Via Federal Register Filing; US Mail

Dockets Management Staff (HFA-305) Food and Drug Administration 5630 Fishers Lane, Rm. 1061 Rockville, MD 20852

HOBAN LAW GROUP

July 16, 2019

GAARETT GIW'f, MAN!.Glf.lG ATTORNEY

303-674-7000 C fFICf

GARRnT@ HC BAN.lAW

1781 JUL 23 '19 P112:31

RE: Docket No. FDA-2019-N-1482 - Scientific Data and Information about Products Containing Cannabis or Cannabis-Derived Compounds; Public Hearing; Request for Comments

Dear Dockets Management Staff:

This firm represents a number of individuals and business engaged in industries regarding Cannabis-related substances, including those derived from "hemp" subject to the Agriculture Improvement Act of 2018 and Section 7606 of the Agricultural Act of 2014 (collectively, the "Fann Bill"), and those derived from "marihuana" pursuant to state-regulated schemes only. In fact, our finn has been deeply embedded for several years in the issues before the FDA now, including working with other sister agencies to U.S. Food and Drug Administration ("FDA") at the federal level, many state and local agencies across the country, as well as stakeholders internationally across many different countries.

This letter is in response to Docket No. FDA-2019-N-1482: Scientific Data and Information about Products Containing Cannabis or Cannabis-Derived Compounds; Public Hearing; Request for Comments (the "Notice"). 1 For purposes hereof, we primarily focus on and discuss products which contain one or more cannabinoid derivatives of hemp (the "Products").

The letter is in supplement to this firm's prior letter, dated May 10, 2019, and subsequent presentation before the FDA on May 31, 2019.

Based on our firm's extensive experience in representing clients in the subject industry, working collaboratively with stakeholders across various industries impacted by the Products, and policy initiatives in establishing federal, state and local regulations concerning the same, this firm hereby submits the following supplemental commentary:

1 See 84 Fed. Reg. 12,969 - 12,975 .

DENVER OFFICE

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Executive Summary

The hemp industry, and more specifically the manufacture of - and interest in and access to - Products containing cannabinoids such as CBD, is exploding across the United States and throughout the world. Understandably, this nascent industry raises certain regulatory considerations of appropriate regulation as the industry and FDA, along with other stakeholders, strike an appropriate regulatory balance. As a result, there is an immediate need for FDA to act and establish the applicability of existing FDA regulations to the manufacture and distribution of the Products, even if only to serve as a starting point to build from.

There is mutual desire from both FDA and the industry in establishing such sensible regulations to ensure uniform regulations for manufacturing, testing and distribution of the Products, to contemplate specific issues such as mislabeling, GMP manufacturing practices and reconciliation of inconsistent regulation across the states and with the FDA. In doing so, there are several important takeaways for FDA' s consideration:

I . FDA should encourage scientific research to gather additional information to better tailor regulations accordingly;

2. FDA does not have to create a completely new regulatory system for the Products ; rather, current FDA regulations, including Good Manufacturing Practices ("GMP") certification, testing, and agency registration, ensure product quality and consumer safety provide sufficient assurances of consumer safety, akin to many other similarly situated agricultural commodities and finished consumer goods;

3. As with any product type, FDA maintains protocols in the event of product contamination or failure of other certain protocols; and

4. FDA's current packaging and labeling requirements provide ample opportunity to inform the consumer of the Product and its contents.

As noted throughout this comment, it is crucial for regulators, the industry, and consumers to be provided with additional scientific data and information to better inform policy and decision making. Ultimately, all stakeholders - FDA itself, its state and local counterparts, the hemp industry and consumers - are seeking regulatory certainty by which manufacturers and other stakeholders may adhere to. Accordingly, both the obligation and opportunity rests with FDA to act in imminently provide such guidance, reconciled to the Fann Bill and forthcoming United States Department of Agriculture ("USDA") regulations in August 2019.

1. Manufacturing and Product Quality:

Products available for purchase, regardless of its form, are subject to regulatory oversight, with few, if any, exceptions. Foods, cosmetics, and drugs commonly available in the marketplace are subject to FDA regulations which ensure product quality and safety. Without regulatory oversight and established standards, however, consumers are not extended adequate protections to ensure that the Products that they have purchased, and potentially consumed, were manufactured

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and stored in the proper conditions and Product quality. In the absence ofregulations, consumers will grow skeptical of products and feel uncertain about the Product's quality.

