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.”