Todd Harrison, Venable11.01.16
The dietary supplement industry once again finds itself in the crosshairs of U.S. regulators. In August, FDA issued its revised draft guidance document regarding New Dietary Ingredient (NDI) notifications. Subsequently, the agency has requested comments related to its tentative conclusion that vinpocetine is not a dietary ingredient—regardless of the fact that FDA, on five previous occasions, had the opportunity to raise an issue regarding its regulatory status.
Meanwhile, the New York Attorney General (AG) reached another settlement with a large dietary supplement company regarding supply chain integrity and DNA testing (NBTY, Inc.). And the Drug Enforcement Agency (DEA) attempted to schedule a benign herb (kratom) through its emergency scheduling process. Additional developments have included recent settlements out of the State Iowa AG office and the state of California.
What do all of these situations have in common? The constant drumbeat from regulators has been that the industry is simply not doing enough to self-regulate. This overall perception has not changed, quite frankly, since the Dietary Supplement Health and Education Act (DSHEA) was passed in October 1994; but is this all the fault of industry, or do regulators bear responsibility in this process?
FDA’s Inaction & Ambivalence
From my perspective, while the industry has not always done its best to comply with the requirements of DSHEA, I would argue that a large part of the blame falls on regulators—FDA in particular. The new NDI draft guidance, the NY AG’s efforts on traceability, DEA’s misstep with kratom, and even the issues surrounding claims can be directly attributable to FDA’s general ambivalence—some would say outright hostility—toward the industry. One only needs to look at the timeline to figure out that many of these issues could have been avoided if FDA would have simply taken a more active approach toward regulating the industry in 1994.
DSHEA became effective on Oct. 14, 1994; yet during the next 22 years, FDA rarely did anything with regard to supply chain integrity and new dietary ingredients. For instance, it should not take the NY AG to enter into agreements with GNC and NBTY to make it clear that ingredient manufacturers are an integral part of ensuring supply chain integrity.
Indeed, the issue of identity testing should not start at the finished product manufacturing stage, but rather at the ingredient manufacturing stage. Especially with botanicals, the ingredient manufacturer is in better position to conduct the initial identity testing than the finished product manufacturer. Yet, FDA made a decision to exempt ingredient manufacturers from Part 111. To this day that decision is dumbfounding to me.
FDA continues to ignore a citizen petition by the Organic & Natural Health Association that requested the agency bring ingredient manufacturers under Part 111, even though state AGs and members of Congress have called for the same. FDA could achieve this task in short order. Instead, the NY AG is making agreements with companies to make this happen; however, these companies by themselves can’t achieve the ultimate goal, as the ingredient manufacturing industry is not of an insignificant size.
New Dietary Ingredients
First, in the immortal words of Green Bay Packers Quarterback Aaron Rodgers: r-e-l-a-x, Relax. The draft guidance is just that—a draft guidance document. Moreover, it only represents FDA’s current thinking on the matter and does not have the effect of law. Forget for a moment that FDA has no ability under the law to reject a notification or to approve new dietary ingredients; as stated in my last column, the document has fundamental issues that the agency still needs to work through (September 2016, “FDA Issues Revised Draft Guidance On New Dietary Ingredients”).
With that said, if the agency had worked with industry in 1994-1995 on developing a positive list of ingredients, as well as a policy around what would be considered a new dietary ingredient—such as a substantial change in concentration of a particular ingredient—we would not be in a situation today where we need to determine what is rightfully an “old” dietary ingredient.
Yet, it has taken FDA more than 22 years to determine that it should compile such a list, even though the industry had compiled a list back in the mid-1990s, which FDA has refused to adopt. The agency should start with that list and request information on ingredients that are not on the list. Yet, for whatever reason, FDA is simply rejecting this approach, which is nonsensical and feeds into the general perception that the industry can’t be trusted. FDA has reinforced this perception with vinpocetine.
Vinpocetine’s Regulatory Status
As everyone knows, including FDA, there were no less than five new dietary ingredient notifications regarding vinpocetine without comment from the agency. Yet, even though this ingredient is reasonably expected to be safe, in what appears to be a purely political decision sparked by Senator Claire McCaskill (D-MO), FDA decided to dig up some old press releases regarding this ingredient.
The industry has a reason to take issue because FDA has, at a minimum, treated the new dietary ingredient notification as a quasi-approval process—if not an outright approval process—and the industry should have been able to rely on it when making decisions about whether to incorporate a new dietary ingredient into a finished dietary supplement. This is not a situation where an ingredient supplier was relying on a Generally Recognized As Safe (GRAS) self-determination, or use in the food supply to escape the notification process. Rather, the notification was actually filed and FDA had no comment. “No comment” does not mean FDA agrees with the notice; however, given FDA’s propensity to question these notifications, it is absurd that the agency now has a concern, stating that because it believes vinpocetine is a synthetic ingredient, subject of an investigational new drug (IND) application and substantial, public clinical trials in the U.S. prior to its introduction as a dietary ingredient.
