Regulatory Developments for Omega-3 Claims

May 2014 US $39.00

SPECIAL REPORT Regulatory Developments for Omega-3 Claims Jurisdictions can vary widely in governing the claims that can be made for omega-3 fatty acids, as evidenced by reviewing the regulatory structures in the United States, the European Union and Australia.

by Kathy Musa-Veloso and Han Youl Lee SPECIAL REPORT Regulatory Developments for Omega-3 Claims by Kathy Musa-Veloso and Han Youl Lee Table of Contents INTRODUCTION ...... 3 SECTION I United States ...... 3 Relevant Legislation and Guidance Documents ...... 3 Claim Categories ...... 4 Nutrient Content Claims ...... 4 Health Claims ...... 5 Structure/Function Claims ...... 6 Claims Permissible for the Omega-3 Fatty Acids ...... 7 Nutrient Content Claims ...... 7 Health Claims ...... 9 Requirements for Claims Related to Coronary Heart Disease ....9 Requirements for Disqualifying Nutrient Levels ...... 10 SECTION II European Union ...... 11 Relevant Legislation and Guidance Documents ...... 11 Claim Categories ...... 11 Nutrition Claims ...... 11 Health Claims ...... 12 Claims Permissible for the Omega-3 Fatty Acids ...... 12 Nutrition Claims ...... 13 Health Claims ...... 13 SECTION III Australia ...... 15 Foods ...... 15 Relevant Legislation and Guidance Documents ...... 15 Claim Categories ...... 15 Nutrition Content Claims ...... 16 Health Claims ...... 16 Food Claims Permissible for the Omega-3 Fatty Acids ...... 17 Nutrition Content Claims ...... 17 General Level Health Claim ...... 18 Complementary Medicines ...... 18 Relevant Legislation and Guidance Documents ...... 18 Claim Categories ...... 19 Claims Permissible for the Omega-3 Fatty Acids ...... 20 SECTION IV Comparative Analysis ...... 20 SECTION V References ...... 23

Omega-3 Insights • Regulatory 2 omega3insights.com Claims Related to Omega-3 Fatty Acids: Latest Regulatory Developments by Kathy Musa-Veloso and Han Youl Lee

laims made in the labeling and advertising of foods and dietary supplements represent an important means of communicating the Cbenefits of nutritional ingredients to consumers who are taking an active role in improving their health and well-being. Omega-3 supplements, particularly long-chain omega-3 supplements, are associated with widespread use globally. Dickinson et al. (2014) reported that, in the United States, 33 percent of supplement users supplemented with omega-3 fatty acids or fish oil, and that the prevalence of use of these supplements was second only to multivitamins. Based on a working document that was prepared in 2008 by the European Commission (EC), which included data from 17 Member States, the most commercially important food supplement ingredients other than vitamins and minerals included fish oils, probiotics and certain herbal ingredients, with these three categories accounting for over 50 percent of the market. In the Australian North West Adelaide Health Study, it was observed that 4.6 percent of males and 8.5 percent of females 20 years of age or older consumed fish oil supplements, with the prevalence of use increasing with age (Hill et al., 2009). This report reviews the claims that can be made in the labeling of foods and dietary supplements containing omega-3 fatty acids in the United States, the European Union (EU) and Australia, and discusses similarities and differences among these jurisdictions.

SECTION I

United States

Relevant Legislation and Guidance Documents Nutrient Content Claims for foods and dietary supplements are regulated in 21 CFR 101.13. Health Claims for foods and dietary supplements are regulated in 21 CFR 101.14. Claims made specifically in the labeling of dietary supplements are regulated in 21 CFR 101.93 (U.S. FDA, 2013a). Relevant Acts include the Nutrition Labeling and Education Act (NLEA) of 1990, which applies to Nutrient Content and Health Claims made in or on the labeling of foods and dietary supplements, the Food and Drug Administration Modernization Act (FDAMA) of 1997, which applies to Nutrient Content and Health Claims made

Omega-3 Insights • Regulatory 3 omega3insights.com in or on the labeling of foods only, and the Dietary Supplement Health and Education Act (DSHEA) of 1994, which applies to Structure/Function Claims made in or on the labeling of dietary supplements. The Food Labeling Guide provides an overall summary of Nutrient Content Claims, Health Claims and Structure/Function Claims in Chapter 8 (U.S. FDA, 2013b). Moreover, FDA has released several guidance documents to assist the industry in ensuring claims are scientifically substantiated, including: • Guidance for Industry: Evidence-Based Review System for the Scientific Evaluation of Health Claims – Final (U.S. FDA, 2009). • Guidance for Industry: Substantiation for Dietary Supplement Claims Made Under Section 403(r) (6) of the Federal Food, Drug, and Cosmetic Act (U.S. FDA, 2008). • Guidance for Industry: FDA’s Implementation of “Qualified Health Claims”: Questions and Answers; Final Guidance (U.S. FDA, 2006). There are three • Guidance for Industry: Interim Procedures for Qualified Health Claims in the Labeling of Conventional Human broad categories Food and Human Dietary Supplements (U.S. FDA, 2003a). of claims that • Guidance for Industry: Structure/Function Claims, Small are permissible Entity Compliance Guide (FDA, 2002). • Guidance for Industry: Notification of a Health Claim or in the labeling of Nutrient Content Claim Based on an Authoritative foods and dietary Statement of a Scientific Body (U.S. FDA, 1998). supplements in the United States. Claim Categories There are three broad categories of claims that are permissible in the labeling of foods and dietary supplements in the United States, including Nutrient Content Claims, Health Claims and Structure/Function Claims.

Nutrient Content Claims Nutrient Content Claims are defined in 21 CFR 101.13(b) as claims that expressly or implicitly characterize the level of a nutrient in the food or dietary supplement. Only Nutrient Content Claims that are specifically defined in 21 CFR 101.13 are permissible in the labeling of foods and dietary supplements; all other Nutrient Content Claims are prohibited by 21 CFR 101.13(b). It is noteworthy that if a Nutrient Content Claim is made, and when a nutrient in that food exceeds certain prescribed levels per Reference Amount Customarily Consumed (RACC), per labeled serving, or, for foods with small serving sizes, per 50 grams, a disclosure statement (i.e., “See nutrition information for X content”) alerting the consumer to the presence of that nutrient is required to be placed immediately adjacent to the Nutrient Content Claim [21 CFR 101.13(h)]. The prescribed limits are for total fat, saturated fat, cholesterol and sodium, and differ depending

Omega-3 Insights • Regulatory 4 omega3insights.com on whether the food product is a food, a main dish or a meal product [see 21 CFR 101.13(h)(1-3)]. For nutrients for which Nutrient Content Claims are not permitted, a declaration of the amount of that ingredient per serving outside of the Nutrition Facts label can be made (e.g., “Contains X mg of astaxanthin per serving” or “X mg of astaxanthin per serving”) [21 CFR 101.13(i)(3)] (U.S. FDA, 2013a).

Health Claims A Health Claim is defined in 21 CFR 101.14(a)(1) as any claim made in or on the labeling of a food, including a dietary supplement, that expressly or by implication characterizes the relationship of any substance to a disease or health-related condition. “Substance” is defined in 21 CFR 101.14(a)(2) as a specific food or component of food, regardless of whether the food is in conventional food form or a dietary supplement that includes vitamins, minerals, herbs or other similar nutritional substances. “Disease” is defined in 21 CFR 101.14(a)(5) as damage to an organ, part, structure or system of the body such that it does not function properly (e.g., cardiovascular disease), or a state of health leading to such dysfunctioning (e.g., hypertension); diseases resulting from essential nutrient deficiencies are not included in this definition (U.S. FDA, 2013a). In order to bear a health claim in or on the labeling of a food, the food must contain, prior to any nutrient addition, 10 percent or more of the Reference Daily Intake (RDI) or the Daily Reference Value (DRV) for vitamin A, vitamin C, iron, calcium, protein or fiber per RACC [21 CFR 101.14(e)(6)]; however, this requirement does not apply to dietary supplements. In 21 CFR 101.14(a)(4), the Disqualifying Nutrient levels are defined; these are levels of total fat, saturated fat, cholesterol or sodium per RACC, per labeled serving or, for foods with small serving sizes, per 50 g, above which the food will be disqualified from making a health claim. The limits for these nutrients differ depending on whether the food product is a food, a main dish or a meal product [see 21 CFR 101.14(a)(4)(i-ii)] (U.S. FDA, 2013a). There are three mechanisms by which FDA oversees the types of claims that can be made in food labeling: • The 1990 NLEA, which allows FDA to, upon its own initiative or following the submission of a Health Claim petition, evaluate the totality of scientific evidence related to the Health Claim and, if substantiated according to the significant scientific agreement (SSA) standard, promulgate a regulation authorizing the use of the Health Claim (NLEA, 1990). • The 1997 FDAMA, which allows a petitioner to submit a 120-day pre- market notification to FDA of a Nutrient Content or Health Claim that is based on an authoritative statement of a scientific body of the U.S. government with responsibility for public health protection or nutrition research (only for food labeling, not dietary supplement labeling) (U.S. FDA, 1997).

