The nexus between science and TCM regulation

1. The nexus between science and TCM regulation Professor Alan Bensoussan Director, CompleMED University of Western Sydney Member of CMEC, TGA

2. Australian & international Context • Ageing population • Increasing cost of healthcare - need to reduce economic and social burden of chronic illness • Increasing international communication and exchange of indigenous healthcare practices • Growing consumer consciousness about medical/healthcare choices • Steadily increasing use of CAM, notably TCM

3. Specific Australian Context • Two in 3 Australians use some form of CAM each year • Location in SE Asia - high exposure to various indigenous medicines (TCM, aborig., Ayurved.) • National regulatory policy that emphasises timely availability of medicines • Challenge: Appropriate regulation of traditional medicines, ensuring timely availability where safe

4. Are science and regulation bedmates? • Does science sufficiently guide regulatory decisions and policy formation? • Is there an adequate balance between therapeutic claims and evidence of efficacy, quality and safety to support those claims? • Does the balance provide sufficient access to TCMs? • Is the balance achieved consistent across medicines?

5. Three distinguishing features of the Australian regulatory approach • The Complementary Medicines Evaluation Committee (CMEC) is comprised of regulators, academic researchers, consumer representation, industry stakeholders and clinicians, who contribute to (effectively make?) regulatory policy and individual regulatory decisions. • There exists a clear delineated path for regulatory approvals of higher order therapeutic claims. • There is a process for formal recognition of traditional (history of use) evidence.

6. Australian Therapeutic Goods Administration (TGA)Principal steps in regulatory process • Licensing and auditing of manufacturers (GMP) • Pre-market assessment of products • Post-market activities (audits, ADR reports)

7. Pre-market assessment of TCM products Two tiered approach to regulating TCMs based on risks: • Listed medicines: limited therapeutic claims, non-serious disease or self-limiting condition, lower risk category, can only contain ingredients determined by TGA to be low risk. Accounts for 99% of TCMs. • Registered medicines: higher claims, higher risk category, individually evaluated for quality, safety and efficacy. Listed medicines Registered medicines Low risk High Risk

8. Disease claims excluded for Listed medicines

9. Pre-market assessment of TCM products

10. Assessment of Quality • British Pharmacopoeial (and other) monographs are used for basic characterisation and quality control of ingredients in both Listed and Registered products. • Good Manufacturing Practice (GMP) applies to starting materials and final products. • Listed products can be Quantified By Input. • Registered products require additional final product characterisation – such as identification one biomarker in each herb.

11. Assessment of SafetyListed Medicines – Permitted ingredients • Only formulated from pre-approved substances • Must be low risk (low tox, not for serious disease) • Herbal ingredients are prepared traditionally (drying, crushing, extracting, but not pharmaceutical preparation) • May be subject to restrictions including: • dosage limits • route of administration • restriction on plant parts, preparation type, extraction solvent, etc • label advisory statements • container type • “Approved list”of approx 2,200 substances http://www.tga.gov.au/docs/html/listsubs.htm

12. Evidence of Efficacy • Risk-based approach requires level of evidence commensurate with the strength of the therapeutic promise to the consumer • The TGA and the CMEC developed guidelines for determining the type of evidence required to support indications/claims for Listed medicines • The Guidelines recognise scientific evidence and evidence based on traditional use as suitable for supporting claims for CAMs Guidelines for Levels and Kinds of Evidence to Support Indications and Claims for Listable Medicines.http://www.tga.gov.au/docs/html/tgaccevi.htm

13. Traditional evidence of efficacy Evidence based on traditional use • Refers to evidence that a substance or product has been used over three or more generations. • Provides an accumulated repository of systematic observation that underpins the medicinal use of the substance or product. All indications/claims based on evidence of traditional use must be worded to the effect that "This (tradition) medicine has been traditionally used for (indication)".

14. Efficacy: levels and requirements of evidence to support indications/claims

15. Levels of Traditional Evidence for Efficacy

16. Examples of claims for Listed medicines May help reduce joint inflammation associated with arthritis (M) May assist peripheral circulation (G) Temporary relief of the cough of bronchitis (M) Relief of the symptoms of colds (M) Relief of mucous congestion (G) Symptomatic relief of upper respiratory tract infections (M) Assists in the treatment of indigestion (M) Relief of the symptoms of eczema (M) Treatment of fungal infections by topical application (M) Temporary relief of headaches (G)

17. Levels of Scientific Evidence required for efficacy claims

18. Concluding features of the TGA approach • Complementary medicines are regulated as medicines (not foods) • Level of regulation is commensurate with low risk nature of CAMs and TCMs • Formally incorporates traditional use evidence - consistent with truth in labelling • Explicit system permitting high level claims for TCMs • Ensures timely availability of TCMs • Academic researchers form an integral part of providing advice to the TGA re policy formation and evaluation of actual applications • Good connection between level of scientific evidence & level of risk, level of therapeutic claim

19. Basic studies required for Registration of herbal medicines in Australia, United States and the European Union

20. Opportunities: Australia as a Preferred CM Clinical Trial Location Benchmarking Comparison of Clinical Trial Locations The Economist’s Intelligence Unit “Benchmarking Study of the Characteristics of the Australian and International Pharmaceuticals Industries (2005)”

21. Challenges • Establishing phytochemical equivalence of modern preparations of traditionally used herbal medicines. When is a herb still a herb? • Standardisation of herbal medicines • Too many traditional medicines to do RCTs to test all claims. Traditional tailoring of treatment to individuals significantly complicates RCTs.

22. Question to the audience • In the absence of scientific data what value should be placed on evidence of traditional use? • How can this be used by regulatory authorities? Can traditional evidence be graded?

23. Thank you