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Amarin’s ITC complaint alleges that synthetically produced omega-3 products that are predominantly composed of EPA in either ethyl ester or re-esterified form are not considered “dietary ingredients” under Section 201(ff)(1) of the Federal Food Drug and Cosmetic Act, and thus, are not legal dietary supplements but unapproved new drugs.
As new omega-3 drugs enter the heart-health market, the relationship between the drug and dietary supplement industries, where omega-3 has been a star player for decades, grows more complicated. Recently, drug firm Amarin Pharma filed a complaint with the International Trade Commission (ITC) alleging that synthetically produced omega-3 dietary supplements that are predominantly composed of EPA in either ethyl ester or re-esterified form are synthetic and therefore not considered “dietary ingredients” under Section 201(ff)(1) of the Federal Food Drug and Cosmetic Act (FD&C Act)-meaning they are not legal dietary supplements at all but unapproved new drugs. Amarin’s own omega-3 Vascepa drug contains EPA omega-3 in ethyl ester form and is synthetically produced.
In its complaint to the ITC, Amarin “respectfully requests that the U.S. International Trade Commission (the “ITC” or “Commission”) commence an investigation into the unlawful importation or sale in the United States of synthetically produced omega-3 products that are predominantly comprised of EPA in either ethyl ester (“EE”) or re-esterified (“rTG”) form and are falsely labeled, and/or promoted for use as, or in ‘dietary supplements’ (the “Synthetically Produced Omega-3 Products”).” The complaint names many of the dietary supplement industry’s leading omega-3 marketers and ingredient suppliers, including DSM, Nordic Naturals, Pharmavite, Carlson Labs, and Nature’s Bounty, among others.
Per the complaint, Amarin alleges that these omega-3 products are falsely labeled as dietary supplements, which it says “constitutes an unfair act and/or unfair method of competition.” Citing the FD&C Act, Amarin says that such supplements are actually unapproved “new drugs.” According to Amarin, the esterified and re-esterified omega-3 ingredients in some supplements undergo manufacturing changes that lead them to be considered synthetic ingredients-and, therefore, according to the FD&C Act, not dietary ingredients. The complaint also specifies that Amarin is not requesting an investigation into “common fish oil” or into “synthetically produced omega-3 products in EE or rTG form that are not predominantly comprised of the omega-3 acid, EPA.”
Amarin takes particular issue with what it deems “false labeling” and unfair promotion of these ethyl ester or re-esterified EPA omega-3 supplement products because, it says, pharmaceutical companies “have invested the necessary resources to bring competing drug products to market.” Ultimately, Amarin states in its complaint, there is no incentive for other drug companies to invest in the development of products containing these forms of omega-3 if supplements manufacturers are able to “avoid the drug approval process and the associated time and investment necessary to conduct clinical trials that show their products are safe and effective for each intended use and to obtain FDA approval for each intended use.”
Nutritional Outlook interviewed Duffy MacKay, ND, senior vice president, scientific and regulatory affairs, Council for Responsible Nutrition (CRN; Washington, DC), on how this ITC complaint could affect the omega-3 dietary supplements industry.
MacKay says he is skeptical that Amarin’s complaint has legs to stand on. “Amarin is trying to stamp out the competition,” MacKay tells Nutritional Outlook. “It also seems they’re lacking in some specificity. They refer to this ethyl ester form or rTG [that are] predominantly EPA. So, they’re really looking at concentrated formulas that are mostly EPA, but that’s a big gray [area]. Does that mean 51% EPA, or does that mean 98% EPA? To me, that signifies that they don’t really know what they’re trying to make a grab for. They’re really trying to eliminate a broad section of their competition.”
As Nutritional Outlook previously reported, ethyl ester EPA fatty acids are chemically connected to ethanol using processing technology that allows the ethyl ester forms of EPA or DHA to be concentrated-via molecular distillation or other procedures-producing omega-3 “concentrates” that can then be used in dietary supplements. These can also be converted back to the triglyceride form for supplements (“re-esterified” triglycerides). As Nutritional Outlook has also previously reported, demand and innovation around omega-3 high concentrates in the dietary supplements market is growing.
