Cannabis Products – Regulatory Frameworks in US and EU
The purpose of this blog is to provide initial info about certain regulatory pathway options, or the lack of these, for products containing cannabis or for cannabis derived compounds in the United States and European Union.
The reader should bear in mind that every product is specific in nature and therefore each manufacturer is encouraged to seek practical advice for the product in each instance from a regulatory expert.
Cannabis or Cannabis-derived Compounds in FDA (US)
Currently, FDA 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. FDA treat products containing cannabis or cannabis-derived compounds as any other FDA-regulated products — meaning they’re subject to the same authorities and requirements as FDA-regulated products containing any other substance. This is true regardless of the source of the substance, including whether the substance is derived from a plant that is classified as hemp under the newly accepted Agriculture Improvement Act.
The FDA recently expressed its concern at the number of drug claims being made about products which had not gained approval from the Agency which claimed to contain CBD or other cannabis-derived compounds. Among other things, the FDA requires a cannabis product (hemp-derived or otherwise) that is marketed with a claim of therapeutic benefit, or any other claim for treatment of illness, to be approved by the FDA for its intended use before it may be introduced into interstate commerce. Cannabis and cannabis-derived products which claim in their marketing and promotional materials that they’re intended for use in the diagnosis, cure, mitigation, treatment or prevention of diseases are considered to be new drugs and must go through the FDA drug approval process for human (or animal use) before they are marketed in the U.S.
“Selling unapproved products with unsubstantiated therapeutic claims”, FDA says – “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 raises significant public health concerns, as it may keep some patients from accessing appropriate, recognized therapies to treat serious and even fatal diseases”.
Dietary Supplements & Cannabis and Cannabis-derived Compounds
The FDA has decisively declared that it is unlawful under the FD&C Act to introduce food containing added CBD or THC into interstate commerce, or to market CBD or THC products as, or in, dietary supplements, regardless of whether the substances are hemp-derived.
This is because both CBD and THC are active ingredients in FDA-approved drugs and were the subject of substantial clinical investigations before they were marketed as foods or dietary supplements. Under the FD&C Act, it’s illegal to introduce drug ingredients such as these into the food supply chain or to market them as dietary supplements. This is a requirement that is applied across the board to food products containing substances that are active ingredients in any drug.
The FDA has, in the past, issued warning letters to companies who illegally sold CBD products that claimed to prevent, diagnose, treat or cure serious diseases. Some of these products were in further violation of the FD&C Act because they were marketed as dietary supplements or because they involved the addition of CBD to food.
https://www.fda.gov/NewsEvents/PublicHealthFocus/ucm484109.htm
This having been said, FDA late Commissioner Gottlieb has stated that the FDA is “aware of the growing public interest in cannabis and cannabis-derived products.” The FDA plans to hold a public meeting soon to seek input as to how to legalize the marketing of cannabis-derived compounds and to make sure the laws are more predictable and efficient.
Medical Devices – Could They Contain CBD or THC?
According to FDA definition, device is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is: recognized in the official National Formulary, or the United States Pharmacopoeia, or any supplement to them:
- intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or
- intended to affect the structure or any function of the body of man or other animals, and which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and
- which does not achieve its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of its primary intended purposes.
Could, for example, CBD mouthwash be regulated as a medical device?
Hypothetically, CBD mouthwash would first have to demonstrate that it is compliant with the definition of a medical device and that its primary intended use (action) does not involve metabolic or chemical activity, such as to act as a mechanical barrier to adhesion of bacteria to teeth/oral mucosa.
In addition, the company would have to provide evidence that the CBD ingredient is included in the product only to support the function of the medical device which represents a significant challenge, specifically when the FDA refers to CBD as a medical substance. This hurdle would probably be easier to overcome if the CBD is extracted from hemp and there is no THC at all.
To my knowledge, there are no medical device products containing CBD (or THC) and therefore a pre-submission meeting with CDRH is recommended.
