Nutrition Industry Executive (NIE) magazine asked Nena Dockery, Regulatory Affairs Manager of Carthage, MO-based Stratum Nutrition to provide comments on questions we posed to her about compliance and quality in the natural products industry. Here are her expanded comments:
NIE: One analysis of FDA (U.S. Food and Drug Administration) data reported that 776 adulterated dietary supplements were identified by the agency from 2007 through 2016, of which 619 were found to contain one unapproved drug ingredient, and 157 products were found to contain more than one pharmaceutical ingredient. What dramatic step can the industry take to try to eliminate the scourge of economic adulteration?
Dockery: The natural products industry has been plagued from its onset by companies desiring to make a quick dollar at the expense of safety and efficacy of the products they sell; and adulteration has been one of the easiest modes of deceit.
Adulteration comes in two main forms. Pharmaceutical adulteration entails the addition of an active drug into a supplement to enhance the effect experienced by the unsuspecting consumer, thus ensuring repeat sales. Economic adulteration involves the use of lesser expensive ingredients, inferior forms of active ingredients or formulating with less of the active ingredient declared on the label. Pharmaceutical adulteration almost always results from an intent to deceive, whereas economic adulteration might occur unbeknownst to the product distributor.
The COVID pandemic greatly increased the incidence of economic adulteration resulting from supply chain shortages of desirable ingredients and the increased demand brought on by anxious consumers trying to protect their health in every means possible. Shortages of key high-quality ingredients, along with extraordinary price increases, led many manufacturers to seek substitute ingredients that were often of much less quality. Document tampering became increasingly more commonplace as well.
Though FDA does play a crucial role in ensuring the safety of supplement products marketed in the U.S., it does not assess their safety prior to market. Therefore, identification of suppliers and manufacturers known to engage in adulteration of products is primarily the responsibility of the natural products industry in policing their own. Once identified, FDA takes on the responsibility of identifying and removing adulterated and unsafe supplements from the market and dealing with the perpetrators.
The industry can take measures to help curb the damage done by adulteration. Manufacturers and distributors should take no piece of documentation at face value. CofAs should be verified, testing should be left to laboratories that are adept at identifying adulterants. Companies can also opt to deal only with reputable suppliers and manufacturers, and they should demand full transparency. Opting for ingredients produced domestically or are completely traceable does help but isn’t always possible. This is a particularly difficult task for manufacturers that deal with multiple overseas suppliers.
NE: In August 2016, FDA published a revised NDI (new dietary ingredient) draft guidance, which has not been finalized. Why is this in limbo?
Dockery: Many of the issues that existed in 2011 when FDA published its first NDI draft guidance remained when the revised guidance was issued in 2016, and some of those significant issues remain unresolved. Among the biggest stumbling blocks to finalization is the call from the industry for FDA to develop a master file program that will provide a way to protect the investment in time and resources of companies filing NDINs.
Another big issue impeding the NDI draft guidance concerns the parameters surrounding the meaning of “chemically altered.” The draft guidelines state that ingredients that have already been submitted through an NDIN might need to be resubmitted because of a manufacturing change that results in a chemical alteration of the structure of the ingredient.
Since the passage of DSHEA (Dietary Supplement Health and Education Act of 1994), there have been tremendous advances in methodologies used to improve an ingredient’s overall profile.
Processes such as those to improve water-solubility or make ingredients more bioaccessible in the human body have proliferated in recent years, and there really needs to be clearer guidance regarding if or when these changes really warrant a new NDIN submission.
Another unresolved issue is the industry’s request for an expansion of FDA’s stance on synthetic dietary ingredients to include ingredients other than vitamins and amino acids. This issue overlaps with issues surrounding the grandfathered list as FDA doesn’t recognize synthetic forms of botanical constituents, even those that were known to be on the market prior to Oct. 15, 1994.
Until FDA recognizes a grandfathered list of ingredients, some of these synthetic botanical constituents will remain in limbo and possibly subject to NDIN submission.
The natural products industry and FDA must come to some consensus or compromise on these outstanding issues. The industry needs sufficient clarity on the NDIN submission process. Without it, many submissions will continue to be rejected by FDA, or companies will opt to simply market ingredients without going through the tedious, time-consuming, and expensive process.
NIE: What is the biggest compliance (legal or regulatory) issue in the natural products industry right now, and how can it be addressed?
There are several issues that have been a source of legal and regulatory confusion ever since DSHEA was passed; and these same issues and related concerns continue to bring frustration to the industry.
One of the biggest issues surrounds the identification of ingredients that qualify as dietary supplement ingredients, and this concern is surrounded by several confounding issues.
First, FDA still hasn’t published a list of ingredients that were marketed as food supplement ingredients prior to 1994 and thus are grandfathered into the supplement market.
This isn’t entirely the responsibility of FDA as the supplement industry has been tasked with providing documentation to support the use of ingredients prior to the Oct. 15, 1994, date. But, regardless of the reasons, there isn’t an accurate ground floor of ingredients to build upon.
This has forced some reputable companies into making the decision to file a New Dietary Ingredient notification when none may be needed; and to complicate matters further, there still isn’t a final NDI guidance document to assist in this tedious process.
So, the door is open for less scrupulous companies to market unsafe ingredients, which has in some cases negatively impacted the reputation of the industry.
In addition, there are some ingredients, such as NAC (N-acetyl cysteine) and CBD (cannabidiol) that have been sold in the natural products market, but also used in drug development research. For these ingredients, there is the hurdle of determining if the ingredient was researched in the development of a drug before or after it was used in the natural products market.
There should be a decision tree established that investigates not only the ingredient itself, but also the ingredient form being used in the research. In the case of NAC, not only is the documentation regarding its approval as a drug suspect, but also the NAC “approved” as a drug in 1963 was in an inhaled form, not orally consumed.
To adequately address this issue, some pathway needs to be developed for guiding the industry into introducing ingredients into the supplement market, beginning with an evolving list of ingredients that are already approved for use, both those that have verified traditional use (grandfathered in) and those that have been submitted as new dietary ingredients.