Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research; Guidance for Industry; Availability, 4186-4188 [2023-01286]
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4186
Federal Register / Vol. 88, No. 15 / Tuesday, January 24, 2023 / Notices
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regulatory review by FDA before the
item was marketed. Under these acts, a
product’s regulatory review period
forms the basis for determining the
amount of extension an applicant may
receive.
A regulatory review period consists of
two periods of time: a testing phase and
an approval phase. For human drug
products, the testing phase begins when
the exemption to permit the clinical
investigations of the drug becomes
effective and runs until the approval
phase begins. The approval phase starts
with the initial submission of an
application to market the human drug
product and continues until FDA grants
permission to market the drug product.
Although only a portion of a regulatory
review period may count toward the
actual amount of extension that the
Director of USPTO may award (for
example, half the testing phase must be
subtracted as well as any time that may
have occurred before the patent was
issued), FDA’s determination of the
length of a regulatory review period for
a human drug product will include all
of the testing phase and approval phase
as specified in 35 U.S.C. 156(g)(1)(B).
FDA has approved for marketing the
human drug product BYFAVO
(remimazolam). BYFAVO is indicated
for the induction and maintenance of
procedural sedation in adults
undergoing procedures lasting 30
minutes or less. Subsequent to this
approval, the USPTO received a patent
term restoration application for
BYFAVO (U.S. Patent No. 9,827,251)
from Acacia Pharma Limited, and the
USPTO requested FDA’s assistance in
determining this patent’s eligibility for
patent term restoration. In a letter dated
June 14, 2022, FDA advised the USPTO
that this human drug product had
undergone a regulatory review period
and that the approval of BYFAVO
represented the first permitted
commercial marketing or use of the
product. Thereafter, the USPTO
requested that FDA determine the
product’s regulatory review period.
II. Determination of Regulatory Review
Period
FDA has determined that the
applicable regulatory review period for
BYFAVO is 4,482 days. Of this time,
3,931 days occurred during the testing
phase of the regulatory review period,
while 551 days occurred during the
approval phase. These periods of time
were derived from the following dates:
1. The date an exemption under
section 505(i) of the Federal Food, Drug,
and Cosmetic Act (FD&C Act) (21 U.S.C.
355(i)) became effective: July 1, 2008.
FDA has verified the applicant’s claim
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Jkt 259001
that the date the investigational new
drug application became effective was
on July 1, 2008.
2. The date the application was
initially submitted with respect to the
human drug product under section 505
of the FD&C Act: April 5, 2019. FDA has
verified the applicant’s claim that the
new drug application (NDA) for
BYFAVO (NDA 212295) was initially
submitted on April 5, 2019.
3. The date the application was
approved: October 6, 2020. FDA has
verified the applicant’s claim that NDA
212295 was approved on October 6,
2020.
This determination of the regulatory
review period establishes the maximum
potential length of a patent extension.
However, the USPTO applies several
statutory limitations in its calculations
of the actual period for patent extension.
In its application for patent extension,
this applicant seeks 796 days of patent
term extension.
III. Petitions
Anyone with knowledge that any of
the dates as published are incorrect may
submit either electronic or written
comments and, under 21 CFR 60.24, ask
for a redetermination (see DATES).
Furthermore, as specified in § 60.30 (21
CFR 60.30), any interested person may
petition FDA for a determination
regarding whether the applicant for
extension acted with due diligence
during the regulatory review period. To
meet its burden, the petition must
comply with all the requirements of
§ 60.30, including but not limited to:
must be timely (see DATES), must be
filed in accordance with § 10.20, must
contain sufficient facts to merit an FDA
investigation, and must certify that a
true and complete copy of the petition
has been served upon the patent
applicant. (See H. Rept. 857, part 1, 98th
Cong., 2d sess., pp. 41–42, 1984.)
Petitions should be in the format
specified in 21 CFR 10.30.
Submit petitions electronically to
https://www.regulations.gov at Docket
No. FDA–2013–S–0610. Submit written
petitions (two copies are required) to the
Dockets Management Staff (HFA–305),
Food and Drug Administration, 5630
Fishers Lane, Rm. 1061, Rockville, MD
20852.
Dated: January 18, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023–01220 Filed 1–23–23; 8:45 am]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2020–D–1079]
Cannabis and Cannabis-Derived
Compounds: Quality Considerations
for Clinical Research; Guidance for
Industry; Availability
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice of availability.
