An FDA official said in an interview his office is seeking to
collaborate in developing an authoritative list of ingredients exempt
from a notification requirement in the 1994 Dietary Supplement Health
and Education Act (DSHEA).
“That’s an area where I think there’s a lot of opportunity for us to
work collaboratively with stakeholders going forward," said Steven Tave,
director of FDA’s Office of Dietary Supplement Programs (ODSP), who
acknowledged the potential benefits of an authoritative list for the
industry and his agency. “To the extent that we don’t have to review
notifications because the law doesn’t require it, it preserves our
resources to work on things that we need to."
In a 102-page draft guidance document published in August, FDA disclosed it is “prepared to develop an authoritative list of pre-DSHEA ingredients, based on independent and verifiable data." The list would reflect ingredients exempt from a notification requirement in the law because they were marketed before Oct. 15, 1994, and presumed safe.
Although dietary supplements aren’t subject to premarket approval, companies must notify FDA at least 75 days before introducing a new dietary ingredient (NDI)—providing evidence the NDI is reasonably expected to be safe. FDA issued draft NDI guidance for the industry in efforts to improve compliance with the notification requirement and improve the quality of submissions.
Tave described the benefits of the NDI notification process for the estimated 170 million Americans who take supplements, saying it reflects FDA’s only premarket opportunity to review the safety of dietary ingredients.
“And from a public health perspective, having a robust, functional, meaningful NDI review process has clear benefits to consumers," he said in a phone interview.
FDA often objects to NDI submissions for various reasons, such as a finding that the notification didn’t provide sufficient evidence of the ingredient’s safety. However, Tave said the notices indicate companies “are trying to do the right thing."
“They’re trying to notify us," Tave said, “and they’re trying to give us the information that we need to see in order to know that they’ve demonstrated a reasonable assurance of safety.
“We want to give them an understanding of what kind of information we need to see," he added. “We want to improve that success rate, and we want companies also to know when they do need to file a notification…."
Pre-DSHEA List Poses Challenges
The development of an authoritative list of pre-DSHEA ingredients is a work in progress.
Tave acknowledged creating such a list poses challenges. For example, what is the standard for determining whether an ingredient was marketed before 1994, and what are the variations of the ingredient that would be covered, he asked.
“And then what’s going to be the process for developing that list," Tave said. “Who is involved? How do we apply it? How do we do it consistently and fairly and in a way that’s meaningfully quick, so that it can be useful to industry and consumers and healthcare providers who are looking at that information as well?"
Tave said he hopes to make progress in this area in the coming months, and he underscored the endeavor would be a collaborative and transparent one involving industry and consumer interests.
Master File: ‘A Win-Win’
The concept of an NDI master file, Tave noted, is one of the areas in the draft guidance in which the agency “absolutely" needs feedback from the industry.
In the draft guidance, FDA cited circumstances in which a company filing an NDI notification could rely on data from a master file, provided the company obtained written permission from the submitter of the master file. The concept could make it easier for several finished supplement manufacturers to take an ingredient to market, while safeguarding an ingredient company’s proprietary information.
Master files would enable companies to “protect and capitalize on their intellectual property," said Tave.
Herbalife Ltd., the multi-level marketer of supplements, proposed the master file concept in 2011 draft NDI guidance. The company sought to eliminate the practice of copycatting or piggybacking in which companies are marketing a substance that is identical to, or resembles, an ingredient that has been the subject of a successful NDI notification to FDA.
Last year in an interview, Herbalife senior executive Vasilios “Bill" Frankos said his company was seeking to avoid “me-too ingredients that are knockoffs of NDIs that were successfully submitted" to FDA.
Herbalife’s master file proposal also reflected an effort to eliminate duplicative NDI submissions to FDA for the same ingredient sold by different supplement manufacturers. The idea seemed to resonate with Tave.
He described the master file as an avenue for his agency to meaningfully review NDIs “without the burden of, No. 1, unnecessarily duplicative submissions on industry’s part and, No. 2, [FDA] having to review unnecessarily duplicative submissions.
“Since we have limited resources, I think that’s a win-win," Tave explained.
But FDA must balance its support of the master file concept with its duty to protect public health. And Tave signaled the agency hasn’t ironed out all the details, such as those related to intellectual property protections.
FDA to ‘Carefully’ Review Comments
FDA received hundreds of comments from the industry and others on the 2016 draft NDI guidance. Larissa Pavlick, VP of Global Regulatory and Compliance with the United Natural Products Alliance (UNPA), met in person with Tave and his colleague, Cara Welch, Ph.D., ODSP’s senior advisor, to discuss the guidance. Pavlick indicated the agency was open to hearing criticisms from the industry.
