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Download Food or medicine? - Chinese Medical Center in Europe
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Chinese herbal medicine in Europe: Are you legal? Regulatory information TCM practitioners need to know You-Ping Zhu Legal/regulatory problems herbal practitioners face Unexpected visitors from: • Medicines agency Food or medicine? • Food safety authority Contaminants? Novel foods? Herbs in “Negative list”? • Customs/police officers Tiger bones or Rhino horns? Chinese herbal products are classified as medicines by UK Licensing Authority Even herbal drinks are classified as medicines by UK Licensing Authority Sales of unregistered CHM products are no longer allowed in UK Chinese herbs no longer legally available ? To: "CMC" <[email protected]> Sent: Tuesday, May 03, 2011 1:50 PM Subject: Herbs in stock Dear sir, Please advise if it is possible to know whether you have a list of the products that you will stop having in stock due to new regulations. If possible, we would like to know so we may stock on products or forumlas you will no longer carry. Best regards José Centro de Terapias Chinesas Av. António Augusto de Aguiar, 56-1º 1050-017 Lisboa Telef. 213161446 Fax: 213142034 Url: www.ctcportugal.com What is a medicine? - The old definition The first limb “Medicine by presentation” The second limb “Medicine by function” What is a medicine? - The new definition What is a medicine? - Old legal case Food or medicine? - New legal cases Food or medicine? - New legal cases The garlic powder capsule case Garlic capsule was classified as medicine in Germany Bundesgerichtshof (Federal Court of Justice, Germany) ruled on 19-01-1995 that a garlic capsule is a medicinal product but not a food supplement for the following reasons: • • • • • Garlic is known to contain constituents that can reduce blood pressure and cholesterol and thus prevent arteriosclerosis. Products in capsule form are usually medicinal products and only in exceptional cases food supplements. Capsule is an unusual form for a garlic product intended for seasoning meals. The use of blisters for packaging the dosage recommendation are further facts indicating the product is a medicinal product. Garlic capsules contain no nutrients that serve the development or preservation of the human body, as opposed to, e.g. vitamins. Therefore, a nutritional purpose is missing and classification as a foodstuff is impossible. Customers would use the capsules not for nutritional or consumption purposes but to prevent arteriosclerosis. ECJ: Garlic powder capsule is not a medicine by presentation The capsule form is not exclusive to medicinal products. ECJ: Garlic powder capsule is not a medicine by function Fishes have similar effects on physiological functions! ECJ: Garlic powder capsule poses no more risk than garlic taken as a food stuff No harm to consumer health! The red yeast rice capsule case ECJ: Red yeast rice capsules: Food or medicine? • All aspects of the product needed to be taken into account when assessing the product, including a consideration of whether or not the dose of any active substance present would result in "appreciable effect" if the product was used as the manufacturer intended. • Absence of any medicinal claims in the product literature, the medicines legislation should not apply unless it had been scientifically established the product could exert a metabolic, pharmacological or immunological effect. • No harm to consumer health • ECJ dismissed the argument that food supplements tended to be taken in higher doses than those recommended and equated this product with a lowdose vitamin preparation, despite evidence of the harmful side-effects. Diabetruw® had been a food supplement was a medicinal product is again a food supplement in Germany Cinnamon case: food–medicine–food Court District Court in Bielefeld Court of Appeals in Hamm Judgment Reasons Foodstuff Show nutritive and not pharmacological effects, based on the evaluation of several university expert opinions and the evidence before the court. Medicinal product Clinical studies undisputedly proven the positive effect of cinnamon in reducing blood glucose levels