Dietary Supplements and Public Safety: A Defense of DSHEA’s “Three-Legged Stool”

This article discusses the passage of the Dietary Supplement Health and Education Act (DSHEA) in 1994 and its effects on the dietary supplement industry. The author addresses criticism of DSHEA and defends the intent and subsequent benefits of the legislation by identifying the “three legs of the stool” of the legislation—protection, safety and watchfulness.  
 
Introduction
 
As the dietary supplement industry prepares to observe the 25th anniversary of the passage of the Dietary Supplement Health and Education Act (DSHEA), it is worth pausing to consider how this law has overseen the phenomenal growth of the dietary supplement industry in the US and around the globe.¹ When Congress enacted the legislation and President Clinton subsequently signed it in October 1994, neither Congress nor the president could have anticipated the industry growth DSHEA fostered. At the time, dietary supplements comprised an estimated $4 billion market in the US.² Today, the Nutrition Business Journal values the US dietary supplement market at more than $46 billion, growing by eleven-fold over the past 25 years.³
 
Although a contributing factor, DSHEA was not the sole cause for this meteoric growth. The predictability and rational regulatory framework it created encouraged market entry and expansion, but DSHEA’s passage was the result of other currents in the American culture fueling the industry’s growth. Prior to DSHEA, consumers expressed increasing interest in self-care and autonomy over the decisions affecting one’s health. Emerging nutrition science had increasingly connected nutrition with disease prevention and health management and growing public distrust of major institutions, such as government, the healthcare system and large corporations, contributed to growing interest in dietary supplements. Consumer groundswell and grassroots lobbying of Congress leading to the passage of DSHEA helped the growth of the industry as much as did the new law. Consumers wanted assurance they would have access to safe and beneficial products to promote better health, and DSHEA provided that assurance.
 
As the US Food and Drug Administration (FDA) recently reaffirmed, DSHEA was the result of a complicated “balancing act” between assuring access and protecting public safety.⁴ As a result, dietary supplements now comprise a wide range of products which are the rightful heirs of the wisdom of centuries of traditional medicine, folk remedies, nutritional practices and self-care. Consumers wanted these products to be easily accessible without a cumbersome and expensive premarket government approval process, limiting the array of these products, restricting access and driving up costs. Subsequently, consumer sentiment largely drove the passage of DSHEA with massive numbers of letters, telephone calls and telegrams flooding Congress in 1992-1993 urging legislators to act.
 
On the regulatory side was FDA’s mission to protect public safety by assuring that products offered on grocery store, health store and community pharmacy shelves would likely not do harm. For an agency charged with oversight of both food and drugs (with the DSHEA-created category of dietary supplements fitting somewhere between the two), FDA undeniably has a role in regulating these products to protect consumers from unsafe products—but the extent of that oversight remains at the core of a controversy with us today.
 
Critics of DSHEA have routinely “slandered” the 1994 law by inaccurately claiming it “defang[ed] FDA by prohibiting the agency from requiring even rudimentary premarket screening for the safety or efficacy of these products,” leaving the industry “free of any meaningful regulation.”⁵ One detractor said DSHEA “enabled thriving trade in ineffective and potentially harmful” supplements, and another simply reduced the name-calling to saying DSHEA is “a travesty of a mockery of a sham.”^6-7 At the heart of many of these criticisms is the suggestion that DSHEA got the balancing act wrong, emphasizing widespread access  at the expense of safeguards to public safety.
 
These critiques reflect not only a fundamental misunderstanding of the delicate balancing act DSHEA achieved, but also show a remarkable lack of appreciation for the wide range of tools DSHEA provided for protecting public safety. Many of the negative comments evidence a disingenuous and revisionist interpretation of the law to construct a case for a much more restrictive replacement, potentially disrupting the balancing act DSHEA achieved. By creating tools to protect public safety in three critical areas, DSHEA did establish the right balance. In the years since 1994, where equilibrium was found lacking, “weights” have been added to the scale on the side of safety, serving to sustain the balance DSHEA sought to achieve. Today, additional items are being considered to enhance the public safety protections DSHEA provides American consumers but, as will be demonstrated, these are minor “course corrections” rather than a wholesale upending of the law as some have proposed. The three “legs” of the safety “stool” (protection, safety and watchfulness) have provided a stable platform on which the industry and consumer confidence have been built and on which confidence can continue to grow.
 