Omega-3 Insights • Regulatory 5 omega3insights.com • The 2003 Consumer Health Information for Better Nutrition Initiative, which allows FDA to exercise its enforcement discretion over Health Claims that are supported by credible scientific evidence but for which the totality of evidence falls short of the SSA standard required for Health Claim authorization (U.S. FDA, 2003b). For these Health Claims, qualifying language is used to convey to the consumer the level of evidence in support of the Health Claim.

Structure/Function Claims According to 21 CFR 101.93(f), Structure/Function Claims describe the role of a nutrient or dietary ingredient intended to affect the structure or function in humans or characterize the documented mechanism by which a nutrient or dietary ingredient acts to maintain such structure or function. Structure/ Function Claims cannot, either implicitly or explicitly, imply an effect on the diagnosis, treatment, cure or prevention of any disease [21 CFR 101.93(g)]. It should be noted that diseases of essential nutrient deficiency are exempt from the definition of disease, and Structure/Function Claims related to diseases of nutrient deficiencies can be made in or on the labeling of dietary supplements, provided that the prevalence of the disease in the United States also is disclosed. In 21 CFR 101.93(g)(1), “disease” is defined in exactly the same way as in 21 CFR 101.14(a)(5). In 21 CFR 101.93(g)(2), 10 criteria are listed which are used by FDA to determine whether a Structure/Function Claim is a disease claim. These criteria are not listed here; however, they should be consulted by the industry to ensure the Structure/Function Claims made in or on the labeling of dietary supplements will not be interpreted by FDA as disease claims. It should be noted that 30 days following the first marketing of a dietary supplement that bears a Structure/Function Claim, the manufacturer, packer or distributor of the dietary supplement must, in writing, notify the Office of Nutritional Products, Labeling and Dietary Supplements (HFS-810), Center for Food Safety and Applied Nutrition, that it has included such a statement on the label or in the labeling of its product. The information required in the notification can be found in 21 CFR 101.93(a)(2). The signature on the notification is an attestation that the information contained in the notice is complete and accurate, and that the notifying firm has substantiation that the statement is truthful and not misleading [21 CFR 101.93(a)(3)]. According to 21 CFR 101.93(b), a disclaimer must appear immediately adjacent to the Structure/Function Claim(s) that “This/ these statement/statements has/have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease” (U.S. FDA, 2013a). 21 CFR 101.93 applies to “Certain types of statements for dietary supplements.” Structure/Function Claims used in or on the labeling of conventional foods will be tolerated by FDA so long as the claim derives from the product’s character as a food—its taste, aroma or nutritive value

Omega-3 Insights • Regulatory 6 omega3insights.com [see Nutrilab, Inc., et al. and Bio-Tech Laboratories, Inc., et al., v. Schweiker and Hayes. 713 F.2d 335 (7th Cir. 1983)]. If, on the other hand, the Structure/ Function Claim alters the primary use of the conventional food for some physiological attribute that is not related to the food’s taste, aroma or nutritive value, then the product may be regarded by FDA as a drug (U.S. FDA, 2013c). Although there is no formal definition of “nutritive value” for the purposes of making Structure/Function Claims, it appears from FDA’s recent guidance on Determining Whether Human Studies Can be Conducted Without an Investigational New Drug (IND) Application that FDA does not regard long-chain omega-3 fatty acids as providing nutritive value, given that it was explicitly stated that “a study of the ability of an infant formula to support growth of infants or of other nutritional properties of the formula would not require an IND. However, a study of other effects of the formula on the structure or function of the body (e.g., an investigation of the effects of docosahexaenoic acid in infant formula on visual acuity of infants) would require an IND” (U.S. FDA, 2013c). Thus, Structure/Function Claims made in or on the labeling of a conventional food containing eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) likely would cause the food to be regulated as a drug as opposed to a conventional food.

Claims Permissible for the Omega-3 Fatty Acids

Nutrient Content Claims Since the FDAMA was signed into law in 1997, there have been three 120-day pre-market notifications to FDA related to Nutrient Content Claims for alpha-linolenic acid (ALA), EPA and DHA, which include: • Collective submission by Alaska General Seafoods, Ocean Beauty Seafoods, Inc., and Trans-Ocean Products, Inc. (herein after referred to as the Seafood Processors Notification) for ALA, EPA and DHA Nutrient Content Claims. Notification: a product containing at least 260 mg, and 130 mg of ALA per RACC should qualify for a “high,” and “good source” or “more” claims, respectively. For EPA or DHA, the qualifying level for “high” claims was set at 130 mg. • Submission by Martek Biosciences Corp. (herein after referred to as the Martek Notification) for ALA and DHA Nutrient Content Claims. Notification: a product containing at least 320 mg and 160 mg of ALA per RACC should qualify for a “high,” and “good source” or “more” claims, respectively. For DHA, the qualifying level for “high” claims was set at 32 mg. • Submission by Ocean Nutrition Canada, Ltd. (herein after referred to as the Ocean Nutrition Notification) for EPA and DHA Nutrient Content Claims. Notification: a product containing at least 32 mg of EPA and DHA combined per RACC should qualify for an “excellent source” claim.

Omega-3 Insights • Regulatory 7 omega3insights.com All of the Nutrient Content Claims that were proposed in the notifications became permissible for use in or on the labeling of foods because FDA did not issue a regulation prohibiting the use of these claims following the receipt of the notifications. In 2007, however, FDA issued a Proposed Rule to prohibit the use of the Nutrient Content Claim for ALA in the Seafood Processors Notification and the use of the Nutrient Content Claims for EPA and DHA in all three notifications (U.S. FDA, 2007). FDA proposed to prohibit the use of the Nutrient Content Claim for ALA in the Seafood Processors Notification because the population-weighted average of the Adequate Intakes (AI) were used to calculate the Daily Value (DV) for ALA; the highest FDA raised concern age and gender-specific reference values have been used over whether the historically to calculate the DVs. FDA proposed to not take use of an Adequate regulatory action with the Martek ALA Nutrient Content Claim notification because the highest age- and gender specific AIs Intake to derive were used to calculate the DVs for ALA. FDA did, however, a Daily Value raise concerns over whether the use of an AI to derive a DV is appropriate. is appropriate. FDA proposed to prohibit the use of the Nutrient Content Claims for EPA and DHA for all three notifications because of the absence of an authoritative statement from a scientific body of the U.S. government or the National Academy of Sciences or any of its subdivisions. In all three notifications, the DVs for EPA or DHA were calculated to be 10 percent of the DV for ALA. For the rationale for the 10 percent in the notifications, the Institute of Medicine (IOM) report was cited (i.e., “approximately 10% of the [Acceptable Macronutrient Distribution Range] AMDR for omega-3 fatty acids (ALA) can be consumed as EPA and/or DHA”). FDA noted that the statement was not meant to be a reference value (e.g., AI) for EPA or DHA. Therefore, FDA concluded that the Nutrient Content Claims for EPA and DHA in all three notifications do not meet the requirements of section 403(r)(2)(G) of the Federal Food, Drug, and Cosmetic Act, and that these claims should be prohibited (U.S. FDA, 2008). On April 22, 2014, the Final Rule to the notice was issued, essentially maintaining the perspectives published in the 2007 Proposed Rule (U.S. FDA, 2014). Specifically, it was decided by FDA that the EPA and DHA Nutrient Content Claims that were notified in all three notifications do not meet the requirements of the Federal Food, Drug, and Cosmetic Act and therefore will be prohibited (U.S. FDA, 2014). As for the ALA Nutrient Content Claim notification, FDA decided the method of derivation of the DV by the Seafood Processors (i.e., population-weighted average of the AIs) was not aligned with the method traditionally used by FDA, and so the ALA Nutrient Content Claims notified by the Seafood Processors also would be prohibited (U.S. FDA, 2014). Regarding the ALA Nutrient Content Claim that was notified

Omega-3 Insights • Regulatory 8 omega3insights.com by Martek, FDA decided to take no regulatory action, and so the only omega-3 Nutrient Content Claim that will be tolerated is that for ALA. The Final Rule will be effective as of January 1, 2016, thereby giving the food industry a transition period of approximately 20 months.

