SALT LAKE CITYFDA has more than 146,000 pages of New Dietary Ingredient (NDI) Draft Guidance comments from around 7,000 unique entries to review, according to Daniel Fabricant, Ph.D., Director, Division of Dietary Supplement Programs, FDA, during a post comment webinar hosted by the United Natural Products Alliance (UNPA).
"We've got a large stack of paper," Fabricant said." And as much as I try, I'm not getting folks to come in on weekends." Fabricant said he could not give a timeline or comment on when a final version of the guidance may be released. The agency has receives requests for meetings with trade associations, and Fabricant said it is happy to hold those discussions.
Concerning to Fabricant, he said, even despite FDA releasing its current thinking on NDI notifications (NDINs), he expects to receive only about 50 NDINs for 2011, which is similar to the amount the agency has received every year since the passage of the Dietary Supplement Health and Education Act of 1994 (DSHEA). According to the Draft Guidance, FDA believes the number of NDINs should be much higher given the number of products on the market. Fabricant said NDINs are a requirement set forth in DSHEA, and is still an obligation firms must meet, regardless of the release of a finalor even draftguidance.
"People have confused the guidance with the statutory obligation," he said. Several times during the webinar, he brought up the point that a guidance is not law. " Whether people like the guidance or not, there's a statutory requirement," he said. "It's fine to be upset with FDA over the guidance, but we didn't write the law."
He added, "The key thing is that it is a Draft Guidance. Guidance or a draft guidance represents the agency's current thinking. It does not create or confer any rights for or on any person and it does not operate to bind FDA or the public."
Furthering this point, he said if a company doesn't like the Draft Guidance, it can choose to use a different approach to NDINs; however, he said, that alternative approach must comply with the relevant statues and legislation. "The agency is more than willing to discuss an alternative approach as long as it complies with statues and regulations," he said.
Next: Common Comment Themes
Common Comment Themes
Fabricant said FDA has just started to dig into the comments, and is just getting to a point of organization. "We're going to spend a good amount of time setting up a system to make sure we handle it all in compliance to good guidance practices and our administrative burden," he said. However, he did address some of the common issued raised.
WithdrawalHe the call to withdraw the Draft Guidance was curious to him because the purpose of the Draft Guidance was to seek comments on FDA's current thinking, not create law.
Supplement vs. ingredientFabricant pointed to sections 413 and 402 of DSHEA to show the law calls for supplement rather than ingredient notification. Section 402 describes conditions of use, and, "conditions of use aren't for dietary ingredients," he said. "A consumer doesn't use a dietary ingredient outside of a finished dietary supplement." Section 413(a)2 says, " on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe." Fabricant said the plain reading of the law calls for supplement notification. "I gather people are interpreting it a different way, but I don't the basis of their interpretation. It's explicit to what it says, 'a supplement containing such an ingredient.' What we did in the guidance echoed what is said in the statue."
However, he said people have confused the Draft Guidance to mean only supplement manufacturers can submit NDINs. He said the law says a manufacturer or distributor of the ingredient or supplement can file. He noted FDA has not objected to a number of notifications submitted by ingredient suppliers that have included a broad range of uses for an ingredient as well as a broad range of uses of that ingredient combined with other ingredients.
Fabricant also addressed FDA's 1997 Final rule, which many commenters said showed FDA expected only 12 firms would be financially burdened each year by NDINs. "It's obviously a very different day and age than 1997," he said. "There were 4,000 products on the market at the time of the passage of DSHEA, and now there are more than 5,500 by our estimates. The market has grown from a about a $2-billion-a-year industry to a $30-billion-a-year industry by some estimates. Obviously, things change."
Old dietary ingredient (ODI) listsFabricant said he wants clarification on how the trade associations made their lists of ingredients on the market before Oct. 15, 1994 and thus do not require NDINs. " This has been an area where we've seen a consistency in comments, but it's somewhat unclear from the comments exactly what documentation was used and the parameters to which it was evaluated. I think it's important to show if the cuts were objective or subjective."