Protection, Safety and Watching: DSHEA as a “Three-Legged Stool”
 
With respect to dietary supplements, protecting the public safety involves answering several fundamental questions. Does the product inherently pose significant safety concerns if manufactured as intended? Or, asked another way, if the product is produced exactly as intended, does it still pose unacceptable safety risks to consumers? Does the product suffer from an inherent design flaw? How do consumers know the product was indeed manufactured to the exacting specifications called for? Is the product free of manufacturing errors? Once the product is released into the marketplace, are there mechanisms to monitor usage, create signals if unexpected detrimental health effects start to occur, and allow removal of offending products? Is the product working as predicted, as revealed through post-market surveillance?
 
A regulatory framework intended to protect public safety should address all of these critical concerns and, if it does, it is likely to catch the vast majority of potential hazards posed by the product. The current three-legged safety regime for dietary supplements does exactly that.
 
The First leg:  DSHEA’s Protection From Inherent Product Flaws
 
Defending the safety apparatus inherent in DSHEA begins with identifying the boundaries of what can and cannot be considered a dietary supplement. The definition of a dietary supplement, first established in the 1994 law, encompasses vitamins, minerals, herbals and other botanicals, as well as amino acids and other dietary substances used to supplement the diet, and any concentrate, metabolite, constituent or extract of those items.⁸ What DSHEA eliminated is as important to the safety question as what it allowed, and FDA has effectively crafted this definition to exclude substances from supplements outside of the six categories enumerated in the law. Numerous incidents involving questionable ingredients, such as DMAA, fluoxetine, ostarine, sildenafil, sibutramine or a variety of steroids and other pharmaceutical agents were declared illegal at the definitional level.^9-14 Because these substances are outside DSHEA’s definition of a dietary ingredient, FDA does not have to determine if they are unsafe; they do not qualify as dietary ingredients in the first place.
 
A fundamental misunderstanding of the new Dietary Ingredient (NDI) provisions also contributes to the misperception that FDA’s “hands are tied” when it comes to the safety of new ingredients. One criticism is that “unlike conventional medications, dietary supplements are not required [by DSHEA] to undergo premarket approval testing for safety or efficacy. Thus, the potential for harm from such products is not evident until the public has consumed them.”¹⁵ FDA has contributed to this mistaken view by making public pronouncements that the new dietary ingredient provision of DSHEA is “FDA’s only opportunity to evaluate the safety of a new ingredient before it becomes available to consumers.”¹⁶ Although the statement is factually true, by stating it is the only avenue to assess safety of new products creates the misimpression that other avenues of market entry exist that permit untested ingredients to flood the dietary supplement market without FDA oversight. In fact, the NDI provision of DSHEA establishes a pre-market notification requirement for dietary supplements. Manufacturers bringing a new dietary ingredient to market must show it is “reasonably expected to be safe.”¹⁷ While the statute creates the possibility that a firm could proceed to market over the FDA’s opinion that safety data is insufficient, the law is clear that a new dietary ingredient for which there is inadequate information to provide reasonable assurance that such ingredient does not present a significant or unreasonable risk of illness or injury is adulterated. The law is also clear about failure to file an NDI notification (thus, alerting FDA to the existence of the ingredient in the market and giving it a chance to object) in fact makes the product adulterated.^18,19
 
As an additional safeguard, an NDI notification is also required for those ingredients already on the market, but which are subsequently produced in a substantially different method than they were in 1994. The safety standard for NDIs (“reasonably expected to be safe”) has been criticized as a less stringent standard than the one governing a food additive petition (“reasonable certainty of no harm.”) However, the standard is sufficiently substantial for FDA to demand scientific data.
 
The 1994 law also created an arbitrary dividing line between those dietary ingredients presumed to be safe and those for which the manufacturers would have to demonstrate safety. Those ingredients already in the market on 15 October 1994 were presumed safe (considered grandfathered or “old” ingredients – ODIs), while those introduced after that date needed to demonstrate they are reasonably expected to be safe by their marketers.
 
It’s ironic that criticism of this provision has grown over the past 25 years when experience suggests criticism should have subsided. At the time of DSHEA’s passage, one might reasonably have argued that a relatively new ingredient introduced to the dietary supplement market in, for example, September of 1994, might not actually have had sufficient time and experience to be deemed “safe,” such that the presumption rested with FDA to demonstrate it was not. Today, with 25 additional years of real-world usage, the justification for a presumption of safety for any ingredient on the market prior to 15 October 1994 is even stronger than it was at that time.
 
