Grief over Grandfathered-Ingredient Lists

Photo © iStockphoto.com/seanami

Grandfathered-ingredient lists are a valuable resource to the dietary supplement industry because they help designate ingredients marketed in the United States prior to October 15, 1994-the regulatory date that separates old dietary ingredients (ODIs) from new dietary ingredients (NDIs). According to the Dietary Supplement Health and Education Act, if supplement firms want to bring a new dietary ingredient to market, they must first submit NDI notification to FDA. No notification is required for old dietary ingredients (or, pre-DSHEA ingredients, the term FDA now uses).

FDA itself has never created an official list of pre-DSHEA ingredients. What’s more, FDA continually refuses to recognize any industry-created grandfathered lists, such as those compiled by trade associations. Just as it did in its July 2011 NDI draft guidance, FDA again said in its August 2016 revised NDI draft guidance that the agency will not recognize these third-party lists.

But the agency has changed its mind on one point: in the revised guidance, FDA said it would consider building an official grandfathered list of its own. “We are prepared to develop an authoritative list of pre-DSHEA ingredients, based on independent and verifiable data,” FDA said in the guidance.

An Official Grandfathered List: Good or Bad for Industry?

Would an official, FDA-created grandfathered list help or hurt the industry? This depends on how the list would be used, industry leaders say.

A centralized list that helps industry companies ascertain whether certain ingredients are “old” or “new” would definitely be helpful and convenient. Not only that, but some companies may be more at ease relying on an official government list over third-party lists.

“I understand why some companies get comfort from the idea that we would have a single, standardized and accepted official list,” says Michael McGuffin, president of the American Herbal Products Association (AHPA).

Part of this comfort lies in the safe-harbor nature of a list, says Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN). “If [your ingredient] is on the list, then you have a safe harbor that [indicates], ‘Okay, so this is something that everybody agrees is old,’” he says.

However, industry leaders say they would only want such a list if the list does not, intentionally or not, come to represent an all-inclusive list.

“FDA said in the guidance that the absence of an ingredient on their official list doesn’t mean that you’re new, but if you are on the list, then you have a safe harbor,” says Mister. “That’s the way I would look at this official list that they’re talking about compiling. It’s the creation of a safe harbor for really tried-and-true ingredients, but the absence of being on the list does not mean that you are going to have a target on your back.”

Not everyone is convinced the list won’t be considered comprehensive, however. “I’m fearful that FDA will reject everything that we’ve got outside of that very narrow list,” says McGuffin, adding, “I will speculate that FDA wants it because they then [can] use it as a positive list…and they make an assumption that if it’s not on the list, it must be new, from a regulatory perspective.”

FDA Rejects Industry Grandfathered Lists, Calls for Evidence

And then there is the matter of creating the official list itself. This is no easy task, mainly due to the evidence FDA requires in order to classify an ingredient as a pre-DSHEA ingredient. In the past, FDA has said it requires material proof showing that an ingredient was sold on the market in the United States prior to October 15, 1994. This evidence could include things like magazine advertisements, bills of sale, or television commercials proving the ingredient was in commerce.

FDA has long said the reason it rejects industry-created grandfathered lists is because not all of the ingredients on those lists are backed by physical evidence of sale. The agency reiterates this in the revised draft guidance: “FDA is unable to verify the accuracy of these lists because we have not seen documentation showing that the ingredients on such lists were marketed as dietary ingredients prior to October 15, 1994.”

In terms of evidence, FDA’s revised guidance also makes mention of AHPA’s Herbs of Commerce, a book containing information on thousands of plant species and that Tony Young, AHPA’s general counsel and partner at Kleinfeld, Kaplan, and Becker LLP, described in an AHPA webcast as “pretty clear evidence of marketing prior to 1994.” Nevertheless, according to FDA in the revised guidance, “If you rely on Herbs of Commerce as evidence that your dietary ingredient is not an NDI, we recommend that you maintain additional documentation showing that the botanical was marketed as a dietary ingredient before October 15, 1994.”

FDA even strikes down the option of affidavits standing in as evidence. “Affidavits attesting to recollection of when a dietary ingredient was first marketed generally would not be adequate to show that an ingredient was marketed prior to October 15, 1994, unless supported by contemporaneous written records,” the revised guidance reads. “Because memory can be unreliable, especially when the event in question took place more than thirty years ago, we are not likely to regard such an affidavit alone, without any sort of objective, verifiable documentation from the time of marketing, as an adequate basis to establish pre-DSHEA marketing of a substance as a dietary ingredient for use in or as a dietary supplement.”

