I have been looking at FDA recall procedures to try to understand what might happen as a result of ChromaDex's complaint and lab report claiming that Elysium's new Basis formulation contains residue of toluene, a toxic solvent.
It seems like (1) the FDA might or might not care, and it seems like (2) Elysium's customers might or might not care.
I'll take a look at both scenarios and examine which are likely to be true, and what the implications might be.
It seems to me that the FDA should care about this but probably will not, and consumers should not care about this but probably will.
Let's start with the FDA:
ChromaDex's petition presents two main complaints. First, the sale of the new formulation of Basis should have been preceded by the filing of a New Dietary Ingredient Notification (NDIN). Second, the presence of toluene renders the new formulation of Basis adulterated.
New Dietary Ingredient Notification (NDIN)
A federal regulation -- 21 CFR 190.6 -- requires a submission to the FDA before a new dietary ingredient is sold. The key questions for Elysium's new Basis are (1) Is the new formulation of Basis a "new" dietary ingredient, and (2) what happens if you break this rule?
The FDA has some new draft guidelines that, although not legally binding, summarize the FDA's thinking on when an NDIN is required. Typically courts give some level of deference to agency guidelines, especially on technical matters, even though courts are free to disagree.
The draft guidelines suggest that an NDIN was required for Elysium's new formulation of Basis. They specifically address the question of changes to manufacturing methods. Here is some boring law from the FDA suggesting that structural changes to the ingredient and the introduction of impurities matters:
12. If I change the manufacturing process for a dietary ingredient [that would otherwise be approved], does that make the ingredient an NDI?
The answer depends on the extent to which the manufacturing process change affects the resulting ingredient...Any changes in your manufacturing process that alter the identity of the ingredient will convert a previously marketed dietary ingredient into an NDI. Manufacturing changes that alter the physicochemical structure or properties, purity and impurities, or biological properties (such as bioavailability or toxicity) of the ingredient result in an NDI. 18 For example, using a solvent to prepare an extract from a pre-DSHEA dietary ingredient creates an NDI because the final extract contains only a fractionated subset of the constituent substances in the original dietary ingredient. (emphasis added)
The Draft Guidelines reference additional FDA guidance on the impact of manufacturing changes, which sends the same message: Manufacturing method changes matter, and the presence of new impurities ought to be taken seriously:
...Changes in the manufacturing process that are significant...may include:
A change in one or more starting materials;
A change in the concentration of starting materials;
A change in catalyst;...
A change in food manufacturing or ingredient technology...
We expect that there will be circumstances where a significant manufacturing process change, impacts the safety, the regulatory status, or both, of a food substance. In such circumstances, a new regulatory submission may be necessary to clearly establish the conditions under which the food substance, manufactured by a new process, is safe and lawful...
We recommend that, whenever there has been a significant manufacturing process change for a food substance that is the subject of a food additive or color additive regulation, you:
Determine what changes have been made to the identity of the food substance as a result of the change in manufacturing process, including its physicochemical structure and properties, purity, and impurities;
...Conduct a safety assessment...
Consult with us about your conclusions... and
Make an appropriate regulatory submission to FDA as circumstances warrant. (emphasis added)
The additional guidance on the impact of manufacturing changes also lists three illustrations of process changes that do NOT significantly impact safety. You can read those yourself, but none of the FDAs examples involved the new appearance of toxic residues.
Implications of Failing to File an NDIN
So what happens if you were supposed to file an NDIN and you did not?
The teeth in the regulatory scheme are clear and apparently very sharp. You can find them in a federal statute, 21 USC 350b(a), which says that your New Dietary Ingredient is adulterated unless either (1) it contains nothing but food, or (2) you filed an NDIN explaining why it is safe.
Toluene is not food, and so if there is no NDIN, then the new Basis formulation is adulterated -- unless, somehow, the new manufacturing process that generated the new impurities was not enough to make new Basis a New Dietary Ingredient.
So my prediction is that Elysium's lawyers will be arguing that this is not a new ingredient because a few micrograms of toluene never hurt anyone, and ChromaDex will be arguing that the whole purpose of the NDIN process is to allow the FDA to make that determination.
Assuming the FDA Agrees with ChromaDex, Will it Do Anything?
If you look through the list of FDA safety recalls for things like illegal adulteration of health supplements, a few things jump out right away:
First, There are a huge number of FDA safety recalls -- like, almost daily.
Second, the recalls are mostly for undisclosed ingredients (e.g., the product contains an undisclosed potential allergen like milk, eggs, nuts, or shellfish), or the product was contaminated with some pathogen or toxin, or something about the manufacturing process concerns the FDA so that there was a "lack of sterility assurance."
Third, some of the recalls are for use of an "unapproved drug." We'll get back to that one.
All of this gives the impression that the FDA is pretty serious about policing this stuff.
But a few details give pause.
First, these recalls are overwhelmingly voluntary recalls and alerts issued by the company itself. It does not usually look like the FDA has strong-armed the companies into issuing a "voluntary" recall (with an exception noted below). Instead, it more often looks like the FDA is an information clearinghouse for documenting and distributing the safety information.
