Medicinal plants and their preparations in the European market: Why has the harmonization failed? The cases of St. John's wort, valerian, ginkgo, ginseng, and green tea.

BACKGROUND: Botanical ingredients based on plants, algae, fungi or lichens have become widely available on the European Union market offering numerous preparations with considerable differences in classification. They are under the categories of food supplements, herbal medicinal products, cosmetics or medical devices. PURPOSE: The aim of the present work is to highlight how the European regulations concerning the different categories of botanicals can lead to different commercial choices such as time/cost for product development, application for a marketing authorisation, permitted indication (medical or health claim), and as a consequence, the same botanical products are sold in European Union as herbal medicinal products, food supplements, cosmetics or medical devices. Five different widely used botanicals, namely St. John's wort, valerian, ginkgo, ginseng, and green tea were selected to better explain the failure of harmonization through European Union. METHODS: A search of PubMed, ScienceDirect, European Medicines Agency and European commission web sites for medical devices and cosmetics, and European Food Safety Authority websites were conducted and the available information on regulation of herbal medicinal products, food supplements, medical devices and cosmetics in the European Union was collected. In addition, a market survey of all the sold botanical products in Europe was analysed by consultation of the medicines, medical devices, cosmetic and food agencies websites of the European countries. RESULTS: The current European legislation needs implementation and follow up because in the different countries the legal positions of the botanical products varied and it is possible to find the same product classified in the different categories, namely registered medicinal product including prescription only medicine, traditional herbal medicinal product, well established herbal medicinal products or food supplement, or medical device, or homoeopathic/anthroposophical medical product, cosmetic. CONCLUSIONS: There is an urgent need of harmonization, together with the implementation of interoperable vigilance databases, to avoid borderline options.

A Review of Regulations Applied to Spices, Herbs, and Flavorings-What Has Changed?

A review of the world-wide regulations pertaining to spices, extracts, and flavorings. The areas covered include (1) guidance documents from trade organizations as well as international and regional regulatory bodies, (2) decontamination of spices and herbs, (3) extraction solvents used to make spice and herb oleoresins, and (4) general flavoring regulations. Specific links and references to guidance documents and regulations have been provided where they have been published on government, organization, and trade association websites.

Unexpected healers: Chinese medicine in the age of global migration (Lima and California, 1850-1930). / Sanadores inesperados: medicina china en la era de migración global (Lima y California, 1850-1930).

The massive waves of Chinese migrants arriving in California and Lima in the second half of the nineteenth century played a crucial role in expanding Chinese medicine in both settings. From the late 1860s on, herbalists expanded their healing system beyond their ethnic community, transforming Chinese medicine into one of the healing practices most widely adopted by the local population. This article uses a comparative approach to examine the diverging trajectories of Chinese healers in Peru and the USA, as well as the social and political factors that determined how this foreign medical knowledge adapted to its new environments.

European regulation model for herbal medicine: The assessment of the EU monograph and the safety and efficacy evaluation in marketing authorization or registration in Member States.

BACKGROUND: The European Union (EU) has created a regulatory framework for herbal medicinal products (HMPs) since the enforcement of Directive 2004/24/EC. Substantial achievements have been made, with 1719 traditional use marketing registrations (TURs) and 859 well-established use marketing authorizations (WEU-MAs) for HMPs granted by the end of 2016. Apparently, the European regulation model has worked out well and in that the essential feature is the use of EU herbal monographs into those granted WEU-MAs and TURs. PURPOSE: A systematic analysis of the European regulation model for HMPs and the EU herbal monograph's part of this model are undertaken to assist understanding of the EU legislation particularly for interested parties those from outside EU area, and afterwards, to help in decision-making in the HMPs registration in European market for pharmaceutical companies, as well as in the establishment of legislation in countries with strong traditional use of herbal remedies. METHODS: A search of PubMed, ScienceDirect, the European Medicines Agency website and the Heads of Medicines Agencies website was conducted (up to December 2017), and the available information on regulation of HMPs in the EU was collected. RESULTS: The evaluation of applications by National Competent Authorities (NCAs) at a national level together with the assessment of EU monographs by the Committee on Herbal Medicinal Products (HMPC) at the European level constitute the European regulation framework for HMPs. As the scientific opinion about the safety and efficacy of HMPs from HMPC, the EU herbal monographs have been given a constitutional-based meaning to the TURs and WEU-MAs of HMPs and play a supportive function in the marketing procedure in Member States. CONCLUSION: The European framework has provided a powerful regulation model for harmonization of scientific assessment and facilitation of product marketing. For the pharmaceutical industries particularly those outside the EU, optimal use of the EU herbal monograph in their marketing procedure in Europe could be of great benefit. Furthermore, this model is well worth learning from for other countries and regions outside the EU to help the establishment of legislation in countries with strong traditional use of herbal remedies and contribute to the safe use of traditional herbal medicine.

