Amarin has hinged its case, which was filed recently before the US International Trade Commission, on the specific chemical forms of fish oil that appear in the products in question. The complaint seeks an investigation into a number of omega-3 ingredient and supplement makers for what it alleges are illegal unapproved new drugs “cloaked as dietary supplements.”
According to the complaint, Amarin has invested over $200 million on the development, testing and clinical study of Vascepa, an FDA-approved drug that is derived from fish oil. A one gram capsule contains one gram of eicosapentaenoic acid (EPA) in ethyl ester form, states the company.
In the filing with the ITC, the company stresses that the complaint is not against “common fish oil”, which represents the majority of the market, but specifically against “synthetically produced omega-3 products that are predominantly comprised of EPA in either ethyl ester (“EE”) or re-esterified (“rTG”) form”.
According to a form 8-K filing with the SEC, Amarin is seeking to prohibit the importation into the US of the purported dietary supplement products and oil. “The lawsuit also seeks related cease and desist orders applicable to inventory of such articles of the named respondents already in the United States. Amarin contends that is has the supply capacity to meet through prescriptions replacement demand for the products targeted for exclusion,” states the SEC filing.
The ITC suit is against a number of different omega-3 players, including DSM, Marine Ingredients, Golden Omega, Nordic Naturals, Croda, TASA, Nature's Bounty, Pharmavite, Carlson Laboratories, and some of their affiliates. The complaint can be read HERE.
“The ITC provides a potent remedy”
When asked about the ITC approach versus seeking FDA enforcement issue, as was done recently when ChromaDex filed a citizen’s petition with the FDA regarding use of nicotinamide riboside (a form of vitamin B3) in dietary supplement products, a spokesperson for Amarin told us that the purpose of this action is to protect competitive interests, and that is not in FDA’s mission statement.
“The Federal law, specifically, the Lanham Act together with Section 337 and the Tariff Act of 1930, provide an efficient and effective venue to address competitive harm when illegal drug products are imported into the US through unfairly competitive means,” said the company.
“That said, Amarin’s arguments are consistent with FDA’s policies. With rare exception related to common use not applicable here, FDA has consistently found that synthetic substances do not fall under the “dietary ingredient” definition (for more than 15 years). And when purported “dietary supplements” have contained a synthetic ingredient FDA has taken action.”
The company also noted that, aside from having different priorities, the FDA is under resourced. “It does not have the ability to detect, or go after, every violation of food and drug law.”
“The ITC provides a potent remedy, available in relatively short order to redress competitive harm,” said the company. “And, it provides regulatory synergies that can both protect the public health and competitive interests, as SCOTUS observed in POM.”
As stated in the company’s Brief on Jurisdiction: ““Dietary supplements,” like beverages, are in fact a type of “food” under the FDCA. See id. § 321(f), (ff). As with beverages, to police purported “dietary supplements,” FDA has to rely on enforcement actions, warning letters, and other measures. Because of limited resources, however, the agency cannot detect every violation nor, as the Supreme Court observed in POM Wonderful, can it pursue every violation it detects.”
“Thus, as in POM Wonderful, the regulatory synergies between the Lanham Act and the FDCA are important here – if a federal district court were to preclude the Lanham Act claims over dietary supplements, commercial interests and, indirectly, the “public at large” would be unprotected.”
Relation of common fish oil to EPA concentrates
Fish oil is made up of about 20-30% omega-3 fatty acids EPA and DHA, with the rest comprised of saturated fat, other omega-3s, plus other fatty acids. The EPA or DHA is bound to a glycerol backbone. Picture a capital E with the vertical line being the glycerol and the three horizontal lines being saturated (like stearic or palmitic acid), monounsaturated, or polyunsaturated fatty acids (EPA or DHA). The omega-3 polyunsaturated fatty acids are typically found in the middle of the three on the glycerol backbone and are labeled SN-2 in chemistry.
To produce higher concentrations, a chemical reaction cleaves the fatty acids away from the glycerol backbone to produce “free fatty acids”, and these are then reacted with ethanol/ethyl alcohol to form ethyl esters. These ethyl ester forms can then be separated from each other using molecular distillation to concentrate the omega-3s. With a higher level of EPA and DHA, the omega-3s can then be reattached to a glycerol backbone to form a re-esterified triglyceride.