Health Claims To date, FDA has issued Letters of Enforcement Discretion for Qualified Health Claims to applications submitted by two different companies: (i) Wellness Lifestyles, Inc. and Life Extension Foundation Buyers Club (collectively, Wellness petition) (U.S. FDA, 2004a); and (ii) Martek Biosciences Corp. (U.S. FDA, 2004b). In both letters, the claim wording that was the subject of enforcement discretion was: “Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease. One serving of [Name of the food] provides [ ] gram of EPA and DHA omega-3 fatty acids. [See nutrition information for total fat, saturated fat, and cholesterol content.]” As discussed previously, Health Claims have general requirements to not exceed the Disqualifying Nutrient levels for total fat, saturated fat, cholesterol or sodium. In addition, Health Claims related to coronary heart disease have generally been required to meet the “low in” criterion for total fat, saturated fat and cholesterol. Due to the properties of long-chain omega-3 fatty acids and the types of foods that contain long-chain omega-3 fatty acids, FDA considered some but not all of the criteria for health claims to be exempt for the Qualified Health Claim on omega-3 fatty acids and reduced risk of coronary heart disease. FDA requirements and exemptions for the Qualified Health Claim are as follows:

Requirements for Claims Related to Coronary Heart Disease • “Low fat” criterion (<5 g fat per RACC and per 100 g) does not have to be met for dietary supplements or conventional foods that bear an omega-3 fatty acid Qualified Health Claim • “Low saturated fat” criterion (< 2 g saturated fat per RACC and per 100 g) have to be met for dietary supplements or conventional foods that bear an omega-3 fatty acid Qualified Health Claim, with a few exceptions: » Conventional food products that are essentially all fish do not have meet the “low saturated fat” criterion » Dietary supplements containing EPA and/or DHA have to meet the “equal to or less than 1 g of saturated fat per RACC” criterion but do not have to meet the “no more than 15% of calories from saturated fat” of the “low saturated fat” criterion. • The “Low cholesterol” criterion has to be met for dietary supplements or conventional foods that bear an omega-3 fatty acid Qualified Health Claim, with a few exceptions:

Omega-3 Insights • Regulatory 9 omega3insights.com » Conventional food products that are essentially all fish do not have meet the “low cholesterol” criterion » Dietary supplements containing EPA and/or DHA weighing equal to or less than 5 g per RACC have to meet the “contain no more than 20 mg of cholesterol on a 50 g basis” of the “low cholesterol” criterion • Products that are essentially all fish have to meet the “extra lean” criterion for cholesterol but not the “extra lean” criterion for saturated fat and total fat.

Requirements for Disqualifying Nutrient Levels • The total fat disqualifying level has to be met for dietary supplements or conventional foods that bear an omega-3 fatty acid Qualified Health Claim, with a few exceptions: » For products that are essentially all fish, a disclosure statement (i.e., “See nutrition information for total fat, saturated fat, and cholesterol content”) is required if the total fat disqualifying level is exceeded » For dietary supplements weighing equal to or less than 5 g per RACC, a disclosure statement is required if the total fat disqualifying level is exceeded • The saturated fat disqualifying level has to be met for dietary supplements or conventional foods that bear an omega-3 fatty acid Qualified Health Claim, with a few exceptions: » For dietary supplements weighing equal to or less than 5 g per RACC, a disclosure statement is required if the saturated fat disqualifying level is exceeded • The cholesterol disqualifying level has to be met for dietary supplements or conventional foods that bear an omega-3 fatty acid Qualified Health Claim, with a few exceptions: » Conventional food products that are essentially all fish do not have to meet the “low cholesterol” criterion • The sodium disqualifying level has to be met for dietary supplements or conventional foods that bear an omega-3 fatty acid Qualified Health Claim

Other Requirements • 10 percent minimum nutrient content requirement is required for conventional foods and products that are essentially all fish [see 21 CFR 101.14(e)(6); U.S. FDA, 2013a]. • For foods, FDA’s enforcement discretion applies only to those in which EPA and DHA is an added ingredient that FDA has approved as a food additive or affirmed as GRAS (generally recognized as safe) or for which the Agency has received a GRAS notification to which it did not object. The daily intake needed to achieve the claimed effect was not quantified for the Qualified Health Claim because the scientific evidence did not support the determination of a recommended daily intake. Therefore, FDA considers any

Omega-3 Insights • Regulatory 10 omega3insights.com label that suggests a dose for achieving an effect on the reduction of the risk of coronary heart disease to be misleading. In addition, EPA- and DHA-containing dietary supplement labels are prohibited from recommending a daily intake that exceeds 2 g of EPA and DHA.

SECTION II

European Union

Relevant Legislation and Guidance Documents In the EU, nutrition and health claims are regulated by Regulation (EC) No 1924/2006, which came into effect on July 1, 2007 (EC, 2006). The Regulation applies to all commercial communications, whether in the labeling, presentation or advertising of foods and food supplements to be delivered as such to the final consumer. The Regulation also applies to foods intended for supply to restaurants, hospitals, schools, canteens and similar mass caterers. According to Article 4(3), nutrition and health claims (other than those that refer to a reduction in the alcohol or energy content) cannot be made in the labeling or advertising of a beverage that contains more than 1.2 percent alcohol by volume. All health claims must undergo pre-market review by the Panel on Dietetic Products, Nutrition and Allergies (NDA Panel) of the European Food Safety Authority (EFSA) and authorization by the European Commission (EC) prior to being used in the labeling and advertising of foods and food supplements. Regulation (EC) No 353/2008 describes the technical requirements for the presentation of information in a health claim application (EC, 2008). The EFSA NDA Panel has released several guidance documents related to health claims in specific health areas, available at efsa.europa.eu/en/nda/ndaguidelines.htm.

Claim Categories There are two broad categories of claims that are permissible in the labeling and advertising of foods and food supplements in the EU, including Nutrition Claims and Health Claims.

Nutrition Claims Nutrition Claims are defined in Article 2 of Regulation (EC) 1924/2006 as any claim which states, suggests or implies that a food has particular beneficial nutritional properties due to: • The energy (calorific value) it » Provides; » Provides at a reduced or increased rate; or » Does not provide; and/or

Omega-3 Insights • Regulatory 11 omega3insights.com • The nutrients or other substances it » Contains; » Contains in reduced or increased proportions; or » Does not contain. According to Article 8 of Regulation (EC) No 1924/2006, Nutrition Claims are only permitted if they are listed in the Annex and conform to the conditions of use set out in the Regulation. According to Article 9 of Regulation (EC) No 1924/2006, Comparative Claims can be made between foods of the same category whereby the comparison is made to a range of foods that do not have a composition which allows them to bear a claim. The Comparative Claim must state the difference in the quantity of a nutrient and/or energy value and shall relate to the same quantity of food (EC, 2006).

