By Robert Martin, Ph.D., EAS Senior Advisor for Food & Color Additive Safety
On August 11, 2016, FDA issued an updated revised draft guidance on new dietary ingredients used in dietary supplements which replaces draft guidance the agency issued in 2011. FDA developed the draft guidance to address confusing issues involving new dietary ingredients, synthetic dietary ingredients, botanicals, and requirements for New Dietary Ingredient Notifications.
In FDA’s own words: “The revised draft guidance, when finalized, will help industry in evaluating whether to submit a premarket safety notification for a new dietary ingredient (NDI), or for a dietary supplement containing an NDI, and in preparing such premarket safety notifications (also referred to as NDI notifications).” FDA is inviting comments on this guidance document. In order for the comments to be considered before FDA begins work on the final version of this guidance, the comments should be submitted no later than October 11, 2016. FDA is specifically requesting comments on three issues as discussed in the Federal Register document announcing the availability of the revised draft guidance document.
While the updated draft is an improvement on the earlier draft, it is still a work in progress. What can be interpreted as improvements are FDA’s intention to establish a “grandfathered” list of dietary ingredients and to establish Master Files for new dietary ingredients. However, judging from comments issued by many stakeholders on this revised draft thus far, this updated draft guidance does not completely answer all of the areas of concern and interpretations regarding dietary ingredients. As such, this is an ongoing and unsettled area. In the meantime, FDA is urging adherence to these guidelines as it best reflects their current thinking in this area.
The major sections of the earlier draft guidance that have been revised are: chemical alteration; manufacturing changes that create an NDI; synthetic substances; NDI definition; list of “grandfathered” dietary ingredients; and structuring NDINs efficiently including how much safety information and types of safety information that should be provided. The revised guidance document also uses a question and answer format to address the pertinent issues involving dietary ingredients along with several examples of what is a dietary ingredient, synthetic ingredient, etc.
There is general agreement that the process involving dietary ingredients has not worked as smoothly as expected… roughly 25% of the NDINs submitted to FDA are accepted while 75% have met with some objection(s) for a variety of reasons.
One area of controversy involving dietary ingredients has been how the interpretation of the legal safety standard is applied. Under DSHEA, dietary ingredients marketed in the U.S. after October 15, 1994, must meet the stated NDI safety standard demonstrating that “… a dietary supplement containing such dietary ingredient will reasonably be expected to be safe.” (21 CFR 190.6(a)) By contrast, the safety standard applied to food additives and GRAS substances must demonstrate that the ingredient meets the safety standard of reasonable certainty of no harm under the intended conditions of use. (21 CFR 170.3(i))
While FDA has published standards as to how to determine safety under the reasonable certainty of no harm under the intended conditions of use safety standard, no such published standards or guidance exists for the reasonably expected to be safe standard. In fact, a comparison of the safety requirements listed under section VI of the revised draft guidance document share a remarkable similarity to the safety requirements for food additives and GRAS substances.
EAS is encouraging clients to offer comments on this draft guidance as this guidance when finalized will reflect FDA’s thinking in this area for years to come. EAS can assist you in this regard by working with you in drafting the comments and serving as a conduit for submission of comments to FDA. In the meantime, it is strongly recommended that clients seek a pre-submission meeting with FDA before submitting an NDIN to answer all questions/concerns beforehand.