In the ITC complaint, Amarin devotes much discussion to comparing the chemical profile and molecular composition of its ingredient versus omega-3 supplements, noting several molecular forms and mixtures of synthetically produced omega-3 supplements in which ethyl ester or re-esterified EPA is the predominant component. But MacKay says that Amarin is overlooking a major detail in how FDA distinguishes between drugs and dietary supplements.
“I’m a scientist, and I see major gaps and flaws in their technical, regulatory, scientific arguments,” MacKay explains. “They’re overplaying the synthetic concept. I think their regulatory argument seems spotty because they keep accusing ethyl ester EPA as being a drug, and they never once address a very important distinction, which is that FDA doesn’t regulate and distinguish between supplements and drugs based on the chemistry. They do it based on the intended use.”
On top of that, he says, EPA has long been a mainstay of the supplements industry as a dietary ingredient naturally found in fish oil. Though Amarin’s complaint cites EPA omega-3 research from the 1980s conducted by the National Institutes of Health (NIH), MacKay notes that this doesn’t necessarily mean that the research that was done on EPA was exploratory research for drug purposes, or that the research was conducted on Amarin’s specific product. “The bottom line is fish oil was already being sold a dietary supplement at the time, and people were already using ethyl ester at the time,” he said.
Now that one drug company has filed a complaint, will more follow suit? Or will it be possible for supplement and drug companies to coexist moving forward? MacKay points out that Lovaza (GlaxoSmithKline) has been able to coexist alongside the omega-3 supplements category for years without trying to erase the competition.
“Amarin is not the first ethyl ester fish oil to become a drug. We already have Lovaza; they’re a drug. They coexisted for over a decade with all the dietary supplement fish oils. Along comes Amarin, and one of their business strategies is obviously to squash the competition by accusing the entire supplements industry of selling an unapproved drug, and going to the International Trade Commission-which is absurd, because this is FDA jurisdiction. FDA should make the decision whether EPA in the ethyl ester form is a drug or not. And it’s not,” he says.
The market for omega-3 supplements can operate separately from the market for omega-3 drugs, says MacKay. While 170 million Americans use supplements, there’s a large swath of the population who do not engage with supplements; rather, their cardiologist may prescribe an omega-3 drug with a higher omega-3 concentration, for example. Those consumers who would not have gravitated towards a supplement may thus be more receptive to EPA omega-3 in drug form. This, Mackay says, is one of the biggest reasons that omega-3 drug and supplements companies have not yet come to blows. When Lovaza entered the market, MacKay says, “it didn’t put a damper on supplement growth in that category.”
Finally, while it’s true that omega-3 supplements formulated with higher concentrations of actives are becoming more popular, MacKay doesn’t think that such products will take over the omega-3 supplements category anytime soon. For one thing, consumers who take omega-3 supplements likely do so for general health, or for general eye- or heart-health, and not necessarily for the same reasons that patients take omega-3 drugs. And, he says, because highly concentrated omega-3 supplements are generally more expensive than standard omega-3 supplements, the audience for high concentrates remains limited.
For now, says MacKay, the dietary supplements industry is going to have to go on the defensive to ensure that Amarin’s complaint is unsuccessful and unable to set a precedent. “The fight is going to be interesting. Will it be the individual companies named going and fighting one by one against Amarin? Or, will…the entire industry, who sees it as a matter of principle, get together and fight another fight against them?” says MacKay. “Because we don’t want to see precedent set. This is a champion ingredient, it’s a safe ingredient, something our industry is very proud of, so they’re going to have the issue of the entire industry, unnamed in the complaint, being very concerned about this.”
According to MacKay, those named in the ITC complaint likely need to rely on a defense based on FDA policy. “They’re trying to skirt things and go to the trade commission, and I think that it needs to be brought back to FDA for determination,” he says. “I think that’s going to be a main strategy.” MacKay emphasizes that FDA is, and should continue to be, the appropriate regulatory body with the final word on this complaint.
While the complaint is undoubtedly concerning to those in the supplements industry, ultimately MacKay says he isn’t too worried about Amarin’s complaint succeeding. “I don’t think they have a chance,” he says. “But,” he adds, “more nonsensical things have happened in DC.”