Botanical products - medicines or food supplements ?

1. Botanical products - medicines or food supplements? • Dr John O’Brien • FSAI

2. Presentation outline • Introduction • Regulatory context • Safety of botanical products • Sources of assistance

3. Consumer Protection Goes to the Top of the Agenda • “In order to promote the interests of consumers and to ensure a high level of consumer protection, the community shall contribute to protecting the health, safey and economic interests of consumers, as well as promoting their right to information, education, and to organize themselves in order to safeguard their interests” • Article 153, Amsterdam Treaty (1999)

4. What is the FSAI? • National agency responsible for the enforcement of food safety legislation in Ireland • Statutory body established under the Food Safety Authority of Ireland Act, 1998 • Came into effect on 1st January 1999 • An independent and science-based agency • Report to the Minister for Health and Children • Transparent and accountable.

5. FSAI mission • Toprotect consumers’ health and consumers’ interests by ensuring that food consumed, distributed, marketed or produced in the state meets the highest standards of food safety and hygiene.

6. Managing Food Safety in Ireland: Vital Statistics • FSAI Budget (2008) €18.6 million • Staff (WTE): • FSAI 86 • Inspectorate 1162 • (DAFF 541) • (Health Service Executive 427) • (Local Authorities 37) • (Marine Institute 31) • (Micro Laboratories 90) • (Public Analyst Labs 71) • (Additional Part-time Temporary VIs: 933) • ..

7. PARTNERSHIP IS ESSENTIAL BECAUSE…

8. Compliance Cannot Be Policed Into the Industry! Put down the sausages and come out with your HACCP plan

9. Definition of a Medicinal product (2004/27/EC) • Any substance or combination of substances presented as having properties for treating or preventing disease in human beings; 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. • “In cases of doubt.......the provisions of this Directive shall apply”

10. Definition of Food (EC 178/2002) • Any substance or product, whether processed, partially processed or unprocessed,intended to be, or reasonably expected to be ingested by humans. • ‘Food’ includes drink, chewing gum and any substance, including water,intentionally incorporated into the food during its manufacture, preparation or treatment. • ‘Food’ shall not include: • (a) feed;(b) live animals unless they are prepared for placing on the market for human consumption;(c) plants prior to harvesting;(d) medicinal products; (e) cosmetics; (f) tobacco and tobacco products; (g) narcotic or psychotropic substances; (h) residues and contaminants.

11. EC 258/1997 • Novel Foods • “..foods and food ingredients which have not hitherto been used for human consumption to a significant degree within the community..” • Including • “..foods and food ingredients consisting of or isolated from plants..”

12. Directive 2002/46/EC • 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, namely forms such as capsules, pastilles, tablets, pills, and other similar forms, sachets of powder, ampoules of liquids, drop dispensing bottles, and other similar forms of liquids and powders designed to be taken in measured small unit quantities”

13. Council Directive 89/398/EEC • Foods for Particular Nutritional Uses (‘Parnuts’) • “foodstuffs which, owing to their special composition or manufacturing process are clearly distinguishable from foodstuffs for normal consumption, which are suitable for their claimed nutritional purposes and which are marketed in such a way as to indicate such suitability“ • e.g. • infant formulae and follow-on formulae • dietary foods for special medical purposes • foods intended for use in energy restricted diets for weight reduction • food intended to meet the expenditure of intense muscular effort, especially for sportspeople • foods for persons suffering from carbohydrate-metabolism disorders, (diabetes).

14. Regulation EC 1924 • Article 13 • Health claims other than those referring to the reduction of disease risk and to children's development and health • Article 14 • Reduction of disease risk claims and claims referring to children's development and health • Scientifically substantiated • Prior approval required

15. SAFETY ASSESSMENT OF BOTANICAL PRODUCTS AND INGREDIENTS

16. EU General Food Law • EC 178/2002 lays down principles of general food law and establishes the European Food Safety Authority. • Definitions, general principles of food law (risk analysis, precautionary principle, protections of consumers’ interests), food safety requirements • General obligations of trade • Presentation • Responsibilities • Traceability • Responsibilities for food and feed withdrawal/recall

17. Identification of starting material Process applied to starting material Standardization and nature of product Production of consistent botanical material

18. Botanical Source Identity Scientific Name (plant family, genus, species with name of authority, and if relevant, variety and chemotype), common names Part(s) of plant used Geographic origin (continent, country, region) Growth Conditions Wild or cultivated Good Agricultural Practice Site of collection, time of harvest, stage of growth Drying, fermentation Storage conditions Pre- and post-harvest phytosanitary treatments (e.g. pesticides) Product Identification and characterization - 1

19. Raw Material (e.g. dried plant material) Specifications according to standard methods including: Identity tests Quantitatives tests to determine constituents relevant to beneficial effects and those of toxicological relevance Process applied to starting material Steps in preparation Methods used Specific precautions Product Identification and characterization - 2

20. Botanical Preparation Standardization criteria Specifications (level/range for markers) Physicochemical properties of relevant constituents Purity criteria Level and nature of excipients Formulation methodology Storage conditions End Product (food or supplement containing botanical) Fate of botanical constituents in product (stability) Industrial food processing Preparation for consumption Product Specification

21. Product Comparison • No difference in composition beyond natural variability from an accepted traditional food, food ingredient orfood additive: proceed to intake assessment • Single or a few well-defined specific characteristics that are different from an accepted traditional food, food ingredient or food additive: safety assessment should focus on these characteristics • The counterpart of the product under investigation is a traditional health product (medicinal product or foodsupplement). In this situation, the relevance to the new food application of the safety data available on theexisting product has to be assessed on a case-by-case basis. Further data to ensure the safety of the foodapplication of the product may be required. • The product under investigation does not have any traditional food or health product counterparts. Such aproduct requires a comprehensive safety assessment, which is discussed below

22. Hazard Identification/characterization in Experimental Animals • The extent of experimental investigation necessary depends on the adequacy of the history of use and the product comparison database • The modes of action of beneficial and adverse effects should be assessed • Special studies may be necessary depending on the history of use and the mode of action • Safety studies should normally be performed on the characterized product of commerce as consumed, at a range of doses including those that produce adverse effects • Studies (in vitro and in vivo) on specific biologically active sub-fractions can provide valuable information for the design of safety studies and/or the interpretation of relevant endpoints • The influence of the matrix on the rate and extent of absorption of active constituents should be studied • Studies based on purer preparations may underestimate or overestimate the potential for adverse effects of less pure preparations

23. Recent safety issues associated with botanical products • Hepatotoxicity of kava-kava and comfrey • Carcinogenicity of Aristolochia spp • Recorded adverse interactions with licensed drugs (eg St John’s Wort)

25. The EC FOSIE Project

26. Further information • Schilter et al. (2003), Guidance for the safety assessment of botanicals and botanical preparation with use in food and food supplements, Food and Chemical Toxicology 41, 1625-1649. • Barlow et al. (eds)(2002), Food Safety in Europe (FOSIE). Risk assessment of chemicals in food and diet, Food and Chemical Toxicology 40, 2/3. • www.efsa.eu.int • www.fsai.ie • www.imb.ie

27. FSAI Contacts • Nutrition: Dr Mary Flynn mflynn@fsai.ie • Novel Foods: Dr Pat O’Mahony pomahony@fsai.ie • Regulatory Affairs: Ms Anne-Marie Boland amboland@fsai.ie • Advice Line: 1890 336677 • Swictboard: 01 817 1300 • Email: info@fsai.ie