Notice2023-01286
Cannabis and Cannabis-Derived Compounds: Quality Considerations for Clinical Research; Guidance for Industry; Availability
Primary source
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Published
January 24, 2023
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
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 This guidance finalizes the draft guidance of the same title issued on July 22, 2020.
Full Text
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<title>Federal Register, Volume 88 Issue 15 (Tuesday, January 24, 2023)</title>
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[Federal Register Volume 88, Number 15 (Tuesday, January 24, 2023)]
[Notices]
[Pages 4186-4188]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2023-01286]
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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.
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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:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
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
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information, or other information that identifies you in the body of
your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> 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:
<bullet> 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.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through
Friday, 240-402-7500.
<bullet> 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 <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> 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
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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.
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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
<a href="https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs">https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
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
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</html>Indexed from Federal Register on January 24, 2023.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.