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FDA Embraces Herbalife Master File Concept in NDI Guidance

<p>In draft guidance released in August, FDA cited circumstances in which a company submitting an NDI notification could rely on data from a master file, provided the person who submitted the master file granted written permission.</p>

Five years ago, in commenting on FDA draft guidance for the dietary supplement industry, Herbalife proposed the concept of a new dietary ingredient (NDI) master file.

Herbalife’s idea was intended, in part, to reduce the burden on industry to submit to FDA duplicative NDI notifications for the same ingredient.

“A system is needed to avoid unnecessary duplication as regards NDIs for the same product sold to different manufacturers," Herbalife explained in 2011 comments filed with FDA. “Also, a number of dietary supplement manufacturers produce products containing the same ingredients. Subsequent NDI notifications for supplement compositions relying in part upon the same ingredients would refer to the relevant master files and would not need to include additional safety data about the referenced ingredient."

In proposing the master file, Herbalife also sought to eliminate a separate problem: the practice of copycatting or piggybacking in which companies are marketing a substance that is identical to, or resembles, an ingredient that has been the subject of a successful NDI notification to FDA.

One argument against the piggybacking concept is that the copycats aren’t operating on a level playing field because they didn’t incur the costs associated with an NDI submission. According to industry sources, the financial burden associated with an NDI notification—including the costs of safety studies—can total hundreds of thousands of dollars or more. There’s also the question of whether, in fact, the copycat ingredient has the same safety profile as the ingredient that was subject to an NDI notification.

Referencing the master file proposal, Herbalife senior executive Vasilios “Bill" Frankos said his company was seeking to avoid “me-too ingredients that are knockoffs of NDIs that were successfully submitted" to FDA.

Last month in new draft NDI guidance, FDA expressed support for the master file concept. The agency cited circumstances in which a company submitting an NDI notification could rely on data from a master file, provided the person who submitted the master file granted written permission. The concept could make it easier for several supplement manufacturers to take an ingredient to market, while safeguarding an ingredient company’s proprietary information.

The master file concept “is supposed to minimize duplicative work," explained Loren Israelsen, president of the United Natural Products Alliance (UNPA), in a phone interview last month. “Number 2, it is to protect and provide value to intellectual property in the form of … safety and [toxicology] research. Number 3, it’s supposed to minimize the piggybacking where companies B, C and D are selling what they claim is the same as … company A."

Herbalife Favors List of Grandfathered Ingredients

In addition to the master file concept, Herbalife in 2011 proposed FDA establish a docket for 18 months in which companies could submit to the agency documents, such as advertisements and product catalogs, establishing an ingredient was sold in the marketplace before the passage of the Dietary Supplement Health and Education Act (DSHEA). Ingredients that were sold before October 1994 are grandfathered or exempt from the requirement to submit to FDA an NDI notification. Herbalife also proposed “FDA exercise enforcement discretion involving the informally grandfathered ingredients" during the 18-month period.

“FDA could opine in a Federal Register document on the acceptability of the data and then include products on a new master list that would be maintained by FDA," explained Frankos, Herbalife’s senior vice president of global regulatory compliance and product safety, in a phone interview.

In the 2016 draft NDI guidance, FDA revealed it is “prepared to develop an authoritative list of pre-DSHEA ingredients based on independent and verifiable data." However, FDA noted the dietary supplement industry would need to provide marketing materials to support the list since the agency “does not generally have access to marketing records for dietary ingredients and dietary supplements."

“There’s too much confusion in the marketplace as to whether or not an ingredient is an old ingredient or a new ingredient, and … companies are confused," Frankos said.

He described Herbalife’s docket proposal for establishing a grandfathered list as a “beginning point."

“It’s only a beginning list, and companies may come up with new information on their own that they would keep for themselves … but it certainly would make the industry more transparent," said Frankos, a former director of FDA’s Division of Dietary Supplement Programs. “Everybody will know that at least this Federal Register list is a starting place for you to decide on whether you have an old dietary ingredient or a new dietary ingredient."

The supplement industry has already started to compile materials to support an authoritative list. Last week, the Natural Products Association (NPA) announced it was “in the later stages of developing a comprehensive safe harbor list of pre-DSHEA dietary ingredients for the industry based largely on evidence from past media reports, advertising and other public sources."

“I know that just a magazine article that has the supplement listed with the ingredient would be enough to argue that it was marketed before 1994," Frankos said. “And in fact, when I was at FDA, I had that kind of evidence provided to me many times as evidence that an ingredient was an old dietary ingredient. Even though we didn’t know the details, at least we knew somebody had sold it."

In the 2011 comments, Herbalife also suggested FDA “accept as ‘grandfathered’ any pre-DSHEA substantiated herb or ingredient, that has not been ‘chemically altered,’ even if the pre-DSHEA documentation did not address the specific form of processing or extraction used to produce the dietary ingredient."

Under DSHEA, dietary ingredients that have been present in the food supply and not chemically altered are also exempt from the requirement to submit an NDI notification to FDA. Frankos asserted there are at least around 250 GRAS (generally recognized as safe) notifications for ingredients used in foods that could be incorporated in dietary supplements without an NDI notification—as long as the ingredients are not chemically modified.

“All you have to do is say these herbs, these spices, all can be used as long as you don’t extract them with anything other than water or alcohol or tincture," Frankos said. “You could just kind of grandfather them all into your master file."

Editor's Note: Interested in learning more about what’s happening at FDA around dietary supplements? Join FDA’s Cara Welch, Ph.D., senior advisor to the Office of Dietary Supplement Programs, in the SupplySide West Featured Speaker session on Thursday, Oct. 6, at SupplySide West 2016.

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