Health Claims Health Claims are defined in Article 2 of Regulation (EC) 1924/2006 as any claim that states, suggests or implies that a relationship exists between a food category, a food or one of its constituents and health (EC, 2006). Within the category of Health Claims, there are Health Claims referring to a reduction of disease risk and Health Claims referring to children’s development and health, which are also known as Article 14(1)(a) and 14(a)(b) claims, respectively. There are also Health Claims other than those referring to the reduction of disease risk and to children’s development and health, which are known as Article 13 claims. Article 13 claims describe: • The role of a nutrient or other substance in growth, development and the functions of the body; or • Psychological and behavioral functions; • Without prejudice to Directive 96/8/EC, slimming or weight-control or a reduction in the sense of hunger or an increase in the sense of satiety or to the reduction of the available energy from the diet (EC, 1996).

Article 13 Health Claims that have been authorized for use in the EU, as well as the conditions for their use, can be found in Commission Regulation (EU) No 432/2012 (EU, 2012). A Community Register of nutrition and health claims made on foods is available online (European Commission, 2013). Article 13 Health Claims that are based on newly developed scientific evidence and/or which include a request for the protection of proprietary are known as Article 13(5) Health Claims.

Claims Permissible for the Omega-3 Fatty Acids There are authorized Nutrition Claims and Health Claims for the omega-3 fatty acids.

Omega-3 Insights • Regulatory 12 omega3insights.com Nutrition Claims According to the Annex of Regulation (EC) 1924/2006, Nutrition Claims that are permitted for omega-3 fatty acids include “a source of omega-3 fatty acids” and “high omega-3 fatty acids.” The conditions of use are: • “Source of omega-3 fatty acids”—the product contains at least 0.3 g alpha-linolenic acid (ALA) per 100 g and per 100 kcal, or at least 40 mg of the sum of EPA and DHA per 100 g and per 100 kcal. • “High omega-3 fatty acids”—the product contains at least 0.6 g ALA per 100 g and per 100 kcal, or at least 80 mg of the sum of EPA and DHA per 100 g and per 100 kcal.

Health Claims To date, a total of nine health claims have been authorized for the long chain omega-3 fatty acids, including six Article 13(1) and three Article 14(1)(b) health claims (Table 1).

Table 1: Health Claims that have been Authorized for Long-chain Omega-3 Fatty Acids in the European Union Type of Omega-3 Claim Conditions of Use of the Claim Fatty Acid Article 13(1) Claims DHA Contributes to • The claim may be used only for foods which contain at maintenance of normal least 40 mg of DHA per 100 g and per 100 kcal. brain function • In order to bear the claim, information shall be given to the consumer that the beneficial effect is obtained with a daily intake of 250 mg of DHA. DHA Contributes to the • The claim may be used only for foods which contain at maintenance of least 40 mg of DHA per 100 g and per 100 kcal. normal vision • In order to bear the claim, information shall be given to the consumer that the beneficial effect is obtained with a daily intake of 250 mg of DHA. DHA Contributes to the • DHA contributes to the maintenance of normal blood maintenance of normal triglyceride levels. blood triglyceride levels • The claim may be used only for food which provides a daily intake of 2 g of DHA and which contains DHA in combination with EPA. In order to bear the claim, information shall be given to the consumer that the beneficial effect is obtained with a daily intake of 2 g of DHA. When the claim is used on food supplements and/or fortified foods, information shall also be given to consumers not to exceed a supplemental daily intake of 5 g of EPA and DHA combined. • The claim shall not be used for foods targeting children. DHA and EPA Contribute to the normal • The claim may be used only for foods which are at least function of the heart a source of EPA and DHA as referred to in the claim SOURCE OF OMEGA 3 FATTY ACIDS as listed in the Annex to Regulation (EC) No 1924/2006. • In order to bear the claim, information shall be given to the consumer that the beneficial effect is obtained with a daily intake of 250 mg of EPA and DHA.

Omega-3 Insights • Regulatory 13 omega3insights.com Table 1: Health Claims that have been Authorized for Long-chain Omega-3 Fatty Acids in the European Union Type of Omega-3 Claim Conditions of Use of the Claim Fatty Acid Article 13(1) Claims DHA and EPA Contribute to the • The claim may be used only for foods which provide a maintenance of normal daily intake of 3 g of EPA and DHA. blood pressure • In order to bear the claim, information shall be given to the consumer that the beneficial effect is obtained with a daily intake of 3 g of EPA and DHA. • When the claim is used on food supplements and/ or fortified foods, information shall also be given to consumers not to exceed a supplemental daily intake of 5 g of EPA and DHA combined. • The claim shall not be used for foods targeting children. DHA and EPA Contribute to the • The claim may be used only for foods which provide a maintenance of normal daily intake of 2 g of EPA and DHA. blood triglyceride levels • In order to bear the claim, information shall be given to the consumer that the beneficial effect is obtained with a daily intake of 2 g of EPA and DHA. • When the claim is used on food supplements and/ or fortified foods, information shall also be given to consumers not to exceed a supplemental daily intake of 5 g of EPA and DHA combined. • The claim shall not be used for foods targeting children. Article 14(1)(b) Claims DHA Contributes to • Information shall be given to the consumer that the the normal visual beneficial effect is obtained with a daily intake of 100 development of infants mg of DHA. up to 12 months of age. • When the claim is used on follow-on formula, the food shall contain at least 0.3 percent of the total fatty acids as DHA. DHA Maternal intake • Information shall be given to pregnant and lactating contributes to women that the beneficial effect is obtained with the normal brain a daily intake of 200 mg of DHA in addition to the development of the fetus recommended daily intake for omega-3 fatty acids for and breastfed infant. adults, i.e., 250 mg DHA and EPA. • The claim can be used only for foods which provide a daily intake of at least 200 mg DHA. DHA Maternal intake • Information shall be given to pregnant and lactating contributes to the women that the beneficial effect is obtained with normal development of a daily intake of 200 mg of DHA in addition to the the eye of the fetus and recommended daily intake for omega-3 fatty acids for breastfed infant. adults, i.e., 250 mg DHA and EPA. • The claim can be used only for foods which provide a daily intake of at least 200 mg DHA.

In 2009 and 2010, the EFSA NDA Panel concluded there was a cause and effect relationship between the consumption of DHA and the maintenance of normal blood triglyceride levels, and between the consumption of EPA and DHA and the maintenance of normal blood pressure and normal blood triglyceride levels (EFSA, 2009, 2010a,b). In order to obtain the claimed effect on normal blood triglyceride levels and normal blood pressure, the NDA Panel

Omega-3 Insights • Regulatory 14 omega3insights.com concluded that 2 to 4 g/d of DHA and EPA and 3 g/d of DHA and EPA, respectively, should be consumed. However, safety concerns related to the intake of 2 to 3 g/d of DHA and EPA were raised to the EC (the legislative body that authorizes health claims), as no tolerable upper intake was established for the long-chain omega-3 fatty acids. Consequently, the EC placed the claims on hold and requested that EFSA conduct a safety evaluation to determine the tolerable upper intake level for EPA, DHA and DPA. The EFSA NDA Panel published its safety evaluation in 2012, and concluded that doses of EPA and DHA up to 5 g/d do not raise safety concerns for adults (EFSA, 2012). One year later, the EC authorized the claims on maintenance of normal blood triglyceride and normal blood pressure, but added a condition for food supplements and/or fortified foods to provide information to consumers to not exceed a daily intake of 5 g of EPA and DHA combined (EU, 2013).

SECTION III

Australia

Foods

Relevant Legislation and Guidance Documents In Australia and New Zealand, nutrition and health claims are regulated under Standard 1.2.7 of the Australia New Zealand Food Standards Code. Standard 1.2.7 came into effect on Jan. 18, 2013. Standard 1.2.7 applies to all claims that are made in the labeling or advertising of foods. According to Part 2 of Standard 1.2.7, Nutrition and Health Claims cannot be made in the labeling or advertising of certain foods; a food that contains more than 1.15 percent alcohol by volume (other than a nutrition content claim about energy content or carbohydrate content); or an infant formula product (which is standardized in Standard 2.9.1 of the Australia New Zealand Food Standards Code). Moreover, Standard 1.2.7 does not apply to a food that is intended for further processing, packaging or labeling prior to retail sale; delivered to a vulnerable person by a delivered meal organization; or provided to a patient in a hospital or other similar institution, other than food in a package (FSANZ, 2013).

