The high cost of drug development in the pharmaceutical industry is well documented, with the cost of developing a novel drug estimated to be around $1.8 billion. The costs of research, development and patent protection are understood to be some of the reasons for this high figure. By comparison, the food industry is noted for less stringent testing requirements, lower costs of product development and smaller profit margins.
Nutraceuticals represent an emerging area that comprises elements of both of these industries, as they are higher value than food products but lack the research cost and patent protection of products developed by the pharmaceutical industry. The lower costs of developing nutraceuticals are complemented by a lack of direct regulation both in the U.K. and European Union (EU).
Recently, food policy expert Miguel da Silva, Global Director of Health and Nutrition Policy at the European Advisory Services (EAS), stated that the European Commission (EC) will be discussing a nutrient profiling system to restrict certain foods when it presents its second proposal on the matter, in 2013. This proposal is in response to criticisms of the first proposal in 2009, which did not offer a sound solution to the issue and was eventually withdrawn. In advance of this proposal, we look at the existing regulatory regimes for food and drugs and assess why nutraceuticals are not regulated by either of these regimes.
Nutraceuticals are products derived from foods, which have substantive physiological effects and are sold in a medical form.
In the EU, the categorization of a substance is made based on its effects on the body. If the substance contributes only to the maintenance of healthy tissues and organs then it may be considered to be a food ingredient. If it can be shown to have modifying effects on the body's natural physiological functions and is sold as treating a medical condition, then it will be considered a medicinal product. Nutraceuticals have elements of both foods and medicinal products, but do not completely satisfy the requirements of either regime. Due to the peculiarity of their design they are presently unregulated.
Currently, there are regulatory regimes in the EU that cover the following areas:
· Foods (EC Regulation 172/2002);
· Medicines (Directive 2001/83/ED); and
· Foods for Particular Nutritional Use (PARNUTS) (Directive 89/398/EEC)
Nutraceuticals do not clearly fit into any of these regulatory regimes, even though they have the following properties, which are assessed by the current regulatory regimes: they are ingested; and they claim to have beneficial physiological effects.
These qualities form part of the criteria for both the food and medicinal products regimes.
In the U.K., the Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicinal products for human use in accordance with several sources of legislation, including the European Community’s Medicinal Products Directive (Directive 2001/83/ED, as amended) (the Directive) and U.K. law, such as the Medicines Act 1968 and the Medicines for Human Use (Marketing Authorizations Etc.) Regulations 1994, as amended.
Article 1 of the Directive contains two alternative tests to determine whether a product should be classified as a medicinal product. Medicinal products are considered to be:
· any substance or combination of substances presented as having properties for treating or preventing disease in human beings (the Presentation Test); OR
· any substance or combination of substances which may be used in or administered to human beings either with a view to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action, or to making a medical diagnosis (the Purpose Test).
A product that satisfies either of these tests will be considered a medicinal product by the MHRA. Nutraceuticals will not normally satisfy the Presentation Test, as they do not hold themselves out as preventing or treating a recognized disease. Often they will be designed to target treatment of the aging process or simply improving general health, which is not the same as claiming to prevent or treat a recognized disease. Nutraceuticals may not satisfy the Purpose Test either, as they do not necessarily exert a pharmacological action on the body to restore, correct or modify a physiological effect by a pharmacological or immunological action.
The quandary is that, although nutraceuticals may work via a method as set out in the Purpose Test, because they do not undergo the level of research and development to explain the mechanisms of the active ingredients (as pharmaceutical companies do when developing new drugs), it is impossible to demonstrate whether they satisfy the test or not. This highlights one of the potential dangers of nutraceuticals. While they aren't intended to have medicinal properties, as described in Article 1 of the Directive, there is a danger that—because they don't have to satisfy any safety testing requirements to consider how they interact on a biological and chemical level with the body—there are many potential short- and long-term side effects that are not exposed. Nutraceuticals could effectively go to market without providing consumers the same level of protection as medicinal products, which have been through a rigorous review process. This fact becomes even more pertinent when considering the large number of examples—such as Vioxx, Bextra, Zelnorm, Tysabri, Cylert, Permax and Baycol—of pharmaceuticals that have been recalled as a result of an undiscovered side effect. While none of these previous examples are nutraceuticals, as nutraceuticals develop and become increasingly advanced and treat more complex ailments, it may only be a matter of time before a longer-term side effect is exposed, resulting in product recall.
Food Products and PARNUTS
In the U.K., food products are regulated under the Food Safety Act 1990, and “Food” is defined in Article 2 of EC Regulation 172/2002 as follows: “… food (or foodstuff) means any substance or product, whether processed, partially processed or unprocessed, intended to be or reasonably expected to be ingested by humans …”
Article 2 of EC Regulation 172/2002 also states that: “Food shall not include … medicinal products within the meaning of Council Directive 2001/83/EC.”
