.

ADDRESSES: To ensure proper handling of comments, please reference
``Docket No. DEA-344'' on all correspondence, including any
attachments.
Electronic comments: The Drug Enforcement Administration
encourages that all comments be submitted electronically through the
Federal eRulemaking Portal, which provides the ability to type short
comments directly into the comment field on the Web page or attach a
file for lengthier comments. Please go to http://www.regulations.gov
and follow the online instructions at that site for submitting
comments. Upon completion of your submission, you will receive a
Comment Tracking Number for your comment. Please be aware that
submitted comments are not instantaneously available for public view on
Regulations.gov. If you have received a Comment Tracking Number, your
comment has been successfully submitted and there is no need to
resubmit the same comment.
Paper comments: Paper comments that duplicate the
electronic submission are not necessary and are discouraged. Should you
wish to mail a paper comment in lieu of an electronic comment, it
should be sent via regular or express mail to: Drug Enforcement
Administration, Attn: DEA Federal Register Representative/DRW, 8701
Morrissette Drive, Springfield, VA 22152.
Hearing requests: All requests for hearing and waivers of
participation must be sent to: Drug Enforcement Administration, Attn:
Acting Administrator, 8701 Morrissette Drive, Springfield, Virginia
22152. All requests for hearing and waivers of participation should
also be sent to: (1) Drug Enforcement Administration, Attn: Hearing
Clerk/LJ, 8701 Morrissette Drive, Springfield, Virginia 22152; and (2)
Drug Enforcement Administration, Attn: DEA Federal Register
Representative/DRW, 8701 Morrissette Drive, Springfield, Virginia
22152.

FOR FURTHER INFORMATION CONTACT: Michael J. Lewis, Diversion Control
Division, Drug Enforcement Administration; Mailing Address: 8701
Morrissette Drive, Springfield, Virginia 22152; Telephone: (202) 598-
8953.

SUPPLEMENTARY INFORMATION:

Posting of Public Comments

Please note that all comments received are considered part of the
public record. They will, unless reasonable cause is given, be made
available by the Drug Enforcement Administration (DEA) for public
inspection online at http://www.regulations.gov. Such information
includes personal identifying information (such as your name, address,
etc.) voluntarily submitted by the commenter. The Freedom of
Information Act (FOIA) applies to all comments received. If you want to
submit personal identifying information (such as your name, address,
etc.) as part of your comment, but do not want it to be made publicly
available, you must include the phrase ``PERSONAL IDENTIFYING
INFORMATION'' in the first paragraph of your comment. You must also
place all of the personal identifying information you do not want made
publicly available in the first paragraph of your comment and identify
what information you want redacted.
If you want to submit confidential business information as part of
your comment, but do not want it to be made publicly available, you
must include the phrase ``CONFIDENTIAL BUSINESS INFORMATION'' in the
first paragraph of your comment. You must also prominently identify the
confidential business information to be redacted within the comment.
Comments containing personal identifying information and
confidential business information identified as directed above will
generally be made publicly available in redacted form. If a comment has
so much confidential business information or personal identifying
information that it cannot be effectively redacted, all or part of that
comment may not be made publicly available. Comments posted to http://www.regulations.gov may include any personal identifying information
(such as name, address, and phone number) included in the text of your
electronic submission that is not identified as directed above as
confidential.
An electronic copy of this document and supplemental information,
including the complete Department of Health and Human Services and Drug
Enforcement Administration eight-factor analyses, to this interim final
rule are available at http://www.regulations.gov for easy reference.

Request for Hearing, Notice of Appearance at Hearing, or Waiver of
Participation in Hearing

Pursuant to 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 the Administrative Procedure
Act (APA), 5 U.S.C. 551-559. 21 CFR 1308.41-1308.45; 21 CFR part 1316,
subpart D. In accordance with 21 CFR 1308.44(a) through (c), requests
for a hearing, notices of appearance, and waivers of an opportunity for
a hearing or to participate in a hearing may be submitted only by
interested persons, defined as those ``adversely affected or aggrieved
by any rule or proposed rule

[[Page 14816]]

issuable pursuant to section 201 of the Act (21 U.S.C. 811).'' 21 CFR
1300.01. Requests for a hearing and notices of participation must
conform to the requirements of 21 CFR 1308.44(a) or (b), as applicable,
and include a statement of the interest of the person in the proceeding
and the objections or issues, if any, concerning which the person
desires to be heard. Any waiver of an opportunity for a hearing must
conform to the requirements of 21 CFR 1308.44(c) including a written
statement regarding the interested person's position on the matters of
fact and law involved in any hearing.
Please note that pursuant to 21 U.S.C. 811(a), the purpose and
subject matter of the hearing are restricted to ``(A) find[ing] that
such drug or other substance has a potential for abuse, and (B)
mak[ing] with respect to such drug or other substance the findings
prescribed by subsection (b) of section 812 of this title for the
schedule in which such drug is to be placed * * *.'' Requests for a
hearing and waivers of participation in the hearing should be submitted
to DEA using the address information provided above.

Legal Authority

Under the Improving Regulatory Transparency for New Medical
Therapies Act (Pub. L. 114-89), which was signed into law on November
25, 2015, DEA is required to commence an expedited scheduling action
with respect to certain new drugs approved by the FDA. As provided in
21 U.S.C. 811(j), this expedited scheduling is required where both of
the following conditions apply: (1) The Secretary of HHS has advised
DEA that a New Drug Application (NDA) has been submitted for a drug
that has a stimulant, depressant, or hallucinogenic effect on the
central nervous system, and that it appears that such drug has an abuse
potential and (2) the Secretary recommends that DEA control the drug in
schedule II, III, IV, or V pursuant to 21 U.S.C. 811(a) and (b). In
these circumstances, DEA is required to issue an interim final rule
controlling the drug within 90 days.
The law further states that the 90-day timeframe starts the later
of (1) the date DEA receives the HHS scientific and medical evaluation/
scheduling recommendation or (2) the date DEA receives notice of the
NDA approval by HHS. In addition, the law specifies that the rulemaking
shall become immediately effective as an interim final rule without
requiring the DEA to demonstrate good cause therefor. Thus, the purpose
of subsection (j) is to speed the process by which DEA schedules newly
approved drugs that are currently either in schedule I or not
controlled (but which have sufficient abuse potential to warrant
control) so that such drugs may be marketed without undue delay
following FDA approval.\1\
---------------------------------------------------------------------------

\1\ Given the parameters of subsection (j), in DEA's view, it
would not apply to a reformulation of a drug containing a substance
currently in schedules II through V for which an NDA has recently
been approved.
---------------------------------------------------------------------------

Subsection (j) further provides that the interim final rule shall
give interested persons the opportunity to comment and to request a
hearing. After the conclusion of such proceedings, DEA must issue a
final rule in accordance with the scheduling criteria of subsections 21
U.S.C. 811(b), (c), and (d) and 21 U.S.C. 812(b).

