Mike Montemarano, Associate Editor 07.05.22
Cara Welch, director of FDA’s Office of Dietary Supplement Programs (ODSP), discussed the agency’s legislative priorities during the American Conference Institute (ACI) and Council for Responsible Nutrition (CRN) Legal, Regulatory, and Compliance Forum on Dietary Supplements held in New York in June.
First off, the agency is discussing a number of options to increase its inspectional capacity, Welch said. According to the National Institutes of Health, at the time the Dietary Supplement Health and Education Act was signed into law in 1994, an estimated 600 U.S. dietary supplement manufacturers marketed about 4,000 products.
With an increase to between 50,000 and 80,000 products on the market today, “I think we can all admit that the dietary supplements marketplace has changed since 1994,” Welch said. “Supply chains have globalized, and the internet was introduced as a retail and marketing channel. Products are precisely designed to include specific formulations and mixtures of ingredients, some of which are designer ingredients or highly concentrated and purified constituents.”
Rethinking Inspections
In the three years prior to the COVID-19 pandemic, FDA conducted about 500-600 facility inspections each year, comprising approximately 5% of all domestic facilities registered with the agency. Since the onset of the pandemic, facility inspections numbered in the mid to high 200s.
“We don’t have a good picture of the compliance status of the industry. There are limitations to how many inspections we can do,” Welch said. “As we move back to typical inspection approaches, we’re looking not just at the ones we need to do now, but an entire backlog of the in-person inspections we missed. Our current perspective is that we need to bring a new sense of urgency to the discussion and I think we’re headed in the right direction.”
Welch said that remote regulatory assessments (RRAs), a program which began during the pandemic, will likely continue in some form based on the success seen when the option was introduced during the pandemic. This voluntary assessment by FDA, which is done outside of formal or official inspections, allows manufacturing firms to have FDA representative evaluate their cGMP (current Good Manufacturing Practices) documentation informally.
“While it doesn’t officially count as a remote inspection, it allows us to keep our fingers on the pulse of manufacturing conditions,” Welch said. “We’re still not getting the kind of number of participants that we want, but it could provide a pretty good picture of a facility’s compliance.”
While Welch said the FDA isn’t quite ready to implement anything of the sort, the agency hasn’t ruled out the idea of outsourcing domestic inspections to third-party certifiers, similar to how foreign facilities are able to be tested under the Food Safety Modernization Act (FSMA).
“ODSP plays a role in policy and regulation, but inspections are handled by the Office of Regulatory Affairs. ORA has a really important part to play in these discussions, and we need to know what their goals are in depth,” Welch said, such as the number of inspections it plans to conduct, what these inspections should prioritize, and if there are similar programs that FDA can model.
New Dietary Ingredients
This May, FDA issued draft guidance on enforcement discretion it plans to give firms that have introduced new dietary ingredients to the marketplace without the proper New Dietary Ingredient Notification (NDIN). The comment period for this draft guidance ends on July 19.
Since the introduction of DSHEA, FDA has received over 1,200 notifications, Welch said, though the agency estimates there are 4,600 products on the market that warranted notifications. The proposed amnesty period, if finalized, would offer ingredient manufacturers the chance to avoid the penalties that come with this failure to notify.
“When this guidance is finalized, firms will have 180 days to submit an NDIN that already should’ve been submitted, and retribution will not happen. We want data, primarily safety information, in order to help substantiate how safe the current marketplace is. The goal here is to increase the amount of information we have,” Welch said. “We hope that the pool of firms not willing to comply with NDI regulations will be much smaller, and this will help us identify those firms who are simply choosing not to be in compliance so that we could take action. I’m really hopeful that we get the buy-in from firms to submit these NDINs.”
Welch stressed her hope that companies will not neglect to submit late NDINs based on unanswered questions about what amnesty entails, and that finalizing certain portions of the 102-page guidance in order to expedite it is the agency’s preference.
The success rate for all NDINs over the past 27 years, in terms of those which receive acknowledgements from the FDA with no objections, sits at 30%; 36% of NDINs resulted in the FDA finding certain inadequacies following a review; 19% of NDINs submitted to the agency contained incomplete information. Lastly, 15% of NDINs were for products that were not legal dietary ingredients.
Amid these 1,200 notifications, various issues tracking the success rate of re-submitted products exist, such as when an ingredient or a firm changes its name, and little data on the success rate of meeting with FDA to discuss an ingredient pre-NDIN exists, though that would likely be a promising figure, Welch said.
“I’m really encouraged by an increase, year over year, in the proportion of NDINs which receive good acknowledgement letters,” Welch said. “Notifications coming in have been better than before at giving us a really good picture of the ingredient at hand. Our staff has also put in a lot of effort into helping firms get a good letter. They work and meet with the notifiers, and might go back to a firm with questions that we think could be answered in order to substantiate an ingredient’s safety.”