Notably, many Product manufacturers have already extended and implemented Product quality protocols to provide consumers with a pure, safe Product - protocols such as adherence to GMP; use of self-regulatory organization certifications; and compliance with state laws which generally mirror FDA regulation through uniform code. Without a doubt, clear and practical federal regulations will fill the regulatory vacancy and provide the necessary regulations to ensure that the Products are safe for consumer protection and promote Product quality.

Importantly, there is very little which could be construed as peculiar or unique about the Products that require special attention or for the FDA to craft a completely new set of standards. Instead, FDA's existing regulatory framework should govern these Products as such regulations apply to foods, cosmetics, and dietary supplements among other product types. Specifically, the FDA framework for these categories of products provide a structured blueprint to apply to the Products. Industry stakeholders, particularly those with knowledge of and experience in the manufacturing process, have furnished the FDA with extensive data and any available information to assist the FDA in promulgating the regulations that will apply to the Products' production. Importantly, the applicable standard that will govern the manufacturing of the Products will determine the degree of scrutiny the Product will receive. Additionally, as with other finished goods, the intended use of the Products determine the applicable GMP and labeling standards that manufacturers must adhere to in order to sell the Products. Further, current FDA regulations also require manufacturers to register with the FDA and the appropriate state and local agencies prior to selling any Product.

GMP Requirements

GMP standards not only provide guidance for manufacturers throughout the entire production process, GMP also reassures consumers that the subject Product was manufactured with safety and quality in mind. Beneficially, as with any other GMP-compliant good, Products that are subjected to GMP standards certify that the manufacturing, processing and storage of the Products were done so under the sufficient production standards that ensure product quality, reproductivity, purity, safety, and sanitation. Importantly, not only does GMP standards assist consumers, GMP certifications will also support the industry and elevate the CBD market to become a well-regulated and reliable industry.

To ensure product quality, GMP standards must be employed throughout the supply chain, including through the manufacturing, processing and storage processes. An important component of GMP are Standard Operating Procedures ("SOP"). SOP detail each step of the production process and guide manufacturers through tasks, such as cultivation, extraction, filling, packaging, and storage. So long as manufacturers and employees involved in production are following the SOP, the frequency and likelihood of error are both reduced. Beneficially, SOP also promote Product consistency and ensure that each batch and individual Product is consistent with Products that were produced in the past and in the future. Importantly, the effectiveness of SOP are correlated to the rate of manufacturers' adherence to such SOP. Additionally, the success of SOP are also dependent on manufacturers thoroughly training, as well as encouraging and maintaining

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employee knowledge and training. SOP also encourage recordkeeping and internal reflection. GMP-certified manufacturers are expected to maintain documents and track the production process by following SOP and documenting progress. Importantly, ifthere are any mistakes or errors made at any point of the production process, regardless of magnitude, the error must be reported to the appropriate agents and properly documented. Further, GMP certification reassures consumers that the Product was produced and stored in a clean facility. In particular, GMP standards ensure that the Product was manufactured and stored in a clean facility that utilizes appropriate equipment throughout the process. GMP requires that all equipment used in production must be well maintained.

Given the high standards and effectiveness of GMP, Product manufacturers will have to invest in capital to pursue GMP certification, in promoting product quality and ensuring consumer safety. Many of the FDA's concerns relating to the Products can be curtailed if manufacturers consistently employ GMP. which promotes consistency, transparency, and quality.

Testing Requirements

Fortunately, the Products are subject to a second layer of quality assurance: Product testing. Testing provides a view into the Product and informs manufacturers and consumers of the Product's potency, purity, and safety. Frequently, consumers rely on specific testing results to assist them in making an informed decision as do regulators and law enforcement, such as those who have interfered with permissible interstate transport of hemp materials due to confusion over testing standards. Some states, however, have set testing standards and Products must meet the testing standards prior to entering the market. To reconcile these varying standards and to promote transparency, the FDA should establish uniform testing standards to guide the industry, reduce costs and inconsistencies, and better support the Farm Bill's intent to allow for interstate transport.

