In summary, the goal of Step One, screening/flagging, is to identify those supplement ingredients that could possibly cause harm. The goal of Step Two, priority setting, is to determine which of the ingredients identified in the screening/flagging step are of the highest concern and should therefore be placed at highest priority for a full evaluation. The goal of Step Three, critical safety evaluation (discussed in Chapter 6), is to provide a detailed review of what is known about the theoretical and demonstrated safety of a dietary supplement ingredient that would allow FDA to determine if further action is needed in regulating the ingredient in the marketplace.
The screening/flagging step was developed on the premise that it is not feasible for FDA to immediately search extensively for information about every dietary supplement ingredient. Readily available information can be used to flag substances that warrant further attention while maintaining enough sensitivity to minimize false negatives and not omit any items with potential safety concerns.
To flag substances warranting some level of attention, “yes or no” questions were developed to identify ingredients that should move forward to Step Two, the priority- setting step. A “yes” answer to any of the following questions flags the dietary supplement ingredient and moves it on to Step Two.
Has a 75-day new ingredient notification been filed with FDA?
Are there serious adverse events reported through MedWatch, poison control centers, or clinical studies that illustrate a pattern in terms of the type of incident reported, that are well-documented in the medical literature, or that may be plausibly linked to the dietary supplement ingredient? Or, does the number of serious adverse events reported appear high compared to the ingredient’s prevalence of use? Or, does it seem plausible that particular subpopulations are particularly susceptible to serious adverse events reported for this dietary supplement ingredient?
Has the ingredient been brought to FDA’s attention because of concerns other than new ingredient status or human adverse event data described above? (A preliminary evaluation of concerns that have come to FDA’s attention will allow PDA to determine which of these ingredients should move into the priority setting process.)
The following are examples of “other concerns” that may bring an ingredient to FDA’s attention for screening and possibly flagging, but this list is by no means exhaustive:
Safety concerns from other groups or organizations that have evaluated substances currently on the market as dietary supplement ingredients. Examples of such safety concerns include compounds previously evaluated as drugs (including over-the-counter drugs), regulatory actions from other governments (e.g., Commission E), usage levels greater than the tolerable upper intake level values set by the Dietary Reference Intakes process (IOM, 1998), and information released by the Office of Dietary Supplements, National Institutes of Health.
Strong evidence of serious interactions with prescription drugs.
Evidence that the ingredient mimics hormonally active compounds.