Star Scientific, FDA Dispute Reflects NDI Uncertainty

WASHINGTON—A warning letter FDA sent to Star Scientific Inc., and the company's response, highlights a potential disagreement between the agency and the dietary supplement industry over the regulation of new dietary ingredients (NDIs).

Anatabloc, a Star Scientific dietary supplement that is intended to maintain lower levels of inflammation, includes an ingredient known as anatabine. In a Dec. 20, 2013 warning letter, FDA claimed Star Scientific needed to submit an NDI notification to the agency because anatabine was a new ingredient that had not been present in the food supply in a form that had not been chemically altered.

While acknowledging "anatabine is present as an inherent constituent of foods such as cauliflower, eggplant, potatoes, and tomatoes," FDA said it was unaware "of any information indicating that anatabine itself is an article used for food."

Star Scientific of Glen Allen, VA, challenged FDA's interpretation of Section 413(a)(1) of the Dietary Supplement Health and Education Act of 1994 (DSHEA). That provision excuses a supplement firm from a requirement to notify FDA about an NDI at least 75 days before introducing a product into interstate commerce so long as the "dietary supplement contains only dietary ingredients which have been present in the food supply as an article used for food in a form in which the food has not been chemically altered."

Per DSHEA, a substance that was marketed as a dietary ingredient before Oct. 15, 1994 is not considered an NDI.

Paul Hyman, outside counsel for Star Scientific, didn't dispute that anatabine is an NDI, but he told FDA his client didn't have to submit a notification because Star Scientific satisfied Section 413(a)(1).

As the agency acknowledged, he noted, anatabine has been present as a constituent of foods. Hyman also said the substance had not been chemically altered.

In a Jan. 31, 2014 letter to FDA, Hyman indicated FDA is imposing a requirement in Section 413(a)(1) that doesn't exist: that an NDI—anatabine in this case—had to have been marketed to qualify for the notification exemption.  

"Applying the exemption from notification in § 413(a)(1) to dietary ingredients that have been 'used as a food or as an ingredient in a food' is tantamount to requiring that the dietary ingredient have been 'marketed' as a food or food ingredient, and essentially reads section § 413(a)(1) out of the statute," Hyman of the Washington, D.C.-based law firm Hyman, Phelps & McNamara wrote.

Star Scientific declined to comment further beyond Hyman's letter.

FDA continued to defend its interpretation of DSHEA. "The answer is that we continue to stand by what we asserted in the warning letter," FDA spokesman Arthur Whitmore said.

Definitional Dispute

The legal question potentially dividing FDA and Star Scientific is what precisely qualifies under Section 413(a)(1) as "present in the food supply as an article used for food."

FDA is essentially declaring the constituent present in the food, such as anatabine, needs to have been marketed for its properties in order to qualify for the notification exemption under Section 413(a)(1), said one dietary supplement lawyer who agreed to speak on condition of anonymity because of the uncertainty surround the issue.

"FDA is going to take a very narrow position as to what that means 'in the food supply," said another supplement lawyer.

The agency may clarify its position in the reissuance of the NDI draft guidance it hopes to release in 2014 after having consulted with dietary supplement representatives. The industry previously raised a number of concerns over the draft guidance FDA released in 2011, which included differences of opinion as to what constitutes chemical alteration under Section 413(a)(1).

"We are currently communicating with the FDA in an effort to reach an amicable resolution of the issues asserted in the warning letter," Star Scientific stated in its annual filing on March 17, 2014. "In light of our receipt of the FDA letter, we have substantially limited the marketing and advertising of our dietary supplements."

Governor's Probe

The warning letter to Star Scientific raised a number of issues and is not the company's only challenge.

Last year, Star Scientific founder Jonnie Williams resigned from his post as CEO amid a political scandal tied to former Virginia governor Robert McDonnell.

According to a 14-count criminal indictment filed in the U.S. District Court for the Eastern District of Virginia against McDonnell and his wife Maureen, from April 2011 through March 2013, the couple improperly accepted more than $135,000 from Williams in direct payments as gifts and loans, thousands of dollars in golf outings and other things of value. In exchange, the indictment claims, McDonnell arranged meetings for Williams with Virginia government officials, hosted events at the Governor's mansion in order to encourage Virginia university researchers to begin studies of Star Scientific's products and promote them to doctors, and contacted other officials part of an effort to support the company.

McDonnell and his wife are seeking separate trials, in a move legal experts told The Washington Post could benefit them. The defendants have pleaded not guilty to the charges, and a jury trial is scheduled for July 28.

Cash Situation

Star Scientific has been operating at a loss for 11 consecutive years with a cumulative deficit of USD $264.4 million as of Dec. 31, 2013, and the company has said investigations into its business have exacerbated its cash crunch.

Although Star Scientific, its directors and others have received subpoenas from the U.S. Attorney's Office (USAO) for the Eastern District of Virginia seeking documents, the company has expressed the view that USAO will not prosecute it for any matters it is investigating.

In its annual report, Star Scientific said it expected to continue incurring legal expenses this year in connection with the USAO investigation. Star Scientific also expressed its opinion that the probe into the company was "nearing completion".

Last month, Star Scientific raised $15.1 million in gross cash proceeds ($9.3 million) and for availability under a credit facility ($5.8 million). Star Scientific said the latest financing is intended to support its operations, including plans to file an investigational new drug application during the second quarter of 2014, and subject to FDA authorization, begin a clinical trial.

The company reported 2013 revenues of $9.1 million and a loss from continuing operations of $33.1 million. Most of Star Scientific's revenues come from Anatabine rather than its product CigRx, which was introduced in 2010 and is intended to reduce the urge to smoke.

According to its annual filing, the supplement company is banking its long-term future revenues on successful implementation of a "drug development program," although Star Scientific cautioned "it has no drug products in advanced development as of this date."