The whole reason why evidence of commerce may be lacking makes sense: companies may not have saved magazine advertisements, etc., from as far back as 1994.

The Natural Products Association (NPA), for instance, is one organization that began compiling its own list of grandfathered ingredients. Dan Fabricant, NPA’s executive director and CEO, says, “That list was developed long before us. Those materials that they used to develop those lists, we have no idea where those are and what those are. So, in a lot of ways, while that list is probative, we’ve got to develop somewhat of a new list.”

Industry leaders are uncertain whether those marketing materials will ever be found. If they aren’t and FDA ultimately refuses to add longstanding dietary ingredients to its list, then the agency’s “official” list would be very narrow-or, as AHPA’s McGuffin says, “I’m fearful that their approach would go toward establishing qualifications that are so extreme as to not produce an actual accurate representation of the ingredients that were in the marketplace in 1994.”

Industry leaders have criticized the agency for taking so long from the time DSHEA passed in 1994 to deliver NDI guidance. During that time, industry says, valuable evidence was lost.

“This is one of the things that we’ve said to FDA: ‘Shame on you FDA. It took you 22 years to do this, and now it’s unrealistic to put those kinds of burdens on the industry when you sat on your hands for 22 years. Because in that time frame, we moved from basically a paper society to an online, digital society, and a lot of those records have been lost,'” says CRN’s Mister.

What’s more, “companies who have only come into the industry [recently] don’t have any records from 1994,” Mister says. “Even for something like a multivitamin, they don’t have records that show that it was being marketed in 1994 because they weren’t around then. So we’ve got to create some ways for newer companies to be able to rely on something for these grandfathered ingredients.”

“It’s going to be an ongoing problem, and as time goes on, it becomes perhaps more and more difficult to establish if something was grandfathered,” said A. Wes Siegner, Jr., of law firm Hyman, Phelps & McNamara, during an AHPA NDI webcast.

Some even believe that FDA is looking for evidence beyond marketing materials.

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“Here is our problem,” said Loren Israelsen, president of the United Natural Products Alliance (UNPA), during an August UNPA NDI webcast. “Twenty-two years have passed, and most of the important data that FDA has described in terms of marketing materials-brochures, catalogues, price lists-these kinds of documents, because they were consumer-facing and retail-facing, they exist. But what FDA seems to want is to see manufacturing records so they can look at the types of solvents that were used, the types of manufacturing processes, to decide if something was old based on how it was made.”

“They’d like to have more information about how the product is made so that they really understand if somebody changes the manufacturing in a significant way, that it’s different,” says Mister. “So, for instance, if I say, ‘Echinacea, it should be a grandfathered ingredient.’ FDA wants to see how was that Echinacea was made. Was it a tincture? Was it an extract? And if it was an extract, what were you using to extract it? Water and alcohol? Because now, if starting in 1998 I started using supercritical CO2 extraction, I may be pulling entirely different phytochemicals out of the Echinacea that I wasn’t pulling out in 1994. That could be a new ingredient.”

However, Israelsen pointed out, obtaining those types of manufacturing records is no mere task. “That is a much more difficult exercise, to get those records, which were always behind the wall in terms of being interior to the company. Standard document-destruction policies would call for getting rid of a lot of those documents, particularly at the end of expiration life of the finished products.”

In short, tracking down this type of information “is a big project that will require discussion to see who can and will share documents and records,” Israelsen said.

Can Industry Help?

FDA continues to place the burden of providing pre-DSHEA marketing evidence squarely on industry’s shoulders. The agency states this plainly and simply in its revised draft guidance: “Because FDA does not generally have access to marketing records for dietary ingredients and dietary supplements, the documentation of pre-DSHEA marketing would have to be supplied by industry.”

FDA is saying that “if you want an [old dietary ingredient] list that’s authoritative, you’re going to have to give us that information,” Israelsen said.

The question, however, is not only whether industry can help provide marketing evidence to create an official grandfathered list; the question is whether the industry needs to help with this. Because while an official grandfathered list might be helpful to industry companies, the fact is that the industry does not have a regulatory burden under DSHEA to prove that ingredients are old.

“The burden is not on the industry to show that you’re old,” CRN’s Mister says. “The burden is on FDA to show that you’re new.”