Claim Categories According to Part 2 of Standard 1.2.7, a claim must not refer to the prevention, diagnosis, cure or alleviation of a disease, disorder or condition, or be compared to a product that is represented in any way for therapeutic use. There are two broad categories of claims that are permissible in the labeling and advertising of foods in Australia/New Zealand, including Nutrition Content Claims and Health Claims (FSANZ, 2013).

Omega-3 Insights • Regulatory 15 omega3insights.com Nutrition Content Claims Nutrition Content Claims are defined in Part 1 of Standard 1.2.7 and are described further in Division 1, Part 3 of Standard 1.2.7. A Nutrition Content Claim describes: • The presence or absence of: » a biologically active substance; or » dietary fibre; or » energy; or » minerals; or » potassium; or » protein; or » carbohydrate; or » fat; or » the components of any one of protein, carbohydrate or fat; or » salt; or » sodium; or » vitamins; or • The glycemic index or glycemic load of a food. Nutrition Comparative Claims are defined in Division 1, Part 3 of Standard 1.2.7 as Nutrition Content Claims that directly or indirectly compare the nutrition content of one food or brand of food with another, and include claims using the following descriptors: (a) light or lite; (b) increased; (c) reduced; or words that impart a similar meaning. Claims that directly or indirectly compare the vitamin or mineral content of a food with that of another food are not allowed, unless permitted by another Standard in the Australia New Zealand Food Standards Code. The Nutrition Content Claims that are permissible in the labeling and advertising of foods, as well as the conditions for their use, are summarized in Schedule 1 of Standard 1.2.7.

Health Claims Health Claims are defined in Part 1 of Standard 1.2.7 and are described further in Division 2, Part 3 of Standard 1.2.7. A Health Claim states, suggests or implies that a food or a property of food has, or may have, a health effect. A health effect is defined in Part 1 of Standard 1.2.7 as an effect on the human body, including an effect on one or more of the following: • a biochemical process or outcome; • a physiological process or outcome; • a functional process or outcome; • growth and development; • physical performance; • mental performance; • a disease, disorder or condition.

Omega-3 Insights • Regulatory 16 omega3insights.com Within the category of Health Claims, there are High Level Health Claims and General Level Heath Claims. A High Level Health Claim is defined in Part 1 of Standard 1.2.7 as a health claim that refers to a serious disease or a biomarker of a serious disease. A General Level Health Claim is defined in Part 1 of Standard 1.2.7 as a health claim that is not a High Level Health Claim. A High Level Health Claim may be made in the labeling or advertising of foods only if: • The claim is listed in Schedule 2 of Standard 1.2.7; and • The food meets the conditions for use of the claim, as listed in Schedule 2 of Standard 1.2.7; and • The Nutrient Profiling Score is less than the threshold listed in Schedule 4 of Standard 1.2.7 (see Schedule 5 for the method for calculating the Nutrient Profiling Score). A General Level Health Claim may be made in the labeling or advertising of foods only if the Nutrient Profiling Score is less than the threshold listed in Schedule 4 of Standard 1.2.7 (see Schedule 5 for the method for calculating the Nutrient Profiling Score); and: • All of the following criteria are met: » The claim is listed in Schedule 3 of Standard 1.2.7; and » The food meets the conditions for use of the claim, as listed in Schedule 3 of Standard 1.2.7; or • The person who is responsible for making the health claim has notified the Chief Executive Officer of the Authority of the details of a relationship between a food or property of food and a health effect that has been established by a process of systematic review that is described in Schedule 6 of Standard 1.2.7. This Notification will result in the addition of a General Level Health Claim to Schedule 3 of Standard 1.2.7.

Food Claims Permissible for the Omega-3 Fatty Acids Thus far, there are authorized Nutrition Content Claims for omega-3 fatty acids and a General Level Health Claim for EPA and DHA (but not for omega-3 fatty acids).

Nutrition Content Claims A Nutrition Content Claim for omega-3 fatty acids can be made if: • The food meets the conditions for a Nutrition Content Claim about omega fatty acids; and • The food contains no less than – » 200 mg ALA per serving; or » 30 mg total EPA and DHA per serving; and • Other than for fish or fish products with no added saturated fatty acids, the food contains

Omega-3 Insights • Regulatory 17 omega3insights.com » As a proportion of the total fatty acid content, no more than 28 percent saturated fatty acids and trans fatty acids; or » No more saturated fatty acids and trans fatty acids than 5 g per 100 g; and • The nutrition information panel indicates the type and amount of omega-3 fatty acids, that is, ALA or DHA or EPA, or a combination of the above. Additional conditions that must be met to use specific descriptors are as follows: • For “Good Source” – In Australia and » The food contains no less than 60 mg total EPA and DHA per serving; and New Zealand, » The food may contain less than 200 mg ALA per serving. the General Level • For “Increased” – Health Claim » The food contains at least 25 percent more omega-3 fatty acids in the same quantity of reference food; and that is permitted » The reference food meets the general claim conditions for a for EPA and nutrition content claim about omega-3 fatty acids. DHA (but not General Level Health Claim omega-3s) is, The General Level Health Claim that is permitted for EPA and DHA "contributes to (but not omega-3s) is, “contributes to heart health,” which has to be heart health," used in a dietary context of a diet containing 500 mg of EPA and DHA per day. Conditions that have to be met in order to use the which has to be claim are: used in a dietary • The food must contain a minimum of 50 mg EPA and DHA context of a combined in a serving of food; • Other than for fish or fish products with no added saturated diet containing fatty acids, the food contains 500 mg of EPA » As a proportion of the total fatty acid content, no more than and DHA per day. 28%; or » No more than 5 g per 100 g saturated fatty acids and trans fatty acids. Thurs far, no High Level Health Claims have been authorized for omega-3 fatty acids.

Complementary Medicines

Relevant Legislation and Guidance Documents In Australia, complementary medicines are regulated as medicines under the Therapeutics Goods Act of 1989 (TGA, 1989). According to the Therapeutics Goods Regulations of 1990, a complementary medicine is defined as a

Omega-3 Insights • Regulatory 18 omega3insights.com therapeutic good consisting primarily of one or more of the active ingredients listed in Schedule 14 of the Regulations (TGA, 1990). The Therapeutics Goods Administration (TGA), which is part of the Australian Government Department of Health, applies a risk-benefit assessment in the regulation of complementary medicines; lower-risk medicines can be listed on the Australian Register of Therapeutic Goods (ARTG), while higher-risk medicines must be registered on the ARTG. In conducting the risk-benefit assessment, the TGA considers the potential benefit of the Complementary Medicine as well as the potential risks such as side effects, safety of prolonged use, toxicity and the seriousness of the medical condition for which the product is intended to be used. Listed Complementary Medicines are assigned a unique AUST L number, which must be displayed on the medicine label. At the time a medicine is listed on the ARTG, the therapeutic indications on the listed medicine are not evaluated by the TGA; however, according to the Therapeutics Goods Act of 1989, sponsors must, at the time of listing, certify that (TGA, 1989): • They hold scientific evidence to substantiate the indications and claims made for their medicine; and • They will share the supporting information, upon the request of the TGA. The TGA has released “Guidelines on the evidence required to support indications for listed complementary medicines” (TGA, 2014). These guidelines are intended to inform applicants on the type of evidence needed to support an indication for a Listed Complementary Medicine, as well as the regulatory obligations with regards to the sharing of the scientific substantiation. In contrast to Listed Complementary Medicines, Registered Complementary Medicines undergo a full evaluation for their safety, quality and efficacy by the TGA prior to being registered on the ARTG and being marketed. Registered Complementary Medicines are assigned a unique AUST R number, which must be displayed on the medicine label.