Putting aside the latter point, which poses significant issues, there is simply not justification for FDA’s position on synthetic botanicals or ingredients synthesized from botanicals. Nowhere in DSHEA or its legislative history does it indicate that synthetics are not permitted. Indeed, the catch-all provision of DSHEA regarding a “dietary substance” when viewed in light of the “new” dietary ingredient notification provisions clearly contemplates that new dietary substances would be developed. Otherwise, the new dietary ingredient notification provision would rarely be used, which was not the intent of Congress.
Moreover, the use of the term “substance,” rather than nutrient or nutritive, clearly indicates that Congress contemplated something other than one of the specific categories delineated in the definition of a dietary supplement. In other words, “substance” contemplates synthetic ingredients that may be developed. Thus, FDA’s position on synthetic botanicals is directly at odds with Congressional intent.
Regardless, if we are going to treat the notification process as just that—a notification process—it is difficult to penalize the agency for not understanding that an IND and substantial, public clinical trials were conducted on an ingredient.
Moreover, it should be required for the notifier to certify that the ingredient was not the subject of the IND and clinical trials prior to the submission of the notification. With that said, FDA is treating this requirement as an absolute bar. However, that is simply not true. More specifically, FDA has the authority to permit its use as a dietary supplement if after notice and comment the agency finds the article can be lawfully marketed as a dietary supplement. (See Federal Food, Drug, and Cosmetic Act § 201(ff)(3)(B)(ii).)
Of particular importance in this instance, if the drug approval had already taken place under §201(ff)(3)(A), this option would not be available. In other words, Congress recognized that there may be instances where a substance is not approved because it did not help in the treatment of a disease but would have value to overall health and well-being as a dietary substance. Accordingly, we would hope FDA understands this important distinction and use its request for comments on vinpocetine to affirm its use as a dietary ingredient; there is no question that it has never been approved as a drug in the U.S., and it has a reasonable expectation of safety based on FDA’s own review.
As an industry, we do need to do better. However, FDA needs to step up and understand that we cannot simply hit a reset button that suddenly sends us back to October 1994. FDA should affirm vinpocetine’s use as a dietary ingredient as permitted under the FFD&C Act, abandon its view on synthetics and bring ingredient manufacturers under Part 111.
Todd Harrison
Venable
Todd Harrison is partner with Venable, which is located in Washington, D.C. He advises food and drug companies on a variety of FDA and FTC matters, with an emphasis on dietary supplement, functional food, biotech, legislative, adulteration, labeling and advertising issues. He can be reached at 575 7th St. NW, Washington, D.C. 20004, Tel: 202-344-4724; E-mail: taharrison@venable.com.
Meanwhile, the New York Attorney General (AG) reached another settlement with a large dietary supplement company regarding supply chain integrity and DNA testing (NBTY, Inc.). And the Drug Enforcement Agency (DEA) attempted to schedule a benign herb (kratom) through its emergency scheduling process. Additional developments have included recent settlements out of the State Iowa AG office and the state of California.
What do all of these situations have in common? The constant drumbeat from regulators has been that the industry is simply not doing enough to self-regulate. This overall perception has not changed, quite frankly, since the Dietary Supplement Health and Education Act (DSHEA) was passed in October 1994; but is this all the fault of industry, or do regulators bear responsibility in this process?
FDA’s Inaction & Ambivalence
From my perspective, while the industry has not always done its best to comply with the requirements of DSHEA, I would argue that a large part of the blame falls on regulators—FDA in particular. The new NDI draft guidance, the NY AG’s efforts on traceability, DEA’s misstep with kratom, and even the issues surrounding claims can be directly attributable to FDA’s general ambivalence—some would say outright hostility—toward the industry. One only needs to look at the timeline to figure out that many of these issues could have been avoided if FDA would have simply taken a more active approach toward regulating the industry in 1994.
DSHEA became effective on Oct. 14, 1994; yet during the next 22 years, FDA rarely did anything with regard to supply chain integrity and new dietary ingredients. For instance, it should not take the NY AG to enter into agreements with GNC and NBTY to make it clear that ingredient manufacturers are an integral part of ensuring supply chain integrity.
Indeed, the issue of identity testing should not start at the finished product manufacturing stage, but rather at the ingredient manufacturing stage. Especially with botanicals, the ingredient manufacturer is in better position to conduct the initial identity testing than the finished product manufacturer. Yet, FDA made a decision to exempt ingredient manufacturers from Part 111. To this day that decision is dumbfounding to me.
FDA continues to ignore a citizen petition by the Organic & Natural Health Association that requested the agency bring ingredient manufacturers under Part 111, even though state AGs and members of Congress have called for the same. FDA could achieve this task in short order. Instead, the NY AG is making agreements with companies to make this happen; however, these companies by themselves can’t achieve the ultimate goal, as the ingredient manufacturing industry is not of an insignificant size.
