1. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© About OMICS Group OMICS Group International is an amalgamation of Open Access publications and worldwide international science conferences and events. Established in the year 2007 with the sole aim of making the information on Sciences and technology ‘Open Access’, OMICS Group publishes 400 online open access scholarly journals in all aspects of Science, Engineering, Management and Technology journals. OMICS Group has been instrumental in taking the knowledge on Science & technology to the doorsteps of ordinary men and women. Research Scholars, Students, Libraries, Educational Institutions, Research centers and the industry are main stakeholders that benefitted greatly from this knowledge dissemination. OMICS Group also organizes 300 International conferences annually across the globe, where knowledge transfer takes place through debates, round table discussions, poster presentations, workshops, symposia and exhibitions. Open Access publicationsscholarly journalsInternational conferencesOpen Access publicationsscholarly journalsInternational conferences

2. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© About OMICS Group Conferences OMICS Group International is a pioneer and leading science event organizer, which publishes around 400 open access journals and conducts over 300 Medical, Clinical, Engineering, Life Sciences, Phrama scientific conferences all over the globe annually with the support of more than 1000 scientific associations and 30,000 editorial board members and 3.5 million followers to its credit. OMICS Group International is a pioneer and leading science event organizer, which publishes around 400 open access journals and conducts over 300 Medical, Clinical, Engineering, Life Sciences, Phrama scientific conferences all over the globe annually with the support of more than 1000 scientific associations and 30,000 editorial board members and 3.5 million followers to its credit. OMICS Group has organized 500 conferences, workshops and national symposiums across the major cities including San Francisco, Las Vegas, San Antonio, Omaha, Orlando, Raleigh, Santa Clara, Chicago, Philadelphia, Baltimore, United Kingdom, Valencia, Dubai, Beijing, Hyderabad, Bengaluru and Mumbai. OMICS Group has organized 500 conferences, workshops and national symposiums across the major cities including San Francisco, Las Vegas, San Antonio, Omaha, Orlando, Raleigh, Santa Clara, Chicago, Philadelphia, Baltimore, United Kingdom, Valencia, Dubai, Beijing, Hyderabad, Bengaluru and Mumbai.

3. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 3 Translating Pharmacognosy Knowledge into Healthcare: Research on Quality and Standards 10:55-11:15 Title: Current research on standards of medicinal plant products: Decoction pieces, granules and proprietary products as phytomedicines Kelvin Chan, The University of Sydney & Western Sydney, Australia 11:15-11:35 Title: Notorious Aristolochic acids in traditional herbal medicines: Successful identification and validation using DNA barcodes, Real-Time PCR with TaqMan technology and UHPLC-HR- MS Wei Sun, China Academy of Chinese Medical Sciences, China 11:35-11:55 Title: Progress of R&D of Chinese materia medica to keep up with advances in technology De-an Guo, Chinese Academy of Sciences, China 11:55-12:15 Title: Authentication and quality control of TCM herbs and herbal preparations Yuan-Shiun Chang, China Medical University, Taiwan

4. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 4 Current research on standards of medicinal plant products: decoction pieces, granules and proprietary products as phyto-medicines Kelvin Chan Joint Chair Professor in TCM Faculty of Pharmacy, USyd The National Institute of Complementary Medicine, UWS

5. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 5 Topics to be touched on The current public views on herbal products Pharmacopoeia standards of Chinese materia medica: Role of methodology development The current global regulations for Chinese herbal products as phyto-medicines The future actions

6. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Frequently Asked Questions/Concerns about Herbal Medicinal Material and Proprietary Herbal Medicinal Products What are the active ingredients prescribed herbal medicines? Do herbal products have to pass through the same strict legislative procedures as pharmaceuticals? What is known about the quality, safety and efficacy of the herbal products? What are the latest research directions towards QC/QA of herbal drugs?

7. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 7 WHO Report on Traditional Medicine

8. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 8 Differences between Orthodox Drugs and Chinese Medicinal Materials (CMM) ** refer to chemically defined established drugs. ** refer to either single herb or combination of several herbs in one prescription. From: Chan & Cheung, Interactions between Chinese Herbal Medicinal Products and Orthodox Drugs, Taylor & Francis Group, September 11, 2000 by CRC Press

9. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 9 Process in quality assurance of herbal medicines Typical procedure for quality standardisation of herbal medicines

10. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Total Quality Management of Chinese Medicines Industry *GACP is now adopted as Good Agricultural & Collection Practice *

11. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Strategies for Achieving Quality Medicinal Herbal Products Establishment of Good Agricultural & Collection Practice for of medicinal plants Good Sourcing Practice for supply of materials Good Laboratory Practice for chemical/biological analyses Establishing reliable pattern recognition procedures for fingerprinting relationship of source materials GMP of ready-made products with approved fingerprinting GCTP of ready-made products

12. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM©

13. Min County, Gansu: Transferring Danggui Young Seedlings in Green House to Open Fields 甘肃岷县：将当归幼苗转至绿色大棚以开辟土地

14. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Danggui’s GAP Test Farms 当归良好农业规范试验田 Min County, Gansu Province 甘肃省岷县

15. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM©

17. Zhang et al (2010), GAP Production of TCM herbs in China. Planta Medica, 76: 1948-1955 GAP production bases of TCM herbs adopted by national certification before 2010 in China Zhang et al (2010), GAP Production of TCM herbs in China. Planta Medica, 76: 1948-1955 GAP refers to: Good Agricultural Practice

18. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© [Zhang et al (2010), GAP Production of TCM herbs in China. Planta Medica, 76: 1948-1955 ] Some Current GAP Bases of Chinese Materia Medica in China [Zhang et al (2010), GAP Production of TCM herbs in China. Planta Medica, 76: 1948-1955 ]  Site of basesCultivated medicinal Plants  Anhui provincePaeonia suffruticosa  Chongqing Pinellia ternata  Gansu provinceAngelica sinensis  Guangxi provinceMomordica grosvenorii  GuiZhou provinceDendrobium candidum; Eucommia ulmoides;  Hebei province Angelica dahurica; Scutellaria baicalensis  Heilongjiang provincePanax ginseng  Henan provincePanax ginseng  Hubei provinceKehmannia gluiinosa  Hunan provinceLespedeza cyrtobotrya  Inner MongoliaEucommia umloides  Jiangsu provinceGlycyrrhiza uralensis  Jilin provinceChrysanthemum morifolium  Liaoning provincePanax ginseng; Panax quinquefolium  Ningxia provincePanax ginseng  Shandong provinceLycium chinensis  ShanghaiLonicera japonica  Shanxi provinceCrocus sativus  Sichuan provinceSalvia miltiorrhiza  Tibet provinceCrocus sativus; Ligusticum chuanxiong  Yunnan provinceRhodiola roseaDracaena draco; Panax notoginseng

19. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Role of European Directorate for Quality Medicines & Healthcare (EDQM)

20. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 20 The EP Commission in Strasbourg 2005 * ‘Monographs on Herbal Drugs used in Traditional Chinese Medicine should be developed to give a modern quality standard according to European Pharmacopoeia principles and to facilitate and encourage use by practitioners for safe, authorised products’ * Slide from Prof Franz-©2009 EDQM, Council of Europe, All rights reserved

21. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 21 Commission of European Pharmacopoeia (2008): Set up Working Party of TCM at Strasbourg, EDQM Président/Chairman Prof. Dr. Gerhard Franz Other Experts: AProf. Dr. Rudolf BAUER ADr. Erich Andreas STOEGER B Dr. Pierre DUEZ CHDr. Albert BLARER CHDr. Thomas LEHMANN CHDr. Eike REICH DDr. Uwe Michael GASSER DDr. Bernhard Klier EMs. Gloria GARCIA LORENTE FProf. Isabelle FOURASTE FMr. Robert SOUSSAIN UKProf. Dr. Kelvin CHAN -- AU Observer (since Mar 2010) IProf. Francesco VINCIERI NLDr. Mei WANG TRProf. Kemal Husnü Can BASER

22. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Multi-disciplinary methods for the quality standardisation of CMM Pharmacognosy: GAP and sample preparation Capillary Electrophoresis Carbohydrate analysis Chemometrics Authentication: TLC DNA finger printing UPLC/ HPLC LC-MS Biological Clinical Studies

23. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Strategic priorities 1.Optimisation of manufacturing and analysis methods to achieve herbal product standardisation and predictable bioactivity. 2.Contribute to R&D product development methodologies in TCM. 3.Progress TCM bioinformatics / data management. 4.Assisting the development of Chinese herb cultivation in Australia (encompassing Good Supply Practice/Good Agriculture Practice issues). 5.Developing the national and international profile of NSW and Australia in TCM. 6.Further development of strategic TCM research priorities (to articulate with NICM TCM priorities).

24. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM©  Salvia Miltiorrhiza Radix & Rhizoma (Danshen)  Panax Notoginseng Radix & Rhizoma (Sanqi)  Angelica Sinensis Radix (Danggui)  Pueraria Lobata Radix (Gegen)  Zingiber officinale Rhizoma (Ginger) Granule comparison with raw materials Standardisation

25. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Analysis  Using TLC and UPLC, quantifying several reference compounds.  Antioxidant activity  Chemometrics Granules

26. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© General results between decoction pieces & granules CMM decoction pieces were in their own group. CMM decoction pieces had consistent yields. Antioxidant activity favoured CMM decoction pieces. Quantification of more markers allowed greater comparison of products. Did industry follow traditional decoction? Pharmacopoeia needs to define standards for herbal granules

27. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 27 Difference in registration of herbal products o China: TCMs treated and registered as a medicine, health-supplement o Europe: Traditional Herbal Medicinal Product Registration Scheme is good for European traditional remedies (NB 30/15 year rule) but is a barrier to entry for TCMs and other non-EU traditional remedies o USA: stringent rules, need to claim efficacy for disease o Canada: ease of access via Natural Health Products route o Australia: risk strategy approach (different levels)

28. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM©  Dantonic® [Danshen Diwan: Radix Salviae miltiorrhizae, Radix notoginseng and Borneolum Syntheticum] developed as a formulation for treating chronic stable angina pectoris in early 1990s  Approved as a Class 4 drug by the SFDA in 1993 CMC information (formulation development, specification, manufacturing process, stability test, etc) pre-clinical data (pharmacological studies and acute and sub-acute toxicity studies clinical evidence (157 patients, positive control studies, Fu Fang Danshen Pian).  Used by more than 25 million people in chronic, 3-5 month administration, with substantial benefits and bioactivity superior to existing pharmaceuticals in one or more aspects in terms of safety, efficacy and cost- effectiveness  In 1996, Dantonic® entered the first foreign market – Vietnam  The currently active IND (70,359) from the FDA received in June 2006 for the treatment and management of chronic stable angina  Phase II, randomized, placebo controlled studies in the USA and Australia conducted 2008-2009  In July 2010, the EOPII meeting with the US FDA was held, and the phase III studies are under active planning in the USA, EU, Australia and Asia Case study: Dantonic® Worldwide Markets (1)

29. ©TCM&NP Symposium-Nanning-2011.08.13-15-Prof. K Chan PhD DSc FSB FCP FRPS FRSM-© Country/RegionLegal statusApproval time USADietary supplementSep 2000 The United Arab EmiratesPrescription drugJun 2001 South KoreaOTCJan 2002 CubaDrug*Jul 2002 SingaporeTPM**Oct 2002 MongoliaDrug*Oct 2002 NambiaCAM**Aug 2003 KazakhstanPrescription drugJan 2004 Ivory coastFunctional product***Mar 2005 Dantonic® Worldwide Markets (2) * Drug: there is no clear classification between prescription drugs and OTC in some developing countries ** TPM: Traditional Patent Medicine; CAM: Complementary and Alterative Medicine; TM: Traditional Medicine; TCM: Traditional Chinese Medicine; *** Functional product: Similar to dietary supplement or food supplement;

30. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Dantonic® Worldwide Markets (3) South AfricaCAM**Sep 2005 VietnamPrescription drugOct 2005 RussiaPrescription drugDec 2005 NigeriaCAM**Dec 2006 IndiaFunctional product***Mar 2007 ThailandTM**Feb 2008 Hong KongTCM**Mar 2008 CanadaOTCJul 2008 PhilippinesOTCJul 2009 UgandaFunctional product***Aug 2009

31. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 31 Di’ao Xinxuekang Capsule - the 1 st authorised THM from outside the EU Approved by Dutch Medicines Evaluation Board (MEB) on 14 March 2012 The application was evaluated very carefully on the basis of:  pharmaceutical qualitysafety and  the justification of traditional use, i.e. 30/15 year rule (Dioscorea nipponica rhizome) The marketing authorisation holder is obliged to implement a pharmacovigilance system The manufacturing site of Di’ao in Chengdu, China was inspected on GMP by the Dutch Pharmaceutical Inspection.

32. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Email Addresses for Regulatory Agencies in various regions  Australia --- http:/www.tga.gov.au/cm/cm.htm#argcm  Canada--http://www.hc-sc.gc.ca/hpfb-dgpsa/nhpd- dpsn/index_e.html  China---http://www.sfda.org.cn/  Hong Kong Chinese Medicine Division-- http://www.cmchk.org.hk/cm/english/idx_ord.htm  The European Agency for the Evaluation of Medicinal Products— http:www.emea.eu.int/  USA-- -FDA---http://www.fda.gov/cder/guidance/index.htm

33. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Pharmacopoeia of various countries or regions that have monographic standards for CMM Chan K, Leung KS, Zhao SS. Harmonization of monographic standards is needed to ensure the quality of Chinese medicinal materials. BMC-Chin Med 2009; 4: 18 Pharmacopoeia and monograph Authority Status WHO Monographs on Selected Medicinal Plants WHO unofficial Chinese Pharmacopoeia SFDA China official AU Regulatory Guidelines for Complementary Medicines TGA Australia official European Pharmacopoeia EDQM official Hong Kong Chinese Materia Medica Standards DHHKSAR, China official Japanese Pharmacopoeia PA Japan official Thai Herbal Pharmacopoeia TFDA official British Pharmacopoeia BPC, UK official American Herbal Pharmacopoeia (AHP) prívate unofficial

34. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© 34 Take home messages Open mindedness collaboration/cooperation/networking Ensure good practices in GACP, GSP, GLP, GMP & GCTP Linking technologies, chemometrics & bioinformatics with regulatory requirements Evidence-based assessment of efficacy & safety Global harmonisation of regulatory control/ pharmaco-vigilance system To achieve these we need: o Updating monographic standards of CMM with R & D data o Local, national and global networking on all issues is a MUST o Recognition of industrial specifications for GCTP- proven brand- named products. o Train local human resources in coping with demand—role of university & educational institutes o Do the utmost to establish a state of harmony between "tradition" and "modern" in the provision of global healthcare

35. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Thank you for your attention

36. ©JCTCM-Professor Kelvin Chan PhD DSc FSB FCP FRPharmS FRSM© Lets Meet again at Pharmacognosy-2015 3 rd International Conference and Exhibition on Pharmacognosy, Phytochemistry and Natural Products October 26-28, 2015 Hyderabad, India Theme: Advanced trends for the future of Herbal Drugs and Products Website: http://pharmacognosy-phytochemistry-natural- products.pharmaceuticalconferences.com/ http://pharmacognosy-phytochemistry-natural- products.pharmaceuticalconferences.com/http://pharmacognosy-phytochemistry-natural- products.pharmaceuticalconferences.com/