FDLI Supplement Regs Conference: Day Two

WASHINGTON—The second day of the Food and Drug Law Institute (FDLI) conference on "What you Need to Know Now about Emerging Dietary Supplements Issues & Trends" featured several key regulatory issues, including New Dietary Ingredients (NCIs), GRAS (generally recognized as safe) status and adverse event reports (AERs), as well as insights on emerging trends and challenges in the supplement industry.

Vasilios Frankos, Ph.D., director of the Dietary Supplement Program at CFSAN/FDA, provided an overview of the AER regulation, from the form for filing AERs to responsibilities of manufacturers and even retailers (private label goods). He made a few key notes, including the FDA's position that a full address of the responsible party must be on each product label, and 3500A forms cannot be submitted via FAX or online—although he said online should be possible in the future, maybe even later this year.

Providing the industry prospective on AERs was David Spangler, senior vice president of the Consumer Healthcare Products Association (CHPA). AER tracking can produce safety signals, which Spangler explained could help companies address quality issues. He also took issue with FDA's assertion that labels must specify the contact address is for AERs, noting consumers contact such companies for a variety of reasons and might be confused by only seeing contact info labeled only with AERs.

Covered more from a scientific perspective in day one of the conference, NDIs were given the legal treatment from Ullman, Shapiro & Ulman partner Marc Ullman, who was instrumental in creating this FDLI conference. Ulman deciphered the finer points of the regulation, including what defines a NDI vs. an "old dietary ingredient," specific on when to notify FDA of an NDI, what information must be contained in an NDI notification, who should prepare and submit the NDI, what happens after the initial NDI is submitted, and common errors made in NDI filings.

Another hot regulatory topic is achieving GRAS status, a process outlined by Michael Falk, Ph.D., executive director of the Life Sciences Research Office (LSRO). Working through a flow-chart, Falk explained the process from the initial decision to market a product as either an FDA-approved food additive or a GRAS to the final stage of either notifying FDA or self-affirming GRAS without the agency's review. He urged leaving GRAS process to the experts by assembling an expert panel for review of the dossier prepared by the company, which should include well-established trials and other scientific publications adequately affirming safety. He further noted the ingredient should be well-characterized chemically and technically, have supporting historical data on food usage, as well as on pharmacokinetics and consensus on safety by other scientific and regulatory bodies.

As part of the exploration of emerging trends, Michael McGuffin, president of the American Herbal Products Association (AHPA), provided an in-depth look at how California's Proposition 65 is affecting and could affect the dietary supplement industry operating in that state. Prop 65 features a state list of more than 800 chemicals "known to cause cancer or reproductive toxicity; every product containing certain levels of any such compound must feature a Prop 65 warning on its label. Due to the writing of the regulation, private plaintiffs can initiate lawsuits against companies for Prop 65 label violations, despite having little to no original evidence. This means, any published report claiming an ingredient or product contains a banned substance above allowable levels is enough for a plaintiff to sue anyone marketing or retailing any product containing that dietary ingredient that is not labeled for Prop 65. McGuffin warned the law is here to stay and, as written and enacted, can not be amended other than to "further the purposes of the law, meaning no weakening its provisions. For supplements, the issue is mainly of heavy metals, which sometimes occur naturally in botanicals and other supplements. He said the best move by industry is to continue to work with the attorneys general in California to reach settlements on special allowances for certain dietary ingredients, as was done for calcium and certain botanicals.

Capping off the informative conference was Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), who looked at several emerging issues for industry, including the FDA Amendments Act of 2007 (FDAAA), the Consumer Products Safety Improvements Act of 2008 (CPSIA) and new OTC-supplement combinations. Mister reported a new section (301LL) of FDAAA sets up a battle between pharma and supplement industries, as it essentially establishes a race-to-market—if an ingredient was marketed as a food first, it remains a dietary supplement, however, if it underwent any substantial clinical investigations, the results of which were made public, before being marketed as a food, then it is prohibited from interstate commerce in food. This has forced the supplement industry to go back to old catalogs and sales invoices to prove certain supplement ingredients were marketed before undergoing clinical investigations as drugs. This has the potential to remove many food ingredients from the market.

On CPSIA, Mister said the primary part of the law affecting supplements is in provisions protecting children from products that pose a risk of poisoning. While this was aimed mostly at lead-containing toys, supplements containing iron are also at risk of enforcement, namely those with more than 250 mg per container (not per dose).

Mister closed the conference on one of most interesting issues facing the industry, OTC-supplement combination products. Bayer recently drew swift reaction from regulators over its combination aspirin-sterols heart health product, which bears both supplement facts and drug facts panels. Among the concerns and issues to confront are: communicating the proper use(s) to consumers; ability to deliver proper dosing instructions (dosing durations for inflammation drug vs glucosamine could be opposite, making a combo product tricky); potential contraindications between OTC and supplement ingredients; and the extent of potential benefit to consumers by such combo products. In the end, Mister's view was these products could be of great benefit to consumers, so it behooves FDA and industry to work together to find ways to solve labeling and marketing issues and allow safe such combo products to market.