He continues, “The very first issue is who has the burden of proof here. That is the piece I think that’s not really answered in the guidance. By doing all of this, FDA is sort of suggesting that the burden is on the industry. And then because the burden is on you, we’re not going to let you use these industry lists. That’s one of those issues where we’re going to continue to disagree with them. As I said, this could play out if they were to go after something that the industry felt very strongly they had no business going after. The industry could push back on them in court and say, ‘No, it’s not our burden. You have to show that it’s new.’”

During the AHPA webcast, McGuffin also emphasized this point, telling listeners: “I want to remind you that you don’t have to have documentation to sell an old ingredient. You just have to have an affirmative responsibility to act if you’re selling a new ingredient.”

If the industry decides to help create an official list, another question is whether industry third-party lists could serve as a starting point for building an official list.

“I think the industry lists can be very helpful in the process,” Mister says.

But bad feelings also remain thanks to FDA’s continued rejection of industry lists. “Where’s the sense of partnership and cooperation?” McGuffin said in an interview with Nutritional Outlook. “I would need to see the Food and Drug Administration acknowledge that our lists have a high level of integrity and a high level of supposition of accuracy in terms of providing documentation of existence in the marketplace. Because those [pre-DSHEA ingredients] aren’t the ingredients that we’re worried about. Those aren’t the truly new ingredients that are coming into the marketplace.”

“FDA should take into account the processes whereby these lists and publications were compiled, as well as the spirt of their compilation,” he added during the AHPA webcast.

There are even some who doubt that FDA intends to create an official list at all. McGuffin criticized the agency for “looking for some level of perfection [in industry-created grandfathered lists] so as to never actually develop a useful list.”

During the AHPA webcast, Siegner said, “I agree that this offer to help develop a grandfathering list…is not worthless, but I don’t really believe that FDA is sincere in that.”

Moving Forward

Some industry leaders say that the industry should just move forward.

“We’re back to the drawing board in developing [a list], and we just have to bite the bullet,” says Corey Hilmas, MD, PhD, NPA’s senior vice president of scientific and regulatory affairs. “Five years ago [when FDA released the first version of the NDI draft guidance], there was a lot of complaining, but I think our backs are against the wall. We just have to develop evidence now” for an FDA grandfathered-ingredient list.

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The industry may also have to move forward despite dissatisfaction with the draft guidance, Mister says. “Some of these provisions that the industry is not really happy about in the guidance document are absolutely based on the law from 1994. I mean, you go back and you read the NDI provision in the statute, and FDA is absolutely within its rights. We may not like that, but that’s the deal we struck in 1994.”

He continues, “As an example, I have heard people say the further we get out into the future, we are going to see fewer and fewer things that are old dietary ingredients, and the universe of NDIs is going to grow over time. And they say that as if that is a bad thing, that it comes as a big surprise. Well, that is exactly what the people who negotiated DSHEA allowed to happen, because they said we will preserve everything that’s on the market today to prevent FDA from taking it off the market. But as new things come to market, we will have an NDI system that we have to notify to the agency. So, you know, the foreseeable consequence of that was that as time moves on, fewer things will be old and more things will be new. And now that it’s actually being implemented, we’re complaining about that, but that’s the deal we agreed to.”

NPA’s Fabricant is one industry member who sounds like he’s looking forward. “I mean, we have some evidence, so if we can use it to carve out a safe space for some ingredients, why wouldn’t we? I know some people are kind of defeatist in that mentality, but I think we’ve got to, as trade associations, start the conversation. So we’re looking to start the conversation.”

“I don’t think it’s going to be as challenging as people think,” he continues. “There’s a lot of documentation that’s out there that we can use and cull for a list. I think that the fact that [FDA is] willing to consider [creating an official list] gives us, our organization, a huge opportunity… and if we can carve out a safe harbor for some ingredients, I think that’s very good for the industry.”

Not creating a list, he says, “is just a wasted opportunity for the industry if we don’t do it.”

Also read:

Which Ingredient Categories Would Be Hit Hardest by FDA’s NDI Draft Guidance?

FDA’s NDI Guidance Offers Reasonable Take on Ingredient Combinations, CRN’s Mister Says

Charting the Path Forward on NDI Guidance in a Time of Industry Criticism

Jennifer Grebow
Editor-in-Chief
Nutritional Outlook magazine
jennifer.grebow@ubm.com