Testing has evolved into a reliable method to establish the contents of a Product. Importantly, in conjunction with many renowned and ISO-certified testing facilities , the hemp industry currently tests for a number of Product characteristics, including potency, purity, and contaminants. As with manufacturing processes, existing FDA testing standards - and without any hemp-specific federal regulations governing Product testing - provide a framework to be applied to the Products to promote industry accountability and consumer education.

There are a number of testing methods labs employ when testing the Products. Of available testing methods, two commonly used testing methods are gas chromatography ("GC") and high­pressure liquid chromatography ("HPLC"). The two test samples differently, but provide accurate results, when conducted correctly, of the cannabinoid content in samples.2 In particular, "HPLC analyzes cannabinoids in the chemical form in which they are actually present in the sample. "3 At this time, the sample contains the pre-decarboxylated cannabinoids, THC- acid ("THCA") and CBD-acid ("CBDA").4 When decarboxylated, CBDA and THCA converts into the "active form" of both cannabinoids: THC, the psychoactive cannabinoid, and non-psychoactive CBD. 5

2 Dale Gieringer, Arno Hazekamp, How Accurate is Potency Testing?, O'Shaughnessy's, 17, 17-18 (2011). 3 Id. 4 Id. Sfd.

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Alternatively, "when samples are analyzed by using GC, the high temperature of the injector causes the cannabinoids in the sample to instantly decarboxylate, converting all THCA into THC before the sample enters the chromatographic column. Therefore, labs using GC have only a single corresponding entry, 'THC Total' ... [and] 'CBD Total."'6 Importantly, the USDA is expected to implement interim final regulations in early August 2019, which may address testing methodologies as to raw hemp material. FDA should ensure its regulations reconcile appropriately with any USDA commentary concerning the use of HPLC and/or GC testing methodologies, decarboxylation and the use of "total THC" data. ·

Importantly, labs test for more than just potency. Pursuant to some states' regulations, manufacturers must also send samples to testing labs to also test for contaminants, such as mycotoxins, pesticides, and solvent residual. Solvents - popularly water, CO2 and ethanol - are used in extraction. Specifically, the solvents assist extractors to extract desired cannabinoids from the plant material. The extracted cannabinoids are then processed into an extract that can be consumed or infused into other products. The extraction processes that manufacturers utilize should not be alarming as there are many traditional products that also use solvents to extract. Most kitchens throughout the United States have a variety of spices and other ingredients that we feel safe cooking with and consuming such as vanilla extract. To make vanilla extract, extractors soak pieces of vanilla bean pods in either ethanol or water to extract. Following extraction and processing, the vanilla extract is bottled and sent to grocery stores for purchase. From there, extractors process the extracted vanilla but, vanilla extract is not tested to detem1ine the residual , if any trace at all, the solvents left behind.

Deficiencies in Testing; Recalls

As with any type of testing and analysis, there is the inherent possibility of error, whether human or not. Any error that is made at any particular point throughout the testing process that could influence the testing results, no matter how minimal. In an effort to limit the frequency of error, use of ISO certification, which provides standardization of testing procedures, could decrease the potential for error, thus ensuring accuracy and reliability. Importantly, it should be considered that the sampling protocol itself could skew results. For example, a homogenized oil is likely to produce more accurate results of the entire batch as compared to testing different parts of the Cannabis plant. Particularly, a single flowered bud from a flowered hemp plant will have a higher CBD-content than the stem. To ensure accurate testing, in conjunction with anticipated USDA regulations, there should be guidance and standardization as to sampling protocols to ensure accurate testing. Additionally, poor storage and delay in testing can also influence results . In particular, if the samples are not properly stored in a cool dry place or if the sample is not tested within a window of time after taking the sample, the cannabinoids will degrade. 7 The degradation of the cannabinoids will alter testing results and produce inaccurate results. However, it should be noted that "the cannabinoid CBN is a main indicator of sample degradation. "8 If results indicate increased levels of CBN, then it is likely that sample had degraded and is no longer representative of the cannabinoid content in the Product.