Background

Syndros is an oral solution that contains 5 mg of dronabinol
(delta-9-THC) per mL of solution. Dronabinol is the generic name
(International Nonproprietary Name, INN) for the (-) delta-9-trans
isomer of tetrahydrocannabinol (THC), the primary psychoactive
substance in marijuana. On June 1, 2015, Insys Therapeutics (Sponsor)
submitted an NDA to the U.S. Food and Drug Administration (FDA) for
Syndros, an oral formulation of dronabinol. The FDA accepted the NDA
filing for Syndros on August 6, 2015 and approved the NDA on July 5,
2016. On December 28, 2016, the DEA received notification that HHS/FDA
approved Syndros for the treatment of anorexia associated with weight
loss in patients with Acquired Immune Deficiency Syndrome (AIDS), and
for the treatment of nausea and vomiting resulting from cancer
chemotherapy in patients who failed to respond to conventional anti-
emetic therapies.

Determination To Schedule FDA-Approved Products Containing Dronabinol
in an Oral Solution

On December 28, 2016, the HHS provided the DEA with a scientific
and medical evaluation and scheduling recommendation related to
dronabinol. Because DEA's authority to issue this interim final rule
under subsection 811(j) is limited to drugs that are the subject of an
approved NDA, and because the NDA was limited to an oral solution
containing dronabinol, DEA's discussion here of the scheduling criteria
is likewise limited to oral solutions containing dronabinol in FDA-
approved drug products.\2\ HHS's scientific and medical evaluation
contained an eight-factor analysis of the abuse potential of FDA-
approved products of oral solutions containing dronabinol and
recommended that such products be placed in schedule II of the CSA.
---------------------------------------------------------------------------

\2\ To the extent HHS's submissions to DEA are outside the scope
of this interim final rule (i.e., those addressing dronabinol beyond
that contained in an FDA-approved oral solution), they will not be
addressed in this document.
---------------------------------------------------------------------------

In response, the DEA reviewed the scientific and medical evaluation
and scheduling recommendation provided by the HHS, along with all other
relevant data, and completed its own eight-factor review document
pursuant to 21 U.S.C. 811(c). The DEA concluded that FDA-approved
dronabinol oral solutions met the 21 U.S.C. 812(b)(2) criteria for
placement in schedule II of the CSA.
Pursuant to subsection 811(j), and based on the HHS recommendation,
NDA approval by HHS/FDA, and DEA's determination, DEA is issuing this
interim final rule to schedule FDA-approved dronabinol oral solution as
a schedule II controlled substance under the CSA.
Included below is a brief summary of each factor as analyzed by the
HHS and the DEA, and as considered by the DEA in its scheduling action.
Please note that both the DEA and HHS analyses are available in their
entirety under ``Supporting Documents'' in the public docket for this
interim final rule at http://www.regulations.gov, under Docket Number
``DEA-344.'' Full analysis of, and citations to, the information
referenced in the summary may also be found in the supporting and
related material.
1. Its Actual or Relative Potential for Abuse: Dronabinol is a
generic name for the (-) delta-9-trans isomer of tetrahydrocannabinol
(THC). THC is the primary psychoactive substance in marijuana.
Dronabinol is the active pharmaceutical ingredient in Syndros. As
stated by HHS, Marinol (synthetic dronabinol in sesame oil and
encapsulated in a soft gelatin capsule) was approved by the FDA for
medical use on May 31, 1985 and placed in schedule II based on its
accepted medical use and high abuse potential. On July 2, 1999, Marinol
was rescheduled from schedule II to schedule III because of the
findings of the DEA that the difficulty of separating dronabinol from
the sesame oil formulation and the delayed onset of behavioral effects
due to oral route administration supported a lower abuse potential of
Marinol as compared to substances in Schedule II. 64 FR 35928.
According to HHS, although Syndros oral solution and Marinol
capsules have

[[Page 14817]]

the same pharmacology, these formulations differ in their physical and
chemical properties. Both these formulations have abuse potential as
demonstrated by their effects on subjective scores of ``Drug Liking''
in human abuse potential studies. HHS indicated that the formulation of
Syndros (oral solution) is easier to abuse than Marinol because this
liquid formulation can be manipulated to produce concentrated extracts
of dronabinol for abuse by inhalation (smoking or vaping) or through
other routes of administration. Because of the large amount of
dronabinol in Syndros oral solution it has a greater potential for
extraction than Marinol and thus has a greater abuse potential. Based
on the data from in vitro studies conducted by the Sponsor, the large
amount of dronabinol in the Syndros formulation, its pharmacokinetics
upon oral administration, and its contribution to marijuana
psychoactivity, HHS stated that the abuse potential of the dronabinol
oral solution is similar to that of other THC containing products such
as concentrates, infused edibles and drinks. Similar to these THC
containing products, Syndros oral solution can be easily manipulated to
other forms that can be easily abused through inhalation and oral
routes of administration.
The 2014 and 2015 Monitoring the Future (MTF) \3\ survey indicated
that THC containing products are being taken orally, smoked, and
vaporized using devices such as e-cigarettes. There is a lack of
evidence pertaining to diversion of Syndros or Marinol from legitimate
drug channels. Syndros is not yet available on the market. Marinol and
generic forms that reference it, have low levels of abuse and diversion
according to the HHS and DEA, and this is attributed to the formulation
of dronabinol in sesame oil.
---------------------------------------------------------------------------

\3\ MTF is a research program conducted at the University of
Michigan's Institute for Social Research, under grants from NIDA.
MTF tracks drug use trends among American adolescents in the 8th,
10th, and 12th grades and high school graduates into adulthood by
conducting national surveys.
---------------------------------------------------------------------------

