SALUS Case: Organic Medicinal Herbal Teas Cannot be Labelled as Organic

The legal framework governing the quality of (traditional) herbal medicinal products in the European Union

The legal framework governing the quality of (traditional) herbal medicinal products in the European Union

Medicinal plants have been used in health care since ancient times. Whereas therapeutic use of herbal medicinal products has a long tradition a formal regulation only started during last century. The European Union has established a common regulatory framework for (traditional) herbal medicinal products. Definitions and basic principles are laid down in Directive 2001/83 EC and its amendments. Quality, efficacy and safety of finished medicinal products have to be evaluated before being introduced into the market. Registration of traditional herbal medicinal products is simplified with respect to the proof of efficacy and data on safety. The Committee on Herbal Medicinal Products (HMPC) at the European Medicines Agency (EMA) in London was established in 2004 and has developed guidance on assessment of (traditional) herbal medicinal products. One of the major tasks of the HMPC is to establish harmonised community monographs on safety and efficacy of herbal substances or combinations. About 130 monographs have been finalised until 2014, representing a substantial progress of harmonisation in the European Union. The development of community monographs is a transparent process which is offering options for scientific input by interested parties. After adoption a complete package of monograph, assessment report, overview of comments and list of references is published at the website of EMA (www.ema.europa.eu). Basically, the provisions of Directive EC 2004/24 offer also options for traditional herbal medicinal products originating from non-European therapeutic systems. Moreover, applicants may seek scientific advice preferably in early developmental stages of professional projects. The HMPC started in its working programme a pilot project on monographs on efficacy and safety of herbal substances of non-European origin. Questions & Answers on the European Union regulatory framework for (traditional) herbal medicinal products, including those from a 'non-European' tradition, have been adressed in a specific document. Communication, scientific research and regulatory dialogue are necessary to improve the options for a harmonised global usage of traditional medicines.

This paper deals with the current regulatory and legal settings of traditional plant food supplements and herbal medicinal products in the European Union (EU). Marketing of botanicals in foods and food supplements in the EU is subject to several provisions of food law, which cover aspects of safety, production, labelling and product composition, including the use of additives and maximum levels of contaminants and residues. However, due to limited harmonization at the EU level, specific national regulations adopted at a Member State level also apply and mutual recognition is the mechanism through which such products can be marketed in EU countries other than those of origin. Unlike food supplements, marketing of traditional herbal medicinal products is regulated by an ad hoc Directive (i.e. Directive 2004/24/EC) covering in detail all the relevant aspects of these products, including a facilitated registration procedure at national level. However, by distinguishing traditional herbal medicinal products from plant food supplements and establishing selective marketing modalities for these two product categories, the EU has been confronted with implementation difficulties for traditional herbal medicinal products and a lack of homogeneity in the regulatory approaches adopted in different EU Member States. In fact, currently the nature of the commercial botanical products made available to consumers as traditional medicinal products or food supplements, depends largely on the EU Member State under consideration as a consequence of how competent National Authorities and manufacturing companies interpret and apply current regulations rather than on the intrinsic properties of the botanical products and their constituents. When the EU approach is compared with approaches adopted in some non-European countries to regulate these product categories, major differences become evident.

IntroductionThe use of the traditional herbal medicinal products (THMPs) has been increasing worldwide due to the readily availability of raw materials and low cost compared to the synthetic industrial preparations. With this trend in mind, the safety and quality of THMPs need to be addressed so as to protect the community. The present study evaluated the magnitude and risk factors associated with microbial contamination of liquid THMPs marketed in Mwanza.MethodsA cross-sectional study was conducted in Mwanza city involving 59 participants from whom 109 liquid THMPs were collected and processed following the standard operating procedures. The data were analyzed using STATA software version 11.ResultsThe median age (interquartile range) of participants was 35 (27-43) years, with males accounting for 36 (61%). Of 109 liquid THMPs collected, 89 (81.7%) were found to be contaminated; with predominant fecal coliforms being Klebsiella spp and Enterobacter spp. fortunately, no pathogenic bacteria like Salmonella spp and Shigella spp were isolated. There was a significant association of liquid THMPs contamination with low education level (p< 0.001), lack of formal training on THMPs (p = 0.023), lack of registration with the Ministry of Health (p = 0.001), lack of packaging of products (p < 0.001) and use of unboiled solvents during preparation of THMPs (p < 0.001).ConclusionThere is high contamination rate of liquid THMPs in Mwanza City which is attributable to individuals and system-centered factors. Urgent measures to provide education to individuals involved in THMPs as well as setting up policies and regulations to reinforce THMPs safety is needed.