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Although the manufacturing and processing methods between hemp and other agricultural commodities are polarizing because of legislation, biologically, hemp can be compared to other agricultural products like carrots, lettuce and spinach. Each of these commodities are grown, cultivated and, if necessary, processed into its final form before reaching the consumer. As with any and all available products, there is the lingering possibility of contamination. In response, the FDA has crafted and enforced effective regulations to promptly respond to contamination. Enforcement of the recall process and other protective measures - by FDA along with its state and local counterparts - provide ample protection in the instance that any Product is contaminated. Current FDA protocols ensure public safety and product integrity by notifying the public of the contamination and promptly removing the contaminated product from stores and other purchase outlets. Additionally, these protections increase consumer awareness and encourage consumers to discard and not consume the contaminated Product.

Label Conformance

Working with test results, label conformance is an important area that should be considered. Throughout the growth of the market for Products, the market has expanded to include a spectrum of manufacturers. Some manufacturers have been diligent and have implemented FDA­compliant production methods while others may not meet FDA standards and have polluted the market with inaccurate and unsafe Products, including mislabeled Products and unsafe additives.9

At the hearing, some presenters presented findings to FDA indicating some manufacturers misrepresented the contents within certain Products. To be clear, the evidence provided supports the premise that FDA, and its state and local counterparts, need to ensure its level of enforcement is sufficient to discourage manufacturers making such (mis)representations, not that new, additional and/or superfluous regulation is necessary. In fact, the large majority of the hemp industry supports sensible regulation by FDA akin to other similar product types.

The role of labeling is explored further below, but it is worth noting here the importance of label conformance. Labels are the first layer of information provided to consumers by manufacturers and represent the content contained in the product. When determining what Product to buy, consumers rely on the Product's labels. Interestingly, an independent study revealed staggering, and concerning, statistics "that the CBD content in almost 70% of CBD-labeled products available online may be mislabeled." 1° Further, a separate study found that "43% of products were underlabeled and 26% were overlabeled for actual CBD content. More than 20% contained detectable levels of THC." 11 Notably, both of the studies did not include hemp, but marijuana, which explains the presence of THC. Within the hemp industry, several states implemented regulations which require the use of QR codes, or other similar devices, to make available test results at the point of sale, as an indication of the industry's commitment to transparency with consumers and regulators.

9 Justin L. Poklis, Haley A. Mulder, Michelle R. Peace, The unexpected identification of the cannabimimetic, 5F­ADB, and dextromethorphan in commercially available cannabidiol e-liquids, 294, Forensic Science International , e25, e25-e27 (2018) . 10 Jamie Corroon, Joy A. Phillips, A Cross-Sectional Study ofCannabidiol Users, 3.1, Cannabis and Cannabinoid Research, 152, 159 (2018). 11 Marcel 0. Bonn-Miller, Mallory J.E. Loflin, Brian F. Thomas, Jahan P Marcu , Travis Hyke and Ryan Vandrey, Labeling Accuracy of Cannabidiol Extracts Sold Online, 318, JAMA, 1707, 1707-1709 (2017).

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Nomenclature

In an effort to promote uniformity within the industry, as well as amongst regulators and consumers, the FDA should adopt standardized definitions that will provide clear definitions for the different variations of ingredient forms. We offer the following definitions for consideration:

a. Full spectrum [ extract/oil]: meaning a full representative profile of the estimated 11 0+ cannabinoids, along with terpenes and other compounds, which naturally occur in hemp.

b. Broad spectrum [extract/oil]: meaning a broad representative profile of the estimated 110+ cannabinoids, along with terpenes and other compounds, which naturally occur in hemp, . but where one or more cannabinoids are nullified or removed ( for example, the rendering of tetrahydrocannabinol ("THC") to be non-detectable);

c. [Cannabidiol or another cannabinoid] isolate: meaning a 98% pure, isolate form of the subject compound;

d. Hempseed oil: meaning those ingredients derived from hempseeds, such as those recently affirmed by GRAS by FDA (as submitted by Manitoba Harvest).

Although the industry understands the different variations of the ingredient types, there is still the possibility of confusion or misunderstanding because the tenns may vary slightly from person to person. However, the FDA can address the confusion by adopting standardized language.

