By Sean Moloughney, Editor05.22.24
The U.S. Food and Drug Administration typically inspects about 500 dietary supplement facilities per year, and the agency appears to be back on track post-Covid, according to Cara Welch, PhD, director of the Office of Dietary Supplement Programs (ODSP) at FDA’s Center for Food Safety and Applied Nutrition (CFSAN).
“The number of facility inspections we could do in a year took a hit with Covid, much like everything else,” Welch said during an education session at SupplySide East in April. “We really think we’ve gotten back to the pre-Covid numbers, and we should be running about 500 inspections a year.”
Is that enough to get an accurate picture of the dietary supplement marketplace? No, Welch admitted. “I don’t think the number we have right now is adequate. That comes down to just plain limitations in so many ways.”
Welch said FDA is aware of about 10,000 dietary supplement facilities, and that’s “probably a low number.” The 500 inspections per year doesn’t count repeats, so the agency is likely getting a glimpse into less than 5% of facilities each year.
“That’s not enough,” said Welch. “The foods program as a whole is dealing with all the food facilities and all the different factors that go into that. So I think dietary supplements has done well in that sense. We have been supported, but we need to be very strategic in what facilities we’re inspecting, why we’re inspecting them. How can we make the most of those resources?”
Meanwhile, Welch said she would like to see “more engagement” from the supplement industry in third-party accredited programs. “There are accreditation bodies and certifying bodies for supplements and it would be great to see how that is helping industry.”
Since fiscal year 2017, the top observations from FDA inspections have generally focused on finished product specifications (21 CFR 111.70(e)) and quality control (21 CFR 111.103), along with product complaints (21 CFR 111.553), written procedures for holding and distributing operations (21 CFR 111.453), ingredient specifications, testing, and other quality-related issues.
“This is an area where we just need to continue to work on,” said Welch. “How do we get the message out to industry members? What is necessary for an adequate specification, documenting the quality control responsibilities, and then the testing.”
Repeated non-compliance with GMPs can progress to an injunction, Welch said, noting the agency has issued two injunctions so far this year (Evig/Premium Production and Total Body Nutrition, for claims and GMP violations).
“These are resource-intensive actions,” said Welch, “but they are really important to reinforce quality manufacturing.”
How does the agency decide what violations of the law to enforce when it only has so many resources?
“There’s a lot wrapped up in the determination in terms of which violation and which activity is needed,” said Welch. “I think we would all like to do more, and we need to be very strategic in how we use our resources. How do we set up the agency to know how to use those resources best?”
Along with other factors, FDA must consider “the biggest impact on public health,” said Welch, “but also the integrity of the marketplace and the ripple effects. Is there a chilling effect when we have a problem and the firm has the impression they don’t need to comply?”
At times, adulterated products pose a risk to consumers and FDA must mobilize to take action and warn the public. “There are times when a problem comes up and we really need to devote attention to getting a product off the market,” said Welch, noting recent issues with weight loss products marketed as Nuez de la India and Mexican Hawthorn (Tejocote root) that actually contained yellow oleander, which can be toxic.
“These are products that are not actually dietary supplements, but they end up hurting the reputation of the legitimate marketplace,” she added.
“If we can find responsible parties, we will follow up on that and seize products, remove them from the market, and take other enforcement actions. The problem is a lot of these firms — there’s not a business. There’s not a location even that we can go to. They’re operating out of a garage or something concerning along those lines.”
Welch also noted concern with tianeptine, sometimes referred to as “gas station heroin." “It has some opioid use disorder ties, and really concerning adverse event reports are sometimes associated with tianeptine or with other adulterants.”
“It’s not renaming the boxes [of the divisions and offices]. It is sort of blowing apart a few different structures and rebuilding something that we think works best for the foods program.”
ODSP will continue to operate as an office, but would be housed within a broader “Office of Food Chemical Safety, Dietary Supplements & Innovation” under the proposed plan.
