In February 2019, prior to leaving FDA, then-Commissioner Scott Gottlieb, M.D.—who said he uses supplements—unveiled a multipronged plan that he said would “modernize” how FDA regulates supplements.” Per Gottlieb, “DSHEA imposes a number of requirements around the manufacture and labeling of supplements.”
He stated: “We know most players in this industry act responsibly. But there are opportunities for bad actors to exploit the halo created by quality work of legitimate manufacturers to instead distribute and sell dangerous products that put consumers at risk. … As the popularity of supplements has grown, so have the number of entities marketing potentially dangerous products or making unproven or misleading claims about the health benefits they may deliver.”
Dr. Gottlieb’s proposed FDA modernization initiatives include:
- Quick communication to the public when FDA has a concern about a dietary supplement on the market. On April 16, FDA unveiled the Dietary Supplement Ingredient Advisory List to alert the public when it identifies ingredients that do not appear to be lawfully marketed. Higenamine and hordenine (the latter occurs in bitter orange) appear on the list based on a preliminary assessment by FDA (FDA views this ‘list’ as the step before issuing warning letters).
- Ensuring the regulatory framework is flexible to adequately evaluate product safety while promoting responsible innovation.
- Establishing a Botanical Safety partnership to promote scientific advances in evaluating the safety of botanical ingredients and mixtures in supplements (underway by the American Botanical Council (ABC), American Herbal Products Association (AHPA), the Supplement Safety and Compliance Initiative (SSCI) and others).
- Consideration of a mandatory supplement listing process. Today, supplement firms may voluntarily “list” products by submitting labels to a database maintained by the Office of Dietary Supplements (ODS) within the National Institutes of Health (NIH). They also can submit labels for inclusion in the Supplement Online Wellness Library (OWL). Or firms can submit labels for evaluation by Natural Products Association’s (NPA) Tru-Label Program. However, I estimate these voluntary databases contain less than one-third of the labels for all products on the market. In May, former U.S. Sen. Orrin Hatch (R-Utah) said in an interview with Natural Products INSIDER that a mandatory listing “makes sense” to him. In its (FY) 2020 budget request to Congress, FDA reported it didn’t have clear authority under the law to require a listing of dietary supplement products on the market.
In passing a January 2019 appropriations bill, Rep. Nita Lowey (D-New York)—Chair of the House Committee on Appropriations—asked FDA to respond within six months as to its activities and staff involving the manufacturing and marketing of supplements. A paragraph in a Wall Street Journal story published April 18 is typical of the media’s perception of the industry’s regulatory framework: “Supplements aren’t tightly regulated by the FDA like prescription drugs. Dietary supplement manufacturers don’t need approval from the FDA before introducing their products to the market. The FDA has oversight for taking action against any misbranded supplement after it reaches the market.”
Some stakeholders say no new regulations or laws are necessary; instead, FDA should do a better job enforcing existing provisions while going after so-called bad actors. As NPA CEO Dan Fabricant, Ph.D., observed in an interview with Nutraingredients-USA, “Why are we talking about modernizing something that has never been fully implemented?”
FDA’s Office of Dietary Supplement Programs (ODSP) has only 24 full-time equivalent positions and three interim staffers responsible for enforcing regulations affecting more than 2,000 firms and perhaps as many as 80,000 products, according to Gottlieb. ODSP lacks the resources it needs to protect the public’s health while ensuring a level regulatory playing field.
At FDA’s May 2019 hearing on “responsible innovation,” some witnesses said:
- Everything should have a new dietary ingredient notification (NDIN) unless grandfathered.
- GRAS (generally recognized as safe) has six to seven times more determinations than NDIs.
- Companies have conflicts of interest when they retain scientists to self-affirm ingredients as GRAS.
- FDA should to create a master file concept applicable to NDIs, in which FDA must keep safety data confidential indefinitely.
- FDA must enforce if companies do not submit NDIs.
- Firms that succeed in receiving an NDI acknowledgement letter should get return for their investment in science from FDA.
In response, FDA said it will update its NDI compliance policy.
FDA has objected to NDI notifications due to safety concerns or for other reasons, including incomplete filings. Critics suggested distributors and manufacturers “dodged” statutory obligations since typically only a handful of NDI notifications are successful each year.
FY18 Data Regarding NDI Notifications (NDINs)
|FDA responses to NDINs||38|
|Acknowledgement letters w/out objection (AKL)||17 (44.7%)|
|Not dietary ingredient/dietary supplement (NDL)||4 (10.5%)|
|Inadequate safety/identity (IAL)||11 (29%)|
|Incomplete (ICL)||6 (15.8%)|
Source: Bodybuilding.com Freedom of Information Act (FOIA) request
During the past quarter century, I have been active within the ingredient and supplement industry while at Pfizer, Herbalife and now Bodybuilding.com. I have served on the boards of AHPA, the Council for Responsible Nutrition (CRN) and have been a member of the Consumer Healthcare Products Association (CHPA) as well ABC. Today, I serve as vice chair of NPA. Based on this experience, I offer structural and procedural recommendations to improve the regulatory framework over dietary supplements.
