FDA again requests industry input on how to "enhance the quality" of its pre-market notification system for new dietary ingredients - a move that could be a step either toward or away from issuing much anticipated draft guidance, industry stakeholders say.

In a March 26 Federal Register notice, FDA says it will extend a provision in the Food, Drug and Cosmetic Act that requires manufacturers and distributors to notify the agency at least 75 days before introducing to the market a supplement with a new dietary ingredient.

Under the provision, FDA requires firms to submit the name and a description of the NDI along with safety information, history of use and other key information, according to the notice.

However, the agency may tweak these requirements. The Center for Food Safety and Applied Nutrition wants to know if there are "ways to enhance the quality, utility and clarity of the information" it collects about NDIs, the notice says.

In addition, the center wants to know if the information is even necessary or appropriate.

The Natural Products Association sees the information request as a positive step toward a much needed draft NDI guidance as well as a way to influence the NDI approval process.

An information gathering period "is not always the most exciting thing," but it frequently comes before the agency publishes a draft guidance, Daniel Fabricant, NPA's VP of science and regulatory affairs, told "The Tan Sheet."

Indeed, CFSAN has said it anticipates completing the guidance by the end of fiscal year 2008. This would include details on what kind of scientific information the center needs for NDI notifications (¹ Also see "NDI Notification Failures Concern FDA; Complete Submissions Urged" - Pink Sheet, 15 October, 2007., p. 8 and ² Also see "CFSAN Seeks Recommendations On Fiscal 2008 Priorities" - Pink Sheet, 9 July, 2007., p. 11).

However, issuing an NDI guidance has been a CFSAN priority for years and the agency requested substantive comments on the NDI system in 2004, American Herbal Products Association President Michael McGuffin points out.

He said he does not "see the fact that FDA issued this statement this week as evidence they have made progress on this topic."

"Three years ago we submitted substantive comments [on this topic] and it [is] of some concern that FDA is now saying, 'Hey, what do you think about this?' when we told them three years ago ... and have not heard from them since," McGuffin told "The Tan Sheet."

AHPA will submit comments again, but McGuffin asked whether FDA will respond this time. "We need FDA to respond. We need this to be a dialogue because the system is not working," he said.

It Is The Time To Identify Problems, Solutions

FDA's information request is a way for the industry and the agency to work together to address perceived problems with the current system, Fabricant said.

For example, he said the current information requirements are vague and firms do not always know what information to submit. He added that this, combined with the general lack of industry guidance, may explain in part why FDA approves less than half of the NDIs the industry submits.

Specifically, he said, the industry needs clarification from FDA on what specific information it requires for the pre-market notification review, such as a list of "minimum criteria."

NPA will confer with its members on what those criteria should be and submit suggestions to FDA by the May 27 deadline for comments.

McGuffin agrees with Fabricant that FDA needs to specify everything firms must submit in their pre-market approval applications.

He said FDA currently does not specify what firms must include in product descriptions, and it is unfair for the agency to deny notifications that do not include information not explicitly required by the regulation.

He said FDA, for example, does not require firms to say what part of a plant a product comes from, but the agency will "kick out" a pre-market approval application if it does not include that information.

In addition, he said FDA should more clearly define what constitutes a new versus old dietary ingredient, under the pre-market notification requirements. The regulations say a new dietary ingredient is one that was not marketed in the U.S. before Oct. 15, 1994 - when the Dietary Supplement Health and Education Act was enacted - but it is unclear how the agency defines "marketed," McGuffin said.

"We went out of our way to say we think 'marketed' means sold or offered for sale, and again we haven't heard back from FDA, so we don't have a clear agreement as to what is the line between old new and old," he said.

FDA Seeks To Reduce Burden: SDLI One Option

FDA also wants to know if it accurately estimated the time it takes firms to gather and submit the necessary information for NDI pre-market approval, and how to reduce this burden, according to the notice.

"FDA is estimating that the burden associated with the filing of an NDI notification is 20 hours per notification, which most companies would say is a substantial underestimate. Over the past few years, nearly 70 percent of all notifications have been rejected by FDA as inadequate, suggesting that the industry is expected to put much more information together for their notifications to satisfy the Agency's requirements," said Andrew Shao, VP of scientific and regulatory affairs for the Council for Responsible Nutrition.

Shao added that "with this expectation to see almost 'GRAS-like' notifications, most companies will have to use consultants or law firms to assist in the process, which will only increase the cost and the length of time necessary to put together a notification."

One way firms can lessen their burden is to use the Standardized Information on Dietary Ingredients protocol, which includes voluntary standards and forms "designed to alleviate some of the issues with questionnaires that get sent between manufacturers and suppliers to really streamline and normalize the process," Fabricant said.

SIDI was established by industry trade groups in 2006 (³ 'The Tan Sheet' Oct. 15, 2007, In Brief).

"FDA has informed us that the information provided in SIDI is exactly the same information presently lacking in most NDI notifications," Shao said. "When it comes to establishing the safety of an NDI, information such as the raw material source, method of manufacturing, potential contaminants, and so on, are all things FDA considers. This is the same information outlined in SIDI and the recommendation to utilize SIDI in this manner comes directly from the agency itself."

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

Request For NDI Input May Portend Much Anticipated Guidance – Industry

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