in diabetics. No significant effect on metabolism; Federal Court of Justice Foodstuff Not health risks for the consumers (harmlessness); “Diabetruw” has a nutritive and not a pharmacological effect. UK still cites old case ! EU legislations applicable to herbal products • Regulation 178/2002 on the general principles and requirements of food law • Regulation 852/2004 on the hygiene of foodstuffs • Directive 2002/46 on food supplements • Regulation 258/97 on novel foods and novel food ingredients • Regulation 1924/2006 on nutrition and health claims • Directive 2004/24 on traditional herbal medicinal products • Directive 2001/83 on medicinal products for human use • Directive 93/42 concerning medical devices • Directives 76/768 and 2003/15 on cosmetics Regulatory categories of herbal products • Medicines • Foods/Food supplements • Medical devices • Cosmetics Herbal products as medicines ? Category Requirements New (botanical) drug Marketing authorization with preclinical tests and clinical trials results Medicines with well established use Bibliographical application with reference to published literature Traditional herbal medicinal products Simplified (not simple!) registration with traditional use evidence of safety for minor indications First FDA approved botanical drug: VeregenTM Polyphenon®/Veregen™ A long journey from tea extract to prescription drug 1997 License 1999 One phase II trial 2004 Two phase III trials 2005 Submission of New Drug Application to the FDA 2006 In October 2006 the US FDA approved Veregen®. 2007 MA application in Germany, Spain, Austria 20092012 MA in Germany, Spain, Austria, ….., Switzerland THMPD Traditional Herbal Medicinal Products Directive EU Traditional Herbal Medicinal Products Directive Principal requirements • Traditional use evidence 30 years in EU or 15 years in EU + 30 years elsewhere, e.g. China • Pharmaceutical quality (GMP) • Minor indications for self-medication EU Traditional Herbal Medicinal Products Directive: “Simplified” registration Pharmacovigilance Consumer information, labeling, advertising Clinical trials Bibliographic Traditional use evidence Animal tests Clinical trials Bibliographic Expert report Bibliographic Post-marketing surveillance Efficacy Safety Quality Control Good Manufacturing Practices Good Agricultural and Collection Practices New drug Well-established use Traditional Quality Keep evidence of traditional use ! Purchasing/sales invoices Prescriptions/recipes Syllables EU Traditional Herbal Medicinal Products Directive A great chance for CHM ? • • • • Give CHM products an identity Improve quality and public confidence Simplified registration Common EU market for herbal products? EU Traditional Herbal Medicinal Products Directive Major problems for TCM products • • • • • Complex composition Traditional TCM indications Traditional use evidence Safety data EU GMP Registered traditional herbal medicinal products 1438 registrations by 31-12-2014 Registrations per country Registered minor indications Dioscorea nipponica in China and Netherlands Commercial name 穿山龙 Chuan Shan Long Legal status Indications Herb Rheumatic arthritis, pain and numbness in the lower back and legs, hernia; Dioscorea nipponica rhizome 9-15 g, >1.1% diosgenin CN Chronic bronchitis, cough and wheezing Prescription drug 地奥心血康 Di’ao Xinxuekang Prevention and treatment of symptoms of coronary artery disease, angina pectoris Dioscorea nipponica rhizome Extract 100mg=35mg diosgenin/capsule Diao Xin Xue Kang NL Dioscorea nipponica rhizome Extract 100mg/capsule Traditional herbal medicinal product Relieve of headaches, muscle pain and muscle spasms in the neck, back and legs Danshen Capsules A traditional herbal medicinal product to relieve mild menstrual pain Herbal products as medicines Category Feasibility New (botanical) drug Costly and risky Medicines with well established use Not applicable to CHM products Traditional herbal medicinal products Possible but …… Herbal products as Food supplements? (+) Other substances: Amino acids, essential fatty acids, fiber, plant and herb extracts. = Positive list system ECJ validated Food Supplements Directive Positive list also for herbs etc. ? Decision on other substances delayed