In the United States, The Food and Drug Administration (FDA) regulates and oversees clinical trials of food and dietary supplements and develops various regulations and guidelines for their use. The FDA defines ‘food’ as per the Food, Drug, and Cosmetic (FD&C) Act as articles for food or drink for man or other animals, chewing gum, and articles used for components of any such article. According to the Dietary Supplement Health and Education Act (DSHEA), a dietary supplement is a product intended for ingestion that, among other requirements, contains a “dietary ingredient” intended to supplement the diet.

The term ‘dietary ingredient’ includes vitamins and minerals; herbs and other botanicals; amino acids; “dietary substances” that are part of the food supply, such as enzymes and live microbials (commonly referred to as “probiotics”); and concentrates, metabolites, constituents, extracts, or combinations of any dietary ingredient from the preceding categories. The FDA regulates dietary supplements under a different set of regulations than those applicable to conventional foods and drug products under the DSHEA Act.

The rise in the uptake and use of alternative treatments has led to a rapid increase in the market share for dietary supplement for the purposes of ensuring proper nutrition and preventive measures related to aging and development of certain diseases. A study in 2021 showed the global dietary supplement to be valued at USD 152 billion with a projected increase to USD 300 billion by 2028.

This has made it important for the FDA to regulate food and dietary supplements. Regulation of the safety and health claims of food in the USA is under the FD&C Act. In general, unless the food is claimed to have certain health benefits, clinical trials are not necessary. Dietary supplements are considered a subset if food and not drugs and are regulated by the FDA differently from drugs under the DSHEA. However, the FDA can require premarket approval of certain food additives and colour additives to make sure that they are safe for human consumption. Issues related to efficacy and safety of dietary supplements, presence of toxic contaminants and heavy metals, pesticide residues, adulteration, and misidentification of ingredients plague the supplement industry requiring comprehensive characterization of the ingredients, in vitro and preclinical studies, animal-to-human extrapolation, and clinical research to ensure safety and efficacy.

Additionally, the competitive market for dietary supplements has prompted many companies to conduct trials to provide substantial evidence for their benefits helping with product differentiation. It is important to bear in mind that clinical studies for dietary supplements differ from those with drugs in subject population, study end points, sample sizes, and surrogates or biomarkers.

Although the FDA does not have the authority to approve dietary supplements, manufacturers of dietary supplements containing new dietary ingredients need to submit a premarket notification to the FDA at least 75 days prior to introduction into the market. Premarket notifications are necessary to be submitted to the FDA for food and food additives.

Whether a clinical trial is required for dietary supplements depends on the claim that is reported. If the dietary supplement claim’s structure/function benefits or nutrient content claims, clinical trials are not required, and substantial scientific evidence is enough. However, if health claims are made, both foods and dietary supplements require clinical trials to support the claim that the food or dietary ingredient directly affects individuals’ health-status.

As with drug clinical trials, the regulations for clinical trials of dietary supplements purporting health claims require the following:

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  • Investigational New Drug (IND): The need for an IND to conduct clinical trials for dietary supplements depends upon whether the endpoint is disease-related and leads to an approvable indication. The Centre for Drug Evaluation and Research (CDER) determines if an IND is required to initiate clinical research based on the study endpoint (diagnostic or disease-related), population and indication, and dosage. The FDA/CDER does not require the sponsor to submit an IND for structure/function claims but requires one when disease claims are made. In case of surrogate end points (cellular mechanisms and diagnostic findings), it is necessary for CDER to review the data thoroughly and use their discretion to determine if an IND is required.
  • Informed consent: This is necessary for all studies involving human subjects to protect their safety and well-being. It is important to ensure that all participants are informed of the risks and benefits associated with the dietary supplement and are well-versed of their ability to withdraw from the study at any time.
  • Institutional Review Board (IRB) approval: The IRB determines if an IND is required based upon the claims made for marketing the dietary supplement and ensures that the protocol is sound with patient safety at the forefront.
  • Good Clinical Practice (GCP): The trial must comply with GCP guidelines and all personnel conducting the trial must be trained on GCP.
  • Good Manufacturing Practices (GMP): It is necessary that the investigational dietary supplement is manufactured, packaged, and stored in a facility that follows GMP ensuring their identity and purity.
  • Safety reporting: Adverse event reporting practices must be implemented and continually updated such that the FDA is aware of any potential safety concerns that the supplement may have. Safety signals should be reported to the FDA in a timely manner and detailed records must be maintained.

Complying with the above-mentioned regulations ensures that dietary supplement clinical trials are trustworthy, reliable, and accurate and meet the health claims that they are purported to have. The FDA’s rigorous standards to make sure that the dietary supplements are safe when used in the general population.

Read More:

Clinical Data Standardization in Clinical Trials: FDA Compliance in Clinical Data Management

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