The Food and Drug
Administration (FDA or Agency) is
announcing the availability of a final
guidance for industry entitled
‘‘Cannabis and Cannabis-Derived
Compounds: Quality Considerations for
Clinical Research.’’ This guidance
outlines FDA’s current thinking on
several topics relevant to the
development of cannabis and cannabisderived human drugs, including the
source of cannabis for clinical research;
general quality considerations for
developing human drugs that contain
cannabis and cannabis-derived
compounds; and calculation of percent
delta-9 tetrahydrocannabinol (THC) in
botanical raw materials, intermediates,
drug substances, and drug products to
determine their control status. This
guidance is being issued to support
clinical research for development of
cannabis and cannabis-derived human
drugs. This guidance finalizes the draft
guidance of the same title issued on July
22, 2020.
DATES: The announcement of the
guidance is published in the Federal
Register on January 24, 2023.
ADDRESSES: You may submit either
electronic or written comments on
Agency guidances at any time as
follows:
SUMMARY:
Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
instructions for submitting comments.
Comments submitted electronically,
including attachments, to https://
www.regulations.gov will be posted to
the docket unchanged. Because your
comment will be made public, you are
solely responsible for ensuring that your
comment does not include any
confidential information that you or a
third party may not wish to be posted,
such as medical information, your or
anyone else’s Social Security number, or
confidential business information, such
as a manufacturing process. Please note
that if you include your name, contact
E:\FR\FM\24JAN1.SGM
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Federal Register / Vol. 88, No. 15 / Tuesday, January 24, 2023 / Notices
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information, or other information that
identifies you in the body of your
comments, that information will be
posted on https://www.regulations.gov.
• If you want to submit a comment
with confidential information that you
do not wish to be made available to the
public, submit the comment as a
written/paper submission and in the
manner detailed (see ‘‘Written/Paper
Submissions’’ and ‘‘Instructions’’).
Written/Paper Submissions
Submit written/paper submissions as
follows:
• Mail/Hand Delivery/Courier (for
written/paper submissions): Dockets
Management Staff (HFA–305), Food and
Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Dockets Management
Staff, FDA will post your comment, as
well as any attachments, except for
information submitted, marked and
identified, as confidential, if submitted
as detailed in ‘‘Instructions.’’
Instructions: All submissions received
must include the Docket No. FDA–
2020–D–1079 for ‘‘Cannabis and
Cannabis-Derived Compounds: Quality
Considerations for Clinical Research.’’
Received comments will be placed in
the docket and, except for those
submitted as ‘‘Confidential
Submissions,’’ publicly viewable at
https://www.regulations.gov or at the
Dockets Management Staff between 9
a.m. and 4 p.m., Monday through
Friday, 240–402–7500.
• Confidential Submissions—To
submit a comment with confidential
information that you do not wish to be
made publicly available, submit your
comments only as a written/paper
submission. You should submit two
copies total. One copy will include the
information you claim to be confidential
with a heading or cover note that states
‘‘THIS DOCUMENT CONTAINS
CONFIDENTIAL INFORMATION.’’ The
Agency will review this copy, including
the claimed confidential information, in
its consideration of comments. The
second copy, which will have the
claimed confidential information
redacted/blacked out, will be available
for public viewing and posted on
https://www.regulations.gov. Submit
both copies to the Dockets Management
Staff. If you do not wish your name and
contact information to be made publicly
available, you can provide this
information on the cover sheet and not
in the body of your comments and you
must identify this information as
‘‘confidential.’’ Any information marked
as ‘‘confidential’’ will not be disclosed
except in accordance with 21 CFR 10.20
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19:17 Jan 23, 2023
Jkt 259001
and other applicable disclosure law. For
more information about FDA’s posting
of comments to public dockets, see 80
FR 56469, September 18, 2015, or access
the information at: https://
www.govinfo.gov/content/pkg/FR-201509-18/pdf/2015-23389.pdf.
Docket: For access to the docket to
read background documents or the
electronic and written/paper comments
received, go to https://
www.regulations.gov and insert the
docket number, found in brackets in the
heading of this document, into the
‘‘Search’’ box and follow the prompts
and/or go to the Dockets Management
Staff, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852, 240–402–7500.