Additionally, justification is further bolstered by the passage in 2006 of the Dietary Supplement and Nonprescription Drug Consumer Protection Act.²⁰ This addition to the original protections of DSHEA requires manufacturers to report all serious adverse events to FDA within two weeks of learning about them, and that they must keep records on all adverse events for up six years, making them available to FDA for inspection upon request.^21-22 Now, FDA is equipped with 10 years of real world safety data from the mandatory adverse event reports, providing further assurance that the ingredients on the market in 1994 are reasonably expected to be safe.
 
As it has taken the FDA 25 years—and counting—to finalize a meaningful guidance interpreting the nuances of the NDI provision of the law, ingredient suppliers are justifiably worried about their ability to take advantage of this presumption by demonstrating a particular ingredient was, indeed, on the market prior to the law’s passage in 1994. As 1994 pre-dates most electronic recordkeeping and many paper files have been eliminated in the intervening time, proving evidence the product was in the market can be a difficult task. As such, the delay in full implementation of the NDI provision has led many to question whether in practice it can foster innovation, although the original purpose behind DSHEA was to balance both innovation and access with reasonable safety hurdles.
 
The Second leg: Safety in Manufacturing Processes
 
The second leg of the three-legged safety stool concerns manufacturing processes, answering the question: Is there assurance the product is being manufactured to the exacting specifications called for once the ingredient is considered safe? Here, critics have wrongly suggested FDA cannot monitor and regulate thousands of individual products, leaving the public virtually unprotected against unsafe supplements and herbs. These contentions ignore the Good Manufacturing Practices (GMPs) prescribed by DSHEA. The law specifically stipulated how FDA may, by regulation, prescribe “good manufacturing practices for dietary supplements” and deems any dietary supplement that “has been prepared, packed or held under conditions that do not meet current good manufacturing practice regulations” to be adulterated.^23,24 The final GMP rules provide comprehensive requirements for all aspects of manufacturing and packaging, from evaluation of incoming materials, through manufacturing, to testing finished products.²⁵
 
Unfortunately, FDA did not issue the final GMP regulation for dietary supplements until 2007, and those regulations did not become fully effective for industry until 2010. By then, too many less than reputable influences had invaded the marketplace and the number of facilities to be inspected had far outpaced FDA’s ability to keep up. Critics rightly point out that far too many manufacturers still fail to comply with all aspects of GMPs. And, eight years after the regulations became fully effective, FDA has acknowledged that while larger companies typically fare well in GMP inspections, many smaller firms have failed to fully embrace the requirements. An analysis of warning letters issued by FDA reveals that the most common violations are failure to establish and meet specification for products and ingredients.²⁶
 
The agency’s reluctance to pursue violations of GMP regulations beyond warning letters points to a lack of resources as well as the resolve to aggressively prosecute, but not to a failing of DSHEA. The law itself is unequivocal: products not produced in accordance with GMPs are adulterated. Failure to fully and adequately enforce the law results from insufficient funding of FDA by Congress, poor training of inspectors and a lack of prioritizing dietary supplements for enforcement. Rather than “throwing rocks” at DSHEA, critics should join those who seek to fully fund FDA’s enforcement mandates or they should suggest alternative policing mechanisms, such as deputizing third-party certification programs to conduct inspections or realigning inspection priorities to be more risk-based.
 
The Third leg: Watching the Marketplace
 
Even with capabilities to oversee product formulation and product manufacturing, a solid regulatory framework requires the regulator to be able to monitor the postmarket world where products are used by consumers. This is one area where DSHEA initially faltered because it failed to require manufacturers to monitor their product’s use. The 1994 law did provide FDA with authority to issue voluntary recalls and the law expressly allowed the agency to remove products or ingredients from the market by regulation if it determined the product presents a serious or unreasonable risk of injury or illness.²⁷ Separately, DSHEA also empowered FDA to remove a product if it posed an imminent hazard to public health; however, the deficiency rested in the inability of FDA to “see” into the market and to identify potential signals of unexpected negative health effects.²⁸ Indeed, the experience with Ephedra between 2000 and 2004 when it was banned by FDA demonstrated some firms’ ability to thwart meaningful oversight by hiding and denying the existence of adverse events.
 
Two subsequent legal developments have addressed gaps in the original law. First, Congress enacted the Nonprescription Drug and Dietary Supplement Consumer Protection Act in 2006 that imposed a mandatory duty on supplement manufacturers to notify the agency within 14 days of learning about a serious adverse event associated with their product, and to maintain for six years records of all events reported to it.²⁹ This amendment has been widely recognized as creating visibility into consumer usage of supplements and aiding FDA by identifying early warnings of health issues.
 