Medicinal products from complementary and alternative medicine are in Germany a regular part of the health care system. Herbal, homeopathic, anthroposophic and traditional medicinal products are highly accepted by the population. The German Medicines Act obliged the competent authorities to consider the particular characteristics of complementary and alternative medicines. The European regulatory framework defined the status of herbal medicinal products, traditional herbal medicinal products and homeopathic medicinal products within the directive 2001/83/EC. The committee for herbal medicinal products (HMPC) was established at the European Medicines Agency in London (EMEA); for homeopathic medicinal products there is a specific working group established by the Heads of Medicines Agencies. Harmonisation of medicinal products from complementary and alternative and traditional medicine in Europe was enforced by implementation of directive 2001/83/EC in national legislations of member states. The provisions of this directive will substantially influence the development of the European market during the forthcoming years.

The European Directive 2004/24/EC has introduced a simplified registration procedure for traditional herbal medicinal products which plays an important role in harmonizing the current legislation framework for all herbal medicinal products in the European Union. Although substantial achievements have been made under this directive, only a limited number of herbal medicinal products from non-European traditions commonly used in Europe have been registered. Identification of the obstacles, and determination of appropriate means to overcome the major challenges in the registration of non-European traditional herbal medicinal products (THMP) are important for the EU herbal medicinal product market. Traditional Chinese Medicine (TCM) is one of the major non-European THMP in the European market. Key for acceptance of TCM is the ability to provide scientific evidence combined with a quality control system based on the bioactive ingredients. Modern scientific technology tools are now available to accomplish standardization of TCM products in order to achieve a high level of efficacy and safety, enhancing the introduction into the international markets. Despite the complexity of ingredients and the aspect of synergistic bioactivities in TCM, so far the analysis for quality control was mainly limited to major components for each herb without evidence for a direct relationship with the bioactive components. In a Systems Biology approach, the multi-dimensional chemical and pharmacological approach enables linking of the complex metabolic profile of herbs with biological effects and is, therefore, a key for quality control of TCM material medica, while providing simultaneous scientific evidence for the underlying efficacy and worldwide acceptance of TCM products. The root extract of Dioscorea nipponica is a well-known component in Traditional Chinese Medicine formula's. The bioactivity of this extract has been described in Chinese medicine as: (1) activating blood circulation to dissipate blood stasis (2) promoting qi circulation to relieve pain and muscle tension due to stress (3) relieving internal resistance of stagnant blood. In order to translate the explanatory system-level functionalities in Chinese medicine into a Western biochemical, functional and clinical understanding, an extensive series of pharmacological experiments was used to obtain insights in various effects of prevention and treatment in the cardiovascular domain. Moreover, the active component profile consisting of saponins was studied and found to be of a system synergetic nature. Integrating this information with the outcome of clinical trials in which over 16.000 patients were involved together with results from over 100 million people treated, yielded a systems pharmacological view on the working mechanism and insights in the effectiveness and safety profile of this product produced and controlled under GALP and GMP. This product was the first tHMP herbal medicine product registered in the EU that was produced in China. It underpins a new view on evaluation of herbal medicine products in general and creates an important systems pharmacology concept applicable in a wider sense.