For example, UNPA expressed concern the draft guidance interprets various manufacturing changes as triggering the NDI notification requirement. According to Pavlick, Tave said the agency needed to clarify the part of the guidance related to manufacturing changes.
"He (Tave) directly told me he didn't want to be flooded with notifications related to manufacturing changes, and that wasn't their intent," she said in a phone interview.
Pavlick said FDA officials planned to hold additional industry meetings, while finalizing the guidance.
"They didn't know if those meetings would be public, or if they would be just with trade organizations, but they did need additional feedback to kind of finalize some of those areas, and they suggested that manufacturing changes would be one of those," she explained.
In the interview with INSIDER, Tave did not address Pavlick’s comments regarding her discussion with him about manufacturing changes. However, he said the agency is open to meeting with representatives from the industry and other third parties.
Tave observed FDA received many substantive comments that addressed various aspects of the draft document. “We’re going to read every single one of them carefully, and we’re going to think about every single point that’s raised in there," he said.
‘It’s a Complex Statute’
Tave also addressed criticisms that the guidance—at 102 pages—may be too complicated given the seemingly straightforward notification requirement in DSHEA.
“It’s always a balance between simplifying and being comprehensive and responsive," he said, explaining much of the document is filled with Q&As for industry. “We want to look at this from a firm’s perspective. Here’s my question. How would I answer it?"
Commenting on DSHEA itself, Tave said, “The statute is short, but it’s a complex marketplace, and it’s a complex statute … speaking as a lawyer and as a human being. It’s not easy to make sense of all the different provisions that are packed into DSHEA.
“We’re trying to give useful guidance," Tave continued, “so that nobody goes down the wrong path."
Publishing Final Guidance is ‘Priority’
Tave couldn’t provide a specific timeline for publishing a final NDI guidance. He noted the many layers of clearance and review that are outside his control.
Industry sources said the final NDI guidance will be subject to review by the White House’s Office of Management and Budget (OMB). Complicating matters, President Donald Trump’s policies have raised the specter that the publication of such documents could be delayed or scrapped entirely by the administration.
Tave said he hoped it wouldn’t take five years to publish a final guidance—the time that elapsed between the 2011 NDI draft and the publication of the 2016 document.
“It’s a priority for the agency to get this out because I think that firms want to see it," he said. “I think industry expects it, and reasonably so."
In a 102-page draft guidance document published in August, FDA disclosed it is “prepared to develop an authoritative list of pre-DSHEA ingredients, based on independent and verifiable data." The list would reflect ingredients exempt from a notification requirement in the law because they were marketed before Oct. 15, 1994, and presumed safe.
Although dietary supplements aren’t subject to premarket approval, companies must notify FDA at least 75 days before introducing a new dietary ingredient (NDI)—providing evidence the NDI is reasonably expected to be safe. FDA issued draft NDI guidance for the industry in efforts to improve compliance with the notification requirement and improve the quality of submissions.
Tave described the benefits of the NDI notification process for the estimated 170 million Americans who take supplements, saying it reflects FDA’s only premarket opportunity to review the safety of dietary ingredients.
“And from a public health perspective, having a robust, functional, meaningful NDI review process has clear benefits to consumers," he said in a phone interview.
FDA often objects to NDI submissions for various reasons, such as a finding that the notification didn’t provide sufficient evidence of the ingredient’s safety. However, Tave said the notices indicate companies “are trying to do the right thing."
“They’re trying to notify us," Tave said, “and they’re trying to give us the information that we need to see in order to know that they’ve demonstrated a reasonable assurance of safety.
“We want to give them an understanding of what kind of information we need to see," he added. “We want to improve that success rate, and we want companies also to know when they do need to file a notification…."
Pre-DSHEA List Poses Challenges
The development of an authoritative list of pre-DSHEA ingredients is a work in progress.
Tave acknowledged creating such a list poses challenges. For example, what is the standard for determining whether an ingredient was marketed before 1994, and what are the variations of the ingredient that would be covered, he asked.
“And then what’s going to be the process for developing that list," Tave said. “Who is involved? How do we apply it? How do we do it consistently and fairly and in a way that’s meaningfully quick, so that it can be useful to industry and consumers and healthcare providers who are looking at that information as well?"