Production of ethyl esters and re-esterified triglycerides is not new and the ingredients have been studied since the 1980s at least. Whether these can be alleged to be ‘synthetic’ is a matter of interpretation, as no one disputes the raw material if from fish oil. The question then becomes what processing steps were used to end up with the finished form, and whether those steps (which would be individual to each supplier’s extraction and concentration process) take the ingredient over the line into ‘synthetic’ category.
Regardless of form, the action is the same
Prominent omega-3s researcher Bill Harris, PhD of the University of South Dakota and a principal in the testing firm OmegaQuant, said the action in body is same whether the omega-3 fatty acids are delivered in a base 18:12 fish oil form or in a higher concentration. The issue is how many pills a consumer would have to take to achieve a high dosage and how likely they are to comply with that regimen, which in the case of Vascepa, Amarin’s product, is 4 grams of EPA daily.
“The body just cleaves the fatty acids off in the gut. Whether it started off as a natural triglyceride or an ethyl ester, they are basically the same thing. The point of their product is that the doctor is going to write you a scrip, and the insurance will pay for it,” Dr Harris said.
Indeed, on Amarin’s own website the differences it lists between Vascepa and fish oil supplements have to do with how the claims on its product have been substantiated via clinical trials and how its product must be manufactured to pharmaceutical GMPs standards. There is no claim that the two types of products – fish oil supplements vs its own pharmaceutical form – are different in their action in the body.
‘Financially motivated’ action
Trade groups have reacted vigorously in response to the complaint. In a brief filed by the law firm Amin Talati Upadhye with the ITC, trade group GOED said: “Complainants’ attempt to construe Respondents’ lawfully marketed products as illegal drugs is a financially motivated, improper effort to expand their near monopoly on their own small subset of Omega-3 products. Removal of Respondents’ lawful dietary supplements would adversely impact consumers’ convenient and affordable access to products that help maintain a healthy diet and lifestyle. Thus, the relief sought in this case would cause harm to public health and welfare and to competitive conditions in the United States.”
GOED's brief noted that a monthly supply of Vascepa costs $200, whereas the products offered by the manufacturers named in the complaint cost a fraction of that, though it should be noted there was no attempt in the brief to match the dosage levels between products.
In a statement, the Council for Responsible Nutrition decried the action as a "financially motivated" attempt to expand Amarin's near monopoly over a subset of omega-3 products that would "dramatically affect consumers' access by making it more difficult and expensive, if not impossible, to obtain the health benefits associated with these products."
According to CRN President & CEO Steve Mister, "This appears to be a case of a company seeking a market monopoly that would deprive both legitimate manufacturers of selling legal fish oil supplements and consumers of having access to products that benefit their health and well-being."
In asking the ITC to make a legal determination whether the products in question "are 'dietary supplements' within the meaning of [Food, Drug & Cosmetic Act (FDCA)] Section 321," CRN says Amarin has crossed a legal boundary. "Amarin is inappropriately seeking to bypass the U.S. Food and Drug Administration's (FDA) rightful authority to make this determination by filing its complaint with the ITC," said Rend Al-Mondhiry, associate general counsel, CRN. "Contrary to Amarin's assertions, FDA has exclusive authority to make this determination."
NutraIngredients-USA asked the FDA to clarify their position on EPA in ethyl ester of re-esterified triglyceride form as dietary ingredients. The Agency declined to comment.
Dr Dan Fabricant, CEO and executive director of the Natural Products Association, told NutraIngredients-USA that he is unaware of any of the dietary supplements in question making disease claims, and therefore questioned how consumers might confuse the two. Dr Fabricant agreed with Dr Harris in that he said the chemically active moiety is the EPA and not the ethyl ester. The body would break down the ethyl ester form to EPA and absorb that.
Putting all that together into a complaint that is not over broad is a trick, noted attorney Marc Ullman, of counsel with the firm Rivkin Radler. The complaint is narrow, he said, which may improve its chances of success. Ullman said this relates to FDA’s failure to protect IP from pioneer companies in the past, which he has dealt with in the case of BioPQQ, a brain health ingredient from Mitsubishi.