ig U.S.

FOOD & DRUG

ADMINISTRATION

John J. Coleman, PhD

President
Drug Watch International, Inc.
P.O. Box 144
Clifton, VA 20124

Re: Docket No. FDA-2017-P-6692 JUL 1 8 2019

Dear Dr. Coleman:

This letter responds to your petition for reconsideration dated July 31, 2018 (Reconsideration
Petition). In your Reconsideration Petition, you request reconsideration of the decision by the
U.S. Food and Drug Administration (FDA or the Agency) not to issue a final rule adding
marihuana (marijuana) and tetrahydrocannabinols (THC) to a list of negative monographs
codified under 21 CFR part 310.

We have carefully considered the Reconsideration Petition and comments submitted to the public
docket for the Reconsideration Petition. For the reasons set forth below, FDA denies your
Reconsideration Petition.

I. BACKGROUND

A. Procedural History of Citizen Petition

Your citizen petition received on November 29, 2017 (Original Petition) requested that FDA
issue a final rule adding marijuana and THC to a list of negative monographs codified under 21
CFR part 310 on the grounds that such an action would send an industry-wide waming to
marijuana businesses in the United States, many of which you asserted were making unsupported
medical claims for marijuana and THC (Original Petition at 1, 5). You asserted that adding
marijuana and THC to the list of negative monographs would "reduce or end the ability of [over-
the-counter (OTC)] sellers of these drugs to assert and advertise unsupported medical claims for
their products" (see Petition at 5).

In our response to your Original Petition, dated July 2, 2018 (Original Petition Response), we
explained that we had determined that the addition of marijuana and THC to the list of negative
monographs codified under 21 CFR part 310 is not necessary for the protection of public health
(see Original Petition Response at 4, 7). While you had suggested in your Original Petition that a
negative rnonograph would reduce or end the unlawful marketing of unapproved new OTC drugs
containing marijuana or THC, we explained that existing law makes very clear that such
unapproved products cannot be marketed under the Federal Food, Drug, and Cosmetic Act
(FD&C Act), regardless of whether they are listed in a negative monograph (Original Petition
Response at 5).

U.S. Food & Drug Administration

10903 New Hampshire Avenue
Silver Spring, MD 20993
www.fda.gov
Docket No. FDA-2017-P-6692

In response, you submitted the Reconsideration Petition renewing your request that FDA
establish through rulemaking a negative monograph for marijuana and THC under 21 CFR part
310 (Reconsideration Petition at 2). You also request that FDA enforce laws regarding
marijuana-containing products (see Reconsideration Petition at 24). In support of your request,
you assert that:

• FDA is not enforcing laws to halt unlawful marketing of unapproved cannabinoid

medicines (see Reconsideration Petition at 3, 5-9, 13-14, 16, 19-20, 23-24), and a
negative rnonograph would strearnline the process for stopping unlawful sales of these
products and would "give the FDA the authority to move quickly against the seller of any
unlawful or unapproved cannabinoid drug(s) and enable the agency to carry through on
its stated warning, namely, that 'Failure to correct the violations promptly may result in
legal action, including product seizure and injunction.'" (Reconsideration Petition at 23).

• A negative monogaph would clarify the status of cannabinoid drugs with respect to the
law (Reconsideration Petition at 15-16), and it would reinforce FDA's policy that
marijuana used for medical purposes must be submitted for testing and approval in
accordance with the law (Reconsideration Petition at 23).

• Marijuana has public health risks (Reconsideration Petition at 9-13, 15), and a negative
monograph may provide additional information for the public to understand health risks
in using unapproved cannabinoid drugs marketed for medicinal purposes
(Reconsideration Petition at 7).

• FDA has previously issued negative monographs for other conditions that are less
dangerous than marijuana (see Reconsideration Petition at 3, 24).

B. Regulatory Framework for Petitions for Reconsideration

The Commissioner may grant a petition for reconsideration if the Commissioner determines the
petition to be in the public interest and in the interest of justice. FDA regulations at 21 CFR
10.33(d) provide that the Commissioner will grant a petition for reconsideration if the
Commissioner determines that all of the following apply:1

• The petition demonstrates that relevant information or views contained in the

administrative record were not previously or adequately considered.

• The petitioner's position is not frivolous and is being pursued in good faith.

• The petitioner has demonstrated sound public policy grounds supporting reconsideration.

