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.
|Different In vitro Studies (Pharmacology and Toxicology)|
|In vivo Studies (Single Dose and Multiple dose studies) (Pharmacology and Toxicology)|
|Toxicokinetic (Rodent) OECD 417|
|Acute Toxicity (Rodents) OECD 423|
|Acute Toxicity (Non-rodents)|
|Short Term Toxicity (Rodents) OECD 407|
|Short Term Toxicity (Non-rodents)|
|Sub Chronic Toxicity OECD 408|
|Sub Chronic Toxicity (Non-Rodents) OECD 409|
|Genotoxicity Studies OECD 471/ 473/ 474/ 487|
|Evaluation of Relevant Body Systems|
|Chronic Toxicity OECD 452|
|Carcinogenecity Studies OECD 451|
|Development & Reproductive Studies OECD 414/ 421|
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.
About BioPharma Services Inc.
BioPharma Services Inc. is a full-service Contract Research Organization (CRO) specializing in the conduct of Phase I/IIa and Bioequivalence clinical trials for international pharmaceutical companies worldwide. BioPharma has clinical facilities both in the USA and Canada with a total capacity of 300 beds with access to healthy volunteers and special populations. Headquartered in Toronto, Canada, BioPharma’s comprehensive services also include Bioanalysis at our GLP Certified Laboratory, Scientific and Regulatory Affairs, Biostatistics and Safety Data Analysis (CDISC), Data Management and Medical Writing.
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What are early phase clinical trials?
Clinical Trials are divided into 4 phases. Phase 1 and 2 trials constitute early phase trials, Phase 3 and 4 research studies are late-phase trials.
The primary objective of Phase 1 studies is to determine the correct drug dosage by evaluating drug safety and determining if there are any side effects. Phase 1 trials are conducted in healthy volunteers.
Phase 2 studies also study the safety of a drug but focus on evaluating its effectiveness. These studies can be conducted in healthy volunteers or in individuals who have a certain disease or condition.
What is a clinical trial?
A Clinical trial is a process which is performed to determine whether an investigational drug, device or therapy is safe and effective. In early phase research (i.e. Phases 1 and 2), the safety and effectiveness of the drug will be evaluated in healthy volunteers.
What is an investigational drug?
An investigational drug can also be called an experimental drug and is being studied to see if your disease or medical condition improves while taking it. Scientists are trying to prove in clinical trials:
- If the drug is safe and effective.
- How the drug might be used in that disease.
- How much of the drug is needed.
- Information about the potential benefits and risks of taking the drug.
Why do you need to take blood draws and how many blood draws will be required?
In order to evaluate the drug profile, we need to understand its pharmacokinetics. This is essentially how the body reacts to a drug after its administration through the mechanisms of absorption, distribution, as well as the metabolic changes. Therefore, blood draws are collected at various time points to better understand this mechanism. Each study requires a specific number of blood draws and total blood volume. These values will be provided to you and clearly stipulated in the informed consent form (ICF). The amount of blood that will be taken is outlined in the ICF.
Should I expect to experience any side-effects while doing studies?
As every study is testing an investigational product, there may be side effects. You will be provided with a list of side effects that have been reported in previous trials (if any), so you can make an informed decision whether or not to participate in the trial. During the trial you will be required to immediately inform clinic study staff of any adverse effects that you are experiencing. These side effects usually resolve upon discontinuation of the study drug.
Will I be compensated for doing a clinical study?
Volunteers are compensated and the amount varies depending on the length of the clinical trial, length of stay and number of follow-up visits. The compensation is not specifically related to the risks or type of drug involved in the trials or studies. Every study is different and therefore, the compensation will vary. Study volunteers may receive between $1000 to $4000 for a trial (based on the factors listed above).
Are food and accommodation provided over the course of the trial?
Food – Clinical trials are conducted in a controlled setting which means that all food is provided and trial volunteers receive standardised meals. Individual meal plans or meal preferences cannot be provided. If you have any food allergies or hypersensitivity to food product(s) that are clinically significant or life-threatening you may not be able to participate in a trial. Please contact us to discuss any food issues.
Accommodation – During your in-clinic stay you will share sleeping areas with other volunteers who are of the same gender. Similar to a hospital setting, supervision will be provided to ensure that your health and safety are being monitored.
What is the length of a study and do I have to complete all the visits?
What is informed consent and how is it carried out?
Before you decide whether or not to take part in a clinical research study, you will be required to read and understand the information provided in an Informed Consent Form (ICF). The ICF describes the clinical research study and the nature of the investigational product to be used, including:
- Your rights and responsibilities as a study participant.
- What you will be asked to do during study participation.
- The potential risks that you should be aware of.
During this process, you will have the opportunity to discuss and ask questions related to the conduct of the clinical research study with the study doctor/ study staff. You are under no obligation to participate and your decision to take part in a clinical trial is voluntary.
Can I bring my own device?
Yes, we encourage you to bring items that will help to pass the time while you are in the clinic. You can use the time to study or work or catch up on the movies you’ve been meaning to watch.
What do I need to pack?
When do I receive compensation for taking part in a study?
You will receive compensation as outlined during the Informed Consent process. Typically, you will receive compensation once all study visits have been completed. If, for any reason, you do not complete all study visits, your compensation will be on a pro-rated basis (i.e. for the time that you have participated in the trial)
Where will I sleep during the clinical study?
What COVID-19 precautions are you taking?
Can I bring my own food?
All aspects of clinical trials are closely monitored including the food and drink consumed by participants. While you are in the clinic, you will be provided with all meals as per the study guidelines. You will need to eat all the food provided to ensure the guidelines are met. Watch video