Claim Categories For Complementary Medicines in Australia, there are no claim categories; rather, Complementary Medicines are grouped according to their risk-benefit assessment, as well as according to the indication for the medicine. An indication is defined in Section 3 of the Therapeutic Goods Act 1989 (the Act) as: ‘the specific therapeutic use/s of the goods’. For Listed Medicines, which are lower-risk medicines, appropriate indications relate to a specific therapeutic use or to health maintenance or enhancement. Listed Medicines generally cannot relate to the treatment or cure of diseases, conditions, ailments or defects (TGA, 1989). Registered Medicines are considered higher-risk medicines either due to the ingredients they contain and/or the condition they are intended to be used for. Registered Medicines can have indications for the treatment or cure of diseases, conditions, ailments or defects.

Omega-3 Insights • Regulatory 19 omega3insights.com Claims Permissible for the Omega-3 Fatty Acids The TGA maintains the Australian Register of Therapeutic Goods (ARTG), which is a searchable engine that can be used to retrieve information on therapeutic goods that can be supplied in Australia. There is an “advanced search” option, wherein the search can be restricted to specific parameters [e.g., keyword, ARTG ID, product name, active ingredients, sponsor name, therapeutic good type (biological, device, medicine, medical device, other), etc.]. Currently, there are no Registered Medicines that contain EPA or DHA. There are 33,503 Listed Medicines that contain either EPA and/or DHA as an active ingredient. Examples of the types of indications that can be made in the labeling and advertising of these Listed Medicines include: • Claims related to reduced joint pain, swelling associated with arthritis. • Claims related to increased joint mobility associated with arthritis. • EPA inhibits platelet aggregation in human platelet-rich plasma and is thought to be utilized by the vessel wall to produce an anti-aggregating prostacyclin and could lead to protection against thrombosis. • EPA has been shown to reduce total serum triglyceride levels in patients and to increase the level of HDL cholesterol. • DHA is a major component of the human brain and retinal lipids, and has a possible role in neural transmission. • Maintains normal healthy brain function. • Supports brain health. • Helps support cognitive health and/or brain function and the development of the brain, eyes and nerves in children. • DHA is essential for the growth and development of the brain in both the fetal and neonatal stages. • Supports/maintains the health of the cardiovascular system. • DHA supports cardiovascular health. • Supports healthy eye function. • Supports the health of the eyes. • Supports visual development and function.

SECTION IV

Comparative Analysis Obviously, there are very different structures governing the types of claims that can be made for omega-3 fatty acids in the United States, the EU and Australia. A comparison of the similarities and differences across the three jurisdictions with regards to claims in general is presented in Table 2 (page 21).

Omega-3 Insights • Regulatory 20 omega3insights.com As can be seen in Table 2, Nutrient Content Claims, Structure/Function type Claims, and Disease Risk-Reduction Claims are permissible in the United States, the EU and Australia; however, the United States is unique in that Structure/ Function Claims made in or on the labeling of foods must derive from the taste, aroma or nutritive value of the food. Only in the EU is a full pre-market review and authorization of Structure/Function type Claims (i.e., Article 13 Health Claims) necessary. In the United States and in Australia, a notification procedure is required for Structure/Function Claims on dietary supplements and for General Level Health Claims on foods, respectively. Listed Complementary Medicines in Australia must be licensed and included in the ARTG prior to marketing; however, a pre-market review of efficacy is not conducted. Disease Risk-Reduction Claims must undergo pre-market review and authorization in

Table 2: A Comparison of Claim Regulations and Categories in the United States, European Union and Australia U.S. EU Australia Scope of claim regulations applies to labeling ✓ ✓ ✓ Scope of claim regulations applies to advertising ✗ ✓ ✓ Claim regulations apply to foods and dietary ✓ ✓ ✗ supplements Specific claim regulations for dietary supplements ✓ ✗ ✓ Permissible Nutrient content claims ✓ ✓ ✓ claim categories for foods Structure/function claims and dietary ✓ ✓ ✓ supplements Disease risk-reduction claims ✓ ✓ ✓

Therapeutic claims ✗ ✗ ✓

Regulations allow for claim exclusivity based on ✗ ✓ ✗ proprietary data

the United States, the EU and Australia, and the only jurisdiction that allows for Therapeutic Claims is Australia (i.e., in the labeling or advertising of Registered Complementary Medicines, which are required to undergo a full pre-market review for efficacy and registration in the ARTG). The EU is unique in that a period of claim exclusivity is permitted for claims based on proprietary data. It should be noted that claim regulations apply to both product labeling and advertising in the EU and Australia; however, in the United States, the claim regulations apply only to product labeling.

Omega-3 Insights • Regulatory 21 omega3insights.com Table 3 presents a comparison of the differences and similarities specifically related to the omega-3 fatty acid claims permissible in the United States, EU and Australia. While Nutrient Content Claims may be made for ALA in all three jurisdictions, Nutrient Content Claims for EPA and DHA are permissible only in the EU and Australia. The United States is unique in that a Qualified Health Claim related to the effects of EPA and DHA in reducing the risk of CHD is permissible under a Letter of Enforcement Discretion; qualifying language is used to convey to the consumer the level of evidence in support of the claim,

Table 3: A Comparison of the Types of Omega-3 Claims that can be Made in the United States, European Union and Australia U.S. EU Australia Nutrient content claim ✓ ✓ ✓ for ALA Nutrient content claim for EPA and/or DHA ✗ ✓ ✓ Coronary heart disease ✓ risk-reduction claim for ✗ ✗ EPA and DHA (qualified) Positive listings of other ✓ claims for EPA and DHA ✓ (n=1 for foods ✗ and lots for Listed (n=9) Complementary Medicines)

which is credible but does not meet a rigorous scientific standard. Disease Risk-Reduction Claims are not permissible for EPA and/or DHA in the EU or Australia. A total of nine claims have been authorized for EPA and DHA in the EU (for foods and food supplements), and in Australia, one General Level Health Claim has been authorized (for foods). In Australia, indications for Listed Complementary Medicines were impressive, and included outcomes such as visual benefits, cognitive benefits, blood lipid benefits, and benefits in patients with osteoarthritis. A Registered Complementary Medicine with an indication for EPA and/or DHA was not identified in the ARTG. In the United States, there are no positive listings of Structure/Function Claims that are maintained; however, it is apparent from 30-day post-market Structure/ Function Claim notifications that the claims are generally “soft” (e.g., helps maintain healthy triglyceride levels”). It is likely that claims for EPA and/or DHA, other than the Qualified Health Claim, will not be tolerated in or on the labeling of foods in the United States, given that EPA and DHA are not recognized as having nutritive value by FDA (U.S. FDA, 2013c).

Kathy Musa-Veloso, Ph.D., is director of health claims and clinical trials within the food and nutrition group at Intertek Scientific and Regulatory Consultancy. She assists both domestic and international clients with the preparation of scientific and regulatory strategies for marketing their foods and dietary supplements with health claims.

Omega-3 Insights • Regulatory 22 omega3insights.com Musa-Veloso joined Cantox in 2003, and since then, has developed a strong team of scientists, skilled in the conduct of systematic evidence-based reviews. The objective of these assessments is to determine, for clients in the food and supplement sectors, whether the efficacy of a food/ingredient can be scientifically substantiated. She also assists clients with the development, placement and management of clinical studies in which the efficacy of a food or supplement is intended to be evaluated. A recognized expert in the area of health claims and clinical trials, Musa-Veloso has been invited to discuss pressing scientific and regulatory issues at various conferences internationally. With her strong food and nutrition background, including a master’s degree and doctorate from the department of nutritional sciences at the University of Toronto, she has also authored several publications. Han Youl Lee is a scientific and regulatory analyst in the food and nutrition group at Intertek Cantox. He applies his scientific knowledge in assisting clients to fulfill the requirements for health claim substantiation internationally. In conjunction, Lee helps design clinical trial protocols that meet accepted scientific and regulatory standards for assessing the efficacy of substances in foods or dietary supplements. Born and raised in South Korea, he has critically appraised the regulations that govern functional foods and dietary supplements, as well as the opportunities in the South Korean functional foods market.

