IHTA Annual Conference

1. IHTA Annual Conference The Irish Medicines Board and the regulation of herbal and other medicines Crowne Plaza Hotel, Dublin Airport - 28th April 2010 Dr. J.M. Morris Senior Scientific Advisor, IMB

2. Overview • Introduction to medicines regulation • Classification of products as medicines • Herbal medicines regulatory framework • Homeopathic medicines • Other medicines • Herbal medicines post 2011 • Conclusions and questions

3. What is a Medicine I • Definition given in Article 1.2 of Directive 2001/83/EC • Revision in Directive 2004/27/EC • IMB guide to definition of a medicinal product for human use based on • Composition • Claim • Presentation • Function

4. What is a Medicine II Article I of Directive 2001/83/EC, as amended by Directive 2004/27/EC makes changes to the definition of a Medicinal Product. The new definition states that a medicinal product is: • 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.

5. Requirements of Medicinal Products • Marketing is controlled by valid authorisation or registration • Protection of consumers • Medicines should be of good quality • Risk of using the product should be reasonable and acceptable in the light of the expected benefit • Demonstrable therapeutic benefit should be anticipated

6. IMB Guideline “Definition of a Human Medicine” • Non-legally binding advice – definition is in the Directive • Borderline between MP’s and foods, cosmetics, Medical Devices etc. • Adjudication by IMB Classification Committee • Application form and fee • Guideline revised February 2008

7. Classification Process 1 • Application form on IMB website www.imb.ie • Complete application form in full • Enclose all labels, leaflets, promotional material • Pay attention to websites used to promote products • Application fee €250 (€200 for supplements) • Submit to Classification Committee • Response usually within 28 days

8. IMB Classification Committee • Multidisciplinary scientific in-house committee • Consists of representatives from Human Medicines, Medical Devices, Compliance Departments • Expertise in medicine, pharmacy, herbal medicine, toxicology, market surveillance and pharmacovigilance , medical devices, cosmetics. • Meets once monthly • Typically 100 applications p.a • Provides a formal response in writing • Decisions can be appealed to ACHM (final)

9. Classification Process 2 • Open to dialogue – removing a claim or even changing language may alter status • Consultation with other interested parties – e.g. FSAI for food supplements • Two way process – FSAI makes referrals to IMB also • Same active may be present in medicines and foods – e.g, garlic, ginger • Some herbs may be present exclusively in foods i.e. not medicines provided no claims made

10. Directive on Traditional Herbal Medicinal Products [THMPs] • Must meet pre-defined standards: • - Quality • - Safety • - Traditional Use

11. Quality • All traditional medicinal products must conform to agreed quality standards as for any other medicinal product • Herbal Medicinal Product Guidelines – HMPWP • 2001/83/EC - where appropriate • New legislation 2004/24/EC • EMA guidelines • European Pharmacopoeia monographs

12. Efficacy • Full product authorisation application => clinical trial data • Well-established use’ => bibliographic applications • 2004/24/EC -30 years on market, at least 15 in EU for THMP registration

13. Manufacturing considerations • Good Agricultural Practice [GAP] • Good Manufacturing Practice [GMP]  Manufacturer’s Authorisation • Good Distribution Practice [GDP]  Manufacturer’s/Wholesaler’s Authorisation Third country importation = manufacture

14. EU/Irish initiatives • European Scientific Co-Operative on Phytotherapy [ESCOP] • Pharmaceutical Committee of the European Union • Herbal Medicinal Products Working Committee [HMPC]/Other Working Parties of the European Medicines Agency • IMB Herbal Medicines Project 2000 - 2002

15. Homeopathic medicines • Simplified Registration Procedure provided for in 2001/83/EC Chapter 2 • No Hom MP on the market unless it has a MA or SRP • National Rules Scheme adopted in Ireland to allow limited claims on basis of supporting data

16. Simplified registration • Products administered orally or topically • No specific medicinal claims on labels and literature • Sufficient degree of dilution I in 10,000 or 1/100th of smallest allopathic dose of POM • That is 4x(4d)-2C – or greater dilution (potency)