In 2011, Congress enacted the Food Safety Modernization Act, which included mandatory recall authority over food (including supplements).³⁰ This provision gave FDA the ability to enforce a recall (even over a company’s objections) when it believed serious adverse health consequences would otherwise result and to require the offending company to pay for the recall. While the agency has voluntary recall over pharmaceuticals (typically imposed through a combination of cajoling and coercing), only food and supplements provide FDA with this added ability to demand a recall. Dietary supplements provided one of the first tests of mandatory recall authority when FDA demanded a supplement marketer issue a recall for a product called OxyElite Pro.³¹ Today, the combination of mandatory adverse event reporting and recordkeeping, along with the authority to issue voluntary or mandatory recalls or detain imported products at border crossings and the ability to declare products adulterated if they pose an unreasonable risk of harm provide a robust system for post-market surveillance.
 
Reinforcing Safety With Mandatory Product Listing
 
While all three legs of the safety stool are present, FDA and industry are currently examining ways to shore up the assurance of safety provided by DSHEA. In February 2019, FDA proposed establishing a mandatory listing of dietary supplement products to provide a broader understanding of what is in the market.³² Although the agency has not provided many specifics, it is generally understood that FDA’s proposal envisions an amendment to the statute to require that product marketers provide the agency with a copy of their labels and certain information from the label, such as product name list of ingredients, dosage levels of all dietary ingredients per dosage unit and contact information for reporting an adverse event whenever they bring a new or reformulated product to market. In subsequent public remarks, FDA has offered that the mandatory listing would not create a premarket approval or review, but would serve more as a registry to provide FDA with a clear appreciation of the breadth of products on the market and their contents.
 
Although the proposal for mandatory product listing has raised objections from some corners of the industry, the creation of a mandatory listing is a reasonable extension of the current safety tools available, without upsetting the balance with consumer access. Indeed, it is difficult to imagine how a simple listing requirement would negatively impact consumer access. Meanwhile, according to FDA, the product listing would provide transparency and “level the playing field for responsible industry participants by making it easier for us to take swift action against illegitimate and dangerous products, such as products that are tainted with drug ingredients.”
 
This proposal provides FDA with the visibility needed to more fully implement its other safety responsibilities. A mandatory listing also would give the agency better ability to identify new ingredients in the market, to identify firms whose facilities should be registered and subject to inspection, and to “track down” suspect products and ingredients when adverse event reports signal a potential problem.
 
Conclusion
 
DSHEA has made possible the safe, vibrant and burgeoning dietary supplement industry we see today. The balance it struck between access and safety with respect to products then on the market has over time proven wise. It provided the foundations for assuring the safety of ingredients, the quality of manufacturing and the authority to remove unsafe products from the market. Additional safeguards have been added to DSHEA to address adequate postmarket surveillance. Today, the proposal for mandatory product listing can provide increased transparency. The regulatory regime is not perfect and, as always, there is room for further improvement but without upsetting the fundamental balance between access and safety. With the regulatory regime working as intended, the industry will continue to grow, bolstered by responsible companies playing by the rules and producing innovative products for enabling greater health and vitality for all.
 