SECTION V

References Commission of the European Communities (2006). Commission Staff Working Document Characteristics and Perspectives of the Market for Food Supplements Containing Substances Other Than Vitamins and Minerals. (COM(2008)824 final, SEC(2008)2977, SEC(2008) 2976). Brussels, Belgium: Commission of the European Communities. Available at: http://ec.europa.eu/food/food/ labellingnutrition/supplements/documents/2008_2976_F_WD1_en.pdf. Dickinson A, Blatman J, El-Dash N, Franco JC (2014). Consumer usage and reasons for using dietary supplements: report of a series of surveys. J Am Coll Nutr 33(2):176-82. DSHEA (1994). Dietary Supplement Health and Education Act of 1994. (Public Law 103-417, 103rd Congress). Washington (DC): U.S. Food and Drug Administration (U.S. FDA). Available at: http://www.fda.gov/ RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/ SignificantAmendmentstotheFDCAct/ucm148003.htm. EC (1996). Commission Directive 96/8/EC of 26 February 1996 on foods intended for use in energy restricted diets for weight reduction. Off J Eur Communities 39(L55):22-26. Available at: http://eur-lex.europa. eu/LexUriServ/LexUriServ.do?uri=CELEX:31996L0008:EN:HTML.

Omega-3 Insights • Regulatory 23 omega3insights.com EC (2006). Regulation (EC) No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods. Off J Eur Union 49(L404):9-25. Available at: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=CONSLEG:200 6R1924:20100302:EN:PDF [Consolidated Version: 2010-03-02]. EC (2008). Commission Regulation (EC) No 353/2008 of 18 April 2008 establishing implementing rules for applications for authorisation of health claims as provided for in Article 15 of Regulation (EC) No 1924/2006 of the European Parliament and of the Council. Off J Eur Union 51(L109):11-16. Available at: http://eur-lex.europa.eu/ LexUriServ/LexUriServ.do?uri=CELEX:32008R0353:EN:NOT. EFSA (2009). EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to EPA, DHA, DPA and maintenance of normal blood pressure (ID 502), maintenance of normal HDL-cholesterol concentrations (ID 515), maintenance of normal (fasting) blood concentrations of triglycerides (ID 517), maintenance of normal LDL-cholesterol concentrations (ID 528, 698) and maintenance of joints (ID 503, 505, 507, 511, 518, 524, 526, 535, 537) pursuant to Article 13(1) of Regulation (EC) no 1924/2006 on Request from the European Commission (question no EFSA-Q-2008-1289, EFSA-Q-2008-1290, EFSA-Q-2008-1292, EFSA-Q-2008-1294, … [etc.], adopted on 01 October 2009 by European Food Safety Authority). EFSA J 7(9):1263. [26 pp.]. doi:10.2903/j.efsa.2009.1263. Available at: http://www.efsa.europa.eu/en/efsajournal/pub/1263.htm. EFSA (2010a). EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion the substantiation of a health claim related to docosahexaenoic acid (DHA) and maintenance of normal (fasting) blood concentrations of triglycerides (ID 533, 691, 3150), protection of blood lipids from oxidative damage (ID 630), contribution to the maintenance or achievement of a normal body weight (ID 629), brain, eye and nerve development (ID 627, 689, 704, 742, 3148, 3151), maintenance of normal brain function (ID 565, 626, 631, 689, 690, 704, 742, 3148, 3151), maintenance of normal vision (ID 627, 632, 743, 3149) and maintenance of normal spermatozoa motility (ID 628) pursuant to Article 13(3) of Regulation (EC) no 1924/2006 (question no EFSA-Q-2008-1320, EFSA-Q-2008-1416, EFSA-Q-2008-1417, EFSA-Q-2008-1478, … [etc.], adopted on 09 July 2010 by European Food Safety Authority). EFSA J 8(10):1734. [27 pp.]. doi:10.2903/j.efsa.2010.1734. Available at: http://www.efsa.europa.eu/en/efsajournal/pub/1734.htm. EFSA (2010b). EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA),

Omega-3 Insights • Regulatory 24 omega3insights.com docosapentaenoic acid (DPA) and maintenance of normal cardiac function (ID 504, 506, 516, 527, 538, 703, 1128, 1317, 1324, 1325), maintenance of normal blood glucose concentrations (ID 566), maintenance of normal blood pressure (ID 506, 516, 703, 1317, 1324), maintenance of normal blood HDL-cholesterol concentrations (ID 506), maintenance of normal (fasting) blood concentrations of triglycerides (ID 506, 527, 538, 1317, 1324, 1325), maintenance of normal blood LDL-cholesterol concentrations (ID 527, 538, 1317, 1325, 4689), protection of the skin from photo- oxidative (UV-induced) damage (ID 530), improved absorption of EPA and DHA (ID 522, 523), contribution to the normal function of the immune system by decreasing the levels of eicosanoids, arachidonic acid- derived mediators and pro-inflammatory cytokines (ID 520, 2914), and “immunomodulating agent” (4690) pursuant to Article 13(1) of Regulation (EC) no 1924/2006 (question no EFSA-Q-2008-1291, EFSA-Q-2008-1293, EFSA-Q-2008-1303, EFSA-Q-2008-1309, EFSA-Q-2008-1310, … [etc.], adopted on 10 September 2010 by European Food Safety Authority). EFSA J 8(10):1796. [32 pp.]. doi:10.2903/j.efsa.2010.1796. Available at: http://www.efsa.europa.eu/en/scdocs/scdoc/1796.htm. EFSA (2012). EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion related to the Tolerable Upper Intake Level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) (question no EFSA-Q-2011-00834, adopted on 26 June 2012 by European Food Safety Authority). EFSA J 10(7):2815. [48 pp.] doi:10.2903/j.efsa.2012.2815. Available at: http://www.efsa.europa.eu/en/efsajournal/pub/2815.htm. EU (2012). Commission Regulation (EU) No 432/2012 of 16 May 2012 establishing a list of permitted health claims made on foods, other than those referring to the reduction of disease risk and to children’s development and health. Off J Eur Union 55(L136):1-40. Available at: http://eur-lex.europa.eu/LexUriServ/ LexUriServ.do?uri=OJ:L:2012:136:0001:0040:EN:PDF. EU (2013). Commission Regulation (EU) No 344/2013 of 4 April 2013 amending Annexes II, III, V and VI to Regulation (EC) No 1223/2009 of the European Parliament and of the Council on cosmetic products. Off J Eur Union 56(L114):1-59. Available at: http://eur-lex.europa.eu/ LexUriServ/LexUriServ.do?uri=OJ:L:2013:114:0001:0059:EN:PDF. European Commission (2013). EU Register of Nutrition and Health Claims. Brussels, Belgium: European Union, European Commission, Health and Consumers, Food and Feed Safety. Available at: http://www.ec.europa.eu/nuhclaims/ [Last Update: 12-06- 2013 – must click “Terms and Conditions” to access].