OTC Monographed Drug
CBD and THC are not included in any OTC monograph and therefore this regulatory pathway is not available for products which contain CBD or THC.
Does Cannabis Have Homeopathic Status?
In order to be regulated as a homeopathic product, the active substances included in the formulation have to be listed in US or another official pharmacopeia.
Cannabis sativa, although previously included in pharmacopeia, was excluded from this compilation in the 1940s and therefore this pathway is not viable for the products containing CBD or THC.
Cosmetic product
Under the FD&C Act, cosmetic products and ingredients, with the exception of color additives, do not require FDA approval before they go on the market. FDA does not approve cosmetic products but it does however regulate them. Today, an increasing number of cosmetics companies are adding CBD to their products.
FDA defines cosmetic by their intended use, as “articles intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body…for cleansing, beautifying, promoting attractiveness, or altering the appearance” [FD&C Act, sec. 201(i)].
Among the products included in this definition are skin moisturizers, perfumes, lipsticks, fingernail polishes, eye and facial makeup preparations, cleansing shampoos, permanent waves, hair colors, and deodorants, as well as any substance intended for use as a component of a cosmetic product.
Cosmetics products have to be manufactured in compliance with Cosmetic GMP.
In addition, the FD&C Act prohibits the marketing of adulterated or misbranded cosmetics in interstate commerce.
“Adulteration” refers to violations involving product composition – whether they result from ingredients, contaminants, processing, packaging, or shipping and handling. Under the FD&C Act, a cosmetic is adulterated if:
- “it bears or contains any poisonous or deleterious substance which may render it injurious to users under the conditions of use prescribed in the labeling thereof, or under conditions of use as are customary and usual”
- “it consists in whole or in part of any filthy, putrid, or decomposed substance”;
- “it has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth, or whereby it may have been rendered injurious to health”;
- “its container is composed, in whole or in part, of any poisonous or deleterious substance which may render the contents injurious to health”
“Misbranding” refers to violations involving improperly labeled or deceptively packaged products. Under the FD&C Act, a cosmetic is misbranded if:
- “its labeling is false or misleading in any particular”;
- its label does not include all required information and the required information is not adequately prominent and conspicuous;
- “its container is so made, formed, or filled as to be misleading”;
- “its packaging or labeling is in violation of an applicable regulation issued pursuant to section 3 or 4 of the Poison Prevention Packaging Act of 1970.”
Under the FD&C Act, a product also may be misbranded due to failure to provide material facts. This means, for example, any directions for safe use and warning statements needed to ensure a product’s safe use.
Medical Cannabis in the United States
In the US, each state has its own list of approved medical conditions.
More information about qualifying conditions by state is available using the following link:
https://www.leafly.com/news/health/qualifying-conditions-for-medical-marijuana-by-state
Currently, there are 10 states in America where marijuana is legalized both medically (legalized medicinal marijuana) and recreationally. This does not include Washington D.C., which also has full legalization. The 10 states where cannabis is legalized are: Alaska, California, Colorado, Maine, Massachusetts, Michigan, Nevada, Oregon, Vermont and Washington.
In addition, in 2018, Indiana passed a law that made it legal to manufacture, sell in retail, possess and use CBD oil provided it had no more than 0.3% THC content in it. This was a major expansion of the legality of CBD, no longer requiring Indiana citizens to be on a patient registry to buy CBD oil.
Likewise, in 2018, Kansas passed a law that exempted CBD products from the state’s criminal code regarding marijuana. This allows for adults to legally purchase and possess CBD products as long as they contain 0% THC.
Hemp Farming Act and Farm Bill
This Hemp Farming Act was a proposed law to remove hemp from Schedule I controlled substances and making it an ordinary agricultural commodity. Its provisions were incorporated in the 2018 United States Farm Bill that became law on December 20, 2018.
