Safety Requirements for NDI Notification

SALT LAKE CITYAccording to FDAs New Dietary Ingredient (NDI) Draft Guidance, NDI notifications should include information that shows the dietary supplement containing the new dietary ingredient is reasonably expected to be safe. This may come in the form of toxicology and safety studies, which are often expensive for companies to conduct. While this may seem onerous, Toxicology is not intended to stop innovation; it is one step in the safety analysis," according to Claire L. Kruger, Ph.D., D.A.B.T., SPHERIX, who gave a presentation on what FDA expects regarding toxicology studies at the United Natural Products Alliances (UNPA) seminar on the NDI Draft Guidance.

While Kruger noted studies are pricy, they are necessary to determine risk.  Safety, she said, is the inverse of risk, but it cannot be absolutely absent. FDA asks supplement manufactures or distributors to use their own judgments when they compile safety data for an NDI notification.

Kruger suggested manufactures explore historical use within the United States and how that compares to the products recommended intake levels, duration and frequency of use, and target population.  She noted new testing is needed when the ingredients compositional analysis shows it has been chemically changed in a way that does not allow a bridging" of existing database of studies.

Establishing a bridge between the NDI and historical use, Kruger said both the NDI and the ingredient historically used must be well characterized; unfortunately, published toxicology studies may not be detailed enough to establish his bridge. Natural ingredients will most likely cause variability in composition, depending on climate and soil, but Kruger pointed out FDA said it will accept a range of components as long as it doesnt result in a qualitatively different composition.

If a company determines that it needs to conduct new toxicology studies for an NDI notification, Kruger said animal studies offer a well-controlled atmosphere. Other options include genotoxicity batterty; repeat dose toxicity; chronic/carcinogenicity; reproductive, developmental/teratology and; absorption, distribution, metabolism and elimination (ADME) studies.

She also offered a table of expected costs for various studies ranging from a two-study genetic toxicity battery for $4,310 to $7,800 to a multi-generation rodent reproductive study for $525,000.