Food in this definition covers any food, drink or supplement ingested and considered to be part of the normal human diet. Products that provide benefits beyond their traditional nutritional value, however, are not considered to be foods under Article 2 of EC Regulation 172/2002. If not considered a food they may be Foods for Particular Nutritional Use (PARNUTS) under Directive 89/398/EEC. This Directive defines PARNUTS as foods which: “owing to their special composition or manufacturing process are clearly distinguishable from food stuffs for normal consumption, which are suitable for the claimed nutritional purpose, and which are marketed in such a way as to indicate such suitability.”
The EU PARNUTS Directive contains rules relating to the specific compositional details and labeling requirements of foods and six categories of permitted substances, listed below:
3) amino acids
4) carnitine and taurine
6) choline and inositol
Nutraceuticals, as previously stated, are normally derived from existing food products, however, they will not fall under the Article 2 definition of food since they purport to provide a benefit beyond their traditional nutritional value. While not a food product, nutraceuticals do not fit the PARNUTS Directive definition either, as their composition does not clearly fit any of the six PARNUTS categories.
The only other basis on which nutraceuticals may be regulated is as “novel ingredients” under Regulation (EC) No. 258/97. These ingredients have not been marketed in an EU Member State before 1997. Companies must apply for authorization from the relevant EU Member State’s competent authority, which will allow the application if no further assessment is necessary and the Commission does not object. Unless the nutraceutical in question contains a new food extract, it is unlikely it would be considered a novel product. It is also clear, from previous decisions made by the Commission, that nutraceuticals made from combinations of ingredients that are not novel have not been considered under Regulation (EC) No. 258/97 to date.
The nutraceutical industry is currently worth an estimated $151 billion in annual worldwide sales, and is anticipated to grow to $207 billion by 2016. A large part of these sales are made in the EU. It is likely that the industry will fight hard against the increased cost implications to which a regulatory regime would inevitably give rise. The industry may also object to regulations that require it to prove efficacy of its products before they can be marketed.
The industry is likely to point to the fact that products have not thus far caused harm to those who take them. However, as it grows, and as possible longer-term side effects become known, it is difficult to see how the EU cannot address issues both of consumer safety and unsubstantiated claims of product efficacy. The question is not whether, but how, the EU will regulate nutraceuticals.
Last year multinational consumer products company Unilever released Strength Within, the first anti-wrinkle treatment to be taken as a dietary capsule. The product, sold through Unilever’s Dove Spa company, was officially released on September 23, 2011. In just more than a month, it had sold out on the company’s website.
Strength Within is one of a number of products that have attracted considerable public interest recently due to potential nutritional and therapeutic effects. Strength Within works through natural active ingredients, such as omega 3 and vitamins E and C, to treat wrinkles by promoting genes to increase production of collagen.
Strength Within & Medicinal Products
Should Strength Within be regulated as a medical product? For the purposes of the Presentation Test, Strength Within does not present itself as a product for the treatment or prevention of diseases in humans. It is concerned only with the treatment of wrinkles, which are not considered a medical disease. Strength Within is only marketed to be used for this purpose, therefore it will not satisfy the presentation test.
However, Strength Within acts by promoting the artificial production of collagen in the body through an internal process by which genes are activated to increase expression and produce more collagen. The Purpose Test states that any substance that alters the physiological functions of the human body through a pharmacological action may be a medicinal product. The process by which the product works is that it modifies the physiological function of the body by increasing gene expression to produce more collagen. This could be interpreted as a pharmacological effect on the body satisfying the Purpose Test. However, to date, the MHRA has not considered Strength Within to be a medicinal product and it is still sold as a nutraceutical.
Strength Within & Foods
Strength Within is a processed substance intended to be ingested by humans, partially satisfying the definition of a food under Article 2 of EC Regulation 172/2002. However, it does not fully satisfy the definition of a food, as it provides benefits beyond the traditional nutritional value. The product does not simply contribute to the maintenance of healthy tissues and organs; instead, it promotes the production of collagen when the body is not producing enough naturally.
Strength Within is also not a nutrient under the PARNUTS Directive as it is not one of the six categories of PARNUTS foods.
Nutraceuticals Regulation Back on European Commission Agenda for 2013
How will the EU classify and regulate nutraceuticals as this growing industry progresses?
By Niall McAlister, Ben Goodger & Adam Lewington, Edwards Wildman Palmer LLP
Published November 1, 2012