[Federal Register Volume 85, Number 141 (Wednesday, July 22, 2020)]
[Notices]
[Pages 44305-44307]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2020-15907]


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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for Clinical Research; Draft Guidance for Industry; Availability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the availability of a draft guidance for industry entitled ``Cannabis 
and Cannabis-Derived Compounds: Quality Considerations for Clinical 
Research.'' This draft guidance outlines FDA's current thinking on 
several topics relevant to the development of cannabis and cannabis-
derived products: The source of cannabis and cannabis-derived compounds 
for clinical research; general quality considerations for developing 
drugs that contain cannabis and cannabis-derived compounds; and 
calculation of percent delta-9 tetrahydrocannabinol (THC) in botanical 
raw materials, extracts, and finished products. This draft guidance has 
been developed to help support clinical research into development of 
cannabis and cannabis-derived products.

DATES: Submit either electronic or written comments on the draft 
guidance by September 21, 2020 to ensure that the Agency considers your 
comment on this draft guidance before it begins work on the final 
version of the guidance.

ADDRESSES: You may submit comments on any guidance 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 information, or other information that identifies you in 
the body of your

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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 the draft 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 draft guidance document.

FOR FURTHER INFORMATION CONTACT: Amy Muhlberg, Center for Drug 
Evaluation and Research, Food and Drug Administration, Bldg. 51, Rm. 
3117, 10903 New Hampshire Ave., Silver Spring, MD 20993-0002, 240-402-
6901 or Cassandra Taylor, Center for Drug Evaluation and Research, Food 
and Drug Administration, Bldg. 51, Rm. 4150, 10903 New Hampshire Ave., 
Silver Spring, MD 20993-0002, 240-402-5290.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance for industry 
entitled ``Cannabis and Cannabis-Derived Compounds: Quality 
Considerations for Clinical Research.''
    This draft guidance outlines FDA's current thinking on several 
topics relevant to the development of drugs containing cannabis and 
cannabis-derived compounds: (1) The source of cannabis and cannabis-
derived compounds for clinical research; (2) general quality 
considerations for developing drugs that contain cannabis and cannabis-
derived compounds; and (3) calculation of percent delta-9 THC in 
botanical raw materials, extracts, and finished products. This draft 
guidance has been developed to help support clinical research into 
development of drugs containing cannabis and cannabis-derived 
compounds.
    Cannabis and cannabis-derived compounds have been the subject of 
interest from consumers, industry, researchers, the public, and 
regulators. The Agriculture Improvement Act of 2018, Public Law 115-334 
(the 2018 Farm Bill), changed certain federal authorities relating to 
the production and marketing of cannabis and cannabis-derived 
compounds. Among other things, the 2018 Farm Bill removed hemp 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 (FD&C Act) and section 351 of the 
Public Health Service Act (PHS Act) (42 U.S.C. 262). In doing so, 
Congress recognized FDA's important public health role with respect to 
all the products it regulates. 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. FDA does not enforce the 
CSA or other laws within DEA's jurisdiction. 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 
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 held a public hearing \1\ on May 31, 2019, to obtain scientific 
data and information about the safety, manufacturing, product quality, 
marketing, labeling, and sale of products containing cannabis or 
cannabis-derived compounds. The hearing was attended by more than 600 
participants in person and over 2,300 joining remotely. Presentations 
by over 100 speakers represented a broad and diverse array of 
stakeholders. Nearly 4,500 comments were submitted to the docket 
associated with the hearing, and the docket's closing date was extended 
to

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accommodate greater participation. FDA developed this draft guidance in 
part to respond to issues and questions raised in the discussion at 
that hearing and in many of the public comments received.
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    \1\ ``Scientific Data and Information About Products Containing 
Cannabis or Cannabis-Derived Compounds''; https://www.fda.gov/news-events/fda-meetings-conferences-and-workshops/scientific-data-and-information-about-products-containing-cannabis-or-cannabis-derived-compounds.
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    Although the hearing was not exclusively about cannabidiol (CBD), 
this compound was a key discussion topic. FDA and many stakeholders 
have concerns about marketed products that contain CBD, including 
concerns about potential contamination and inaccurate or misleading 
labeling. FDA would like to reiterate that EPIDIOLEX[supreg] 
(cannabidiol) is the sole FDA-approved \2\ product derived from an 
extract of the cannabis plant.
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    \2\ See Epidiolex drug approval package and labeling, available 
at https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210365Orig1s000TOC.cfm.
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    Many sponsors initiating clinical research for drugs containing 
cannabis and cannabis-derived compounds may be unclear regarding, or 
unfamiliar with, applicable drug quality expectations. 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 Research (CDER \3\) to 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. CDER 
has published extensive regulations and guidance documents regarding 
the drug development and review process. In addition, FDA's website 
contains useful explanations regarding drug research and development. 
Finally, CDER's Small Business and Industry Assistance helps small 
pharmaceutical businesses and industry navigate the wealth of 
information that FDA offers, and assists in understanding the 
regulation of human drug products.
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    \3\ FDA's Center for Biologics Evaluation and Research (CBER) 
also has regulatory responsibilities with respect to the review of 
human drugs.
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    FDA's support of drug development extends to drugs containing 
cannabidiol and other compounds found in cannabis. One important 
element is encouraging drug developers to meet with FDA early in their 
development programs--ideally, before submitting an investigational new 
drug (IND) application. The pre-IND meeting is an opportunity to obtain 
FDA input on research plans and required content for an IND submission. 
The pre-IND meeting can be valuable in planning a drug development 
program, especially if sponsors' questions are not fully answered by 
guidances and other information provided by FDA. Early interactions 
with FDA staff through a pre-IND meeting can answer sponsors' questions 
related to a specific drug development program and provide information 
that will assist them in preparing complete IND applications. Efficient 
use of FDA resources can lead to more efficient drug development.
    The FDA web page ``FDA and Cannabis: Research and Drug Approval 
Process'' (available at https://www.fda.gov/news-events/public-health-focus/fda-and-cannabis-research-and-drug-approval-process) provides the 
basic roadmap for conducting clinical research at FDA using cannabis 
and cannabis-derived compounds. The resources on this page may be 
helpful to those interested in better understanding FDA processes for 
conducting clinical trials using cannabis and cannabis-derived 
compounds.
    Calculating the amount of a substance in a botanical raw material 
by dry weight is a standard procedure. However, the calculation of dry 
weight for an extract or solid oral dosage form is less familiar to 
many stakeholders than the standard calculation for botanical raw 
materials. Therefore, the draft guidance recommends calculating delta-9 
THC by dry weight in intermediates and drug products by removing the 
water content, including water contained in excipients. We invite 
comment from the public on this recommended approach. In addition, FDA 
invites public comment on the appropriate manufacturing controls over 
materials that cross under the 0.3 percent delta-9 THC by dry weight 
threshold during the production of a drug that contains cannabis or 
cannabis derived compounds.
    This draft guidance is being issued consistent with FDA's good 
guidance practices regulation (21 CFR 10.115). The draft guidance, when 
finalized, will represent 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

    FDA tentatively concludes that this draft guidance contains no 
collection 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.
    However, this draft guidance refers to previously approved FDA 
collections of information. These 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; and 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 draft guidance 
at either https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs or https://www.regulations.gov.

    Dated: July 16, 2020.
Lowell J. Schiller,
Principal Associate Commissioner for Policy.
[FR Doc. 2020-15907 Filed 7-21-20; 8:45 am]
BILLING CODE 4164-01-P