There are “some exciting aspects of the reorganization proposal,” Welch said. “Part of that is integrating the supplements program more tightly with food, because we are a category of foods. ‘Food chemicals’ is broader than ‘food additives,’ just to be clear. Food chemicals would really be all of the ingredients, active-added/purposefully-added, obviously the additives, the excipients, even contaminants, all fit in the broader category of food chemicals.”
Ingredients that are used in foods do also show up in supplements, she added. “So dietary supplements need to be part of that conversation. We need to be integrated. Having similar expertise is really important. We then need to apply that use to the appropriate authority. Food additive review will continue to be applied to the food additive standard,” Welch noted.
Food additives are used in supplements too, she added, pointing to the whitening agent titanium dioxide.
“That’s applied to the food additive standard. When that ingredient is showing up in supplements, that same science can be applied to the supplement safety standard. And that’s absolutely appropriate. I think that’s an area where we’ll be able to leverage each other’s expertise and improve the agency’s activities” with food and dietary supplements.
She noted an increase in the percentage of acknowledgment letters over the past 5 years though. “I am really encouraged about that. Percentage wise, we’re seeing an increase. Is that a true increase? I don’t know. We’re going to keep watching it.”
Welch stressed the value of pre-notification meetings with the agency. “Early and often communication with FDA seems to trend to a good response, and we really want to encourage that.”
The agency first issued guidance on NDIs in 2011, then issued a revised draft in 2016 that is 102 pages long. Acknowledging the challenge of updating a document that large, the agency decided to break it up into sections and published its first final guidance on procedures and timeframes in March.
And in April, FDA published a draft guidance document on master files. “There’s a lot in there that would be new to our stakeholders,” said Welch. “I really hope people are taking the opportunity to read this draft guidance and putting together comments. That’s going to be very helpful for us as we prepare for finalizing that guidance. It’s a proposal at this point, but having that feedback is very important.”
About the Author: Sean Moloughney has been the editor of Nutraceuticals World since 2012. He can be reached at smoloughney@rodmanmedia.com.
“The number of facility inspections we could do in a year took a hit with Covid, much like everything else,” Welch said during an education session at SupplySide East in April. “We really think we’ve gotten back to the pre-Covid numbers, and we should be running about 500 inspections a year.”
Is that enough to get an accurate picture of the dietary supplement marketplace? No, Welch admitted. “I don’t think the number we have right now is adequate. That comes down to just plain limitations in so many ways.”
Welch said FDA is aware of about 10,000 dietary supplement facilities, and that’s “probably a low number.” The 500 inspections per year doesn’t count repeats, so the agency is likely getting a glimpse into less than 5% of facilities each year.
“That’s not enough,” said Welch. “The foods program as a whole is dealing with all the food facilities and all the different factors that go into that. So I think dietary supplements has done well in that sense. We have been supported, but we need to be very strategic in what facilities we’re inspecting, why we’re inspecting them. How can we make the most of those resources?”
Meanwhile, Welch said she would like to see “more engagement” from the supplement industry in third-party accredited programs. “There are accreditation bodies and certifying bodies for supplements and it would be great to see how that is helping industry.”
GMP Basics & Product Integrity
What does FDA typically find in the facilities it does inspect? “We continue to see (483) observations with what I would consider the basics, the essential aspects of GMPs (Good Manufacturing Practices),” said Welch.Since fiscal year 2017, the top observations from FDA inspections have generally focused on finished product specifications (21 CFR 111.70(e)) and quality control (21 CFR 111.103), along with product complaints (21 CFR 111.553), written procedures for holding and distributing operations (21 CFR 111.453), ingredient specifications, testing, and other quality-related issues.
“This is an area where we just need to continue to work on,” said Welch. “How do we get the message out to industry members? What is necessary for an adequate specification, documenting the quality control responsibilities, and then the testing.”
Repeated non-compliance with GMPs can progress to an injunction, Welch said, noting the agency has issued two injunctions so far this year (Evig/Premium Production and Total Body Nutrition, for claims and GMP violations).
“These are resource-intensive actions,” said Welch, “but they are really important to reinforce quality manufacturing.”
How does the agency decide what violations of the law to enforce when it only has so many resources?