Sanadores inesperados: medicina china en la era de migración global (Lima y California, 1850-1930) / Unexpected healers: Chinese medicine in the age of global migration (Lima and California, 1850-1930)

Resumen Las masivas olas de migrantes chinos que llegaron a California y Lima en la segunda mitad del siglo XIX jugaron un rol clave en la expansión de la medicina china en ambos contextos. Desde fines de la década de 1860, los herbolarios expandieron su sistema de sanación más allá de su comunidad étnica, transformando la medicina china en una de las prácticas de sanación más adoptada por la población local. Desde una perspectiva comparada, este artículo examina las divergentes trayectorias de los sanadores chinos en Perú y EEUU, así como los factores sociales y políticos que determinaron la adaptación de este conocimiento médico, foráneo, en su nuevo entorno.

Abstract The massive waves of Chinese migrants arriving in California and Lima in the second half of the nineteenth century played a crucial role in expanding Chinese medicine in both settings. From the late 1860s on, herbalists expanded their healing system beyond their ethnic community, transforming Chinese medicine into one of the healing practices most widely adopted by the local population. This article uses a comparative approach to examine the diverging trajectories of Chinese healers in Peru and the USA, as well as the social and political factors that determined how this foreign medical knowledge adapted to its new environments.

Benefits and Limitations of DNA Barcoding and Metabarcoding in Herbal Product Authentication.

INTRODUCTION: Herbal medicines play an important role globally in the health care sector and in industrialised countries they are often considered as an alternative to mono-substance medicines. Current quality and authentication assessment methods rely mainly on morphology and analytical phytochemistry-based methods detailed in pharmacopoeias. Herbal products however are often highly processed with numerous ingredients, and even if these analytical methods are accurate for quality control of specific lead or marker compounds, they are of limited suitability for the authentication of biological ingredients. OBJECTIVE: To review the benefits and limitations of DNA barcoding and metabarcoding in complementing current herbal product authentication. METHOD: Recent literature relating to DNA based authentication of medicinal plants, herbal medicines and products are summarised to provide a basic understanding of how DNA barcoding and metabarcoding can be applied to this field. RESULTS: Different methods of quality control and authentication have varying resolution and usefulness along the value chain of these products. DNA barcoding can be used for authenticating products based on single herbal ingredients and DNA metabarcoding for assessment of species diversity in processed products, and both methods should be used in combination with appropriate hyphenated chemical methods for quality control. CONCLUSIONS: DNA barcoding and metabarcoding have potential in the context of quality control of both well and poorly regulated supply systems. Standardisation of protocols for DNA barcoding and DNA sequence-based identification are necessary before DNA-based biological methods can be implemented as routine analytical approaches and approved by the competent authorities for use in regulated procedures. © 2017 The Authors. Phytochemical Analysis Published by John Wiley & Sons Ltd.

Do We Need Plant Food Supplements? A Critical Examination of Quality, Safety, Efficacy, and Necessity for a New Regulatory Framework.