According to legislation of EU, as well as of our country, herbal medicinal products (HMPs) and traditional herbal medicinal products (THMPs) are categories of medicinal products. As active ingredients, they contain herbal drugs (herbal substances) and/or herbal drug preparations (herbal preparations). HMPs are authorized based on proved quality, clinical efficacy and safety. THMPs are registered based on proved quality and sufficient data on traditional use (acceptable safety level and plausible efficacy). The Committee on Herbal Medicinal Products (HMPC) of the European Medicines Agency (EMA) publishes EU herbal monographs, which comprise preclinical and clinical data on HMPs with well-established use (WEU), as well as data on traditional use (TU) for THMPs. HMPC also develops drafts of EU list entries for THMPs, which are adopted and their final versions are published by the European Commission. By the end of July 2019, HMPC issued 160 final monographs, which are available on the EMA website (157 monographs for 156 herbal drugs and herbal drug preparations, two monographs for two herbal drug combinations, and monograph for herbal tea combinations); EU list entries on 13 herbal drugs and preparations were finalized. This paper provides an overview of the therapeutic areas and indications approved in these final EU monographs. In addition, overview of HMPs and THMPs, which are authorized/registered in the Republic of Serbia is given.

European regulation of herbal medicinal products on the border area to the food sector

An assessment of genotoxicity is a precondition for marketing authorization respectively registration of herbal medicinal products (HMPs), as well as for inclusion into the ‘Community list of herbal substances, preparations and combinations thereof for use in traditional herbal medicinal products’ established by the European Commission in accordance with Directive 2001/83/EC as amended, and based on proposals from the Committee on Herbal Medicinal Products (HMPC).In the ‘Guideline on the assessment of genotoxicity of herbal substances/preparations’ (EMEA/HMPC/107079/2007) HMPC has described a stepwise approach for genotoxicity testing, according to which the Ames test is a sufficient base for the assessment of genotoxicity in case of an unequivocally negative result. For reducing efforts for testing of individual herbal substances/preparations, HMPC has also developed the ‘guideline on selection of test materials for genotoxicity testing for traditional herbal medicinal products/herbal medicinal products’ (EMEA/HMPC/67644/2009) with the aim to allow testing of a standard range of test materials which could be considered representative of the commonly used preparations from a specific herbal drug according to a ‘bracketing/matrixing’ approach.The purpose of this paper is to provide data on the practical application of this bracketing and matrixing concept using the example of Valerianae radix, with the intention of facilitating its inclusion in the “Community list”. Five extraction solvents, representing the extremes of the polarity range and including also mid-range extraction solvents, were used, covering the entire spectrum of phytochemical constituents of Valerianae radix, thereby including polar and non-polar constituents. Extracts were tested in the Ames test according to all relevant guidelines. Results were unequivocally negative for all extracts. A review of the literature showed that this result is in accordance with the available data, thus demonstrating the lack of a genotoxic potential.In conclusion the two guidelines on genotoxicity provide a practically applicable concept. Valerianae radix has no genotoxic potential, supporting its use in HMPs and its inclusion in the Community list.

Directive 2004/24/EC of the European Parliament and the Council entered into force on April 30th, 2004. After 7 years, there is no Chinese medicine to be registered successfully in European market as traditional herbal medicinal products. The thesis gives some ideas to tackle this problem. Procedure for the Preparation of Community Monographs for Traditional Herbal Medicinal Products (EMEA/HMPC/182320/2005) published by European Medicines Agency is an important guidance for traditional herbal products to enter European Community monographs. The thesis introduces and details the procedure as well as gives feasible suggestions about the procedure. It suggests that Chinese medicines enter European Community monographs first, and then apply the registration according to the directive 2004/24/EC. This is an easier access to European market. Key words: Chinese medicines; European Community monographs; Directive 2004/24/EC; Traditional herbal medicinal products

From medical tradition to traditional medicine: A Tibetan formula in the European framework