• Reconsideration is not outweighed by public health or other public interests.

21 CFR 10.33(d).

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In addition, a petition for reconsideration may not be based on inforrnation and views not
contained in the administrative record on which the decision was made.2

II. DISCUSSION

We have reviewed the Original Petition and the Reconsideration Petition. In the Reconsideration
Petition, you included new information and views that were not submitted in the Original
Petition and were not otherwise previously included in the administrative record. Under 21 CFR
10.33(e), a petition for reconsideration may not be based on information and views not contained
in the administrative record on which the decision was made. Nevertheless, on our own
initiative, we have reviewed the new information and views included in the Reconsideration
Petition.

We conclude that the Reconsideration Petition does not warrant modifying or overruling the
Original Petition Response. We have not found that granting the Reconsideration Petition would
be in the public interest or in the interest of justice.3 Additionally, the relevant information and
views in the administrative record were adequately considered when we denied the Original
Petition.4

A. Agency Enforcement Action May Not be Sought Through a Citizen Petition

or Related Request for Reconsideration

In your Reconsideration Petition, you assert that FDA is not enforcing its laws to halt unlawful
marketing of "unapproved cannabinoid medicines," and you request that FDA enforce the law
regarding marijuana-containing products (see Reconsideration Petition at 3, 5-9, 13-14, 16, 19-
20, 23-24). You also assert that a negative monograph would streamline the process for stopping
unlawful sales of unapproved cannabinoid rnedicines, and it would "give the FDA the authority
to move quickly against the seller of any unlawful or unapproved cannabinoid drug(s) and enable
the agency to carry through on its stated warning, namely, that 'Failure to correct the violations
promptly may result in legal action, including product seizure and injunction.(Reconsideration
Petition at 23).

The relief you seek, namely that the FDA move quickly to carry out product seizure and
injunctions, cannot be sought under 21 CFR 10.30. The Agency's reconsideration of a matter
relating to a citizen petition submitted under 21 CFR 10.25(a)(2) is subject to §10.30(k),5 which
states that § 10.30 does not apply to ``referral of a matter to a United States attorney for the
initiation of court enforcement action and related correspondence . . . ." Agency decisions to
take, or refrain from taking, enforcement actions are decisions related to the referral of a matter

2 21 CFR 10.33(e).
3See § 10.33(d) ("The Commissioner may grant the petition when the Commissioner determines it is in the public
interest and in the interest of justice.")
4 See § 10.33(d)(1).
5 See § 10.33(j).

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Docket No. FDA-2017-P-6692

to a United States attorney for the initiation of court enforcement action for violations of the
FD&C Act. Therefore, your request that the Agency enforce the law regarding marijuana-
containing products may not properly be the subject of a citizen petition or a related request for
reconsideration under § 10.30.6 7

B. Existing Authorities Address FDA Approval Requirements for OTC New

Drugs

You also assert that a negative monograph would clarify the status of cannabinoid drug products
with respect to the law and would reinforce FDA's policy that cannabinoid drug products used
for medical purposes must be submitted for testing and approval in accordance with the law
(Reconsideration Petition at 15-16, 23).

As described in greater detail in our Original Petition Response, the status of unapproved new
OTC drugs containing marijuana or THC with respect to the law is unambiguous, as existing law
makes very clear unapproved new drug products cannot be marketed under the FD&C Act.8
Therefore, it is not necessary to establish a negative monograph to "clarify the status" of these
products with respect to the law.

With respect to your request to reinforce FDA's policy that cannabinoid drug products used for
medical purposes must be submitted for testing in accordance with the law (Reconsideration
Petition at 23), we note that as a preliminary matter, drug products generally are not submitted to
FDA for testing as part of the drug approval process. Rather, it is the responsibility of the
sponsor seeking drug approval to conduct the testing necessary to demonstrate the safety and
effectiveness of a proposed new drug and to submit that information to FDA for review by

