FDA is stumped on interpreting and enforcing a provision in the FDA Amendments Act of 2007 that could have a chilling effect on development of new functional food and dietary supplement ingredients, an FDA official and an industry leader say.

The little known provision, added to section 301 of the Food, Drug and Cosmetic Act, prohibits the sale of any food product to which a firm has added an approved drug, licensed biological or "a drug or biological product for which substantial clinical investigations have been instituted and ... made public," according to the FDA reauthorization legislation signed into law by President Bush in September 2007 (¹ Also see "Pre-emption Limits Survive Congress, But Will Face Supreme Court" - Pink Sheet, 1 October, 2007., p. 11).

The provision is "incredibly broad" and "conceivably could block ... an awful lot of new food or dietary ingredients from getting to the market," if FDA interprets the provision literally, Marc Ullman, a food and drug attorney, told "The Tan Sheet."

Ullman explained that the law does not define "substantial clinical investigation." As a result, it could prohibit firms from selling foods with a new supplement ingredient that underwent any clinical study - including safety or intentional-claims studies - unless it has formal FDA approval or fits into one of the law's narrow exceptions.

"If you read it literally, you could" interpret the law that way, Laura M. Tarantino, an FDA Center for Food Safety and Applied Nutrition executive, said at a Feb. 20 Food and Drug Law Institute conference.

However, Tarantino, director of CFSAN's Office of Food Safety, said "one would assume that the intent" of the provision "is not to have a disincentive to have studies you need to show that something is safe."

She acknowledged, though, that "you could read this as a real disincentive to do studies" to identify additional health benefits of ingredients.

Tarantino explained the law does not limit the definition of "substantial clinical investigation" to ingredients investigated as part of a new drug application, as an investigational new drug or authorized for investigation in a new drug, antibiotic or biologic.

Existing language in the FDC Act's dietary supplement exclusionary clause limits "substantial clinical investigation" to those activities.

Rather, the new law "implies that ... as long as there have been substantial investigations on the substance, then you've got a problem," Tarantino said.

For example, she said, "What if you do a clinical investigation to support the use of a new ingredient in infant formula. Have you now taken that new ingredient out of the possibility of adding it to infant formula because it is now prohibited under" the provision?

While under a literal interpretation of the law the answer is yes, FDA is unsure whether that is how it should interpret the law, Tarantino said.

"We are spending a lot of time thinking about this," and trying to determine the significance of the different language in this law compared to the Dietary Supplement Health and Education Act, she said.

"We don't know how much discretion we will have in terms of how broadly or narrowly to interpret this. ... There is no legislative history for this particular provision ... so we don't have that to fall back on," she added.

FDA Likely To Seek Industry Guidance

Facing a dearth of congressional guidance, FDA will likely ask the industry for help interpreting this provision, either through guidance, a notice, a meeting, a regulation or some other process, Tarantino said.

"We are interested in finding out what is the universe of products [affected by this provision and] what is the impact of various ways we might interpret some of these terms," she said.

"People should be looking at this and thinking about it. ... We are encouraging people very much to engage with us and give us any useful information," Tarantino added.

While there is currently no mechanism for communicating with FDA on this issue, industry leaders should review the provision and watch for additional guidance from the agency, said Ullman, of the New York-based Ullman, Shapiro and Ullman.

Enforcement, But Also Exceptions

Until FDA determines how to interpret the provision, the agency likely will not take action against foods with functional or dietary supplement ingredients under clinical investigation that entered the market after the provision went into effect, Tarantino said.

Likewise, exemptions in the provision could protect new foods or products from enforcement if they are introduced after FDAAA became effective, she said.

However, lawyers participating at the conference and in commenting in FDAAA analyses say the exceptions are narrow and in some cases just as difficult to interpret as the law.

One exemption protects foods with drugs or biologics if the ingredient "was marketed in food" before it was approved as a drug or biologic and before researchers undertook any substantial clinical investigations.

The law also exempts foods with drugs or biologics that are FDA-approved for use in food products.

While this appears to be a "broad" exception, firms must petition FDA for approval which is a lot of work, Ullman said.

Likewise, under another exemption FDA will allow foods with drugs or biological products if the ingredients are added to food "to enhance the safety of the food" and do not have an "independent biological or therapeutic effect on humans," FDAAA says.

For example, "adding antimicrobials to food to reduce the level of food borne pathogens" would be covered by this exception, Tarantino explained.

However, to qualify for this exception, products also must be approved food additives or accepted by FDA as generally recognized as safe, or must have been marketed as a smoking cessation product prior to the enactment of FDAAA, according to the provision.

Finally, the law allows exemptions for new animal drugs that are "not unsafe."

- Elizabeth Crawford (e.crawford@elsevier.com)

FDA Stymied By Reauthorization Terms That May Slow Ingredient Development

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