Further, the agency is less concerned about confusion as to whether an ingredient should have entered the marketplace via the Generally Recognized As Safe (GRAS) route, reserved for dietary ingredients already in the food supply.
“The burden is on us to prove this is the case, and I think that’s an important thing to think about when it comes to the amnesty period,” Welch said. “We want to go ahead and make it easy as possible for people to participate in amnesty, and the best thing for us to do right now is shrink the pool of unknown elements.”
Enforcement
This year, the roundup of FDA’s enforcement activity within the dietary supplements market included 111 warning letters issued to firms the agency deemed to be in regulatory violation, up from 49 warning letters issued in 2020. “These warning letters serve as a notice to a firm which provides them with what we consider to be our complaint,” Welch said. “Almost all firms choose to comply, and when they don’t comply, we may progress to more serious enforcement action. Generally, we have 1-4 injunctions per year, along with one or two product seizures.”
Welch said that despite FDA’s warning letter campaigns, which tend to publicly target and highlight one or more problematic ingredients that the agency considers illegal to market in dietary supplements, several ingredients continue to present issues. Specifically, she named 1,3-DMAA, which was being sold in products that were the subject of one high-profile seizure, along with products containing other ingredients such as DMHA, phenibut, and kratom.
“We ask ourselves how we could get better at this and get to the point that the first time we warn about an ingredient, we are presented with information that shows us we were mistaken, or that this ingredient disappears from commerce,” Welch said. “We’ve gotten some suggestions, and these suggestions are not far from our approach.”
Most notably, aside from engaging in more seizures and injunctions following warning letters, Welch said that the agency received suggestions to collaborate with retailers in order to remove illegal products from the marketplace in a more swift and widespread manner.
“Sometimes a seizure or an injunction isn’t the best option, or it isn’t feasible. It takes a lot of resources between us and the Office of Regulatory Affairs, and the Department of Justice,” Welch said. “I see both educating and communicating as something I’d like to see us do more of.
“Responsible retailers, when made aware of a violation,” she suggested, “will do their due diligence to not sell these products. FDA’s role here comes down to communicating a violation, and differentiating compliant products from those other products that are just profiting off of the industry’s efforts to be compliant. Retailers are a part of differentiating the compliant side of the marketplace.”
Welch said that FDA’s communication should also go beyond retailers themselves.
“To this end, FDA recently commissioned and released an education initiative called ‘Supplement Your Knowledge’ which contains information for consumers, educators, and healthcare professionals to broaden their understandings of dietary supplements,” Welch said.
First off, the agency is discussing a number of options to increase its inspectional capacity, Welch said. According to the National Institutes of Health, at the time the Dietary Supplement Health and Education Act was signed into law in 1994, an estimated 600 U.S. dietary supplement manufacturers marketed about 4,000 products.
With an increase to between 50,000 and 80,000 products on the market today, “I think we can all admit that the dietary supplements marketplace has changed since 1994,” Welch said. “Supply chains have globalized, and the internet was introduced as a retail and marketing channel. Products are precisely designed to include specific formulations and mixtures of ingredients, some of which are designer ingredients or highly concentrated and purified constituents.”
Rethinking Inspections
In the three years prior to the COVID-19 pandemic, FDA conducted about 500-600 facility inspections each year, comprising approximately 5% of all domestic facilities registered with the agency. Since the onset of the pandemic, facility inspections numbered in the mid to high 200s.
“We don’t have a good picture of the compliance status of the industry. There are limitations to how many inspections we can do,” Welch said. “As we move back to typical inspection approaches, we’re looking not just at the ones we need to do now, but an entire backlog of the in-person inspections we missed. Our current perspective is that we need to bring a new sense of urgency to the discussion and I think we’re headed in the right direction.”
Welch said that remote regulatory assessments (RRAs), a program which began during the pandemic, will likely continue in some form based on the success seen when the option was introduced during the pandemic. This voluntary assessment by FDA, which is done outside of formal or official inspections, allows manufacturing firms to have FDA representative evaluate their cGMP (current Good Manufacturing Practices) documentation informally.
“While it doesn’t officially count as a remote inspection, it allows us to keep our fingers on the pulse of manufacturing conditions,” Welch said. “We’re still not getting the kind of number of participants that we want, but it could provide a pretty good picture of a facility’s compliance.”
While Welch said the FDA isn’t quite ready to implement anything of the sort, the agency hasn’t ruled out the idea of outsourcing domestic inspections to third-party certifiers, similar to how foreign facilities are able to be tested under the Food Safety Modernization Act (FSMA).
“ODSP plays a role in policy and regulation, but inspections are handled by the Office of Regulatory Affairs. ORA has a really important part to play in these discussions, and we need to know what their goals are in depth,” Welch said, such as the number of inspections it plans to conduct, what these inspections should prioritize, and if there are similar programs that FDA can model.