That matters, because careful watchers of Elysium Health are not expecting Elysium to voluntarily recall all inventory of their only product. Instead, Elysium is more likely to say what they were alleged on a Yahoo Finance message board to have said:
"I got a response from Elysium saying that their product conforms to the residual solvents limits set International Conference on Harmonisation which the FDA relies upon..."
So when DOES the FDA order companies to stop selling substances over the company's objection? It does happen.
In June the FDA seized contaminated products from a warehouse in Minnesota. The warehouse had failed inspections two years earlier, and the suppliers failed to make promised changes.
Just last week the FDA seized some vaccines from a California company that was offering unapproved stem cell treatments. The FDA said, "The FDA has serious concerns about how StemImmune obtained the product for use as part of an unapproved and potentially dangerous treatment. The FDA is actively investigating the circumstances by which StemImmune came to possess the vaccine."
Tough talk, because as the enforcement arm of the pharmaceuticals industry, the FDA REALLY gets upset when a prescription drug gets sold without a prescription. Rancid food can sit in a warehouse for years before the FDA completes the legal process of doing something about it. BUT...
Imagine if Viagra got sold without a prescription? The FDA would pounce like a cat.
That's the third category I mentioned above, "Unapproved Drug."
So, for example, "SuperPanther 7K" is an herbal supplement marketed for erectile dysfunction.
But the problem with SuperPanther was not that it didn't work, but that it did work -- the owners apparently slipped in some undeclared-but-proven-efficacious sildenafil (Viagra) and tadalafil, active ingredients in two FDA-approved prescription drug products used to treat erectile dysfunction. "The presence of sildenafil and tadalafil in Super Panther 7K renders it an unapproved drug for which safety and efficacy have not been established and, therefore subject to recall."
This quote comes from a document that is styled as a voluntary recall, but the quoted language above sounds like it was authored and imposed by the FDA. I don't see a safety risk -- Viagra is very widely used for this precise purpose. Instead, I see a profit risk.
Lest there be any doubt about what the FDA considers dangerous, note that the antihistamine Claritin (Loratadine) was considered so dangerous by the FDA that it required a prescription until 2002 -- that's coincidentally when the patent ran out, and with the inevitable arrival of generic competitors, the profit driver moved from margin to volume, and suddenly the FDA agreed that Claritin had become safe for everybody to use.
So my admittedly cynical conclusion is that even though toluene is FAR more toxic and dangerous than milk, eggs, and many other undisclosed recalled food ingredients, the FDA is unlikely to spring into action unless its general ability to protect pharmaceutical profits is implicated.
Will the FDA view the newly formulated Basis as improper and unnecessary poisoning of the public (yawn) or as an assault on a patented medicine (red alert)?
The latter is certainly plausible, because the subtext of this entire Elysium/ChromaDex dispute is really about who gets to produce patented ingredients, and the risk in this kind of battle is that someone like Elysium Health would decide to use an undisclosed manufacturer with an inferior production process -- exactly the kind of business behavior that warrants scrutiny to make sure that public safety isn't being compromised.
Nonetheless, the FDA's Regulatory Procedures Manual doesn't make me optimistic about an aggressive response. It contemplates urgent situations and serious adverse health consequences:
FDA Requested Recall
An FDA request that a firm recall a product is ordinarily reserved for urgent situations. The request is directed to the firm that has primary responsibility for the manufacture or marketing of the product when the responsible firm does not undertake a product recall on its own initiative. FDA requested recalls are most often classified as Class I. Generally, before FDA formally requests recall action, the agency will have evidence capable of supporting legal action, i.e. seizure. Exceptions include situations where there exists a real or potential danger to health, or in emergency circumstances such as outbreak of disease involving epidemiological findings...
Mandatory Food Recalls
FDA will...provide a responsible party...an opportunity to voluntarily cease distribution and recall a food when FDA has determined that there is a reasonable probability that the article of food (other than infant formula) is adulterated under section 402 of the Act or misbranded under section 403(w) of the Act AND the use of or exposure to such article will cause serious adverse health consequences or death to humans or animals (SAHCODHA). FDA may exercise its authority to mandate a recall under section 423(b)-(d) if FDA has provided the responsible party with an opportunity to voluntarily cease distribution or recall the article of food; and the responsible party has refused to or has not voluntarily ceased distribution or recalled the article of food within the time and manner prescribed, if so prescribed, by FDA. (emphasis added)
The FDA's heavy reliance on voluntary recalls by the producer except in these extreme circumstances makes sense, because by far the most common recall scenario is that the producer of a wide variety of goods needs to recall a single batch of a single product. That producer typically has every incentive to cooperate with the recall and protect the reputation of the rest of its business.
Those typical producers are not like Elysium Health, which appears to have bet its entire business on a single product. If Elysium concedes that Basis is unsafe, there isn't much left of their business.