6 You spend several pages in your Reconsideration Petition discussing your view that a negative monograph for all
cannabinoids is necessary because the Agency's enforcement actions with respect to cannabidiol (CBD) are
inadequate (see, e.g., Reconsideration Petition at 3, 16, 19-23). As described in this section, a citizen petition is not
the proper vehicle to make requests regarding FDA enforcement. In addition, as discussed in sections II.0 and II.D
of this response and in our Original Petition Response, a negative monograph is not necessary in order for FDA to
take actions regarding unapproved new drugs. Therefore, your request is denied.
7 You have also asserted that a negative monograph may assist victims in their pursuit of tort claims against
rnarketers of unapproved marijuana drugs (Reconsideration Petition at 7). The ability to bring a tort claim is not a
factor we consider in determining whether to place a substance in a negative monograph and we decline to issue a
negative monograph on this ground.
8 See, e.g., section 505(a) of FD&C Act (21 U.S.C. 355(a)) (requiring "new drugs" to have an approved new drug
application (NDA) or abbreviated new drug application (ANDA) prior to marketing); 21 CFR 330.1 (general
conditions for general recognition as safe, effective and not misbranded) (Any product which fails to conform to
each of the conditions contained in this part and in an applicable monograph is liable to regulatory action"); 21 CFR
330.10(b) ("Any product which fails to confonn to an applicable monograph after its effective date is liable to
regulatory actioe). See also section 502(a) of the FD&C Act (21 U.S.C. 352(a)) (deeming a drug to be misbranded
if its labeling is false or misleading in any particular); section 301(a) of the FD&C Act (21 U.S.C. 331(a))
(prohibiting introduction or delivery for introduction into interstate commerce of any drug that is misbranded);
section 301(d) of the FD&C Act (21 U.S.C. 331(d)) (prohibiting the introduction or delivery for introduction into
interstate commerce of any article in violation of section 505 of the FD&C Act).

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physicians, statisticians, chemists, pharmacologists, and other scientists in FDA's Center for
Drug Evaluation and Research (CDER).

To address your broader concerns regarding preapproval requirements, existing law is very clear
that sponsors must adhere to investigational new drug (IND) requirements when conducting a
clinical investigation of any new drug subject to section 505 of the FD&C Act (21 U.S.C. 355).9
Moreover, with respect to the types of products that are the subject of your Reconsideration
Petition, FDA has taken various measures to support the conduct of clinical investigations
conducted under an IND application, as further described in our Original Petition Response.

C. Establishment of a Negative Monograph for Marijuana and THC is Not

Necessary for the Protection of Public Health

You assert that there are a variety of risks of marijuana use (e.g., acute use of marijuana, possible
association between the use of marijuana and other illicit drugs) (Reconsideration Petition at 9-
13, 15) and that a negative monograph may provide additional inforrnation for the public to
understand health risks in using unapproved cannabinoid drug products marketed for medicinal
purposes (see Reconsideration Petition at 7).

FDA recognizes there are public health concerns related to unapproved cannabis or cannabis-
derived products that have unsubstantiated therapeutic claims. For instance, FDA has recognized
our concern with a proliferation of products asserting to contain CBD that are marketed for
therapeutic or medical uses although they have not been approved by FDA.' Often such
products are sold online and are therefore available throughout the country. Selling unapproved
products with unsubstantiated therapeutic claims is not only a violation of the law, but also can
put patients at risk, as these products have not been proven to be safe or effective. This
deceptive marketing of unproven treatments also raises significant public health concerns,
because patients and other consumers may be influenced not to use approved therapies to treat
serious and even fatal diseases.

Consistent with our recognition that there are public health concerns related to unapproved
cannabis or cannabis-derived products that have unsubstantiated therapeutic claims, FDA also
recognizes the importance of communicating effectively to achieve our mission of protecting and
promoting the public health. The Agency generally considers many options when determining
the most effective way to communicate to the public about potential health risks. FDA regularly
uses drug safety cornmunications, press releases, FDA and CDER statements, social media
announcements, and listserv messages, among other avenues, to communicate important
information about drug safety to the public. Given these available means of communication, we
do not believe, in this case, that undertaking the monograph rulemaking process is a necessary,

9 See, generally, 21 CFR part 312.

19 See FDA Regulation of Cannabis and Cannabis-Derived Products: Questions and Answers, available at
https://www.fda.gov/newsevents/publichealthfocus/ucm421168.htrn.

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effective, or efficient way to communicate to the public about potential risks related to the types
of products that are the subject of your Reconsideration Petition.11

D. Existence of Other Negative Monographs Does Not Necessitate a Negative

Monograph for Marijuana and THC

You state that FDA has issued negative monographs for other active ingredients that you assert
are less dangerous than marijuana, and you question why FDA has issued negative monographs
for such active ingredients, but not for marijuana (see Reconsideration Petition at 3, 24).