2. Scientific Evidence of Its Pharmacological Effects, if Known:
Dronabinol, also known as THC, is the primary psychoactive substance in
marijuana and is also the active pharmaceutical ingredient in Syndros
and Marinol. Dronabinol binds to and activates the cannabinoid
receptors (CB1 and CB2). HHS states that CB1 receptors activation
underlie the psychotropic effects and many other pharmacological
effects of dronabinol. Some behavioral and other effects of dronabinol
in humans consist of dizziness, nausea, tachycardia, euphoria, enhanced
sensory perception, heightened imagination, impaired judgment,
emotional lability, and increased appetite. Dronabinol has been
reported to be self-administered intravenously by squirrel monkeys and
intracerebroventricularly by rats. Discriminative stimulus effects of
dronabinol are specific to CB1 cannabinoids, and unique because
stimulants, hallucinogens, opioids, benzodiazepines, barbiturates, NMDA
antagonists, and antipsychotics do not generalize to dronabinol.
3. The State of Current Scientific Knowledge Regarding the Drug or
Other Substance: Dronabinol is the generic name for (-)delta-9-trans-
tetrahydrocannabinol (THC) and is chemically known as (-)-(6aR-trans)-
6a,7,8,10a-tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]pyran-1-
ol and has the chemical formula
C21H30O2. At room temperature (25
[deg]C), dronabinol is a light-yellow oil and hardens upon
refrigeration (4 [deg]C) and is insoluble in water. The FDA-approved
Syndros formulation consists of 5 mg dronabinol/mL of a 50 percent w/w
alcoholic solution. Syndros will be marketed as 30 mL aliquots in
clear, amber glass bottles and each bottle will contain 150 mg
dronabinol.
In vitro manipulation studies with Syndros and Marinol (positive
control) were conducted by the Sponsor. It was found that Syndros oral
solution and Marinol capsules differ in their physiochemical
properties. Specifically, Syndros, unlike Marinol, can be manipulated
such that the dronabinol can be evaporated into residues that can be
reconstituted for smoking or abused intravenously. According to HHS,
Syndros contains a large amount of dronabinol (150 mg of dronabinol in
30 mL of solution) and would be an easily accessible source for abuse
via the oral route.
4. Its History and Current Pattern of Abuse: There is a long
history of abuse of THC in the United States. HHS noted that dronabinol
in Marinol capsules is difficult to extract and therefore, cannot be
used for smoking, vaping, or as an edible. The dronabinol in Syndros,
however, is relatively easy to extract and concentrated forms can be
used for smoking, vaping, or the sweetened alcoholic dronabinol in
Syndros can be used as a substitute for THC in edibles. In the 2015 MTF
survey, it was reported that teens were more likely to use e-cigarettes
(vaping) than regular cigarettes (smoking). In this survey, 6.1 percent
of 12th graders reported vaporizing marijuana or hash oil in their last
e-cigarette. Additionally, in a recent analysis of marijuana users, 12
percent of users preferred vaping the drug over any other method and
considered it a safer alternative to smoking. As a result, these data
suggest that if dronabinol extracts or concentrates are available from
dronabinol sources such as Syndros, a certain percent of the population
are likely to vape these substances.
5. The Scope, Duration, and Significance of Abuse: As noted by HHS,
information on the scope, duration, and significance of abuse of
dronabinol was considered for both oral and inhalation routes. Data
analyzed from the 2014 Summer Styles Survey, a national representative
consumer panel survey of adult marijuana users aged 18 or older, showed
that the majority of current marijuana users prefer smoking marijuana.
In the same survey, it was reported that 16 percent of the current
users consumed THC containing edibles or drinks. Individuals who
preferred vaping (using a device to vaporize liquid THC) believed that
vaping is ``healthier, better tasting'' and resulted in ``better
effects'' associated with marijuana and THC.
6. What, if any, Risk There is to the Public Health: As stated by
HHS, labeling on the Marinol packaging indicates that Central Nervous
System (CNS) adverse reactions are dose-related and subject to patient
variability. CNS adverse reactions are more likely to occur at higher
doses of dronabinol. Following oral Marinol (dronabinol) doses of 0.4
mg/kg, CNS symptoms such as amnesia, confusion, delusions, depression,
and hallucinations have been observed. According to HHS, it is assumed
that Syndros oral solution will have similar adverse effects to
Marinol. One concern with Syndros is that there is a large amount of
dronabinol present in the product (150 mg dronabinol per bottle, 30 mL
solution) that can easily be abused orally and may result in unintended
overdoses.
Oral consumption of dronabinol, compared to inhaled THC, may result
in psychoactive effects that are delayed and stronger with an increased
risk of experiencing serious adverse events. When dronabinol (THC) is
smoked, the drug rapidly reaches the brain and psychoactive effects are
felt within minutes of inhalation, which allows the subject to control
the dose more readily. Due to the absorption and metabolism by the
liver following oral ingestion of dronabinol, it takes longer for an
individual to feel the psychoactive effects. Therefore, the individual
may underestimate the ingestion amount needed to feel the psychoactive
effects

[[Page 14818]]

which may potentially result in an overdose.
7. Its Psychic or Physiological Dependence Liability: As stated in
labeling for Marinol and Syndros, psychological and physical dependence
has been observed in healthy individuals following use of dronabinol.
Abrupt discontinuation of dronabinol in individuals receiving 210 mg/
day (25 times the recommended daily dose for the treatment of anorexia
associated with weight loss in AIDS patients) for 12 to 16 days
resulted in undesirable symptoms including insomnia, irritability, and
restlessness at 12 hours after discontinuation. These symptoms worsened
to include hot flashes, anorexia, sweating, rhinorrhea, loose stools,
and hiccoughs at 24 hours after discontinuation of dronabinol.
8. Whether the Substance is an Immediate Precursor of a Substance
Already Controlled under the CSA: Dronabinol oral solution is not an
immediate precursor of any controlled substance.
Conclusion: After considering the scientific and medical evaluation
conducted by the HHS, the HHS' recommendation, and its own eight-factor
analysis, the DEA has determined that these facts and all relevant data
constitute substantial evidence of a potential for abuse of dronabinol
oral solution. As such, the DEA hereby schedules FDA-approved products
containing dronabinol oral solution as controlled substances under the
CSA.

Determination of Appropriate Schedule

The CSA lists the findings required to place a drug or other
substance in any particular Schedule (I, II, III, IV, or V). 21 U.S.C.
812(b). After consideration of the analysis and recommendation of the
Assistant Secretary for Health of the HHS and review of all available
data, the Acting Administrator of the DEA, pursuant to 21 U.S.C.
812(b)(2), finds that:
1. FDA-approved products containing dronabinol in an oral solution
have a high potential for abuse. The physicochemical properties of
Syndros allow extraction of dronabinol for abuse through oral or
inhalation (smoking or vaping) routes. Dronabinol is not easily
extractable from Marinol. Oral abuse of dronabinol-containing products
is associated with hallucinations, mood alterations, and paranoia. The
2015 MTF Survey reported that 6.1 percent of the 12th graders used e-
cigarettes to vaporize marijuana or cannabinoid substances. Similarly,
the 2014 Summer Styles Survey, 16 percent of current marijuana users
indicated that they have consumed dronabinol containing edibles or
drinks. These data collectively indicate FDA-approved oral solutions
containing dronabinol have high potential for abuse.
2. FDA-approved products containing dronabinol in an oral solution
have a currently accepted medical use in treatment in the United
States. The FDA approved an oral solution containing dronabinol
(Syndros) for the treatment of anorexia associated with weight loss in
patients with AIDS, and for the treatment of nausea and vomiting
associated with cancer chemotherapy in patients who have failed to
respond adequately to conventional antiemetic treatments.
3. FDA-approved products containing dronabinol in an oral solution
may lead to severe physical dependence. Following discontinuation of
dronabinol at a dose 210 mg/day (25 times higher than the recommended
daily dose for anorexia associated with weight loss in AIDS patients)
for 12 to 16 consecutive days, withdrawal symptoms including
irritability, insomnia, and restlessness were observed at 12 hours
after discontinuation. These withdrawal symptoms worsened to include
hot flashes, sweating, rhinorrhea, loose stools, hiccoughs, and
anorexia at 24 hours after discontinuation of dronabinol. The
withdrawal symptoms decreased gradually over the next 48 hours and
patients reported having disturbed sleep for several weeks after
discontinuation of dronabinol.
Based on these findings, the Acting Administrator of the DEA
concludes that FDA-approved products containing dronabinol [(-)-delta-
9-trans tetrahydrocannabinol (delta-9-THC)] in an oral solution warrant
control in schedule II of the CSA. 21 U.S.C. 812(b)(2).

Requirements for Handling FDA-Approved Products Containing Dronabinol
in an Oral Solution.