You may submit comments on any
guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single
copies of this guidance to the Division
of Drug Information, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10001 New
Hampshire Ave., Hillandale Building,
4th Floor, Silver Spring, MD 20993–
0002. Send one self-addressed adhesive
label to assist that office in processing
your requests. See the SUPPLEMENTARY
INFORMATION section for electronic
access to the guidance document.
FOR FURTHER INFORMATION CONTACT:
Susan Zuk, Center for Drug Evaluation
and Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 75, Rm. 6684, Silver Spring,
MD 20993–0002, 240–402–9133; or
Cassandra Taylor, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 4150,
Silver Spring, MD 20993–0002, 240–
402–5290.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of
a guidance for industry entitled
‘‘Cannabis and Cannabis-Derived
Compounds: Quality Considerations for
Clinical Research.’’ This guidance
outlines FDA’s current thinking on
several topics relevant to the
development of human drugs containing
cannabis and cannabis-derived
compounds, including the source of
cannabis for clinical research; general
quality considerations for developing
human drugs that contain cannabis and
cannabis-derived compounds; and
calculation of percent delta-9 THC in
botanical raw materials, intermediates,
drug substances, and drug products to
determine their status as a controlled
substance. This guidance is being issued
to support clinical research for
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development of human drugs containing
cannabis and cannabis-derived
compounds.
Cannabis and cannabis-derived
compounds (i.e., compounds that occur
naturally in the Cannabis sativa L plant)
have been the subject of interest from
consumers, industry, researchers, the
public, and regulators. The Agriculture
Improvement Act of 2018 (Pub. L. 115–
334) (often called the 2018 Farm Bill)
changed certain Federal authorities
relating to the production of cannabis
and cannabis-derived compounds.
Among other things, the 2018 Farm Bill
removed hemp, defined as cannabis and
derivatives or extracts of cannabis
having not more than 0.3 percent delta9 THC by dry weight, from Schedule I
controls in the Controlled Substances
Act (CSA). The 2018 Farm Bill also
explicitly preserved FDA’s authority to
regulate products containing cannabis
or cannabis-derived compounds under
the Federal Food, Drug, and Cosmetic
Act and section 351 of the Public Health
Service Act (42 U.S.C. 262).
Accordingly, consistent with the 2018
Farm Bill, drugs that contain cannabis
and cannabis-derived compounds are
subject to the same authorities and
requirements as FDA-regulated products
containing any other substance,
regardless of whether the products fall
within the definition of hemp under the
2018 Farm Bill.
The Drug Enforcement
Administration (DEA) is the lead
Federal Agency for regulating controlled
substances. Activities related to growing
and manufacturing cannabis for use as
an investigational drug for research
must comply with CSA and DEA
requirements if the cannabis is a
controlled substance (i.e., it exceeds the
threshold of 0.3 percent delta-9 THC by
dry weight). Sponsors and investigators
are encouraged to contact DEA with
questions regarding Schedule I cannabis
or the CSA. FDA does not enforce the
CSA or other laws within DEA’s
jurisdiction.
Many sponsors initiating clinical
research for drugs containing cannabis
and cannabis-derived compounds may
be unclear regarding, or unfamiliar with,
applicable drug quality expectations.
Early interaction with FDA may prevent
clinical hold issues and aid sponsors in
developing a complete investigational
new drug (IND) application.
In general, drugs containing cannabis
and cannabis-derived compounds are
subject to the same authorities and
requirements as drugs containing any
other substance. Drugs intended for
human use are evaluated by FDA’s
Center for Drug Evaluation and
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Research 1 to help ensure that drugs
marketed in the United States are safe
and effective for their intended uses and
will be manufactured in a manner that
ensures quality.
The recommendations in this
guidance are intended to address the
legal definitions and regulatory controls
related to cannabis, and to address
certain questions raised about drugs
containing cannabis. The guidance also
introduces key FDA regulatory concepts
to stakeholders who may be less familiar
with FDA or our authorities than other
drug developers.
This guidance finalizes the draft
guidance entitled ‘‘Cannabis and
Cannabis-Derived Compounds: Quality
Considerations for Clinical Research’’
issued on July 22, 2020 (85 FR 44305).