indefinitely Other substances: Amino acids, essential fatty acids, fiber, plant and herb extracts Plant food supplements National rules still apply Different FS administrative systems in EU Member States Country Notification Positive/Negative list Country Notification Positive/Negative list Austria No Both Latvia Yes No. (medicinal plant list) Belgium Yes Both Lithuania Yes No Bulgaria Yes Negative list Luxemburg Yes No Cyprus Yes No Malta Yes Negative list Czech Rep. Yes Negative list Netherlands No Negative list Denmark Yes Negative list (Norway) Yes Both Estonia Yes Negative list Poland Yes Both Finland Yes Negative list Portugal Yes No France Yes Positive list Romania Yes Both Germany Yes Both Slovakia Yes No Greece Yes No Slovenia Yes Both Hungary Yes Negative list Spain Yes No Ireland Yes No Sweden No Negative list Italy Yes Both UK No No Chinese herbs prohibited for use in food products in NL “Negative list” Herbs 中药名 Pharmaceutical Latin name 药材拉丁名 Plant Latin name 原植物拉丁名 Cao Wu 草 乌 Radix Aconiti Kusnezoffii Aconitum kusnezoffii Chuan Wu 川 乌 Radix Aconiti Aconitum carmichaeli Fu Zi 附 子 Radix Aconiti Preparata Aconitum carmichaeli Guan Mu Tong 关木通 Caulis Aristolochiae Manshuriensis Aristolochia manshuriensis Guang Fang Ji 广防己 Radix Aristolochiae Fangchi Aristolochia fangchi Huo Ma Ren 火麻仁 Fructus Cannabis Cannabis sativa Ma Dou Ling 马兜铃 Fructus Aristolochiae Aristolochia contorta Aristolochia debilis Ma Huang 麻 黄 Herba Ephedrae Ephedra spp. Ma Qian Zi 马钱子 Semen Strychni Strychnos nux-vomica Qing Mu Xiang 青木香 Radix Aristolochiae Aristolochia debilis Tian Xian Teng 天仙藤 Herba Aristolochiae Aristolochia debilis Aristolochia contorta Xi Xin 细 辛 Herba Asari Asarum heterotropoides Asarum sieboldii Yang Jin Hua 洋金花 Flos Daturae Datura metel Ying Su Qiao 罂粟壳 Pericarpium Papaveris Papaver somniferum • Novel foods: No history of “significant” consumption in the European Union prior to 15 May 1997. • Any food or food ingredient that falls within this definition must be authorized according to Regulation (EC) No 258/97. • Two routes of authorization: – Simplified application (only if substantially equivalent to an existing food or food ingredient): Supercritical CO2 extract of Hou Po (Magnolia officinalis) Bark – Full application: Flavonoids from Gan Cao (Glycyrrhiza glabra) Gou Qi Zi (Frucuts Lycii, Goji berry): A novel food candidate Goji berry: Old enough not to be new ! Powdered Ling Zhi mushroom capsules classified as a novel food Ling Zhi (Reishi, Ganoderma) is not a novel food! Evidence of use before May 1997 ? Herbal products as Medical devices ? What is a medical device? Classification and CE marking of medical devices Classification Risk Notification Class I Low risk Notification (self-certification) Claas IIa Medium-low risk Notified body Class IIb Medium-high risk Notified body Class III High risk Notified body Criteria for classification: – Invasiveness – Duration and contact – Active or non-active Type of CE Notified bodies • A notified body is an organization accredited by the national competent authority of a member state to carry out the conformity assessment procedures described in the annexes of the medical devices directives. • Applicant has a free choice of notified body. • Each notified body has an identification number. Notified bodies of medical devices How to obtain a CE-Mark? • Prepare a CE Marking Technical File that includes data demonstrating compliance with the applicable directives. • Establish and maintain a compliant Quality Management System (typically by implementing ISO 13485) if your medical device is class I provided sterile or has a measuring function, or Class IIa, IIb, III devices. • Obtain your CE certificates from a Notified Body, if applicable, or self-certify your compliance with the MDD (Class I non-sterile, non-measuring devices) or IVDD (general/other IVDs). Classification of medical devices Technical documentation • • • • • • • Intended use Mode of action Clinical and biological evaluation Classification and conformity assessment Declaration of conformity Description of the raw material Finished product • Production process • Composition • Specification • Packaging material • CE mark, Package leaflet, instruction