Let’s make government more efficient. Supplements are regulated as food in the U.S. Let’s consolidate all of America’s food policy activities under one roof. Move the Center for Food Safety and Applied Nutrition (CFSAN) plus ODSP from FDA into an enhanced U.S. Department of Agriculture & Nutrition (USDAN) having jurisdiction over all U.S. food and nutrition policy, regulations and enforcement.
Increase accountability. FDA centers and offices should be held accountable, and not be allowed to defer or delay the issuance of rules or final guidance for unreasonable periods of time; key is defining “unreasonable.” Within one to two years of seeking public comment on an issue, the agency must take final action concerning matters in question. Rules or guidance should be declared null and void if they cannot be completed and issued as final in less than two years from their initial publication in the Federal Register seeking public comment. Further, we should require FDA or USDAN to notify the Office of Inspector General (OIG) when the agency learns of potentially violative products from tips or inspections. Monthly, USDAN must inform OIG as to the status of investigations that should be completed in no more than one year following receipt of the initial complaint. Federal employees found to have not properly executed their responsibilities should be held accountable and be subject to demotion or termination .
Make more resources available. Let’s give FDA/USDAN the authority not only to seize violative products, but also to disgorge assets from offending parties. Seized assets could be used to add full-time employees (FTEs) to ODSP so it could more effectively enforce current regulations.
Give the director of ODSP more authority. ODSP’s current director, Steven Tave, and his successors, should be able to sign warning letters as directors of other FDA centers can today.
ODSP and other FDA personnel should be precluded from misinterpreting DSHEA. They should also be precluded from making policy decisions not supported by the law. This is subtle and needs broad industry involvement. An example is suggesting NDIs cannot be synthetically derived. FDA has confused matters by previously accepting NDINs for synthetically derived ingredients.
Increase transparency. FDA does not post all 483s following cGMP (current good manufacturing practices) inspections. Nor does FDA make public summaries of signal detection assessments of post-marketing surveillance serious adverse events (SAEs) received by the agency. ODSP should be required to:
- Post all 483s within one month (update with new info).
- Post all NDINs (without disclosing confidential information) and indicating status of the NDIN.
- Quarterly, redacted summaries of SAEs and its data assessment so stakeholders can understand the potential for health risks given signal detection.
Also, FDA should promulgate a list of sanctioned, validated analytical methods by which industry or consulting labs can have confidence when conducting content analysis.
Create a ‘living list’ of ODIs. With input from stakeholders, government should sanction a “living” list of old dietary ingredients (ODIs) to provide surety of ingredients the industry may use without having to file an NDIN.
Implement a mandatory product listing. Industry should embrace a proposal articulated by Gottlieb and supported by attorney Scott Bass of Sidley Austin—a key player in drafting DSHEA—to establish a mandatory listing requirement. Marketers could go online and list the name of each dietary supplement they sell together with contact information for both the marketing company and the manufacturer. However, this must come with federal preemption.
Protect investment in science by implementing a master file concept for NDINs. FDA should promulgate a legal mechanism to establish master file provisions providing exclusivity—similar to a concept currently available to the pharmaceutical industry. This will help innovators who make a successful NDIN secure a type of exclusivity supported by FDA enforcement to preclude the marketing of knock-off ingredients from entities that did not invest in the science unless they licensed the compound from the owner of the successful NDIN.
Help consumers better understand product benefits. Since DSHEA was enacted, science has advanced. The capacity for responsible firms to communicate ingredient benefits to consumers is limited to simplistic structure/function claims, nutrient-content claims, or to qualified or full health claims sanctioned by FDA. A regulatory framework should be established permitting claims such as “enhances” or “improves” when well-designed clinicals confirm such benefits when specific ingredients are used at efficacious levels. Also, we should consider adoption of “permitted” health claims from Australia, Canada or the U.K.
More inspections, more enforcement. ODSP should be required to conduct more cGMP inspections of manufacturers and holding facilities. Set as a benchmark a minimum of 15% of the registered facilities be inspected annually (those found in non-compliance to be re-inspected more quickly). Perhaps it’s time to consider a nominal inspection fee as well to help defray personnel costs for inspection. If FTEs cannot be hired and trained, FDA might contract with qualified third-party independent inspectors.
Take action on CBD. NPA is lobbying Congress to pass legislation (now in the Senate) mandating FDA to conduct a health hazard assessment (costing $100,000) to evaluate available CBD safety data to determine a safe per serving and daily exposure limit. Following its May 31 CBD hearing, FDA said it would keep stakeholders informed as it considered its policy options that may include time-consuming rule-making. Yet, thousands of products in the market contain CBD/CBD oil (that FDA repeatedly stated is a violative ingredient). Some of these products may contain heavy metals, pesticide residues, synthetic substances or ingredients of concern.
DSHEA has worked well. However, without improvements, we face a growing dichotomy between responsible companies and industry outliers. As industry reflects on 25 years of DSHEA, now is the time to give serious consideration to the proposals above.
John Venardos is vice president of regulatory and government affairs with Bodybuilding.com. He also serves as vice chair of the board of directors of the Natural Products Association (NPA), a trade association in Washington for dietary supplements.
Editor's note: If you are attending SupplySide West, don't forget to check out the featured session on DSHEA at 25 years old. Business executives and trade show leaders will discuss implementation of DSHEA, its future and new expectations.