Preliminarily, it should be noted that any form of dronabinol other
than in an FDA-approved drug product remains a schedule I controlled
substance, and those who handle such material remain subject to the
regulatory controls, and administrative, civil, and criminal sanctions,
applicable to schedule I controlled substances set forth in the CSA and
DEA regulations. However, for those who handle dronabinol oral solution
exclusively in the form of an FDA-approved drug product, the following
is a summary of the schedule II regulatory requirements that apply as a
result of this interim final rule:
1. Registration. Any person who handles (manufactures, distributes,
reverse distributes, dispenses, imports, exports, engages in research,
or conducts instructional activities or chemical analysis with, or
possesses) FDA-approved products containing dronabinol in an oral
solution, or who desires to handle such products, must be registered
with the DEA to conduct such activities pursuant to 21 U.S.C. 822, 823,
957, and 958 and in accordance with 21 CFR parts 1301 and 1312. Any
person who currently handles FDA-approved products containing
dronabinol in an oral solution, and is not registered with the DEA,
must submit an application for registration and may not continue to
handle such products, unless the DEA has approved that application for
registration, pursuant to 21 U.S.C. 822, 823, 957, and 958, and in
accordance with 21 CFR parts 1301 and 1312.
2. Quota. Only registered manufacturers are permitted to
manufacture FDA-approved products containing dronabinol in an oral
solution in accordance with a quota assigned pursuant to 21 U.S.C. 826
and in accordance with 21 CFR part 1303.
3. Disposal of stocks. Upon obtaining a schedule II registration to
handle FDA-approved products containing dronabinol in an oral solution,
any person who does not desire or is not able to maintain such
registration must surrender all quantities of such products, or may
transfer all quantities of such products to a person registered with
the DEA in accordance with 21 CFR part 1317, in addition to all other
applicable federal, state, local, and tribal laws.
4. Security. FDA-approved products containing dronabinol in an oral
solution are subject to schedule II security requirements and must be
handled and stored pursuant to 21 U.S.C. 821, 823, and in accordance
with 21 CFR 1301.71-1301.93.
5. Labeling and Packaging. All labels, labeling, and packaging for
commercial containers of FDA-approved products containing dronabinol in
an oral solution must comply with 21 U.S.C. 825 and 958(e), and be in
accordance with 21 CFR part 1302.
6. Inventory. Every DEA registrant who possesses any quantity of
FDA-approved products containing dronabinol in an oral solution must
take an inventory of such products on hand, pursuant to 21 U.S.C. 827
and 958, and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
Any person who becomes registered with the DEA to handle FDA-
approved products containing dronabinol in an oral solution must take
an initial inventory of all stocks of controlled

[[Page 14819]]

substances (including FDA-approved products containing dronabinol in an
oral solution) on hand on the date the registrant first engages in the
handling of controlled substances, pursuant to 21 U.S.C. 827 and 958,
and in accordance with 21 CFR 1304.03, 1304.04, and 1304.11.
After the initial inventory, every DEA registrant must take a new
inventory of all stocks of controlled substances (including FDA-
approved products containing dronabinol in an oral solution) on hand
every two years, pursuant to 21 U.S.C. 827 and 958, and in accordance
with 21 CFR 1304.03, 1304.04, and 1304.11.
7. Records and Reports. Every DEA registrant must maintain records
and submit reports for FDA-approved products containing dronabinol in
an oral solution, pursuant to 21 U.S.C. 827 and 958(e), and in
accordance with 21 CFR parts 1304, 1312, and 1317.
8. Orders for FDA-approved products containing dronabinol in an
oral solution. Every DEA registrant who distributes FDA-approved
products containing dronabinol in an oral solution is required to
comply with order form requirements, pursuant to 21 U.S.C. 828, and in
accordance with 21 CFR part 1305.
9. Prescriptions. All prescriptions for FDA-approved products
containing dronabinol in an oral solution must comply with 21 U.S.C.
829, and be issued in accordance with 21 CFR parts 1306 and 1311,
subpart C.
10. Manufacturing and Distributing. In addition to the general
requirements of the CSA and DEA regulations that are applicable to
manufacturers and distributors of schedule II controlled substances,
such registrants should be advised that (consistent with the foregoing
considerations) any manufacturing or distribution of FDA-approved
products containing dronabinol in an oral solution may only be for the
legitimate purposes authorized by the FDCA and CSA.
11. Importation and Exportation. All importation and exportation of
FDA-approved products containing dronabinol in an oral solution must be
in compliance with 21 U.S.C. 952, 953, 957, and 958, and in accordance
with 21 CFR part 1312.
12. Liability. Any activity involving FDA-approved products
containing dronabinol in an oral solution not authorized by, or in
violation of, the CSA or its implementing regulations, is unlawful, and
may subject the person to administrative, civil, and/or criminal
sanctions.

Regulatory Analyses

Administrative Procedure Act

As explained above, under 21 U.S.C. 811(j), where a new drug is (1)
approved by the Department of Health and Human Services (HHS) and (2)
HHS recommends control in CSA schedule II-V, the DEA is required to
issue an interim final rule scheduling the drug within 90 days.
Additionally, the law specifies that the rulemaking shall become
immediately effective as an interim final rule without requiring the
DEA to demonstrate good cause. Therefore, the standard notice-and-
comment requirements of section 553 of the APA, 5 U.S.C. 553, do not
apply to this scheduling action.

Executive Orders 12866, Regulatory Planning and Review, and 13563,
Improving Regulation and Regulatory Review

In accordance with 21 U.S.C. 811(j), this scheduling action is
subject to formal rulemaking procedures performed ``on the record after
opportunity for a hearing,'' which are conducted pursuant to the
provisions of 5 U.S.C. 556 and 557. The CSA sets forth the procedures
and criteria for scheduling a drug or other substance. Such actions are
exempt from review by the Office of Management and Budget (OMB)
pursuant to section 3(d)(1) of Executive Order 12866 and the principles
reaffirmed in Executive Order 13563.

Executive Order 12988, Civil Justice Reform

This regulation meets the applicable standards set forth in
sections 3(a) and 3(b)(2) of Executive Order 12988 to eliminate
drafting errors and ambiguity, minimize litigation, provide a clear
legal standard for affected conduct, and promote simplification and
burden reduction.

Executive Order 13132, Federalism

This rulemaking does not have federalism implications warranting
the application of Executive Order 13132. The rule does not have
substantial direct effects on the States, on the relationship between
the national government and the States, or on the distribution of power
and responsibilities among the various levels of government.

Executive Order 13175, Consultation and Coordination With Indian Tribal
Governments

This rule does not have tribal implications warranting the
application of Executive Order 13175. It does not have substantial
direct effects on one or more Indian tribes, on the relationship
between the Federal government and Indian tribes, or on the
distribution of power and responsibilities between the Federal
government and Indian tribes.

Regulatory Flexibility Act

In accordance with 5 U.S.C. 603(a), ``[w]henever an agency is
required by [5 U.S.C. 553], or any other law, to publish general notice
of proposed rulemaking for any proposed rule, or publishes a notice of
proposed rulemaking for an interpretive rule involving the internal
revenue laws of the United States, the agency shall prepare and make
available for public comment an initial regulatory flexibility
analysis.'' As noted in the above discussion regarding applicability of
the Administrative Procedure Act, the notice-and-comment requirements
of section 553 of the APA, 5 U.S.C. 553, do not apply to this
scheduling action. Consequently, the RFA does not apply to this interim
final rule.

Unfunded Mandates Reform Act of 1995

In accordance with the Unfunded Mandates Reform Act (UMRA) of 1995,
2 U.S.C. 1501 et seq., the DEA has determined that this action would
not result in any Federal mandate that may result ``in the expenditure
by State, local, and tribal governments, in the aggregate, or by the
private sector, of $100,000,000 or more (adjusted for inflation) in any
one year.'' Therefore, neither a Small Government Agency Plan nor any
other action is required under UMRA of 1995.