The Farm Bill removes “hemp” from the Controlled Substances Act (“CSA”) definition of “marijuana,” and expressly excludes THC in “hemp” from scheduling under the CSA. Consistent with the definition of “industrial hemp” under the Agricultural Act of 2014, the Farm Bill defines “hemp” as “the plant Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol [“THC”] concentration of not more than 0.3 percent on a dry weight basis.”
Consequently, any Cannabis plant and plant part with a THC concentration of 0.3 percent or less is no longer a controlled substance, and any product derived from the plant or parts of the plant is also not controlled. By the same token, a Cannabis plant and any part of a Cannabis plant that contains a THC concentration above 0.3 percent on a dry weight basis is not “hemp,” and remains a schedule I controlled substance unless otherwise excluded from the CSA definition of marijuana.
THC not “in hemp” also remains controlled under the CSA as a schedule I controlled substance. Hemp, like marijuana, derives from the Cannabis sativa plant. Unlike marijuana, hemp lacks significant THC, the cannabinoid that produces psychoactive effects in humans. And unlike marijuana, hemp is an agricultural commodity used in the production of a wide array of products including paper, rope, clothing, personal care products like lotions and shampoos, industrial solvents, and even conventional foods and dietary supplements. By removing hemp and THC in hemp from control, the Farm Bill fosters hemp manufacturing and commerce.
Turning specifically to CBD, the effect of the Farm Bill is that CBD and other cannabinoids derived from hemp are not controlled. CBD derived from a Cannabis plant or part of Cannabis plant that is not hemp, remains a schedule I controlled substance under the CSA unless it is excluded from the definition of marijuana.
Therefore, the enactment of the Farm Bill obviously eliminates a major obstacle for production and marketing of hemp and its derivatives (including CBD).
Cannabis or Cannabis-derived Compounds in European Union
Medical Products in the EU
One important distinction between different forms of cannabis preparations and cannabinoids for medical use is between those that have marketing authorisation for the medical use of cannabis and those that do not. Having a marketing authorisation means that an application for a medical product was submitted to a regulatory authority and, after evaluating the application, the regulatory authority granted such authorisation. This usually implies that the product underwent extensive clinical trials and that the drug has been thoroughly tested for safety, effectiveness and side effects.
Regulatory authorities also consider whether the product can be manufactured to a required level of quality. In this post, we use ‘Medical product’ to refer to the (plant-derived and synthetic) cannabinoid-containing products with marketing authorisation.
Medicines can be authorised in the European Union by one of three routes.
- The first is a centralised procedure under the responsibility of the European Medicines Agency (EMA) that allows a single EU-wide authorisation for marketing of a pharmaceutical drug. The use of the centralised authorisation procedure is compulsory for most innovative medicines, including biotechnology-derived Medical products, advanced therapy Medical products, medicines with a new active substance indicated for major therapeutic areas (AIDS, cancer, neurodegenerative disorders, diabetes, autoimmune diseases and other immune dysfunctions, and viral diseases) and medicines for rare diseases (orphan Medical products).
- The second is a decentralised procedure in which companies can apply for simultaneous authorisation of a medicine in more than one EU Member State. This applies if the medicine has not yet been authorised in any EU country and does not fall within the scope of the centralised procedure.
- The third is a mutual recognition route in which companies that have a medicine authorised in one EU Member State can apply for this authorisation to be recognised by other EU countries.
The approved Medical products that have followed the pharmaceutical regulatory path are very few and include Cesamet, Marinol, Sativex and Epidiolex.
Cannabis Preparations in EU
The general term ‘cannabis preparations’ refers to items derived from the Cannabis sativa plant that do not have a marketing authorisation for medical use. These may include the raw cannabis, such as the flowering tops, compressed resin or hash; oils extracted from the plant; concentrated cannabis extracts; and other cannabis preparations, such as soft gels, tinctures or edibles. Examples of standardized cannabis preparations include preparations of cannabis flowers, such as Bedrocan; granulates, such as Bediol; and oil extracts, such as Tilray 10:10 Balance.
https://bedrocan.com/products-services/healthcare/prescribing-cannabis/
Cannabis preparations can vary greatly in composition, depending, for example, on the strain of cannabis, the growing conditions and how the preparations are stored.