The FDA's concerns can be addressed and solved by implementing existing FDA standards. As noted above, the current FDA standards provide manufacturers with encompassing regulations to ensure Product quality and safety. There is no need for the FDA to create a completely new regulatory scheme for Products . Safeguards, including GMP registration and Product testing, encourage transparent manufacturing and high-quality production.

2. Marketing/Labeling/Sales:

As previously mentioned, packaging and labeling are extremely important aspects of marketing and selling the Products. Reiterating previous themes, the FDA does not need to create a completely new framework to regulate packaging and labeling for the Products. Instead, the existing FDA packaging and labeling regulations for conventional products - foods, dietary supplements, and cosmetics - provide manufacturers ample opportunity to inform the consumer of associated risks that the consumer should be aware of. Product consumers should be furnished with a similar degree of warnings and disclaimers that are included on labels for traditional products. Importantly, the success of packaging and labeling requirements largely rests on the manufacturers to comply with FDA regulations. Currently, there are many manufacturers that already meet FDA standards. Additionally, when a manufacturer is not adhering to FDA regulations, the FDA has the authority to enforce the regulations, as well as additional consequences, to ensure compliance and consumer safety.

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Current FDA labeling regulations provide ample opportunity to inform the consumer of associated risks, as well as the safety and contents of the Product. Disclaimers and the necessary warnings are a product of research, however, at this time, as mentioned above, limited research has hindered the industry's, and regulators', knowledge of the Products. As a result of this failure to investigate Product safety, it is unclear at this time what exact warnings the labels should include. However, traditional disclaimers have advised consumers to consult with a physician prior to use generally, including warnings for women who are pregnant, attempting to become pregnant, or who are breastfeeding, for individuals who are using other medicines or have preexisting medical conditions, and children. As additional data becomes available, manufacturers have the ability to implement the necessary amendments to tailor the labels to display the new information. However, until data that supports the need for certain disclaimers has been collected, manufacturers should err on the side of caution, but also refrain from including too much information on the label that it makes it difficult to read.

At the public hearing, the FDA asked stakeholders about the considerations that should be included for vulnerable populations. At this time, manufacturers, out of caution, have included warnings for children, those with preexisting medical conditions or taking other medication, and women who are pregnant, attempting to become pregnant or breastfeeding. However, few states have established requirements to include specific warnings for vulnerable populations because there is currently little to no established data and research to indicate the need for additional disclaimers. As additional research supplies answers to these unresolved lines of inquiry, manufacturers will make the necessary adaptations to ensure safety and transparency.

To illustrate the success of thorough regulations, we can look towards successful state programs such as the programs in Colorado, Kentucky and Oregon. These states have embraced fruitful programs, though certainly there is always room for improvement, and have established encompassing rules that promote transparency and informed decision making. The FDA should look to states with successful hemp programs and should be should inspired by the prosperous programs in the states.

Importantly, these three states do not categorize the Products as different from other conventional products. Instead, these particular states have subjected the Products to many of the same requirements as conventional products. In Colorado, manufacturers producing these Products must obtain a food manufacturing registration. This registration subjects manufacturers of the Products to the same applicable GMP standards that applies to any other product - such as Pepsi - that is produced in the state. The underlying reasoning to require the same production standards as all other products is to ensure product quality by mirroring current FDA requirements. Importantly, Colorado also requires Product manufacturers to abide by GMP standards. Further, as an additional layer of protection, all Colorado-manufactured Products must be tested upon harvest and in the Product's finished form.

Current FDA labeling standards that govern foods, dietary supplements, cosmetics, and drugs provide extensive opportunity to inform the consumer about the contents and effects of the Product. However, the labeling requirements that will ultimately apply to the Products are contingent on in the intended use of each Product. Regardless of the intended use, the existing

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labeling requirements will provide satisfactory information to encourage the consumer to make an informed decision.

All labeling is subject to the Federal Food, Drug, and Cosmetic Act ("FD&C Act") and the Fair Packaging and Labeling Act ("FP&L Act"). These two pieces of legislation provide a strong framework to guide manufacturers to generate compliant labels, as well as offer adequate information to encourage informed decision making. To illustrate the effectiveness of the labels, we can look to the labeling requirements for cosmetics, dietary supplements, and foods.

