Preclinical Studies: Food Additives, Dietary Supplements or Natural Health Products. Where Does Cannabis Stand?

In addition to being developed as prescription medications, products such as turmeric and cannabis are also being developed as food additives, dietary supplements, and natural health products. The aim is to provide health benefits in products that are readily available to those interested in improving their health or treating certain conditions. The approval path, including the preclinical testing, needs to be considered in order to be able to make safety and efficacy claims.

Before testing any food additive, dietary supplement or natural health product intended for use in preventing or treating a disease in humans, researchers must investigate both the efficacy of the compound and whether it has the potential to be harmful, the same as it would apply to a prescription drug. Prior to initiating the human clinical studies, it is very important to understand that the goal of preclinical studies is to investigate if these products have a very safe profile that is acceptable by regulators when they are being used by a large population without medical supervision.

There are two types of preclinical studies: 1) in-vitro and 2) in-vivo that need to be completed such as pharmacokinetic studies, pharmacodynamic studies and toxicology studies. These studies must provide detailed information on dosing and toxicity levels. The amount of preclinical information recommended to support clinical studies with food additive or dietary supplements, or natural health products will depend on the extent of previous human use and the design of the proposed clinical studies. At least the following aspects should be considered in the design, conduct and interpretation of toxicology studies on food additives, dietary supplements, and natural health products.

• Preclinical studies must comply with the guidelines dictated by Good Laboratory Practice (GLP) and regulations such as the Food and Drug Administration (FDA) or European Food Safety Authority (EFSA) or Health Canada. Test methods described in OECD test guidelines (OECD TG) are also recommended. Use of any methods differing from guidelines should be justified.
• For a food additive, dietary supplements or natural health products that is currently marketed as a dietary supplement, initial clinical studies may be allowed to proceed without further preclinical studies, provided that the previous use is similar to the proposed use. Nevertheless, literature and other available information related to the safety of the product should be provided.
• For a food additive, dietary supplements and/or natural health products that is not currently marketed but there is extensive prior human experience, literature and other available information should be provided to support initial clinical studies without additional preclinical assessments.
• Regardless of whether a food additive, dietary supplements or natural health products is currently marketed, if the anticipated exposure in the proposed clinical studies exceeds that of the prior human use (e.g., higher doses or a longer duration), a preclinical assessment is warranted to adequately address the difference between the prior human use and the proposed use.
• For non-traditional routes of administration of a food additive, dietary supplements or natural health products (e.g., if a product has been traditionally used only topically and the sponsor is proposing oral use), additional preclinical studies may be warranted to support this difference before initial clinical studies are allowed to proceed.
• For a food additive, dietary supplements or natural health products for which extensive prior human use is not available, a more extensive preclinical assessment is warranted. This assessment should be similar to that of prescription drugs and recommendations should follow appropriate regulatory guidances.
• Products to be tested, should normally be administered via oral route in in vivo preclinical studies. In general, the form in which humans are likely to consume the substance and the impact it will have on the rate of absorption and subsequent systemic exposure should be considered. For products being added to solid foods or to both solid foods and beverages, administration should normally be via diet.

If preclinical studies have not been performed for the food additive, dietary supplements or natural health products, the researcher should conduct a literature search to identify any publicly available information pertaining to the safety of the following:

• Final formulation of the intended commercial product,
• Known active or chemical constituents of the product

In general, the following issues should be addressed by either an integrated summary of available data from literature or conducting the preclinical studies listed in Table 1.

• General toxicity,
• Toxicity of target organs,
• Genetic or reproductive toxicity of any constituents of the product,
• Relationship of dosage and duration to toxic responses, and
• Pharmacologic effects reported for the active constituents.

Make sure to consult with experts as the clinical development path may vary widely and be unique for your situation. Expert advice can help you decide which trials you should do and determine if you are ready to move into clinical stage.

How About Cannabinoids Identified in Cannabis Plant? Can They Be Marketed as Food Additive or Natural Health Products?

With respect to cannabis plants, as all cannabinoids are subject to the Prescription Drug List, any product that will contain Cannabidiol (CBD) and make a health claim can not be marketed as food additives or natural health products and would require approval as a prescription drug under the Food and Drugs Act. Based on available evidence, the FDA has also concluded that tetrahydrocannabinol (THC) and CBD products are excluded from the dietary supplement definition and food additive. This is because, THC is responsible for intoxication when consuming cannabis and CBD is an active ingredient in the approved marketed drug product. Ingredients that are derived from parts of the cannabis plant that do not contain THC or CBD such as Cannabinol (CBN) and Terpenoids might fall outside the scope of this exclusion and therefore they could be marketed as dietary supplements. Different countries in Europe implement different rules on how to categorize CBD and other Cannabinoids. Therefore, it is important to consult with experts to evaluate if preclinical trials are required to be conducted for different ingredients derived from cannabis according to each regulatory guidance.

At BioPharma Services Inc. we have the expertise to guide you through these preclinical trails. Schedule a Discovery call, we are here to help.

References

Guidelines: OECD

Food: US, Canada, EU

Drugs: US, Botanical Drugs, Canada, EU

OTC/Non-prescription: US, Canada, EU

NHP (Canada), Dietary Supplements (US), Food Supplements (EU)

Cannabis: Canada, US

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