Paperwork Reduction Act of 1995

This action does not impose a new collection of information
requirement under the Paperwork Reduction Act of 1995. 44 U.S.C. 3501-
3521. This action would not impose recordkeeping or reporting
requirements on State or local governments, individuals, businesses, or
organizations. An agency may not conduct or sponsor, and a person is
not required to respond to, a collection of information unless it
displays a currently valid OMB control number.

Congressional Review Act

This rule is not a major rule as defined by section 804 of the
Small Business Regulatory Enforcement Fairness Act of 1996
(Congressional Review Act (CRA)). This rule will not result in: an
annual effect on the economy of $100,000,000 or more; a major increase
in costs or prices for consumers, individual industries, Federal,
State, or local government agencies, or geographic regions; or
significant adverse effects on

[[Page 14820]]

competition, employment, investment, productivity, innovation, or on
the ability of U.S.-based companies to compete with foreign based
companies in domestic and export markets. However, pursuant to the CRA,
the DEA has submitted a copy of this interim final rule to both Houses
of Congress and to the Comptroller General.

List of Subjects in 21 CFR Part 1308

Administrative practice and procedure, Drug traffic control,
Reporting and recordkeeping requirements.

For the reasons set out above, the DEA amends 21 CFR part 1308 as
follows:

PART 1308--SCHEDULES OF CONTROLLED SUBSTANCES

0
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.

0
2. In Sec. 1308.12, add paragraph (f)(2) to read as follows:

Sec. 1308.12 Schedule II.

* * * * *
(f) * * *

(2) Dronabinol [(-)-delta-9-trans tetrahydrocannabinol] in (7365)
an oral solution in a drug product approved for marketing
by the U.S. Food and Drug Administration...................

* * * * *

Dated: March 20, 2017.
Chuck Rosenberg,
Acting Administrator.
[FR Doc. 2017-05809 Filed 3-22-17; 8:45 am]
BILLING CODE 4410-09-P

Federal Register / Vol. 82, No. 55 / Thursday, March 23, 2017 / Rules and Regulations 14815

DEPARTMENT OF JUSTICE • Electronic comments: The Drug Information Act (FOIA) applies to all
Enforcement Administration encourages comments received. If you want to
Drug Enforcement Administration that all comments be submitted submit personal identifying information
electronically through the Federal (such as your name, address, etc.) as
21 CFR Part 1308 eRulemaking Portal, which provides the part of your comment, but do not want
[Docket No. DEA–344] ability to type short comments directly it to be made publicly available, you
into the comment field on the Web page must include the phrase ‘‘PERSONAL
Schedules of Controlled Substances: or attach a file for lengthier comments. IDENTIFYING INFORMATION’’ in the
Placement of FDA-Approved Products Please go to http://www.regulations.gov first paragraph of your comment. You
of Oral Solutions Containing and follow the online instructions at must also place all of the personal
Dronabinol [(-)-delta-9-trans- that site for submitting comments. Upon identifying information you do not want
tetrahydrocannabinol (delta-9-THC)] in completion of your submission, you will made publicly available in the first
Schedule II receive a Comment Tracking Number for paragraph of your comment and identify
your comment. Please be aware that what information you want redacted.
AGENCY: Drug Enforcement submitted comments are not If you want to submit confidential
Administration, Department of Justice. business information as part of your
instantaneously available for public
ACTION: Interim final rule, with request view on Regulations.gov. If you have comment, but do not want it to be made
for comments. received a Comment Tracking Number, publicly available, you must include the
your comment has been successfully phrase ‘‘CONFIDENTIAL BUSINESS
SUMMARY: On July 1, 2016, the U.S. Food
submitted and there is no need to INFORMATION’’ in the first paragraph
and Drug Administration (FDA)
resubmit the same comment. of your comment. You must also
approved a new drug application for
• Paper comments: Paper comments prominently identify the confidential
Syndros, a drug product consisting of
that duplicate the electronic submission business information to be redacted
dronabinol [(-)-delta-9-trans-
are not necessary and are discouraged. within the comment.
tetrahydrocannabinol (delta-9-THC)] Comments containing personal
oral solution. Thereafter, the Should you wish to mail a paper
comment in lieu of an electronic identifying information and confidential
Department of Health and Human business information identified as
Services (HHS) provided the Drug comment, it should be sent via regular
or express mail to: Drug Enforcement directed above will generally be made
Enforcement Administration (DEA) with publicly available in redacted form. If a
a scheduling recommendation that Administration, Attn: DEA Federal
Register Representative/DRW, 8701 comment has so much confidential
would result in Syndros (and other oral business information or personal
solutions containing dronabinol) being Morrissette Drive, Springfield, VA
22152. identifying information that it cannot be
placed in schedule II of the Controlled effectively redacted, all or part of that
Substances Act (CSA). In accordance • Hearing requests: All requests for
hearing and waivers of participation comment may not be made publicly
with the CSA, as revised by the available. Comments posted to http://
Improving Regulatory Transparency for must be sent to: Drug Enforcement
Administration, Attn: Acting www.regulations.gov may include any
New Medical Therapies Act, DEA is personal identifying information (such
hereby issuing an interim final rule Administrator, 8701 Morrissette Drive,
as name, address, and phone number)
placing FDA-approved products of oral Springfield, Virginia 22152. All requests
included in the text of your electronic
solutions containing dronabinol in for hearing and waivers of participation
submission that is not identified as
schedule II of the CSA. should also be sent to: (1) Drug
directed above as confidential.
DATES: The effective date of this Enforcement Administration, Attn: An electronic copy of this document
rulemaking is March 23, 2017. Hearing Clerk/LJ, 8701 Morrissette and supplemental information,
Interested persons may file written Drive, Springfield, Virginia 22152; and including the complete Department of
comments on this rulemaking in (2) Drug Enforcement Administration, Health and Human Services and Drug
accordance with 21 CFR 1308.43(g). Attn: DEA Federal Register Enforcement Administration eight-factor
Electronic comments must be Representative/DRW, 8701 Morrissette analyses, to this interim final rule are
submitted, and written comments must Drive, Springfield, Virginia 22152. available at http://www.regulations.gov
be postmarked, on or before April 24, FOR FURTHER INFORMATION CONTACT: for easy reference.
2017. Commenters should be aware that Michael J. Lewis, Diversion Control
the electronic Federal Docket Division, Drug Enforcement Request for Hearing, Notice of
Management System will not accept Administration; Mailing Address: 8701 Appearance at Hearing, or Waiver of
comments after 11:59 p.m. Eastern Time Morrissette Drive, Springfield, Virginia Participation in Hearing
on the last day of the comment period. 22152; Telephone: (202) 598–8953. Pursuant to 21 U.S.C. 811(a), this
Interested persons, defined at 21 CFR SUPPLEMENTARY INFORMATION: action is a formal rulemaking ‘‘on the
1300.01 as those ‘‘adversely affected or record after opportunity for a hearing.’’
aggrieved by any rule or proposed rule Posting of Public Comments Such proceedings are conducted
issuable pursuant to section 201 of the Please note that all comments pursuant to the provisions of the
Act (21 U.S.C. 811),’’ may file a request received are considered part of the Administrative Procedure Act (APA), 5
for hearing or waiver of hearing public record. They will, unless U.S.C. 551–559. 21 CFR 1308.41–
pursuant to 21 CFR 1308.44. Requests reasonable cause is given, be made 1308.45; 21 CFR part 1316, subpart D.
for hearing and waivers of an available by the Drug Enforcement In accordance with 21 CFR 1308.44(a)
opportunity for a hearing or to Administration (DEA) for public through (c), requests for a hearing,
nlaroche on DSK30NT082PROD with RULES

participate in a hearing must be inspection online at http:// notices of appearance, and waivers of an
received on or before April 24, 2017. www.regulations.gov. Such information opportunity for a hearing or to
ADDRESSES: To ensure proper handling includes personal identifying participate in a hearing may be
of comments, please reference ‘‘Docket information (such as your name, submitted only by interested persons,
No. DEA–344’’ on all correspondence, address, etc.) voluntarily submitted by defined as those ‘‘adversely affected or
including any attachments. the commenter. The Freedom of aggrieved by any rule or proposed rule