For example, Bedrocan’ products are produced under GMP conditions (according to EU standards for the manufacturers of active substance).
Today in Europe, access to cannabis preparations, including magistral preparations, where allowed, appears to be provided primarily through compassionate or exceptional use programmes (HPRA, 2017). In countries where access to cannabis preparations is given in this way, it is usually granted for the treatment of a narrow range of medical conditions.
The overview of the current evidence for the medical use of cannabis and cannabinoids as well as highlighting the limitations of and important gaps in the evidence is presented in the table:
Cannabis as a Herbal Medicine in EU
Most pharmaceutical regulatory systems allow the use of herbal medicines that do not meet the same requirements as those for pharmaceutical medicines (Ekor, 2014; WHO, 2015). For example, manufacturers of traditional herbal medicines with well-established uses are not usually required to provide evidence of efficacy and safety from clinical trials. Instead, they are required only to show evidence of product quality and consistency to ensure that consumers receive standardized doses of herbal products that are free from contaminants and adulterants.
As for today, it would be very hard to regulate cannabis products as a traditional herbal medicine in the European Union while it remains a drug under international control or while the national legislation in many countries classifies cannabis as a drug that has no medical uses. Major challenges in regulating cannabis products as herbal medicines would remain even if these obstacles were removed.
These would include characterizing and standardizing the cannabinoid and other chemical constituents of herbal cannabis, assessing their stability in stored medicines, and ensuring that herbal cannabis products were free of contamination by microbes (e.g. fungi and molds), heavy metals and pesticides.
Low-THC Products and Cannabis Products Associated With Health And Well-Being in EU
In the past few years a range of items derived from cannabis (herbs, hemp, oils) have been offered for open sale in shops in several EU countries based on the claim that they have little or no psychoactive effect because they contain less than the legal minimum level of THC and therefore are not controlled under drug laws. These and other products may claim to be high in CBD, which is not controlled under drug laws in most countries (e.g. in Finland it is classed as a Medical product).
They are sometimes referred to as ‘cannabis light’ products. Many of these, sometimes claiming to be high in CBD, are purported to be good for ‘health and well-being’. Any claims that they prevent or treat disease, or relieve symptoms, would bring these products under medicines law, which requires a product authorization for sale. The marketing of these products therefore often contains non-specific words or phrases, such as ‘health and well-being’, ‘wellness’, ‘nutraceuticals’, etc.
EU countries differ in their response towards low-THC products. Some countries state that a product containing less than 0.3% or 0.2% THC is not controlled under drug laws (for e.g., see also legal summary in Germany: https://canna-biz.legal/legal-admissibility-of-cbd-products-in-germany-may-2018/).
For others, an unlicensed product must not contain any THC at all. But these quantitative limits may also come with conditions, such as ‘originating from an authorised variety of cannabis’, ‘if not viable for narcotic purposes’, ‘if not misused’.
In addition, countries have developed different responses towards products containing CBD. Although there seems to be few quantitative limits to CBD, there are many more conditions. The legality of marketing the product may depend on the source of the CBD, it may depend on the format of the product and also on how the product is presented.
In most countries, legislators are expected to provide more clarity with regards to the legal concentrations and the conditions which are required to be met.
It is clear that each EU country has its own specific approach to cannabis-based products which is dynamically evolving.
Therefore, it is recommended that a company discusses the specific conditions in each case for the approval and/or marketing of a product containing CBD/THC with the national regulatory authority.
BioReg can assist you with any questions you may have related to cannabis-based products.
BioRegards,
Daniel
+972-(0)54-6896-868