While we appreciate the public health concerns that you list in your Reconsideration Petition, the
Agency's previous decisions to promulgate negative monographs for certain therapeutic
categories and active ingredients do not persuade us to also promulgate a negative monograph
for marijuana and THC. First, negative monographs are not intended to provide a
comprehensive list of all classes of OTC products, active ingredients, and conditions of use that
cannot be marketed without FDA approval. Second, negative monographs are not intended to
provide a scale from which to judge potential public health risks, by comparing therapeutic
categories and active ingredients included in the negative monographs against those which are
not included in the negative monographs. That the Agency has established negative monographs
for certain therapeutic categories and active ingredients does not necessarily rnean that
therapeutic categories and active ingredients that are not included in negative monographs pose
cornparatively more or less serious potential risks to the public health. Third, the Agency's prior
decisions to issue negative monographs for certain therapeutic categories and active ingredients
are generally the result of a nurnber of factors, including historical factors related to the
development of the OTC Drug Review.I2 Accordingly, the Agency's prior decisions to issue

I I While we are denying your negative monograph request, FDA acknowledges that risk communication remains a
critical component of FDA's mission to protect and promote the public health. See, e.g., FDA Press Release,
Statement from FDA Commissioner Scott Gottlieb, MD., on new steps to advance agency's continued evaluation of
potential regulatory pathways for cannabis-containing and cannabis-derived products (April 2, 2019) (noting that
selling products with unsubstantiated claims can put patients and consumers at risk), available at
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm635048.htrn; FDA Press Release, Statement
by FDA Commissioner Scott Gottlieb, MD., on the importance of conducting proper research to prove safe and
effective medical uses for the active chemicals in marijuana and its components (June 25, 2018) (noting that
promotion and use of unapproved products rnay keep some patients from accessing appropriate, recognized
therapies to treat serious and even fatal diseases), available at
https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611047.htm; FDA Press Release, FDA
approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy
(June 25, 2018) (noting that marketing unapproved products, with uncertain dosages and formulations can keep
patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases), available at
https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm611046.htm; FDA Regulation of Cannabis
and Cannabis-Derived Products: Questions and Answers (warning that it is important to protect children from
accidental ingestion of marijuana and products containing marijuana), available at
https://wwwfda.gov/newsevents/publichealthfocus/ucm421168.htm.
12In 1972, FDA established the OTC Drug Review to evaluate the safety and effectiveness of OTC drug products
that were on the US market. Under the OTC Drug Review, FDA evaluated active ingredients under certain
conditions of use (such as dose, dosage form, route of administration, and indication) and determined whether they
were generally recognized as safe and effective (GRASE) for their intended OTC uses. FDA published regulations

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Docket No. FDA-2017-P-6692

negative rnonographs for certain therapeutic categories and conditions do not persuade us to also
promulgate a negative monograph for marijuana and THC.

E. The Agency Has Adequately Considered Information and Views Contained

in the Administrative Record

FDA regulations at 21 CFR 10.33(d) provide that the Commissioner will grant a petition for
reconsideration if the Commissioner deterrnines that four factors apply (see Part I.B, supra). We
conclude that the Reconsideration Petition does not meet at least one factor under § 10.33(d), as
the relevant information and views in the administrative record were adequately considered when
we denied the Original Petition. Therefore, we need not address whether the other criteria in §
10.33(d) apply to the Reconsideration Petition.

III. CONCLUSION

While we appreciate the safety and public health concerns that motivate your requests, the
Reconsideration Petition does not persuade us to modify or overrule the Original Petition
Response. We have not found that granting the Reconsideration Petition would be in the public
interest or in the interest of justice. Additionally, the relevant information and views in the
administrative record were adequately considered when we denied the Original Petition. The
Reconsideration Petition fails to meet the standards for granting a petition for reconsideration as
set forth in § 10.33(d). Therefore, your Reconsideration Petition is denied.

Sincerely,

Lowell J. Schiller
Principal Associate Commissioner for Policy

to establish OTC monographs for these GRASE conditions. As part of the OTC Drug Review, FDA finalized a
number of negative monographs that list therapeutic categories andJor active ingredients intended for certain
indications that are not generally recognized as safe and effective for OTC use and may not be marketed without
FDA approval. However, neither marijuana nor THC has been considered for inclusion in the OTC Drug Review.