[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]


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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This guidance finalizes the draft guidance of the same title issued on 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:
     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

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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 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

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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 
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