FDA considered comments received on
the draft guidance as the guidance was
finalized. Changes from the draft to the
final guidance include clarifying
sources of cannabis for clinical research
(including Schedule I sources), adding
resources that explain expectations for
INDs in various stages of drug
development, and providing guidance
on quality considerations for INDs. The
final guidance also lists applicable U.S.
Pharmacopeia chapters on quality
testing, including the assessment of
leachables from packaging and delivery
systems. Further, the guidance
addresses the calculation of delta-9 THC
content, which is relevant to determine
control status for cannabis and
cannabis-derived compounds. In
addition, editorial changes were made
to improve clarity, including better
explaining FDA’s authority to regulate
human drugs and renaming subsection
III.C to emphasize that this section
relates to control status considerations
under the CSA.
This guidance is being issued
consistent with FDA’s good guidance
practices regulation (21 CFR 10.115).
The guidance represents the current
thinking of FDA on ‘‘Cannabis and
Cannabis-Derived Compounds: Quality
Considerations for Clinical Research.’’ It
does not establish any rights for any
person and is not binding on FDA or the
public. You can use an alternative
approach if it satisfies the requirements
of the applicable statutes and
regulations.
II. Paperwork Reduction Act of 1995
While this guidance contains no
collection of information, it does refer to
previously approved FDA collections of
information. Therefore, clearance by the
1 FDA’s Center for Biologics Evaluation and
Research also has regulatory responsibilities with
respect to the review of human drugs.
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19:17 Jan 23, 2023
Jkt 259001
Office of Management and Budget
(OMB) under the Paperwork Reduction
Act of 1995 (PRA) (44 U.S.C. 3501–
3521) is not required for this guidance.
The previously approved collections of
information are subject to review by
OMB under the PRA. The collections of
information in 21 CFR parts 312 and
314 for submission and approval of
applications for investigational drugs
and new drugs have been approved
under OMB control numbers 0910–0014
and 0910–0001, respectively. The
collections of information pertaining to
current good manufacturing practices
for finished pharmaceuticals as outlined
in 21 CFR parts 210 and 211 have been
approved under OMB control number
0910–0139.
III. Electronic Access
Persons with access to the internet
may obtain the guidance at https://
www.fda.gov/drugs/guidancecompliance-regulatory-information/
guidances-drugs, https://www.fda.gov/
regulatory-information/search-fdaguidance-documents, or https://
www.regulations.gov.
Dated: January 18, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023–01286 Filed 1–23–23; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2022–N–0691]
Peripheral and Central Nervous
System Drugs Advisory Committee;
Notice of Meeting; Establishment of a
Public Docket; Request for Comments
AGENCY:
Food and Drug Administration,
HHS.
Notice; establishment of a
public docket; request for comments.
ACTION:
The Food and Drug
Administration (FDA) announces a
forthcoming public advisory committee
meeting of the Peripheral and Central
Nervous System Drugs Advisory
Committee. The general function of the
committee is to provide advice and
recommendations to FDA on regulatory
issues. The meeting will be open to the
public. FDA is establishing a docket for
public comment on this document.
DATES: The meeting will be held
virtually on March 22, 2023, from 10
a.m. to 6 p.m. Eastern Time.
ADDRESSES: Please note that due to the
impact of the COVID–19 pandemic, all
SUMMARY:
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meeting participants will be joining this
advisory committee meeting via an
online teleconferencing platform.
Answers to commonly asked questions
about FDA advisory committee meetings
may be accessed at: https://
www.fda.gov/AdvisoryCommittees/
AboutAdvisoryCommittees/
ucm408555.htm.
FDA is establishing a docket for
public comment on this meeting. The
docket number is FDA–2022–N–0691.
Please note that late, untimely filed
comments will not be considered. The
docket will close on March 21, 2023.
The https://www.regulations.gov
electronic filing system will accept
comments until 11:59 p.m. Eastern Time
at the end of March 21, 2023. Comments
received by mail/hand delivery/courier
(for written/paper submissions) will be
considered timely if they are received
on or before that date.
Comments received on or before
March 8, 2023, will be provided to the
committee. Comments received after
that date will be taken into
consideration by FDA. In the event that
the meeting is cancelled, FDA will
continue to evaluate any relevant
applications or information, and
consider any comments submitted to the
docket, as appropriate.
You may submit comments as
follows:
Electronic Submissions
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
instructions for submitting comments.