“There’s a lot wrapped up in the determination in terms of which violation and which activity is needed,” said Welch. “I think we would all like to do more, and we need to be very strategic in how we use our resources. How do we set up the agency to know how to use those resources best?”
Along with other factors, FDA must consider “the biggest impact on public health,” said Welch, “but also the integrity of the marketplace and the ripple effects. Is there a chilling effect when we have a problem and the firm has the impression they don’t need to comply?”
At times, adulterated products pose a risk to consumers and FDA must mobilize to take action and warn the public. “There are times when a problem comes up and we really need to devote attention to getting a product off the market,” said Welch, noting recent issues with weight loss products marketed as Nuez de la India and Mexican Hawthorn (Tejocote root) that actually contained yellow oleander, which can be toxic.
“These are products that are not actually dietary supplements, but they end up hurting the reputation of the legitimate marketplace,” she added.
“If we can find responsible parties, we will follow up on that and seize products, remove them from the market, and take other enforcement actions. The problem is a lot of these firms — there’s not a business. There’s not a location even that we can go to. They’re operating out of a garage or something concerning along those lines.”
Welch also noted concern with tianeptine, sometimes referred to as “gas station heroin." “It has some opioid use disorder ties, and really concerning adverse event reports are sometimes associated with tianeptine or with other adulterants.”
FDA Reorganization
FDA has continued to advocate for modernizing the 30-year-old Dietary Supplement Health and Education Act (DSHEA). At the same time, the agency is undergoing a “massive reorganization,” as Welch put it, with a unified Human Foods Program.“It’s not renaming the boxes [of the divisions and offices]. It is sort of blowing apart a few different structures and rebuilding something that we think works best for the foods program.”
ODSP will continue to operate as an office, but would be housed within a broader “Office of Food Chemical Safety, Dietary Supplements & Innovation” under the proposed plan.
There are “some exciting aspects of the reorganization proposal,” Welch said. “Part of that is integrating the supplements program more tightly with food, because we are a category of foods. ‘Food chemicals’ is broader than ‘food additives,’ just to be clear. Food chemicals would really be all of the ingredients, active-added/purposefully-added, obviously the additives, the excipients, even contaminants, all fit in the broader category of food chemicals.”
Ingredients that are used in foods do also show up in supplements, she added. “So dietary supplements need to be part of that conversation. We need to be integrated. Having similar expertise is really important. We then need to apply that use to the appropriate authority. Food additive review will continue to be applied to the food additive standard,” Welch noted.
Food additives are used in supplements too, she added, pointing to the whitening agent titanium dioxide.
“That’s applied to the food additive standard. When that ingredient is showing up in supplements, that same science can be applied to the supplement safety standard. And that’s absolutely appropriate. I think that’s an area where we’ll be able to leverage each other’s expertise and improve the agency’s activities” with food and dietary supplements.
New Dietary Ingredient Notifications
Over the past 27 years, since the final rule for New Dietary Ingredient Notifications was issued, FDA has received about 1,300 notifications, Welch said. “We usually only receive somewhere between 40 and 50 NDI notifications a year.”She noted an increase in the percentage of acknowledgment letters over the past 5 years though. “I am really encouraged about that. Percentage wise, we’re seeing an increase. Is that a true increase? I don’t know. We’re going to keep watching it.”
Welch stressed the value of pre-notification meetings with the agency. “Early and often communication with FDA seems to trend to a good response, and we really want to encourage that.”
The agency first issued guidance on NDIs in 2011, then issued a revised draft in 2016 that is 102 pages long. Acknowledging the challenge of updating a document that large, the agency decided to break it up into sections and published its first final guidance on procedures and timeframes in March.
And in April, FDA published a draft guidance document on master files. “There’s a lot in there that would be new to our stakeholders,” said Welch. “I really hope people are taking the opportunity to read this draft guidance and putting together comments. That’s going to be very helpful for us as we prepare for finalizing that guidance. It’s a proposal at this point, but having that feedback is very important.”
About the Author: Sean Moloughney has been the editor of Nutraceuticals World since 2012. He can be reached at smoloughney@rodmanmedia.com.