The FP&L Act expressly requires that cosmetic manufacturers state the ingredients used in the Product and the net content weight of the Product's contents. 12 Manufacturers must place labels on both the inside, fixed directly to the Product, and the outside of packaging, 13 thus ensuring adequate opportunity for the consumer to read the labels. Importantly, manufacturers must list the ingredients used in the Product in descending order of content. Further, to promote uniformity, all ingredients must be listed as the same identifying names that the FDA has already been established.14 Additionally, labels must provide the manufacturer name and address, the name of the Product itself, and the particular use of the Product. If the cosmetic "may be hazardous to consumers when misused," then the manufacturer must include applicable warnings, as well as directions for safe use. 15 Also, if the cosmetic has not been tested for safety, which includes contaminant testing, then the label must state, "Warning - The safety of this product has not been determined." If a manufacturer fails to include such warning when necessary, the FDA can intervene and enforce the regulations. 16

Importantly, misbranded or adulterated Products are subject to FDA enforcement, as well as other consequences enforced by other agencies, whether it be federal, state or local. Specifically, "a cosmetic is considered adulterated if it contains a substance which may make the product harmful to consumers under customary conditions of use; if it contains a filthy, putrid, or decomposed substance; if it is manufactured or held under insanitary conditions whereby it may have become harmful to consumers." 17 As mentioned above, the FDA has already crafted successful response protocols, including recall and public notice, if a contaminated Product does reach the market and effective regulation of the Products warrants an appropriate response to recall unsafe Products.

Similarly, dietary supplement and food labels also provide ample opportunity to inform consumers of risks and contents. Specifically, labels for dietary supplements require: "l) the statement of identity (name of the dietary supplement), 2) the net quantity of contents statement (amount of the dietary supplement), 3) the nutrition labeling, 4) the ingredient list, and 5) the name and place of business of the manufacturer, packer, or distributor." 18 As with foods, the FDA requires that all food labeling requires a statement of identity, net quantity statement, and

12 21 CFR 701 ; 21 CFR 740. 13 Id. 14 21 CFR 701.3(a). 15 21 CFR 740. 16 21 CFR 740.10. 17 21 CFR 740. 18 21 CFR 101.

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information about nutrition and ingredients. 19 Regardless of the category, all labeling must be easy to read and the consumer should be able to comprehend what the label is trying to convey. To assist consumers, simple modifications, such as bullet points, spacing and defined sections, can be made to clearly display the information to the consumer.20

3. Health and Safety

Public health is a primary concern of the FDA and its counterpart regulators along with the hemp industry. At the public hearing, stakeholders professed their desire to comply with FDA regulations, but also promoted the industry's willingness to provide input and answers to the FDA's questions. The industry recognizes the importance of regulations and the successes of thoughtful regulations are evident in the quality of foods, drugs, and cosmetics production. The regulations we see today are a result of decades of research, analysis, discussion and amendment of the rules. Currently, there are many questions circling the Products, such as: 1) why are people deciding to use these Products; 2) how are consumers determining what dose to take; 3) are there additional concerns to be aware of, including drug interaction and consideration of vulnerable populations; and 4) what side effects are consumers experiencing? The answers to these questions, as well as other related questions, do not have concrete answers, however, through extensive research and clinical studies, answers can be provided to regulators, the industry, and consumers.

Currently, available research is limited and some pondered questions have yet to be explored. Fortunately, the limited data can be expanded and monitored to ensure unbiased, yet fruitful, results. Unfortunately, further research has been hindered by the extensive red tape and obstacles that the federal government has imposed, whether knowingly or negligently. For example, numerous research institutions and organizations have rejected opportunities to research hemp given unclear rhetoric expressed by various federal agencies and without clarity surrounding the need for threshold requirements such as an Investigational New Drug application ("IND"). Many stakeholders repeatedly expressed these concerns and requested FDA loosen the rigid boundaries that obscure access to conduct meaningful research. Still, of the data and information currently available, the potential of CBD and these Products remain positive and optimistic. Needless to say, as more research becomes available, as with any other products, FDA could address any evolving issues through regulatory changes while providing imminent guidance now.