Comments submitted electronically,
including attachments, to https://
www.regulations.gov will be posted to
the docket unchanged. Because your
comment will be made public, you are
solely responsible for ensuring that your
comment does not include any
confidential information that you or a
third party may not wish to be posted,
such as medical information, your or
anyone else’s Social Security number, or
confidential business information, such
as a manufacturing process. Please note
that if you include your name, contact
information, or other information that
identifies you in the body of your
comments, that information will be
posted on https://www.regulations.gov.
• If you want to submit a comment
with confidential information that you
do not wish to be made available to the
public, submit the comment as a
written/paper submission and in the
manner detailed (see ‘‘Written/Paper
Submissions’’ and ‘‘Instructions’’).
E:\FR\FM\24JAN1.SGM
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Agencies
[Federal Register Volume 88, Number 15 (Tuesday, January 24, 2023)]
[Notices]
[Pages 4186-4188]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-01286]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2020-D-1079]
Cannabis and Cannabis-Derived Compounds: Quality Considerations
for Clinical Research; Guidance for Industry; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
the availability of a final guidance for industry entitled ``Cannabis
and Cannabis-Derived Compounds: Quality Considerations for Clinical
Research.'' This guidance outlines FDA's current thinking on several
topics relevant to the development of cannabis and cannabis-derived
human drugs, including the source of cannabis for clinical research;
general quality considerations for developing human drugs that contain
cannabis and cannabis-derived compounds; and calculation of percent
delta-9 tetrahydrocannabinol (THC) in botanical raw materials,
intermediates, drug substances, and drug products to determine their
control status. This guidance is being issued to support clinical
research for development of cannabis and cannabis-derived human drugs.
This guidance finalizes the draft guidance of the same title issued on
July 22, 2020.
DATES: The announcement of the guidance is published in the Federal
Register on January 24, 2023.
ADDRESSES: You may submit either electronic or written comments on
Agency guidances at any time as follows:
Electronic Submissions
Submit electronic comments in the following way:
Federal eRulemaking Portal: https://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to https://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact
[[Page 4187]]
information, or other information that identifies you in the body of
your comments, that information will be posted on https://www.regulations.gov.
If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2020-D-1079 for ``Cannabis and Cannabis-Derived Compounds: Quality
Considerations for Clinical Research.'' Received comments will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at https://www.regulations.gov or at
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through
Friday, 240-402-7500.
Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on https://www.regulations.gov.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of this guidance to the
Division of Drug Information, Center for Drug Evaluation and Research,
Food and Drug Administration, 10001 New Hampshire Ave., Hillandale
Building, 4th Floor, Silver Spring, MD 20993-0002. Send one self-
addressed adhesive label to assist that office in processing your
requests. See the SUPPLEMENTARY INFORMATION section for electronic
access to the guidance document.
FOR FURTHER INFORMATION CONTACT: Susan Zuk, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 75, Rm. 6684, Silver Spring, MD 20993-0002, 240-402-9133; or
Cassandra Taylor, Center for Drug Evaluation and Research, Food and
Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 4150,
Silver Spring, MD 20993-0002, 240-402-5290.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a guidance for industry
entitled ``Cannabis and Cannabis-Derived Compounds: Quality
Considerations for Clinical Research.'' This guidance outlines FDA's
current thinking on several topics relevant to the development of human
drugs containing cannabis and cannabis-derived compounds, including the
source of cannabis for clinical research; general quality
considerations for developing human drugs that contain cannabis and
cannabis-derived compounds; and calculation of percent delta-9 THC in
botanical raw materials, intermediates, drug substances, and drug
products to determine their status as a controlled substance. This
guidance is being issued to support clinical research for development
of human drugs containing cannabis and cannabis-derived compounds.
Cannabis and cannabis-derived compounds (i.e., compounds that occur
naturally in the Cannabis sativa L plant) have been the subject of
interest from consumers, industry, researchers, the public, and
regulators. The Agriculture Improvement Act of 2018 (Pub. L. 115-334)
(often called the 2018 Farm Bill) changed certain Federal authorities
relating to the production of cannabis and cannabis-derived compounds.
