“Until there is a final NDI guidance it won’t be fully clear what the answer is,” said Loren Israelsen, executive director of the United Natural Products Alliance.
FDA’s draft guidance on NDIs remains in limbo after several high level meetings between agency staff and industry stakeholders on revising the document. But that hasn’t stopped new ingredients from coming to market, nor has it stopped the questions about the exact scope of those notifications which the agency has accepted without comment.
At its core, the NDI process is about safety, not about marketability or the protection of intellectual property, though those aspects play into it, too.
“FDA is looking for assurances that you know what you are doing and that you can do the same thing every time,” Marc Ullman, an attorney with the firm Ullman, Shapiro & Ullman told NutraIngredients-USA. “An NDI includes detailed manufacturing information. As a matter of public policy, we are requiring the manfacturer to say we know what we are doing and we have adequate controls in place.”
“In some of the notifications that are rejected it’s a significant issue. FDA says, you didn’t tell us (adequately) what it is you are making,” he said.
Is it identical?
If a company were to assert that while they are admitting they have an ingredient that qualifies as an NDI that they don’t have to file a notification because one is already in place that filed by someone else, you’d still have to be able to prove quite specifically the identity of your ingredient, Ullman said.
“It would be incumbent on the (follow on) company to demonstrate that the ingredient was absolutely identical to the substance for which the NDI was filed,” Ullman said. Considering that much of the manufacturing information would be redacted in the public portion of an NDI notification in order to protect trade secrets, Ullman said this could then entail buying a competing ingredient in the open market, testing it via a variety of methods and comparing those results to those from your own ingredient. By the time a company has spent that kind of money, it may not have saved much over filing its own NDI notification, observers say.
The crude botanical umbrella
The question about duplicative NDI filings is a complicated one, said Michael McGuffin, president of the American Herbal Products Association and a major voice on the NDI issue.
On the question of crude botanicals, one filing might in theory provide an umbrella for competing ingredients, he said.
“Let’s suppose that company X does an NDI filing on the leaf of Japanese New Tree. If that’s all it is, the unprocessed leaf, then maybe they have accomplished the NDI notification for that ingredient. But as soon as you make an extract, then we think you’d probably have a different ingredient (requiring a new filing),” McGuffin said.
Manufacturing process changes
So manufacturing changes figure into an ingredient’s status, McGuffin said. It’s one of the reasons why he has a hard time wrapping his mind around the idea that a NDI notification, which includes detailed manufacturing information on a specific ingredient, could be applied to a similar, but perhaps not identical ingredient that might have been manufactured via a different process.
“My understanding of the NDI obligation is that it is specific to the ingredient. (Let’s say) the inventor of Herbal Extract No. 9 files a NDI notification and redacts all of its manufacturing information as it is allowed to do, and a competitor comes along and reads the notification. If Dr. Oz talks about the ingredient two weeks later and says you gotta have this thing and then suddenly there are 30 different versions of Extract No. 9 on the market, if none of those manufacturers or distributors of those products had filed their own notifications, I don’t know how they could possibly assert that their extract process is the same as the ingredient for which the notification was filed, because they have never seen it,” he said.
Israelsen said some of the questions on the issue may resolved once FDA issues a final NDI guidance, which might take some years yet. After the round of high level meetings mentioned earlier, indications are that the agency will issue a second draft version of the guidance which would likely include a new round of comments.
“Are there occasions when follow on ingredients can stand under the umbrella of that initial NDI? And if so under what specific conditions can that happen? There are differing views,” Israelsen said. “How do you determine if the substances are identical? A subset of that is what if one of them is natural and another is synthetic?
“Are there occasions where the holder of an NDI can put their customers under their wing if they exercise due diligence with how the ingredient is used in the finished product?
“The answer to all of the above at the moment is ‘undetermined.’ ” Israelsen said.