New Dietary Ingredients
First, in the immortal words of Green Bay Packers Quarterback Aaron Rodgers: r-e-l-a-x, Relax. The draft guidance is just that—a draft guidance document. Moreover, it only represents FDA’s current thinking on the matter and does not have the effect of law. Forget for a moment that FDA has no ability under the law to reject a notification or to approve new dietary ingredients; as stated in my last column, the document has fundamental issues that the agency still needs to work through (September 2016, “FDA Issues Revised Draft Guidance On New Dietary Ingredients”).
With that said, if the agency had worked with industry in 1994-1995 on developing a positive list of ingredients, as well as a policy around what would be considered a new dietary ingredient—such as a substantial change in concentration of a particular ingredient—we would not be in a situation today where we need to determine what is rightfully an “old” dietary ingredient.
Yet, it has taken FDA more than 22 years to determine that it should compile such a list, even though the industry had compiled a list back in the mid-1990s, which FDA has refused to adopt. The agency should start with that list and request information on ingredients that are not on the list. Yet, for whatever reason, FDA is simply rejecting this approach, which is nonsensical and feeds into the general perception that the industry can’t be trusted. FDA has reinforced this perception with vinpocetine.
Vinpocetine’s Regulatory Status
As everyone knows, including FDA, there were no less than five new dietary ingredient notifications regarding vinpocetine without comment from the agency. Yet, even though this ingredient is reasonably expected to be safe, in what appears to be a purely political decision sparked by Senator Claire McCaskill (D-MO), FDA decided to dig up some old press releases regarding this ingredient.
The industry has a reason to take issue because FDA has, at a minimum, treated the new dietary ingredient notification as a quasi-approval process—if not an outright approval process—and the industry should have been able to rely on it when making decisions about whether to incorporate a new dietary ingredient into a finished dietary supplement. This is not a situation where an ingredient supplier was relying on a Generally Recognized As Safe (GRAS) self-determination, or use in the food supply to escape the notification process. Rather, the notification was actually filed and FDA had no comment. “No comment” does not mean FDA agrees with the notice; however, given FDA’s propensity to question these notifications, it is absurd that the agency now has a concern, stating that because it believes vinpocetine is a synthetic ingredient, subject of an investigational new drug (IND) application and substantial, public clinical trials in the U.S. prior to its introduction as a dietary ingredient.
Putting aside the latter point, which poses significant issues, there is simply not justification for FDA’s position on synthetic botanicals or ingredients synthesized from botanicals. Nowhere in DSHEA or its legislative history does it indicate that synthetics are not permitted. Indeed, the catch-all provision of DSHEA regarding a “dietary substance” when viewed in light of the “new” dietary ingredient notification provisions clearly contemplates that new dietary substances would be developed. Otherwise, the new dietary ingredient notification provision would rarely be used, which was not the intent of Congress.
Moreover, the use of the term “substance,” rather than nutrient or nutritive, clearly indicates that Congress contemplated something other than one of the specific categories delineated in the definition of a dietary supplement. In other words, “substance” contemplates synthetic ingredients that may be developed. Thus, FDA’s position on synthetic botanicals is directly at odds with Congressional intent.
Regardless, if we are going to treat the notification process as just that—a notification process—it is difficult to penalize the agency for not understanding that an IND and substantial, public clinical trials were conducted on an ingredient.
Moreover, it should be required for the notifier to certify that the ingredient was not the subject of the IND and clinical trials prior to the submission of the notification. With that said, FDA is treating this requirement as an absolute bar. However, that is simply not true. More specifically, FDA has the authority to permit its use as a dietary supplement if after notice and comment the agency finds the article can be lawfully marketed as a dietary supplement. (See Federal Food, Drug, and Cosmetic Act § 201(ff)(3)(B)(ii).)
Of particular importance in this instance, if the drug approval had already taken place under §201(ff)(3)(A), this option would not be available. In other words, Congress recognized that there may be instances where a substance is not approved because it did not help in the treatment of a disease but would have value to overall health and well-being as a dietary substance. Accordingly, we would hope FDA understands this important distinction and use its request for comments on vinpocetine to affirm its use as a dietary ingredient; there is no question that it has never been approved as a drug in the U.S., and it has a reasonable expectation of safety based on FDA’s own review.
As an industry, we do need to do better. However, FDA needs to step up and understand that we cannot simply hit a reset button that suddenly sends us back to October 1994. FDA should affirm vinpocetine’s use as a dietary ingredient as permitted under the FFD&C Act, abandon its view on synthetics and bring ingredient manufacturers under Part 111.
Todd Harrison
Venable
Todd Harrison is partner with Venable, which is located in Washington, D.C. He advises food and drug companies on a variety of FDA and FTC matters, with an emphasis on dietary supplement, functional food, biotech, legislative, adulteration, labeling and advertising issues. He can be reached at 575 7th St. NW, Washington, D.C. 20004, Tel: 202-344-4724; E-mail: taharrison@venable.com.