The European legislation on medicinal products also addresses the medicinal use of products originating from plants. The objective of the legislation is to ensure the future existence of such products and to consider particular characteristics when assessing quality, efficacy, and safety. Two categories are defined: i) herbal medicinal products can be granted a marketing authorisation; and ii) traditional herbal medicinal products can be granted a registration based on their longstanding use if they are complying with a set of provisions ensuring their safe use. The Committee on Herbal Medicinal Products (HMPC) was established at the European Medicines Agency (EMA) to provide monographs and list entries on herbal substances and preparations thereof. Meanwhile, approx. 100 monographs have been published, which define a current scientific and regulatory standard for efficacy and safety of herbal substances and herbal preparations used in medicinal products. This harmonised European standard will facilitate the availability and adequate use of traditional herbal medicinal products and herbal medicinal products within the European Union. Consequent labelling shall also enable patients and health care professionals to differentiate medicinal products from other product categories like cosmetics, food supplements, and medical devices.

Traditional medicine is an important part of human health care in many developing countries and also in developed countries, increasing their commercial value. Although the use of medicinal plants in therapy has been known for centuries in all parts of the world, the demand for herbal medicines has grown dramatically in recent years. The world market for such medicines has reached US $ 60 billion, with annual growth rates of between 5% and 15%. Researchers or companies may also claim intellectual property rights over biological resources and/or traditional knowledge, after slightly modifying them. The fast growth of patent applications related to herbal medicine shows this trend clearly. This review presents the patent applications in the field of natural products, traditional herbal medicine and herbal medicinal products. Medicinal plants and related plant products are important targets of patent claims since they have become of great interest to the international drug and cosmetic industry.

Herbal medicines have a long tradition of therapeutic use. However, they may occasionally cause dose-related (type A) or idiosyncratic (type B) toxicity and herb-drug interactions are also possible. Toxicity can arise as a result of misidentification or adulteration of the preparation. Legislation (the Directive on traditional herbal medicinal products 2004/24/EC) was enacted on 30 April 2004 to improve public health protection and promote the free movement of traditional medicinal products in the EU. It requires each Member State to set up a simplified registration scheme for manufactured traditional herbal medicines that are suitable for use without medical supervision. Evidence of 30 years of traditional use, at least 15 years of which should normally be within the EU, is required to permit minor claims, replacing the requirement to demonstrate efficacy. Safety is based on evidence in the published literature, although the regulator can also ask for more data if there are safety concerns. The pharmacovigilance requirements and quality standards are the same as for licensed medicines. Patient information is similar to that for any over-the-counter medicine, with an additional requirement for a statement on labels and in advertisements that the indication is based on traditional use. A European positive list of herbal substances will set out the indication, strength, dosing recommendations, route of administration and other information on safe use. Where a product complies with the list, the applicant will not need to demonstrate either the traditional use or the safety of the product. The list will be compiled by the recently established Committee on Herbal Medicinal Products at the European Medicines Agency. EU Member States were required to comply with the Directive by 30 October 2005. Traditional herbal medicinal products already on the market when the Directive became law need not comply with its provisions for 7 years after its coming into force. The public need to be aware that 'natural' does not necessarily mean 'safe' in all circumstances. They should be fully informed about all medicines they take. Consideration also needs to be given to effective regulation of herbal medicines practitioners, so that they are identifiable in law, are governed by professional codes of practice and have agreed standards of training and competency. There are many references to herbal medicines in Shakespeare's tragedy, Romeo and Juliet, which was written around 1595. A herbal medicine (distilled liquor) was almost certainly used to put Juliet into a deep sleep. A poison, possibly of herbal origin, was used by Romeo to take his own life when he thought his beloved Juliet was dead, rather than sleeping. While European herbal medicines regulation seeks to protect the public health by ensuring the necessary guarantees of quality, safety and efficacy, it was poor communication that appears to have triggered the chain of events leading to the death of Romeo and Juliet. Good communication between regulators, practitioners, patients and the public is necessary so that those who choose to take herbal medicines can do so with acceptable safety.