New Dietary Ingredients
This May, FDA issued draft guidance on enforcement discretion it plans to give firms that have introduced new dietary ingredients to the marketplace without the proper New Dietary Ingredient Notification (NDIN). The comment period for this draft guidance ends on July 19.
Since the introduction of DSHEA, FDA has received over 1,200 notifications, Welch said, though the agency estimates there are 4,600 products on the market that warranted notifications. The proposed amnesty period, if finalized, would offer ingredient manufacturers the chance to avoid the penalties that come with this failure to notify.
“When this guidance is finalized, firms will have 180 days to submit an NDIN that already should’ve been submitted, and retribution will not happen. We want data, primarily safety information, in order to help substantiate how safe the current marketplace is. The goal here is to increase the amount of information we have,” Welch said. “We hope that the pool of firms not willing to comply with NDI regulations will be much smaller, and this will help us identify those firms who are simply choosing not to be in compliance so that we could take action. I’m really hopeful that we get the buy-in from firms to submit these NDINs.”
Welch stressed her hope that companies will not neglect to submit late NDINs based on unanswered questions about what amnesty entails, and that finalizing certain portions of the 102-page guidance in order to expedite it is the agency’s preference.
The success rate for all NDINs over the past 27 years, in terms of those which receive acknowledgements from the FDA with no objections, sits at 30%; 36% of NDINs resulted in the FDA finding certain inadequacies following a review; 19% of NDINs submitted to the agency contained incomplete information. Lastly, 15% of NDINs were for products that were not legal dietary ingredients.
Amid these 1,200 notifications, various issues tracking the success rate of re-submitted products exist, such as when an ingredient or a firm changes its name, and little data on the success rate of meeting with FDA to discuss an ingredient pre-NDIN exists, though that would likely be a promising figure, Welch said.
“I’m really encouraged by an increase, year over year, in the proportion of NDINs which receive good acknowledgement letters,” Welch said. “Notifications coming in have been better than before at giving us a really good picture of the ingredient at hand. Our staff has also put in a lot of effort into helping firms get a good letter. They work and meet with the notifiers, and might go back to a firm with questions that we think could be answered in order to substantiate an ingredient’s safety.”
Further, the agency is less concerned about confusion as to whether an ingredient should have entered the marketplace via the Generally Recognized As Safe (GRAS) route, reserved for dietary ingredients already in the food supply.
“The burden is on us to prove this is the case, and I think that’s an important thing to think about when it comes to the amnesty period,” Welch said. “We want to go ahead and make it easy as possible for people to participate in amnesty, and the best thing for us to do right now is shrink the pool of unknown elements.”
Enforcement
This year, the roundup of FDA’s enforcement activity within the dietary supplements market included 111 warning letters issued to firms the agency deemed to be in regulatory violation, up from 49 warning letters issued in 2020. “These warning letters serve as a notice to a firm which provides them with what we consider to be our complaint,” Welch said. “Almost all firms choose to comply, and when they don’t comply, we may progress to more serious enforcement action. Generally, we have 1-4 injunctions per year, along with one or two product seizures.”
Welch said that despite FDA’s warning letter campaigns, which tend to publicly target and highlight one or more problematic ingredients that the agency considers illegal to market in dietary supplements, several ingredients continue to present issues. Specifically, she named 1,3-DMAA, which was being sold in products that were the subject of one high-profile seizure, along with products containing other ingredients such as DMHA, phenibut, and kratom.
“We ask ourselves how we could get better at this and get to the point that the first time we warn about an ingredient, we are presented with information that shows us we were mistaken, or that this ingredient disappears from commerce,” Welch said. “We’ve gotten some suggestions, and these suggestions are not far from our approach.”
Most notably, aside from engaging in more seizures and injunctions following warning letters, Welch said that the agency received suggestions to collaborate with retailers in order to remove illegal products from the marketplace in a more swift and widespread manner.
“Sometimes a seizure or an injunction isn’t the best option, or it isn’t feasible. It takes a lot of resources between us and the Office of Regulatory Affairs, and the Department of Justice,” Welch said. “I see both educating and communicating as something I’d like to see us do more of.
“Responsible retailers, when made aware of a violation,” she suggested, “will do their due diligence to not sell these products. FDA’s role here comes down to communicating a violation, and differentiating compliant products from those other products that are just profiting off of the industry’s efforts to be compliant. Retailers are a part of differentiating the compliant side of the marketplace.”
Welch said that FDA’s communication should also go beyond retailers themselves.
“To this end, FDA recently commissioned and released an education initiative called ‘Supplement Your Knowledge’ which contains information for consumers, educators, and healthcare professionals to broaden their understandings of dietary supplements,” Welch said.