Concerningly, a study found that "75.85% of respondents reported learning about CBD from internet research, family members or friends." 21 Although some of the information consumers are learning from their circle may be true, the likelihood of misinformed decisions is extremely troubling and warrants regulatory oversight to encourage informed decision-making. In an effort to better inform and protect consumers, the FDA should restrain and other regulatory agencies from deterring additional research, and instead, should encourage expansive research and clinical studies. Importantly, future research and clinical studies will generate additional questions that will further our understanding the Products and our approach to implement the most balanced regulations.

ig Id. 20 Id. 21 Id. at 156.

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The safety of CBD has been supported in a number of studies, including a 2011 study that evaluated the safety and side effects of CBD. The study specifically stated that "an impressive number of acute and chronic studies in humans," have shown that CBD is safe "for a wide array of side effects."22 Further, a separate study also concluded, after evaluating a number of other studies, CBD's "safety profile is already established in a plethora of ways."23 Research has shown that CBD offers a number of general wellness benefits and therapeutic uses, supporting a framework which offers access to CBD and other cannabinoids in a variety of product types, including conventional foods, supplements and cosmetics. A common theme seen throughout the available scientific research is that clinical research is required to determine the effects CBD has on the human body. However, the studies cannot fully establish conclusions because "more research is warranted."24

In addition to private studies, there are also a number of studies completed by universities and other institutions of higher learning, aided by state-established exceptions to allow for universities and colleges to investigate Cannabis for specified research purposes. In response, some universities established Cannabis research programs. Currently, as with all Cannabis research, there are limited university studies published which detail the effects of CBD on the human body, though some studies are complete as to animals, such as dogs and other studies remain pending.

Not only is the United States exploring the potential of Cannabis, the World Health Organization ("WHO") has also evaluated CBD and the cannabinoid's effects. In 2018, the Expert Committee on Drug Dependence ("ECDD") completed its review of CBD and published the committee's finding. The ECDD analyzed the safety of CBD and detennined that: (1) there are no reported adverse effects in humans, (2) there are no reports of or potential for dependence, (3) there are no reports of or potential for abuse, and ( 4) there are no public health problems, like driving under the influence, associated with the use of pure CBD.25 After publishing these findings, the WHO, supplied with the ECDD's advice, clarified that pure CBD is not to be treated as listed within the United Nations' International Drug Conventions.26 Throughout its analysis, the ECDD recognized that most of the current research surrounding Cannabis is limited, but of the available studies, much attention has been dedicated to studying the successes of CBD used to treat epilepsy.27 As the ECDD states, "[t]he clinical use of CBD is most advanced in the treatment of epilepsy;"28 however, in addition to epilepsy, the ECDD notes other potential benefits that CBD

22 Kerstin Iffland and Franjo Grotenhermen, An Update on Safety and Side Effects of Cannabidiol: A Review of Clincial Data and Relevant Animal Studies, 2, Cannabis Cannabinoid Res., 139, 145 (2017). 23 Id. at 152. 24 Deiana S, Watanabe A, Yamasaki Y, et al., Plasma and brain pharmacokinetic profile of Cannabidiol (CBD) , cannabidivarine (CBDV), Delta-9-tetrahydrocannabivarin (delta-9-THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive compulsive bahaviour, 219, Psychopharmacology, 859, 859-973, (2012). 25The Expert Committee on Drug Dependence, Cannabidiol (CBD) Critical Review Report, (2018) https://www.who.int/medicines/access/controlled-substances/CannabidiolCriticalReview.pdf 26 Alfredo Pascaul, World Health Organization recommends rescheduling cannabis, provides clarity on CBD, https://mjbizdaily.corn/world-health-organization-rescheduling-cannabis-clarity-cbd/ (last visited July 2, 2019). 27 The Expert Committee on Drug Dependence, Cannabidiol (CBD) Critical Review Report, 16, (2018) https://www.who.int/medicines/access/controlled-substances/CannabidiolCriticalReview.pdf 2& Id.

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might provide, such as, assisting patients accept transplants and to combat addiction, in particular, opioids.29 However, the ECDD noted the looming need for additional research.30

Among the other questions that require further inquiry are questions about dose, vulnerable populations, drug interactions, and side effects. As noted earlier, and as is corroborated throughout scientific publications, further research is needed in order to answer these particular questions. Currently, there is no established recommended dose that should be recommended to consumers. As stated at the public hearing, studies have suggested varying biological responses to the frequency of use and dosage amount and stakehoiders validated these results. Although manufacturers are listing providing suggested uses on Product labeling, consumers are often experimenting with dosage amounts to determine what works best for them. Importantly, for consumers, the benefits seem to outweigh the potential risks.