Tave said he hopes to make progress in this area in the coming months, and he underscored the endeavor would be a collaborative and transparent one involving industry and consumer interests.
Master File: ‘A Win-Win’
The concept of an NDI master file, Tave noted, is one of the areas in the draft guidance in which the agency “absolutely" needs feedback from the industry.
In the draft guidance, FDA cited circumstances in which a company filing an NDI notification could rely on data from a master file, provided the company obtained written permission from the submitter of the master file. The concept could make it easier for several finished supplement manufacturers to take an ingredient to market, while safeguarding an ingredient company’s proprietary information.
Master files would enable companies to “protect and capitalize on their intellectual property," said Tave.
Herbalife Ltd., the multi-level marketer of supplements, proposed the master file concept in 2011 draft NDI guidance. The company sought to eliminate the practice of copycatting or piggybacking in which companies are marketing a substance that is identical to, or resembles, an ingredient that has been the subject of a successful NDI notification to FDA.
Last year in an interview, Herbalife senior executive Vasilios “Bill" Frankos said his company was seeking to avoid “me-too ingredients that are knockoffs of NDIs that were successfully submitted" to FDA.
Herbalife’s master file proposal also reflected an effort to eliminate duplicative NDI submissions to FDA for the same ingredient sold by different supplement manufacturers. The idea seemed to resonate with Tave.
He described the master file as an avenue for his agency to meaningfully review NDIs “without the burden of, No. 1, unnecessarily duplicative submissions on industry’s part and, No. 2, [FDA] having to review unnecessarily duplicative submissions.
“Since we have limited resources, I think that’s a win-win," Tave explained.
But FDA must balance its support of the master file concept with its duty to protect public health. And Tave signaled the agency hasn’t ironed out all the details, such as those related to intellectual property protections.
FDA to ‘Carefully’ Review Comments
FDA received hundreds of comments from the industry and others on the 2016 draft NDI guidance. Larissa Pavlick, VP of Global Regulatory and Compliance with the United Natural Products Alliance (UNPA), met in person with Tave and his colleague, Cara Welch, Ph.D., ODSP’s senior advisor, to discuss the guidance. Pavlick indicated the agency was open to hearing criticisms from the industry.
For example, UNPA expressed concern the draft guidance interprets various manufacturing changes as triggering the NDI notification requirement. According to Pavlick, Tave said the agency needed to clarify the part of the guidance related to manufacturing changes.
"He (Tave) directly told me he didn't want to be flooded with notifications related to manufacturing changes, and that wasn't their intent," she said in a phone interview.
Pavlick said FDA officials planned to hold additional industry meetings, while finalizing the guidance.
"They didn't know if those meetings would be public, or if they would be just with trade organizations, but they did need additional feedback to kind of finalize some of those areas, and they suggested that manufacturing changes would be one of those," she explained.
In the interview with INSIDER, Tave did not address Pavlick’s comments regarding her discussion with him about manufacturing changes. However, he said the agency is open to meeting with representatives from the industry and other third parties.
Tave observed FDA received many substantive comments that addressed various aspects of the draft document. “We’re going to read every single one of them carefully, and we’re going to think about every single point that’s raised in there," he said.
‘It’s a Complex Statute’
Tave also addressed criticisms that the guidance—at 102 pages—may be too complicated given the seemingly straightforward notification requirement in DSHEA.
“It’s always a balance between simplifying and being comprehensive and responsive," he said, explaining much of the document is filled with Q&As for industry. “We want to look at this from a firm’s perspective. Here’s my question. How would I answer it?"
Commenting on DSHEA itself, Tave said, “The statute is short, but it’s a complex marketplace, and it’s a complex statute … speaking as a lawyer and as a human being. It’s not easy to make sense of all the different provisions that are packed into DSHEA.
“We’re trying to give useful guidance," Tave continued, “so that nobody goes down the wrong path."
Publishing Final Guidance is ‘Priority’
Tave couldn’t provide a specific timeline for publishing a final NDI guidance. He noted the many layers of clearance and review that are outside his control.
Industry sources said the final NDI guidance will be subject to review by the White House’s Office of Management and Budget (OMB). Complicating matters, President Donald Trump’s policies have raised the specter that the publication of such documents could be delayed or scrapped entirely by the administration.
Tave said he hoped it wouldn’t take five years to publish a final guidance—the time that elapsed between the 2011 NDI draft and the publication of the 2016 document.
“It’s a priority for the agency to get this out because I think that firms want to see it," he said. “I think industry expects it, and reasonably so."