manual Cranberry extract: A class IIa medical device to prevent and treat urinary tract infection Other (herbal) medical devices Weight management Liposinol™ contains Litramine®, a natural fibre complex derived from dehydrated leaves of a cactus (Opuntia ficus-indica). Liposinol™, with its ability to bind fats without any pharmacological action, is certified as a Class IIa medical device. Medical devices woth pharmacological action? Yes, however: Main action has to be achieved by physical means, but may be assisted by pharmacological, immunological, or metabolic actions Examples – – – – Bone cement with antibiotics Catheter coated with heparin Lens cleaner Wound dressing with antibacterial substances Herbal plaster a class I medical device ! Regulatory advantages of medical devices • Less time- and cost-intensive than drug registration • Less documentation • Strong medical claims are possible • With a CE-mark, the products can be distributed in all 30 EEA countries • Medical devices with herbals are an interesting alternative to herbal drug registration. Herbal products as Cosmetics ? Key requirements • • • • • Notification Responsible person Product information file Cosmetic product safety report No prohibited substances (Annex II: Aconitum, Rauwolfia serpentina, Atropa belladonna, Strychnos, …) • • • • Substances subject to restrictions (Annex III) Allowed colorants (Annex IV) No animal testing unless no validated alternative methods Labeling requirements valid from 5 February 2015 Legal trade of CITES listed species Appendix Degree of protection Permission for trade I Species threatened with extinction Export permit + Import permits II Species not necessarily threatened with extinction, but in which trade must be controlled in order to avoid utilization incompatible with their survival Export permit + (Import permits) III Species that are protected in at least one country, which has asked other CITES Parties for assistance in controlling the trade Export permit China asks to protect turtles ! Chinese herbs derived from protected species 来源于受国际公约保护的濒危动植物的中药品种 Herbs中药名 Pharm. Latin 药材拉丁名 Source plant/animal 原动/植物 备 注 Note Bai Ji 白及 Rhizoma Bletillae Bletilla striata Chen Xiang 沉香 Lignum Aquilariae Resinatum Aquilaria sinensis Gou Ji 狗脊 Rhizoma Cibotii Cibotium barometz (Hu Huang Lian) (胡黄连) Rhizoma Picrorhizae Picrorhiza kurrooa 中国药典品种 Picrorhiza scrophulariiflora不受保护 (芦荟) Aloe Aloe ferox 库拉索芦荟 Aloe barbadensis (A. vera) 不受保护 Mu Xiang 木香 Radix Aucklandis Aucklandia lappa Synonym Saussurea lappa, Saussurea costus (Ren Shen) (人参) Radix Ginseng Panax ginseng Only apply to the population of the Russian Federation Rou Cong Rong 肉苁蓉 Herba Cistanches Cistanche deserticola Shi Hu 石槲 Herba Dendrobii Dendrobium cruentum Tao Er Qi 桃耳七 Radix Podophylli Podophyllum emodi Tian Ma 天麻 Rhizoma Gastrodiae Gastrodia elata Xi Yang Shen 西洋参 Radix Panacis Quinquefolii Panax quinquefolium Chuan Shan Jia 穿山甲 Squma Manis Manis pentadactyla Gui Jia 龟甲 Carapax et Plastrum Testudinis Mauremys reevesii 动 Hai Ma 物 类 Hu Gu 海马 Hippocampus Hippocampus spp. 虎骨 Os Tigris Panthera tigris Ling Yang Jiao 羚羊角 Cornu Antelopis Saiga tatarica She Xiang 麝香 Moschus Moschus spp. Xi Niu Jiao 犀牛角 Cornu Rhinocerotis Rhinoceros spp. Xiang Ya 象牙 Dens Elephantis Elephas spp. Xiong Dan 熊胆 Fel Ursi Ursidae spp. 植 物 (Lu Hui) 类 PLANTS Synonym Podophyllum hexandrum Synonym Chinemys reevesii in Chinese Pharmaceopoeia ANIMALS Herbal products in the EU Legal category Medicines Requirements Marketing authorization Cost Claims High Medical claims Notification or no notification Food supplements Positive list entry Negative list restriction Low No medical claims Maybe health claims Medical devices Notification and CE-marking Medium Medical claims Cosmetics Notification Negative list restriction Low Cosmetic claims Legal status of Chinese herbal products in the Netherlands Foods Medicines Others Legal status of Chinese herbal products in the Netherlands Foods Medicines • Not in the negative list • No medical claims • Hygiene and contaminants control • Marketing authorization • GMP compliance • Post-marketing surveillance Others (medical devices, cosmetics) • Notification • Risk management RESTRICTED