During the Q&A, an audience member asked Fabricant if FDA or a company had the burden of poof to show when an ingredient was first marketed. "Depending on the argument made, a judge or a court could look at either side of things," Fabricant replied. "I don't know if I can answer per say because we really don't have a lot of case law, and I think that's something where they're may be some changes." He added FDA expects a company to be able to substantiate that a product was on the market before the cut-off date.
Safety requirementsSome comments, such as the Council for Responsible Nutrition and the Consumer Healthcare Products Association (CHPA) took issue with FDA's references to the Redbook, which was designed to assess the safety standards applicable to food additives. "What isn't helpful about the agency's thinking on how we arrived at reasonable expectation of safety?" Fabricant asked the UNPA webinar audience. He questioned if FDA would have received so much resistance if it had citied references the Redbook used verses citing the Redbook. "It certainly seems to be a differences between semantics versus science," he said. "Toxicology is toxicology. This is how the agency looks at toxicology whether its dietary supplements or bread."
AdulterationDuring the Q&A section of the webinar, Loren Israelsen, executive director, United Natural Products Alliance, asked Fabricant if the NDIN process would help reduce the number of adulterated products on the market, and if companies with such products would even choose to file. Fabricant said this process addresses those concerns, especially in regard to steroidal ingredients. "Those tend to be on the label," Fabricant said. "If they came to us first, we could point out that they are not dietary supplements to start with. Let's say someone believed they were a dietary ingredient and submitted an NDIN. That would give us a useful tool in terms of limiting those products on the market." Fabricant also noted some companies have submitted NDINs on products that have safety issues; he said the agency even received a notification for E. Coli. "The gate is there, and some people do go through it."
Chemical alternationMany commenters sid FDA's definition of chemically altered is too broad. Many noted supercritical carbon dioxide, for example, does not chemically alter an ingredient, yet, it's not on FDA's list of manufacturing techniques that do not trigger an NDI. Fabricant said FDA looks at these on a case-by-case basis. "Is would depend on the ingredient; is it chemically different than what's in the food supply? Does it break bonds? I think we were pretty clear on that in the guide." However, he noted, "We're still reviewing comments on this."
Intellectual Property (IP)Fabricant said FDA does an adequate job at keeping trade secret confidential. He said if firms indicate upon submission what's confidential, commercial information or trade secrets, the agency redacts it appropriately when they publish it in the docket. "If folks indicated on the way in, which most do if they want the information kept secret, I think we've done a good job of keeping that information redacted," he said.
GRAS/food additive as an alternativeA number of companies have questioned if they could be exempt from NDINs if their ingredient had GRAS (generally recognized as safe) or food additive status. In response, Fabricant turned to section 413(a)1 of DSHEA: "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." That includes GRAS substances, he said. "But the presumption is those are in the food supply. It's not just the GRAS gets submitted, and the ingredient goes into a dietary supplement. There needs to be evidence that it's in the food supply. That's how the statue reads."
EnforcementFabricant said FDA does not have the authority to grant an enforcement discretionary period to companies that have NDIs currently on the market without NDINs. "You read 413(a) [of DSHEA], and if it's something new, you've got to submit 75 days before going to market. If you're already on the market and you didn't submit , if would seem you're at odds with that."
When an audience member asked if NDIs would be a part of FDA GMP (good manufacturing practice) inspection, Fabricant said, "On any inspection, you should expect the unexpected and be prepare to be compliant."
For more on the industry's comments to FDA, read INSIDER's article, "NDI Draft Guidance CommentsIndustry Has its Say"
'Interesting Absent'Fabricant said the agency expected to get more comments on nanotechnology, the template for NDINs and the calculation of the number of supplements on the market. He said that must mean FDA did an accurate job of detailing its thinking on these issues.
Fabricant also reiterated FDAs believes its review of NDINs are an important preventive control mechanism to ensure consumers are not exposed to unnecessary risks.
For those who would like to see the comments, Fabricant said they can go to the docket at Regulations.gov and search for FDA-1995-S-0039. He said some of comments submitted by paper may not be available yet, and he noted that Rgulations.gov is not an FDA-only entity and this is a new system that may have bugs.
He also noted the agency will continue to accept comments on the Draft Guidance, but the reason for the formal comment period is to be sure FDA could consider them before issuing a final document.