The scope of such research must be expanded and modified to accommodate for the precise questions regulators, manufacturers, and consumers are asking. In particular, the majority of the studies completed up to this point are extremely small in comparison to the consumer demographic. In order to evaluate the spectrum of potential risks and benefits, researchers must study the effects of CBD in large, diverse sample sizes that are representative of the consumers themselves. Additionally, many studies impose limitations on who can participate to individuals with only one medical condition and preclude participants that may have more than one medical condition. While the intentions are understood, this is not representative of the consumers and researchers should expand the studies to include individuais with multiple conditions to determine the potential effects of drug interactions and concerns that should be considered when administering CBD to those with preexisting medical conditions.

Of the current limited research suggests that CBD possesses benefits, however, established conclusions cannot be made yet. Red tape and federal intimidation has hindered CBD research up to this point. To expand the scope of CBD research, the FDA and other federal agencies should encourage thorough research to provide answers to the array of questions that have been presented. As further information and data becomes available, regulators can implement appropriate regulations, as well as make necessary amendments to accommodate for the update. Additionally, beyond general CBD research, researchers must conduct clinical studies to determine dose, drug interactions, considerations for vulnerable populations, and side effects. Further, modifications should be made to accommodate for participants that are representative of the consumer demographic. In particular, the clinical studies must be larger to accommodate a variety of types of bodies and participation should be expanded to include individuals with more than one medical condition. All in all, the future of CBD is optimistic and regulations are welcomed.

Conclusion

The hemp industry, and more specifically the manufacture of - and interest in and access to - Products containing cannabinoids such as CBD, is exploding across the United States and throughout the world. Understandably, this nascent industry raises certain regulatory considerations of appropriate regulation as the industry and FDA, along with other stakeholders,

29 Id. 30 Id. at 18.

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strike an appropriate regulatory balance. As a result, there is an immediate need for FDA to act and establish the applicability of existing FDA regulations to the manufacture and distribution of the Products, even if only to serve as a starting point to build from.

There is mutual desire from both FDA and the industry in establishing such sensible regulations to ensure uniform regulations for manufacturing, testing and distribution of the Products, to contemplate specific issues such as mislabeling, GMP manufacturing practices and reconciliation of inconsistent regulation across the states and with the FDA. In doing so, the FDA should encourage scientific research to gather additional information to better tailor regulations accordingly. Further, FDA does not have to create a completely new regulatory system for the Products; rather, current FDA regulations, including GMP certification, testing, and agency registration, ensure product quality and consumer safety provide sufficient assurances of consumer safety, akin to many other similarly situated agricultural commodities and finished consumer goods. And, as with any product type, FDA maintains protocols in the event of product contamination or failure of other certain protocols. Additionally, the current packaging and labeling requirements set forth in FDA regulations provide ample opportunity to inform the consumer of the Product and its contents. As noted throughout this comment, it is crucial for regulators, the industry, and consumers to be provided with additional scientific data and information to better inform policy and decision making. Ultimately, the industry is looking for regulations to efficiently guide manufacturers, as well as ensure product quality and consumer safety. Accordingly, both the obligation and opportunity rests with FDA to act in imminently provide guidance desired by FDA itself, its state and local counterparts, the hemp industry and consumers alike.

Thank you for your thoughtful consideration of the foregoing materials, in supplement to our May 10, 2019 letter and subsequent presentation before the FDA on May 31 , 2019. We also extend a standing offer to further discuss this issue to ensure that any policy considered and promulgated accurately reflects both the law and sensible policymaking regarding the Products as well as those derived from "marihuana" varieties of Cannabis. Please do not hesitate to contact my office with any questions. Thank you.

CC (via U.S. Mail; via email) : Beth F. Fritsch Food and Drug Administration 10903 New Hampshire Bldg. 32, Rm 5308 Silver Spring, MD 2099 3 Phone: 301-796-8451 Email: StakeholderEngagement@(da.lihs. go):'.

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