VerDate Sep<11>2014 14:46 Mar 22, 2017 Jkt 241001 PO 00000 Frm 00005 Fmt 4700 Sfmt 4700 E:\FR\FM\23MRR1.SGM 23MRR1

14816 Federal Register / Vol. 82, No. 55 / Thursday, March 23, 2017 / Rules and Regulations

issuable pursuant to section 201 of the newly approved drugs that are currently scientific and medical evaluation
Act (21 U.S.C. 811).’’ 21 CFR 1300.01. either in schedule I or not controlled contained an eight-factor analysis of the
Requests for a hearing and notices of (but which have sufficient abuse abuse potential of FDA-approved
participation must conform to the potential to warrant control) so that products of oral solutions containing
requirements of 21 CFR 1308.44(a) or such drugs may be marketed without dronabinol and recommended that such
(b), as applicable, and include a undue delay following FDA approval.1 products be placed in schedule II of the
statement of the interest of the person in Subsection (j) further provides that CSA.
the proceeding and the objections or the interim final rule shall give In response, the DEA reviewed the
issues, if any, concerning which the interested persons the opportunity to scientific and medical evaluation and
person desires to be heard. Any waiver comment and to request a hearing. After scheduling recommendation provided
of an opportunity for a hearing must the conclusion of such proceedings, by the HHS, along with all other
conform to the requirements of 21 CFR DEA must issue a final rule in relevant data, and completed its own
1308.44(c) including a written statement accordance with the scheduling criteria eight-factor review document pursuant
regarding the interested person’s of subsections 21 U.S.C. 811(b), (c), and to 21 U.S.C. 811(c). The DEA concluded
position on the matters of fact and law (d) and 21 U.S.C. 812(b). that FDA-approved dronabinol oral
involved in any hearing. solutions met the 21 U.S.C. 812(b)(2)
Please note that pursuant to 21 U.S.C. Background criteria for placement in schedule II of
811(a), the purpose and subject matter Syndros is an oral solution that the CSA.
of the hearing are restricted to ‘‘(A) contains 5 mg of dronabinol (delta-9- Pursuant to subsection 811(j), and
find[ing] that such drug or other THC) per mL of solution. Dronabinol is based on the HHS recommendation,
substance has a potential for abuse, and the generic name (International NDA approval by HHS/FDA, and DEA’s
(B) mak[ing] with respect to such drug Nonproprietary Name, INN) for the (-) determination, DEA is issuing this
or other substance the findings delta-9-trans isomer of interim final rule to schedule FDA-
prescribed by subsection (b) of section tetrahydrocannabinol (THC), the approved dronabinol oral solution as a
812 of this title for the schedule in primary psychoactive substance in schedule II controlled substance under
which such drug is to be placed * * *.’’ marijuana. On June 1, 2015, Insys the CSA.
Requests for a hearing and waivers of Therapeutics (Sponsor) submitted an Included below is a brief summary of
participation in the hearing should be NDA to the U.S. Food and Drug each factor as analyzed by the HHS and
submitted to DEA using the address Administration (FDA) for Syndros, an the DEA, and as considered by the DEA
information provided above. oral formulation of dronabinol. The in its scheduling action. Please note that
FDA accepted the NDA filing for both the DEA and HHS analyses are
Legal Authority
Syndros on August 6, 2015 and available in their entirety under
Under the Improving Regulatory approved the NDA on July 5, 2016. On ‘‘Supporting Documents’’ in the public
Transparency for New Medical December 28, 2016, the DEA received docket for this interim final rule at
Therapies Act (Pub. L. 114–89), which notification that HHS/FDA approved http://www.regulations.gov, under
was signed into law on November 25, Syndros for the treatment of anorexia Docket Number ‘‘DEA–344.’’ Full
2015, DEA is required to commence an associated with weight loss in patients analysis of, and citations to, the
expedited scheduling action with with Acquired Immune Deficiency information referenced in the summary
respect to certain new drugs approved Syndrome (AIDS), and for the treatment may also be found in the supporting and
by the FDA. As provided in 21 U.S.C. of nausea and vomiting resulting from related material.
811(j), this expedited scheduling is cancer chemotherapy in patients who 1. Its Actual or Relative Potential for
required where both of the following failed to respond to conventional anti- Abuse: Dronabinol is a generic name for
conditions apply: (1) The Secretary of emetic therapies. the (-) delta-9-trans isomer of
HHS has advised DEA that a New Drug tetrahydrocannabinol (THC). THC is the
Application (NDA) has been submitted Determination To Schedule FDA- primary psychoactive substance in
for a drug that has a stimulant, Approved Products Containing marijuana. Dronabinol is the active
depressant, or hallucinogenic effect on Dronabinol in an Oral Solution pharmaceutical ingredient in Syndros.
the central nervous system, and that it On December 28, 2016, the HHS As stated by HHS, Marinol (synthetic
appears that such drug has an abuse provided the DEA with a scientific and dronabinol in sesame oil and
potential and (2) the Secretary medical evaluation and scheduling encapsulated in a soft gelatin capsule)
recommends that DEA control the drug recommendation related to dronabinol. was approved by the FDA for medical
in schedule II, III, IV, or V pursuant to Because DEA’s authority to issue this use on May 31, 1985 and placed in
21 U.S.C. 811(a) and (b). In these interim final rule under subsection schedule II based on its accepted
circumstances, DEA is required to issue 811(j) is limited to drugs that are the medical use and high abuse potential.
an interim final rule controlling the subject of an approved NDA, and On July 2, 1999, Marinol was
drug within 90 days. because the NDA was limited to an oral rescheduled from schedule II to
The law further states that the 90-day solution containing dronabinol, DEA’s schedule III because of the findings of
timeframe starts the later of (1) the date discussion here of the scheduling the DEA that the difficulty of separating
DEA receives the HHS scientific and criteria is likewise limited to oral dronabinol from the sesame oil
medical evaluation/scheduling solutions containing dronabinol in FDA- formulation and the delayed onset of
recommendation or (2) the date DEA approved drug products.2 HHS’s behavioral effects due to oral route
receives notice of the NDA approval by administration supported a lower abuse
HHS. In addition, the law specifies that
nlaroche on DSK30NT082PROD with RULES

1 Given the parameters of subsection (j), in DEA’s potential of Marinol as compared to
the rulemaking shall become view, it would not apply to a reformulation of a substances in Schedule II. 64 FR 35928.
immediately effective as an interim final drug containing a substance currently in schedules
According to HHS, although Syndros
rule without requiring the DEA to II through V for which an NDA has recently been
approved. oral solution and Marinol capsules have
demonstrate good cause therefor. Thus, 2 To the extent HHS’s submissions to DEA are
the purpose of subsection (j) is to speed outside the scope of this interim final rule (i.e., in an FDA-approved oral solution), they will not be
the process by which DEA schedules those addressing dronabinol beyond that contained addressed in this document.