17. Documents to be submitted • Details of product and stock • Details of preparation and control of stock(s) • Manufacturing and control file for product • Manufacturing authorisation • Registrations in other MS • Mock-ups of packaging • Product stability data

18. SRP Products • Exempt from authorisation-no SPC • Exempt from pharmacovigilance • Labelling requirements- Article 69 • Scientific name of stock(s) and dilution level • Name and address of reg holder • “Homeopathic medicinal product without approved therapeutic indication” • No other detail other than as specified

19. Homeopathic Medicines National Rules Scheme 2010 • Article 16.2 of Directive 2001/83/EC • Implemented by Regulation 11 of SI 540 of 2007 • Product is a homeopathic medicine i.e. prepared from homeopathic stocks using a recognised manufacturing procedure (Pharmacopoeia) • Indication is appropriate • Indication does not need medical diagnosis/intervention • Efficacy established in Ireland • Safety evaluated

20. Homeopathic National Rules (2) Safety evaluation • Reference to published literature • Oral products derived from food substances • Active used in allopathic medicine dilution of 1 in 10,000 minimum (nmt1/100th therapeutic dose) • 1 part per 10,000 MT

21. Homeopathic medicines national rules labelling • General labelling requirements of Directive (TitleV) • The product is a homeopathic medicinal product authorised by this procedure • Any evidence of efficacy is not based on clinical trials • Use for symptomatic relief of the condition specified • Consult a Doctor if symptoms persist

22. Other medicines • Anthroposophic medicines - regulated as medicines when manufactured by a homeopathic (pharmacopoeial) method • “Spagyrics” – methods unlikely to be approved in the pharmacopoeia • HMM Group of Experts at Ph. Eur making good progress

23. Other medicines 2 • Korsakovian dilutions (k potencies) may be included in pharmacopoeia • Bach flower remedies remain outside legislation • Aromatherapy products not regarded as medicines unless specific claims made

24. Herbal Medicines post 2011 • Since July 27th 2007 no new THMP can come on the market without PRIOR IMB approval • Existing herbal medicines can remain on the market up to 30/4/2011 • Applications should be received by IMB for by end April 2010 (THMP or WEU) • Products with PA’s can of course continue to be marketed • Few applications received • Problem not restricted to Ireland – same across EU generally

25. Herbal Medicines post 2011 (2) • Few registrations • Herbal medicines masquerading as foods • “Health claims” vs. medicinal claims • Illegal products • Marketplace availability of herbal products?

26. Herbal Medicines post 2011 (3) • What can IMB do? • All products need to be registered - as herbal medicines - as food supplements • Registration with IMB or FSAI as appropriate • Documented proof of legal status • No documentation - expect products to be seized

27. Herbal Medicines Registration • Registration process is feasible and user friendly • IMB is now the primary authority for determining method of sale and supply • No longer bound by the restrictions of prescription legislation • For example Ginkgo biloba could be accepted for THM registration provided suitable indication

28. Herbal Medicines Registration (2) • IMB aiming constantly to improve clarity of the registration process • Developing lists of herbal substances which can only be considered as medicines • Examples G. biloba A. belladonna H. perforatum • Some of these might be acceptable OTC once registered as THM’s e.g. Ginkgo Valerian

29. Herbal Medicine Registration (3) • IMB also developing a list of herbal substances acceptable for marketing as foods provided no medicinal claims made • Developing policy in conjunction with - IMB expert Herbal sub-Committee - FSAI - DOHC - Industry • Draft list has approximately 150 entries • Looking forward to further discussion

30. Conclusion • Need to be aware of the distinction between medicines and foods • IMB Classification process is there to assist • Herbal and homeopathic medicines require registration or authorisation by April 2011 • New national rules scheme introduced for authorisation of homeopathic medicines with limited indications • Herbal medicines registration scheme up and running • “Positive” and “negative” lists being developed to help improve clarity • 30/4/2011 is only 1 year away

31. Questions Thank you for your attention