Among other things, the 2018 Farm Bill removed hemp, defined as
cannabis and derivatives or extracts of cannabis having not more than
0.3 percent delta-9 THC by dry weight, from Schedule I controls in the
Controlled Substances Act (CSA). The 2018 Farm Bill also explicitly
preserved FDA's authority to regulate products containing cannabis or
cannabis-derived compounds under the Federal Food, Drug, and Cosmetic
Act and section 351 of the Public Health Service Act (42 U.S.C. 262).
Accordingly, consistent with the 2018 Farm Bill, drugs that contain
cannabis and cannabis-derived compounds are subject to the same
authorities and requirements as FDA-regulated products containing any
other substance, regardless of whether the products fall within the
definition of hemp under the 2018 Farm Bill.
The Drug Enforcement Administration (DEA) is the lead Federal
Agency for regulating controlled substances. Activities related to
growing and manufacturing cannabis for use as an investigational drug
for research must comply with CSA and DEA requirements if the cannabis
is a controlled substance (i.e., it exceeds the threshold of 0.3
percent delta-9 THC by dry weight). Sponsors and investigators are
encouraged to contact DEA with questions regarding Schedule I cannabis
or the CSA. FDA does not enforce the CSA or other laws within DEA's
jurisdiction.
Many sponsors initiating clinical research for drugs containing
cannabis and cannabis-derived compounds may be unclear regarding, or
unfamiliar with, applicable drug quality expectations. Early
interaction with FDA may prevent clinical hold issues and aid sponsors
in developing a complete investigational new drug (IND) application.
In general, drugs containing cannabis and cannabis-derived
compounds are subject to the same authorities and requirements as drugs
containing any other substance. Drugs intended for human use are
evaluated by FDA's Center for Drug Evaluation and
[[Page 4188]]
Research \1\ to help ensure that drugs marketed in the United States
are safe and effective for their intended uses and will be manufactured
in a manner that ensures quality.
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\1\ FDA's Center for Biologics Evaluation and Research also has
regulatory responsibilities with respect to the review of human
drugs.
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The recommendations in this guidance are intended to address the
legal definitions and regulatory controls related to cannabis, and to
address certain questions raised about drugs containing cannabis. The
guidance also introduces key FDA regulatory concepts to stakeholders
who may be less familiar with FDA or our authorities than other drug
developers.
This guidance finalizes the draft guidance entitled ``Cannabis and
Cannabis-Derived Compounds: Quality Considerations for Clinical
Research'' issued on July 22, 2020 (85 FR 44305). FDA considered
comments received on the draft guidance as the guidance was finalized.
Changes from the draft to the final guidance include clarifying sources
of cannabis for clinical research (including Schedule I sources),
adding resources that explain expectations for INDs in various stages
of drug development, and providing guidance on quality considerations
for INDs. The final guidance also lists applicable U.S. Pharmacopeia
chapters on quality testing, including the assessment of leachables
from packaging and delivery systems. Further, the guidance addresses
the calculation of delta-9 THC content, which is relevant to determine
control status for cannabis and cannabis-derived compounds. In
addition, editorial changes were made to improve clarity, including
better explaining FDA's authority to regulate human drugs and renaming
subsection III.C to emphasize that this section relates to control
status considerations under the CSA.
This guidance is being issued consistent with FDA's good guidance
practices regulation (21 CFR 10.115). The guidance represents the
current thinking of FDA on ``Cannabis and Cannabis-Derived Compounds:
Quality Considerations for Clinical Research.'' It does not establish
any rights for any person and is not binding on FDA or the public. You
can use an alternative approach if it satisfies the requirements of the
applicable statutes and regulations.
II. Paperwork Reduction Act of 1995
While this guidance contains no collection of information, it does
refer to previously approved FDA collections of information. Therefore,
clearance by the Office of Management and Budget (OMB) under the
Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-3521) is not
required for this guidance. The previously approved collections of
information are subject to review by OMB under the PRA. The collections
of information in 21 CFR parts 312 and 314 for submission and approval
of applications for investigational drugs and new drugs have been
approved under OMB control numbers 0910-0014 and 0910-0001,
respectively. The collections of information pertaining to current good
manufacturing practices for finished pharmaceuticals as outlined in 21
CFR parts 210 and 211 have been approved under OMB control number 0910-
0139.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs, https://www.fda.gov/regulatory-information/search-fda-guidance-documents, or https://www.regulations.gov.
Dated: January 18, 2023.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2023-01286 Filed 1-23-23; 8:45 am]
BILLING CODE 4164-01-P