VerDate Sep<11>2014 14:46 Mar 22, 2017 Jkt 241001 PO 00000 Frm 00006 Fmt 4700 Sfmt 4700 E:\FR\FM\23MRR1.SGM 23MRR1

14818 Federal Register / Vol. 82, No. 55 / Thursday, March 23, 2017 / Rules and Regulations

which may potentially result in an edibles or drinks. These data reverse distributes, dispenses, imports,
overdose. collectively indicate FDA-approved oral exports, engages in research, or
7. Its Psychic or Physiological solutions containing dronabinol have conducts instructional activities or
Dependence Liability: As stated in high potential for abuse. chemical analysis with, or possesses)
labeling for Marinol and Syndros, 2. FDA-approved products containing FDA-approved products containing
psychological and physical dependence dronabinol in an oral solution have a dronabinol in an oral solution, or who
has been observed in healthy currently accepted medical use in desires to handle such products, must
individuals following use of dronabinol. treatment in the United States. The FDA be registered with the DEA to conduct
Abrupt discontinuation of dronabinol in approved an oral solution containing such activities pursuant to 21 U.S.C.
individuals receiving 210 mg/day (25 dronabinol (Syndros) for the treatment 822, 823, 957, and 958 and in
times the recommended daily dose for of anorexia associated with weight loss accordance with 21 CFR parts 1301 and
the treatment of anorexia associated in patients with AIDS, and for the 1312. Any person who currently
with weight loss in AIDS patients) for treatment of nausea and vomiting handles FDA-approved products
12 to 16 days resulted in undesirable associated with cancer chemotherapy in containing dronabinol in an oral
symptoms including insomnia, patients who have failed to respond solution, and is not registered with the
irritability, and restlessness at 12 hours adequately to conventional antiemetic DEA, must submit an application for
after discontinuation. These symptoms treatments. registration and may not continue to
worsened to include hot flashes, 3. FDA-approved products containing handle such products, unless the DEA
anorexia, sweating, rhinorrhea, loose dronabinol in an oral solution may lead has approved that application for
stools, and hiccoughs at 24 hours after to severe physical dependence. registration, pursuant to 21 U.S.C. 822,
discontinuation of dronabinol. Following discontinuation of 823, 957, and 958, and in accordance
8. Whether the Substance is an dronabinol at a dose 210 mg/day (25 with 21 CFR parts 1301 and 1312.
Immediate Precursor of a Substance times higher than the recommended 2. Quota. Only registered
Already Controlled under the CSA: daily dose for anorexia associated with manufacturers are permitted to
Dronabinol oral solution is not an weight loss in AIDS patients) for 12 to manufacture FDA-approved products
immediate precursor of any controlled 16 consecutive days, withdrawal containing dronabinol in an oral
substance. symptoms including irritability, solution in accordance with a quota
Conclusion: After considering the insomnia, and restlessness were assigned pursuant to 21 U.S.C. 826 and
scientific and medical evaluation observed at 12 hours after in accordance with 21 CFR part 1303.
conducted by the HHS, the HHS’ discontinuation. These withdrawal 3. Disposal of stocks. Upon obtaining
recommendation, and its own eight- symptoms worsened to include hot a schedule II registration to handle FDA-
factor analysis, the DEA has determined flashes, sweating, rhinorrhea, loose approved products containing
that these facts and all relevant data stools, hiccoughs, and anorexia at 24 dronabinol in an oral solution, any
constitute substantial evidence of a hours after discontinuation of person who does not desire or is not
potential for abuse of dronabinol oral dronabinol. The withdrawal symptoms able to maintain such registration must
solution. As such, the DEA hereby decreased gradually over the next 48 surrender all quantities of such
schedules FDA-approved products hours and patients reported having products, or may transfer all quantities
containing dronabinol oral solution as disturbed sleep for several weeks after of such products to a person registered
controlled substances under the CSA. discontinuation of dronabinol. with the DEA in accordance with 21
Based on these findings, the Acting CFR part 1317, in addition to all other
Determination of Appropriate Schedule
Administrator of the DEA concludes applicable federal, state, local, and tribal
The CSA lists the findings required to that FDA-approved products containing laws.
place a drug or other substance in any dronabinol [(-)-delta-9-trans 4. Security. FDA-approved products
particular Schedule (I, II, III, IV, or V). tetrahydrocannabinol (delta-9-THC)] in containing dronabinol in an oral
21 U.S.C. 812(b). After consideration of an oral solution warrant control in solution are subject to schedule II
the analysis and recommendation of the schedule II of the CSA. 21 U.S.C. security requirements and must be
Assistant Secretary for Health of the 812(b)(2). handled and stored pursuant to 21
HHS and review of all available data, U.S.C. 821, 823, and in accordance with
the Acting Administrator of the DEA, Requirements for Handling FDA-
21 CFR 1301.71–1301.93.
pursuant to 21 U.S.C. 812(b)(2), finds Approved Products Containing 5. Labeling and Packaging. All labels,
that: Dronabinol in an Oral Solution. labeling, and packaging for commercial
1. FDA-approved products containing Preliminarily, it should be noted that containers of FDA-approved products
dronabinol in an oral solution have a any form of dronabinol other than in an containing dronabinol in an oral
high potential for abuse. The FDA-approved drug product remains a solution must comply with 21 U.S.C.
physicochemical properties of Syndros schedule I controlled substance, and 825 and 958(e), and be in accordance
allow extraction of dronabinol for abuse those who handle such material remain with 21 CFR part 1302.
through oral or inhalation (smoking or subject to the regulatory controls, and 6. Inventory. Every DEA registrant
vaping) routes. Dronabinol is not easily administrative, civil, and criminal who possesses any quantity of FDA-
extractable from Marinol. Oral abuse of sanctions, applicable to schedule I approved products containing
dronabinol-containing products is controlled substances set forth in the dronabinol in an oral solution must take
associated with hallucinations, mood CSA and DEA regulations. However, for an inventory of such products on hand,
alterations, and paranoia. The 2015 those who handle dronabinol oral pursuant to 21 U.S.C. 827 and 958, and
MTF Survey reported that 6.1 percent of
nlaroche on DSK30NT082PROD with RULES

solution exclusively in the form of an in accordance with 21 CFR 1304.03,
the 12th graders used e-cigarettes to FDA-approved drug product, the 1304.04, and 1304.11.
vaporize marijuana or cannabinoid following is a summary of the schedule Any person who becomes registered
substances. Similarly, the 2014 Summer II regulatory requirements that apply as with the DEA to handle FDA-approved
Styles Survey, 16 percent of current a result of this interim final rule: products containing dronabinol in an
marijuana users indicated that they have 1. Registration. Any person who oral solution must take an initial
consumed dronabinol containing handles (manufactures, distributes, inventory of all stocks of controlled

VerDate Sep<11>2014 14:46 Mar 22, 2017 Jkt 241001 PO 00000 Frm 00008 Fmt 4700 Sfmt 4700 E:\FR\FM\23MRR1.SGM 23MRR1

