The United States has a unique regulatory environment for dietary supplements established under the Dietary Supplement Health & Education Act (DSHEA); this includes guidance on bringing unique dietary ingredients to market as ‘new dietary ingredients’ or NDIs. Manoeuvring successfully through the regulatory tape in the way in which it was fashioned to be travelled is truly a road less travelled. More commonplace is reliance on pre-DSHEA, old dietary ingredient (ODI) alignment, even when unique manufacturing and claims of enhanced absorption should otherwise exclude such ingredients from this pathway. ODI alignment for most products has been more the rule, than the exception. The approach of surfing below the radar has allowed many products, due to their assumed low risk, to settle into an obscure fit that will become more uncomfortable in the post-COVID explosion of this once underrated industry.
Instead, companies will need to take a more safety-centric approach to market. As an example, DolCas Biotech invested in a toxicological research study confirming the long-term safety of its CURCUGEN curcumin formulation, which was recently published in Biomedical Research International. Having already established self-determined GRAS status last year from an expert panel, this new study puts DolCas in a position to file a formal FDA notification for the use of CURCUGEN in foods and beverages.
The safety evaluation led by Somashekara Nirvanashetty, PhD et al., sought to establish the safety of CURCUGEN using a standard series of in vitro and in vivo safety studies, in accordance with OECD guidelines. The globally recognized Organization for Economic Cooperation and Development (OECD) guidelines assured consistency of alignment to the standards of the food, beverage, and dietary supplement industries; the evaluations provided in vitro and in vivo data about the bioavailability-enhanced formulation’s safety, when administered orally.
The study’s design included the toxicological assessment of genotoxicity, acute and 90-day repeated dosing. The single dose of CURCUGEN administered orally to Sprague-Dawley (SD) rats demonstrated a non-lethal dose of as high as 5,000 mg/kg body weight. A sub chronic assessment of CURCUGEN, as administered to SD rats of over 90 days resulted in a no observed adverse effect level (NOAEL) at a dose of 2,000 mg/kg body weight/day. This was confirmed through comprehensive screening of blood serum markers encompassing organ function and urine analysis. Moreover, CURCUGEN did not elicit any genotoxic or mutagenic abnormalities with long-term use.
The uptick in interest in functional foods and beverages, and the acquisition of smaller dietary supplement/consumer goods manufacturers by large food multinationals as an evolving trend, is making comprehensive regulatory profiling more requisite, than voluntary. Safety risks can directly affect a company’s bottom line, so for larger organizations more evidence means a higher risk ceiling. Independently, there exists a broader public safety concern about how much of an ingredient will be consumed in foods of varying types over time without the suggested dosing parameters that loosely govern adequate intake of a dietary supplement. Both interests establish an obvious need for evidence of an ingredient’s safety in product-specific, versus borrowed or referenced research.
The build out of CURCUGEN’s comprehensive safety portfolio for foods/beverages and referencing in commercialization, position it for a comparable level of confidence when marketed for health-supportive and restorative claims in dietary supplement use. Self-GRAS, with subsequent GRAS notification and food/beverage commercialization is a viable safety pathway for crossover ingredients like CURCUGEN (i.e. have applicability in both the dietary supplement and food and beverage markets), but it is not the only way. As mentioned earlier, FDA’s NDI Notification (NDIN) mechanism would offer a path for non-food/beverage applicable ingredients that don’t quite fit the ODI specification. Over the last nearly 30 years, from 1995 to 2022, only 1226 ingredients or formulations have taken on this 75-day premarket approval process, none of which were bioavailability-enhanced curcumin ingredients (1).
With recent restrictions within the FDA to circumvent the NDIN route through non-commercialized GRAS-approved food and beverage applications and medical foods-use GRAS claims, amidst greater pressure from large organizations with little tolerance for risky ventures, the safety road may be less travelled today—but will likely be bumper to bumper in the years to come.
Dr. Shavon Jackson-Michel is the director of medical & scientific affairs at DolCas Biotech, LLC (www.dolcas-biotech.com).
- Submitted 75-Day Premarket Notifications for New Dietary Ingredients https://www.fda.gov/food/new-dietary-ingredients-ndi-notification-process/submitted-75-day-premarket-notifications-new-dietary-ingredients