References
 

1. Dietary Supplement Health and Education Act of 1994. Pub. L. 103-417, 108 Stat. 4325. https://ods.od.nih.gov/About/DSHEA_Wording.aspx. Accessed 14 June 2019.
2. Sharpless N. Public Meeting to Discuss Responsible Innovation in Dietary Supplements, Food and Drug Administration, 16 May 2019, Center for Food Safety and Applied Nutrition, College Park, MD. Opening Remarks.
3. Ibid.
4. “FDA Statement: Statement from FDA Commissioner Scott Gottlieb, MD, on the agency’s new efforts to strengthen regulation of dietary supplements by modernizing and reforming FDA’s oversight.” US Food and Drug Administration, 11 February 2019. FDA website. www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-agencys-new-efforts-strengthen-regulation-dietary. Accessed 14 June 2019.
5. Austin B. “Kim Kardashian-Jameela Jamil Feud has Done More to Expose Detox tea Lies Than the FDA.” NBC News, 7 April 2019. www.nbcnews.com/think/opinion/kim-kardashian-jameela-jamil-feud-has-done-more-expose-detox-ncna991816. Accessed 14 June 2019.
6. Cohen P. “How America’s Flawed Supplement Law Creates the Mirage of Weight Lost Cures.” Harvard Public Health Review. Vol. 2, 2014. harvardpublichealthreview.org/how-americas-flawed-supplement-law-creates-the-mirage-of-weight-loss-cures. Accessed 14 June 2019.
7. Lipson P. “DSHEA: a Travesty of a Mockery of a Sham.” Science-Based Medicine. 20 July 2009, sciencebasedmedicine.org/dshea-a-travesty-of-a-mockery-of-a-sham. Accessed 14 June 2019.
8. FD&C Act, 21 USC§ 321(ff)(1).
9. “DMAA in Products Marketed as Dietary Supplements.” US Food and Drug Administration, August 2018. FDA website. www.fda.gov/food/dietary-supplement-products-ingredients/dmaa-products-marketed-dietary-supplements. Accessed 14 June 2019.
10. “Public Notification: Oxy ELITE Pro Super Thermogenic Contains Hidden Drug Ingredient.” US Food and Drug Administration. 28 February 2015. FDA website. www.fda.gov/drugs/medication-health-fraud/public-notification-oxy-elite-pro-super-thermogenic-contains-hidden-drug-ingredient. Accessed 14 June 2019.
11. “Warning Letter: Panther Sports Nutrition.” US Food and Drug Administration.  31 October 2017. FDA website www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/panther-sports-nutrition-535341-10232017. Accessed 14 June 2019.
12. “Warning Letter: Sharim Distributing Co Inc.” US Food and Drug Administration. 8 March 2016. FDA website. www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/sharim-distributing-co-inc-02112016. Accessed 14 June 2019.
13. “Warning Letter” Lucy’s Weight Loss (dba. Wasted With Lucy).” US Food and Drug Administration 1 March 2016. FDA website. www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/lucys-weight-loss-dba-waisted-lucy-02172016. Accessed 14 June 2019.
14. “Warning Letter: Andropharm, LLC.” US Food and Drug Administration 20 June 2017. FDA website. www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/andropharm-llc-522784-06052017. Accessed 14 June 2019.
15. “UAMS Establishes Center for Dietary Supplement Research.” Healthcare Journal of Little Rock, 13 May 2019. healthcarejournallr.com/news/uams-establishes-center-for-dietary-supplements-research. Accessed 14 June 2019.
16. Statement from FDA Commissioner Scott Gottlieb, MD.
17. FD&C Act, 21 USC§ 350b.
18. FD&C Act, 21 USC§ 342(f).
19. FD&C Act, 21 USC§ 350b (a).
20. Dietary Supplement and Nonprescription Drug Consumer Protection Act. Pub. L. 109 – 462, 120 Stat. 3469 (2006). https://www.congress.gov/109/plaws/publ462/PLAW-109publ462.pdf. Accessed 14 June 2019.
21. FD&C Act, 21 USC§ 379aa–1 (c).
22. FD&C Act, 21 USC§ 379aa–1 (e).
23. FD&C Act, 21 USC§ 342 (g)(2).
24. FD&C Act, 21 USC§ 342 (g)(1).
25. Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling or Holding Operations for Dietary Supplements, 21 CFR § 111 (2007).
26. Swift S. “Dietary Supplement Enforcement Statistics, Trends and Lessons Learned.” Dietary Supplements Regulatory Summit, 14 May 2019, Mayflower Hotel, Washington, DC. Conference Presentation.
27. FD&C Act, 21 USC § 342(f)(1)(A).
28. Ibid at (f)(1)(C).
29. Op cit 20.
30. FD&C Act, 21 USC § 350l.
31. “FDA Exercised FSMA Recall Authority for OxyElite Pro Dietary Supplements.” Food Safety News, 20 April 2005. www.foodsafetynews.com/2015/04/fda-exercised-fsma-recall-authority-for-oxyelite-pro-dietary-supplements. Accessed 14 June 2019.
32. Statement from FDA Commissioner Scott Gottlieb, MD.

 
About the Author
 
Since 2005, Steve Mister, Esq, has been president and CEO of the Council for Responsible Nutrition (CRN), the leading trade association for the dietary supplement industry. Under his leadership, CRN has experienced increased membership, refined its strategic focus and launched initiatives that center on increasing industry responsibility and consumer education. Prior to joining CRN, Mister served in several legal and legislative roles for over a decade at the Consumer Healthcare Products Association (CHPA), most recently as vice president and associate general counsel. Mister also worked as an attorney in the Washington, DC, law firm of Wiley, Rein and Fielding in general litigation, government ethics, and federal election law practice groups. Mister holds a law degree from the College of William and Mary and an MA in political communication from the University of Maryland. He can be contacted at smister@crnusa.org.
 
Cite as: Mister S. “Dietary Supplements and Public Safety: A Defense of DSHEA’s Three-Legged Stool.” Regulatory Focus. June 2019. Regulatory Affairs Professionals Society.