“What kind of animal is man, that he creates his own cage”? – Anonymous
Despite the fact that 18 years have elapsed since passage of the Dietary Supplement Health and Education Act (DSHEA), FDA has yet to recognize the gift given to it by Congress and embodied within the Act – a new standard by which supplement safety could be judged – “a reasonable expectation of no harm.” Instead, FDA has built its own cage by implying that safety has only one standard, that the reasonable expectation of no harm for supplements and reasonable certainty of no harm for food ingredients is a distinction without a difference. This has led to the continued high rejection rate of new dietary ingredient notifications (NDIN).
Further, it is as if the Division of Dietary Supplement Programs (DDSP)[1] has raised the bar for safety even further with the July 2011 proposed guidelines with a more daunting rule set than suggested for food additives in the Redbook and, further, the only concession for an automatic NDIN approval would be a successful GRAS notification. This concession has not been the sharpest rebuke of Congressional will on record, but certainly one that has not escaped the notice of Congress in the form of a letter from Senators Hatch and Harkin to the Commissioner. Still, even with the guidelines draft supposedly re-set to zero since the firestorm of protest from industry (although the repudiated guidelines remain on the FDA website) and a newly promised more balanced approach from FDA, communications from DDSP have included demands for unquantified safety factors, extensive and unnecessary studies and aggregate consumption estimates to include concomitant use in supplements and food (the latter of which is generally unavailable from food manufacturers). All of the above proceeds even in light of Congress’ stated findings that: “although the Federal Government should take swift action against products that are unsafe or adulterated, the Federal Government should not take any actions to impose unreasonable regulatory barriers limiting or slowing the flow of safe products and accurate information to consumers.”[2]
FDA’s historical resistance to claims for non-drug, non-food/nutritive substances is rooted in its eminently justified struggle in the early part of the last century in the days of snake oil, food faddism, cultists and quackery. Unfortunately however, when laws specifically prohibiting such things were not available, the agency resorted to a regulatory “sleight of hand”, such as when megadoses of vitamins were declared drugs and supplements were banned as unapproved food additives. The same regulatory “sleight of hand” approach is being applied today by establishing unrealistically high thresholds for safety of supplements, when Congress specifically expressed the will of the people by establishing a standard of “reasonable expectation” of safety in DSHEA. Still, FDA maintains that it protects public health and safety by maintaining a 70% rejection rate of NDINs – granted, many rejections are the fault of the notifier by including foreign language documents in the notification, inadequate identification of a botanical, incomprehensive labeling instructions or obvious drug claims. Notwithstanding the foregoing however, a healthy percentage of rejections are based on DDSP’s conclusion of an inadequate demonstration of safety. Is it any wonder then why, with only a few hundred NDIN “no objections”, there are by the agency’s own estimate, approximately 55,000 supplements on the market? Manufacturers, many of whom are woefully undercapitalized and unprepared for the costs of extensive testing, may have decided that a warning letter or even a recall is simply a cost of doing business, especially in the face of a high probability of an NDIN rejection letter. Going to market with an unnotified supplement is simply a roll of the dice for some manufacturers, but it is an even greater roll of the dice for consumers who have been placed in harm’s way by the agency indirectly encouraging bad behavior by manufacturers. The bottom line – the high threshold for approval ostensibly in place to protect the consumer has had the opposite effect by exposing consumers to unvetted and potentially adulterated substances.
FDA’s release from the cage of its own making is simple, but requires some fortitude on the part of the agency to recognize there is a distinction and a difference between the standards of safety reasonable expectation and reasonable certainty. That is, while safety may be a binary decision, the data supporting the decision is not. FDA opened the door to this argument of gradation when it made a distinction between significant scientific agreement (SSA) supporting a health claim and something less (i.e., emerging science) supporting a qualified health claim. While efficacy and safety are both binary questions (i.e., yes or no), FDA has already made the decision that the evidence supporting efficacy may have gradations of rigor. So also for the evidence supporting safety – whether a substance has a basic data set supporting safety or twenty studies supporting safety, the twenty studies does not make the substance safer, it only makes the decision to declare safety less of a risk to the risk assessor. Still too, more data with a broader scope of investigation practically guarantees an errant value will be revealed and if the finding is of marginal influence on the homeostasis of the subject, is the presence of a false positive going to make the decision of safety a riskier undertaking? Safety is never absolute and is why the framers of the food additives amendment opted for reasonable certainty rather than absolute certainty of no harm. So too, DDSP should discard the concept of what has become absolute expectation of no harm, provide notifiers with an expectation of a pragmatic safety review and protect the public from unvetted supplements.
References
[1] DSSP is the division within the Office of Nutrition Product Labeling and Dietary Supplements charged with reviewing New Dietary Ingredient Notifications.
[2] Dietary Supplement Health and Education Act of 1994, Pub. L. No. 103-417, 108 Stat. 4325 (1994) §2 Congressional findings.http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/ucm148003.htm