Omega-3 Insights • Regulatory 25 omega3insights.com FSANZ (2013). Chapter 1—General Food Standards, Part 1.2—Labelling and other Information Requirements. Standard 1.2.7— Nutrition, health and related claims. In: Australia New Zealand Food Standards Code. Canberra, Australia / Wellington, NZ: Foods Standards Australia New Zealand (FSANZ), Australian Government ComLaw. Available at: http:// www.comlaw.gov.au/Details/F2013L00054 [Last amended: 07 Jan 2013]. Hill C, Gill TK, Appleton S, Clealand LG, Taylor AW, Adams RJ (2009). The use of fish oil in the community: results of a population-based study. Rheumatology 48(4):441-442. http:// rheumatology.oxfordjournals.org/content/48/4/441.full.pdf. Holvik K, Meyer HE, Haug E, Brunvand L (2005). Prevalence and predictors of vitamin D deficiency in five immigrant groups living in Oslo, Norway: the Oslo Immigrant Health Study. Eur J Clin Nutr 59(1):57-63. Nutrilab, Inc., et al. and Bio-Tech Laboratories, Inc., et al., v. Schweiker and Hayes. 713 F.2d 335 (7th Cir. 1983). Nutrilab, Inc., et al. and Bio-Tech Laboratories, Inc., et al., Plaintiffs-Appellants, v. Richard S. Schweiker, U.S. Secretary of Health and Human Services; and Arthur Hull Hayes Jr., Commissioner of the U.S. Food and Drug Admin., Defendants-Appellees Nos. 82-2746, 82-2747. United States Court of Appeals For The Seventh Circuit, 713 F.2d 335; 1983 U.S. April 22, 1983, Argued August 8, 1983, Decided. Available at: https://www.msu.edu/~lawdoc/ANR-USFL/Nutrilabs.htm. TGA (1989). Therapeutic Goods Act 1989 (Act No. 21 of 1990 as amended). Canberra, Australia: Therapeutic Goods Administration (TGA), Office of Legislative Drafting and Publishing, Attorney- General’s Department. Available at: http://www.comlaw.gov. au/Details/C2014C00102 [Amendments up to 2014]. TGA (1990). Therapeutic Goods Regulations 1990 (Statutory Rules 1990 No. 394 as amended made under the Therapeutic Goods Act 1989). Canberra, Australia: Therapeutic Goods Administration (TGA), Office of Legislative Drafting and Publishing, Attorney-General’s Department. Available at: http://www.comlaw.gov.au/Details/F2013C00670 [Amendments up to 2013]. TGA (2014). Evidence Guidelines: Guidelines on the Evidence Required to Support Indications for Listed Complementary Medicines. Canberra, Australia: Therapeutic Goods Administration (TGA), Department of Health and Ageing. Available at: http:// www.tga.gov.au/pdf/cm-evidence-listed-medicines.pdf. U.S. FDA (1990). Nutrition Labeling and Education Act of 1990 (NLEA). (101-535). Washington (DC): U.S. Food and Drug Administration (U.S. FDA). Cited In: http://www.law.cornell.edu/ uscode/topn/N.html; Text available from: http://www.law.cornell. edu/usc-cgi/get_external.cgi?type=pubL&target=101-535.

Omega-3 Insights • Regulatory 26 omega3insights.com U.S. FDA (1997). FDA Modernization Act of 1997 (FDAMA) Claims. Washington (DC): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CFSAN). Available at: http://www.fda.gov/RegulatoryInformation/ Legislation/FederalFoodDrugandCosmeticActFDCAct/ SignificantAmendmentstotheFDCAct/FDAMA/default.htm U.S. FDA (1998). Guidance for Industry: Notification of a Health Claim or Nutrient Content Claim Based on an Authoritative Statement of a Scientific Body. College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CFSAN). Available at: http://www.fda.gov/food/ guidanceregulation/guidancedocumentsregulatoryinformation/ labelingnutrition/ucm056975.htm [Page Last Updated: 02/20/2014].

U.S. FDA (2002). Guidance for Industry: Structure/Function Claims, Small Entity Compliance Guide. College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CFSAN). Available at: http://www.fda.gov/Food/ GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ DietarySupplements/ucm103340.htm [Page Last Updated: 02/21/2014]. U.S. FDA (2003a). Guidance for Industry: Interim Procedures for Qualified Health Claims in the Labeling of Conventional Human Food and Human Dietary Supplements. College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Nutritional Products, Labeling and Dietary Supplements. Available at: http://www.fda.gov/Food/GuidanceRegulation/ GuidanceDocumentsRegulatoryInformation/LabelingNutrition/ ucm053832.htm [Supersedes the Dec. 18 2002 guidance]. U.S. FDA (2003b). Consumer Health Information for Better Nutrition Initiative: Task Force Final Report. College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CFSAN). Available at: http://www.fda. gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ ucm096010.htm [Page Last Updated: 03/13/2013]. U.S. FDA (2004a). Letter Responding to Health Claim Petition dated June 23, 2003 (Wellness petition): Omega-3 Fatty Acids and Reduced Risk of Coronary Heart Disease (Docket No. 2003Q-0401). College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CFSAN). Available at: http:// www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ ucm072936.htm [Sep. 8, 2004, Page Last Updated: 04/18/2013].

Omega-3 Insights • Regulatory 27 omega3insights.com U.S. FDA (2004b). Letter Responding to Health Claim Petition dated November 3, 2003 (Martek Petition): Omega-3 Fatty Acids and Reduced Risk of Coronary Heart Disease (Docket No. 2003Q-0401). College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CFSAN). Available at: http:// www.fda.gov/Food/IngredientsPackagingLabeling/LabelingNutrition/ ucm072932.htm [Sep. 8, 2004, Page Last Updated: 04/18/2013]. U.S. FDA (2006). Guidance for Industry: FDA’s Implementation of “Qualified Health Claims”: Questions and Answers; Final Guidance. U.S. Department of Health and Human Services. College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CFSAN). Available at: http://www.fda.gov/ Food/GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ LabelingNutrition/ucm053843.htm. U.S. FDA (2007). Food labeling: nutrient content claims; alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid omega-3 fatty acids [21 CFR Part 101; Docket Nos. 2004N–0217, 2005P–0189, and 2006P–0137; RIN No. 0910–ZA28]. Fed Regist (US) 72(227):66103-66118. Available at: http://www.fda.gov/OHRMS/DOCKETS/98fr/E7-22991.pdf. U.S. FDA (2008). Guidance for Industry: Substantiation for Dietary Supplement Claims Made Under Section 403(r) (6) of the Federal Food, Drug, and Cosmetic Act. (OMB Control No. 0910-0626). College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CSFAN), Office of Nutrition, Labeling, and Dietary Supplements (ONPLDS). Available at: http://www.fda.gov/ food/guidanceregulation/guidancedocumentsregulatoryinformation/ dietarysupplements/ucm073200.htm [Dec. 2008]. U.S. FDA (2009). Guidance for Industry: Evidence-Based Review System for the Scientific Evaluation of Health Claims – Final. College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CFSAN), Office of Nutritional Products, Labeling and Dietary Supplements, Division of Nutrition Programs and Labeling (ONPLDS). Available at: http://www.fda.gov/ food/guidanceregulation/guidancedocumentsregulatoryinformation/ labelingnutrition/ucm073332.htm. U.S. FDA (2013a). U.S. Code of Federal Regulations (CFR). Title 21— Food and Drugs (Food and Drug Administration). Washington (DC): U.S. Government Printing Office (GPO). Available at: http://www. gpo.gov/fdsys/browse/collectionCfr.action?collectionCode=CFR.

Omega-3 Insights • Regulatory 28 omega3insights.com U.S. FDA (2013b). Chapter 8. Claims: Health Claims. In: Guidance for Industry: A Food Labeling Guide. College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Food Safety and Applied Nutrition (CSFAN), Office of Nutritional Products, Labeling, and Dietary Supplements (ONPLDS). Available at: http://www.fda.gov/Food/ GuidanceRegulation/GuidanceDocumentsRegulatoryInformation/ LabelingNutrition/ucm064908.htm [Jan. 2013]. U.S. FDA (2013c). Guidance for Clinical Investigators, Sponsors, and IRBs: Investigational New Drug Applications (INDs) — Determining Whether Human Research Studies Can Be Conducted Without an IND. College Park (MD): U.S. Food and Drug Administration (U.S. FDA), Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER), Center for Food Safety and Applied Nutrition (CFSAN). Available at: http:// www.fda.gov/downloads/Drugs/Guidances/UCM229175.pdf. U.S. FDA (2014). Food labeling: nutrient content claims; alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid omega-3 fatty acids [21 CFR Part 101; Docket Nos. FDA–2007–0601, FDA–2004–N–0382, FDA–2005–P–0371, and FDA–2006–P–0224 (formerly Docket Nos. 2004N–0217, 2005P–0189, and 2006P–0137, respectively); RIN 0910– ZA28]. Final rule. Fed Regist (US) 79(81):23262-23273. Available at: http://www.gpo.gov/fdsys/pkg/FR-2014-04-28/pdf/2014-09492.pdf.

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