1. Borderline products Foods or medicines? Martijn Martena, PhD the Netherlands Food and Consumer Product Safety Authority Utrecht, the Netherlands Belgrade 19-20 March 2012

2. Workshop on PARNUTS - Belgrade, 19-20 June 2012 2 Food supplements: Foodstuffs the purpose of which is to supplement the normal diet and which are concentrated sources of nutrients or other substances with a nutritional or physiological effect, alone or in combination, marketed in dose form… source: article 2 (a) of Directive 2002/46/EC Similarities with medicines Pharmaceutical appearance, in the form of tablets, powders, liquids in small quantities indicated to support or maintain a good health status

3. Workshop on PARNUTS - Belgrade, 19-20 June 2012 3 Differences medicinal products and food supplements (Dutch situation) Medicinal productsFood supplements Pharmacy, drug store-Supermarket, drug store, internet etc. Medical indication-Health or nutrition claim Contra-indications-No contra-indications Pharmacological activity-Physiological or nutritional activity Synthetic ingredients (mostly )- ‘Natural’ ingredients Marketing authorisation-Notification (in 22 of 25 MS, not in Nl) Medicines inspection- Food inspection

4. Workshop on PARNUTS - Belgrade, 19-20 June 2012 4 Medical claims on foods The labelling and methods used must not: attribute to any foodstuff the property of preventing, treating or curing a human disease, or refer to such properties These prohibitions also apply to: a)the presentation of foodstuffs (shape, appearance or packaging), the way in which they are arranged and the setting in which they are displayed b)advertising source: article 2 of Directive 2000/13/EC

5. Workshop on PARNUTS - Belgrade, 19-20 June 2012 5 Medical claims on foods An example of a medical claim: “omega 3-fatty acids lower cholesterol levels. High cholesterol levels increase the risk on cardiovascular disease” Health claims are possible however, but: health claims may only link foods to maintaining good health An example of a health claim: “Omega 3 fatty acids support healthy blood vessels”

6. Workshop on PARNUTS - Belgrade, 19-20 June 2012 6 Commodities which can overlap with medicinal products Foods: Food supplements Herbal preparations ( under Dutch Commodities act) Novel foods Foodstuffs for particular nutritional purposes Dietary foods for medical purposes (FSMPs) Fortified foods Cosmetics (topical application for cleaning, perfuming etc.)

7. Workshop on PARNUTS - Belgrade, 19-20 June 2012 7 Commodities act decree “Herbal preparations” In the Netherlands food supplements containing herbal ingredients also fall under the definition of “herbal preparation”. The decree contains amongst others a: Ban on several potent herbs and fungi used in phytotherapy (e.g. Datura stramonium, Atropa belladonna, Mandragora officinarum, Claviceps purpurea, kava kava) Mandrake ( Mandragora officinarum ) Thornapple ( Datura stramonium)

8. Workshop on PARNUTS - Belgrade, 19-20 June 2012 8 Novel foods or medicinal products? Becel Pro-active: A vegetable fat spread with plant sterol esters Commission decision 2000/500/EC concerning Becel Pro-active: Labelling requirements: Article 2, c. There shall be a statement that the product is for people who want to lower their blood cholesterol levels. Novel food Regulation 258/97/EC

9. Workshop on PARNUTS - Belgrade, 19-20 June 2012 9 Food supplement? BMI 23: product for weight loss containing cellulose powder The product is classified as a medical device as assessed by a notified body A medical device can bear a medical indication –Characteristics of a food supplement –Labelling contains a CE marking

10. Workshop on PARNUTS - Belgrade, 19-20 June 2012 10 Borderline products and 2001/83/EC In Europe the number of ‘borderline’ products between medicinal products and other regulated products is growing To resolve this issue directive 2001/83/EC on medicinal products for human use was amended by Directive 2004/27/EC In principal 2001/83/EC does not apply to foods, food supplements, cosmetics, biocides or cosmetics, but: In cases of doubt 2001/83/EC applies! Even when the product may fall within a definition covered by other legislation

11. Workshop on PARNUTS - Belgrade, 19-20 June 2012 11 Medicinal products Definitions: ‘Regular’ medicinal products ‘Regular’ herbal medicinal product Traditional herbal medicinal products Homeopathic medicinal products

12. Workshop on PARNUTS - Belgrade, 19-20 June 2012 12 Medicinal product: a)Any substance or combination of substances presented as having properties for treating or preventing disease in human beings; or a)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. Source: article 1, Directive 2001/38/EC, amended by Directive 2004/27/EC

13. Workshop on PARNUTS - Belgrade, 19-20 June 2012 13 Herbal medicinal product: “Any medicinal product, exclusively containing as active ingredients one or more herbal substances or one or more herbal preparations, or one or more such herbal substances in combination with one or more such herbal preparation” Source: Directive 2001/83/EC, as amended by Directive 2004/24/EC

14. Workshop on PARNUTS - Belgrade, 19-20 June 2012 14 Traditional herbal medicinal product: Herbal medicinal product with a long tradition of use in the EU ( > 30 or > 15 years) Simplified registration procedure Efficacy of the medicinal product is plausible on the basis of long- standing use and experience Its traditional use proves not to be harmful in specified conditions of use Products should comply with quality standards in relevant European Pharmacopoeia monographs or those in the pharmacopoeia of a MS Source: Directive 2001/83/EC, as amended by Directive 2004/24/EC

15. Workshop on PARNUTS - Belgrade, 19-20 June 2012 15 How to classify Borderline products: case by case! Approach 1: Is the product presented as having therapeutic qualities? Food supplements aim to maintain physiological homeostasis, medicinal products aim to prevent or treat diseases. Presence of a medical claim on the labelling (even when it has no therapeutic value) or on accompanying information in leaflets or internet. ( ECJ ruling C- 219/91; Ter Voort) Food supplements lawfully manufactured and/ or marketed as such in a member state can be considered as a medicinal product by an other Member State where the product is imported!

16. Workshop on PARNUTS - Belgrade, 19-20 June 2012 16 How to classify Borderline products: case by case! Approach 2: Does the product provide a dose of active ingredients that is pharmacologically active?, for instance: Synthetic pharmacological substances ‘Natural’ active ingredients, such as pharmacologically active amount of a herbal ingredient Vitamins above 3 times the RDA were considered medicinal products in some Member States but European Court of Justice does not accept such a general rule for classification

17. Workshop on PARNUTS - Belgrade, 19-20 June 2012 17 Food supplements classified as a medicinal product in the Netherlands (1) Plants from the genus Ephedra (Ma-huang) and Sida contain ephedra alkaloids (e.g. ephedrine or norephedrine) Products with ephedra alkaloids were sold as “Herbal ecstacy” in smart shops in the Netherlands Effects similar to adrenaline Toxicity of ephedra alkaloids: anxiety, tremors, hypertension and cardiovascular events (even myocardial infarction) Products with ephedra alkaloids were therefore classified as medicinal products in 2005 Smart shop product with Ephedra W. Beltman, A. van Riel, NVIC

18. Workshop on PARNUTS - Belgrade, 19-20 June 2012 18 FOOD VERY URGENT - TRES URGENT ALERT NOTIFICATION: 2005.004-add09 ADDITIONAL INFORMATION SUBJECT: UNAUTHORISED SUBSTANCE ACETILDENAFIL IN FOOD SUPPLEMENT FROM CHINA VIA THE NETHERLANDS AND VIA SWITZERLAND Food supplements classified as a medicinal product (2)