Federal Register / Vol. 82, No. 55 / Thursday, March 23, 2017 / Rules and Regulations 14819

substances (including FDA-approved Regulatory Analyses have substantial direct effects on one or
products containing dronabinol in an more Indian tribes, on the relationship
Administrative Procedure Act
oral solution) on hand on the date the between the Federal government and
registrant first engages in the handling As explained above, under 21 U.S.C. Indian tribes, or on the distribution of
of controlled substances, pursuant to 21 811(j), where a new drug is (1) approved power and responsibilities between the
U.S.C. 827 and 958, and in accordance by the Department of Health and Human Federal government and Indian tribes.
with 21 CFR 1304.03, 1304.04, and Services (HHS) and (2) HHS
recommends control in CSA schedule Regulatory Flexibility Act
1304.11.
After the initial inventory, every DEA II–V, the DEA is required to issue an In accordance with 5 U.S.C. 603(a),
registrant must take a new inventory of interim final rule scheduling the drug ‘‘[w]henever an agency is required by [5
all stocks of controlled substances within 90 days. Additionally, the law U.S.C. 553], or any other law, to publish
(including FDA-approved products specifies that the rulemaking shall general notice of proposed rulemaking
containing dronabinol in an oral become immediately effective as an for any proposed rule, or publishes a
solution) on hand every two years, interim final rule without requiring the notice of proposed rulemaking for an
pursuant to 21 U.S.C. 827 and 958, and DEA to demonstrate good cause. interpretive rule involving the internal
in accordance with 21 CFR 1304.03, Therefore, the standard notice-and- revenue laws of the United States, the
1304.04, and 1304.11. comment requirements of section 553 of agency shall prepare and make available
the APA, 5 U.S.C. 553, do not apply to for public comment an initial regulatory
7. Records and Reports. Every DEA flexibility analysis.’’ As noted in the
this scheduling action.
registrant must maintain records and above discussion regarding applicability
submit reports for FDA-approved Executive Orders 12866, Regulatory
of the Administrative Procedure Act, the
products containing dronabinol in an Planning and Review, and 13563,
notice-and-comment requirements of
oral solution, pursuant to 21 U.S.C. 827 Improving Regulation and Regulatory
section 553 of the APA, 5 U.S.C. 553, do
and 958(e), and in accordance with 21 Review
not apply to this scheduling action.
CFR parts 1304, 1312, and 1317. In accordance with 21 U.S.C. 811(j), Consequently, the RFA does not apply
8. Orders for FDA-approved products this scheduling action is subject to to this interim final rule.
containing dronabinol in an oral formal rulemaking procedures
solution. Every DEA registrant who performed ‘‘on the record after Unfunded Mandates Reform Act of 1995
distributes FDA-approved products opportunity for a hearing,’’ which are In accordance with the Unfunded
containing dronabinol in an oral conducted pursuant to the provisions of Mandates Reform Act (UMRA) of 1995,
solution is required to comply with 5 U.S.C. 556 and 557. The CSA sets 2 U.S.C. 1501 et seq., the DEA has
order form requirements, pursuant to 21 forth the procedures and criteria for determined that this action would not
U.S.C. 828, and in accordance with 21 scheduling a drug or other substance. result in any Federal mandate that may
CFR part 1305. Such actions are exempt from review by result ‘‘in the expenditure by State,
9. Prescriptions. All prescriptions for the Office of Management and Budget local, and tribal governments, in the
FDA-approved products containing (OMB) pursuant to section 3(d)(1) of aggregate, or by the private sector, of
dronabinol in an oral solution must Executive Order 12866 and the $100,000,000 or more (adjusted for
comply with 21 U.S.C. 829, and be principles reaffirmed in Executive Order inflation) in any one year.’’ Therefore,
issued in accordance with 21 CFR parts 13563. neither a Small Government Agency
1306 and 1311, subpart C. Plan nor any other action is required
Executive Order 12988, Civil Justice under UMRA of 1995.
10. Manufacturing and Distributing. Reform
In addition to the general requirements Paperwork Reduction Act of 1995
of the CSA and DEA regulations that are This regulation meets the applicable
standards set forth in sections 3(a) and This action does not impose a new
applicable to manufacturers and
3(b)(2) of Executive Order 12988 to collection of information requirement
distributors of schedule II controlled
eliminate drafting errors and ambiguity, under the Paperwork Reduction Act of
substances, such registrants should be
minimize litigation, provide a clear legal 1995. 44 U.S.C. 3501–3521. This action
advised that (consistent with the
standard for affected conduct, and would not impose recordkeeping or
foregoing considerations) any
promote simplification and burden reporting requirements on State or local
manufacturing or distribution of FDA-
reduction. governments, individuals, businesses, or
approved products containing
organizations. An agency may not
dronabinol in an oral solution may only Executive Order 13132, Federalism conduct or sponsor, and a person is not
be for the legitimate purposes
This rulemaking does not have required to respond to, a collection of
authorized by the FDCA and CSA.
federalism implications warranting the information unless it displays a
11. Importation and Exportation. All application of Executive Order 13132. currently valid OMB control number.
importation and exportation of FDA- The rule does not have substantial
approved products containing Congressional Review Act
direct effects on the States, on the
dronabinol in an oral solution must be relationship between the national This rule is not a major rule as
in compliance with 21 U.S.C. 952, 953, government and the States, or on the defined by section 804 of the Small
957, and 958, and in accordance with 21 distribution of power and Business Regulatory Enforcement
CFR part 1312. responsibilities among the various Fairness Act of 1996 (Congressional
12. Liability. Any activity involving levels of government. Review Act (CRA)). This rule will not
FDA-approved products containing result in: an annual effect on the
nlaroche on DSK30NT082PROD with RULES

dronabinol in an oral solution not Executive Order 13175, Consultation economy of $100,000,000 or more; a
authorized by, or in violation of, the and Coordination With Indian Tribal major increase in costs or prices for
CSA or its implementing regulations, is Governments consumers, individual industries,
unlawful, and may subject the person to This rule does not have tribal Federal, State, or local government
administrative, civil, and/or criminal implications warranting the application agencies, or geographic regions; or
sanctions. of Executive Order 13175. It does not significant adverse effects on

VerDate Sep<11>2014 14:46 Mar 22, 2017 Jkt 241001 PO 00000 Frm 00009 Fmt 4700 Sfmt 4700 E:\FR\FM\23MRR1.SGM 23MRR1

Document Created: 2017-03-23 02:45:57
Document Modified: 2017-03-23 02:45:57

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Rules and Regulations
Action		Interim final rule, with request for comments.
Dates		The effective date of this rulemaking is March 23, 2017. Interested persons may file written comments on this rulemaking in accordance with 21 CFR 1308.43(g). Electronic comments must be submitted, and written comments must be postmarked, on or before April 24, 2017. Commenters should be aware that the electronic Federal Docket Management System will not accept comments after 11:59 p.m. Eastern Time on the last day of the comment period.
Contact		Michael J. Lewis, Diversion Control
FR Citation		82 FR 14815
CFR Associated		Administrative Practice and Procedure; Drug Traffic Control and Reporting and Recordkeeping Requirements

82 FR 14815 - Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] in Schedule II

DEPARTMENT OF JUSTICEDrug Enforcement Administration

Federal Register Volume 82, Issue 55 (March 23, 2017)

DEPARTMENT OF JUSTICE
Drug Enforcement Administration