So I imagine Elysium's response to the FDA will be something like what I told my friend, which is that 100 mg/kg sounds like a lot, but it would take me more than a year to consume a kilogram of Basis. Therefore, the actual amount of nail polish remover in each pill would be very minute.
Chromadex measured about 100 mg/kg, but there are maybe 5,000 pills in a kilogram. So that's 100mg/5000 per pill, or about one-fiftieth of a milligram, or 20 micrograms, somebody check my math.
That is a tiny, tiny amount of toluene. It doesn't sound like an urgent health hazard. If I were Elysium I would tell the FDA that people routinely inhale more toluene while dining at a sidewalk cafe near a busy street -- no biggie.
So I strongly suspect that Elysium violated the NDIN regulations, as ChromaDex claimed in the petition -- or at least Elysium is a bad citizen when it comes to complying with industry standards on supplement science and transparency (the opposite of what it promised to be, see my earlier Jeremiad about Elysium's failure to attempt to clean up the Supplement industry).
But I'm not very convinced that the FDA is going to do much about it. Which brings us to our second big question:
Do Consumers Care If There is Toluene in Elysium Basis?
When I told my friend that there was only a tiny amount of gasoline additive in each Elysium Basis pill, she responded, "Yes, but how many pills do you take, each day, and day after day?"
That response, I think, is a real problem for Elysium.
Over time, things add up. Or if they don't actually add up, it feels like they do. And sometimes substances turn out over time to be more dangerous than we originally thought -- obvious examples would be lead, asbestos, and cigarette smoke.
So I predict that a LOT of health-conscious people will say, however much toluene I am already involuntarily ingesting from my environment by sitting at sidewalk cafes, I absolutely do not want to be increasing that number every day when I take a health supplement.
So if Elysium Health's strategy is to say, along with me, 20 micrograms of industrial solvent per day never hurt anybody, I think they are going to encounter a very skeptical audience.
And it's tempting to call that skeptical audience irrational, and anti-science, but I'm not sure it is irrational. The health benefits of Nicotinamide Riboside are somewhat speculative, but the dangers of toluene are well-documented. It just feels like a stupid bet to ingest a small quantity of something that is DEFINITELY toxic in order to get a large quantity of something with a potential benefit.
At least it is a stupid bet when you can get someone else's Nicotinamide Riboside -- ChromaDex's TruNiagen -- without the toluene. Who, given a choice, would choose the product that comes with a mandatory dose of safely ingestible paint thinner?
Actually, I can imagine a VERY small market of what we might refer to as "Supplement Rationalists" -- people who believe that there is no harm from ingesting trace amounts of almost anything, so why not save a bundle of dough and buy the product that is adulterated with 20 micrograms of methyl benzene -- surely it must cost less.
Well, it doesn't cost less. Elysium Basis ($50/month - free shipping) and TruNiagen ($50/month -- with shipping) cost about the same.
So TruNiagen is an easy call for nearly all consumers.
Elysium could respond, I suppose, by lowering their price, and playing a mind-experiment with their customers: How much would we have to pay you to ingest 20 micrograms per-day-per-pill of toxic industrial chemicals -- $5/month? $10/month? Call it "Elysium Roulette."
But Elysium can't easily drop price like that. Elysium's business model requires high margins to support significant marketing investment. They can't survive as a low-price leader without completely changing their business model -- it takes a lot of margin to pay for fancy packaging and Nobel Laureate advisors.
So I don't see them lowering their price to make up for their process impurities. And I don't see Elysium's customers choosing to ignore the process impurities when they can switch to TruNiagen for about the same price and not have to worry about it.
So I predict that Elysium now has a serious marketing problem that they can only solve by (1) convincing the world that the ChromaDex test results are inaccurate or non-representative, or (2) modifying their production processes. Elysium has not so far taken a visible step down either path, and it is not clear that they can.
Brand Risk
I should add, also, that Elysium's sticking with the "20-micrograms-per-day, that's all we ask," marketing program represents potential brand risk to Elysium. ChromaDex twisted the knife in a portion of its Citizen's Petition that hasn't gotten much attention. ChromaDex noted:
Finally, Elysium represents to the public that...The ingredients in Basis have been tested for safety and are produced in facilities that meet FDA requirements. Basis also undergoes rigorous third party purity testing...Elysium's website also emphasizes the "purity" of its supply chain: "During the course of manufacturing Basis there are a total of five quality and purity audits before a batch is shipped. All manufacturing facilities are located in the US and are compliant with the cGMP regulations as stipulated by the FDA." (emphasis added)
Lawyers will argue about whether a new manufacturing process warrants a new regulatory filing, and what is the technical definition of "adulterated." But there is absolutely no argument about whether undisclosed toluene is consistent with an obsessive focus on purity. It's not.
CONCLUSION
I doubt that the FDA is going to make any significant sudden moves in response to the ChromaDex petition, even though the changes to the manufacturing process appear to have required a New Dietary Ingredient Notification, and the legal standard for adulteration seems to have been met.
However, if Elysium is unable to rebut the ChromaDex lab results or change their production processes, their business is going to be in a world of hurt.