Given the expanding market of plant food supplements (PFSs) not undergoing any pre-marketing authorization, the overall quality, safety and efficacy of PFSs were subjected to a critical examination. Although many high-quality PFSs exist on the legal market, quality concerns are in general justified. Besides economic adulteration, active ingredients dramatically differing from label claims and among products were reported in several studies. In addition, PFSs sold via the Internet may be intentionally adulterated with undeclared prescription drugs. Compared to PFSs with only one single herb, PFSs containing herbal mixtures were more involved in moderate and severe clinical courses. Although prohibited by regulation, misleading labels on PFSs are common. Above all, only vague evidence for the efficacy of PFSs exists. Notwithstanding the unproven efficacy and insufficient safety assessment, PFSs represent a relevant source for consumers to get access to herbal preparations in the United States and meanwhile also in Europe, as launching of licensed/registered European herbal medicinal products (HMPs) has steadily decreased. However, being non-vitamin, non-mineral products, PFSs are neither food nor drugs. In terms of protecting public health and providing the consumer with high-quality, effective, and safe PFSs, possibilities are shown how to deal with the many challenges of PFSs. Last but not least, suggestions are made for assigning PFSs a separate regulatory category being less regulated compared to HMPs but more strictly regulated compared to food laws including implementation of good manufacturing practices and a scientific pre-marketing review process by an expert commission.

The Brazilian market of herbal medicinal products and the impacts of the new legislation on traditional medicines.

ETHNOPHARMACOLOGICAL RELEVANCE: the herbal medicinal products (HMP) market is expanding in the world, an expansion that has not occurred in Brazil when considering the number of licensed products. Despite being a megadiverse country, the number of HMP licensed in Brazil is small, and the number of HMP obtained from native species is even smaller. A new legislation for herbal products licensing, which divides the products into two categories, Herbal Medicine (HM) and Traditional Herbal Product (THP) was launched in Brazil focusing on traditional use, as well as a law regulating the use of biodiversity and traditional knowledge. AIM OF THE STUDY: to evaluate the situation of HMP licensed in Brazil and to make a comparison with the data obtained in 2008 and 2011, discussing the evolution of the licensed products and the possible impacts of the new legislation. MATERIALS AND METHODS: a survey was carried out in the Brazilian Health Regulatory Agency (Anvisa) database to verify the HMP licensed in Brazil in September 2016. The data obtained were compared with two surveys previously published. RESULTS: There are 332 single, and 27 combined HM, totaling 359 HM licensed in Brazil. There is no THP notified in Anvisa's system yet. There are 214 HM classified as nonprescription (OTC), while 145 are sold under prescription, one of them with prescription retention. There are 101 plant species licensed as active in HM in Brazil, 39 of which are native, adapted or cultivated. The most licensed plant species is Mikania glomerata Spreng., with 25 HM licensed. The article includes tables with plant species that have derivatives licensed as simple and combined HM, their therapeutic classification, the native plant species indication and the distribution of the companies by Brazilian regions. CONCLUSIONS: There are few licensed HM in Brazil, and this number has been decreasing in recent years. It is expected that the data obtained, together with the changes promoted in sanitary and environmental rules, will help to develop and regulate HMP chain in Brazil.

[Analysis of difficult problems on European Union laws and regulations of traditional herbal medicinal products].

Registration of Chinese patent medicine in European Union (EU) is of great significance to the internationalization of traditional Chinese medicine as EU market acts as an important position in the global botanical market. In retrospect, the domestic studies on EU regulations of traditional herbal medicinal products have been conducted for more than 10 years, but there is still some cognitive bias and lack of research. In this paper, a review of the relevant research progress and the main misunderstanding problems about Directive 2004/24/EC, like the centralized and decentralized supervision system of traditional herbal medicinal products in the EU, marketing authorization procedures for traditional herbal medicinal products, Community Herbal Monograph and List Entries, would be systematically analyzed, so as to provide reference for the registration of Chinese patent medicine in EU.

[European Union regulatory and quality requirements for botanical drugs and their implications for Chinese herbal medicinal products development].

This paper introduces regulatory pathways and characteristic quality requirements for marketing authorization of herbal medicinal products in the European Union（EU）, and the legal status and applications of "European Union list of herbal substances, preparations and combinations" and "European Union herbal monographs". Also introduced are Chinese herbs that have been granted the EU list entry, those with EU herbal monographs, and registered EU traditional herbal medicinal products with Chinese herbs as active ingredients. Special attention is paid to the technical details of three authorized EU herbal medicinal products (Veregen, Sativex and Episalvan) in comparison with Andrographis paniculata extract HMPL-004 that failed the phase Ⅲ clinical trial for ulcerative colitis. The paper further emphasizes the importance of enriching active fractions of herbal extracts and taking regulatory and quality considerations into account in early stage of botanical drug development.

POLITICS OF BIOPIRACY: AN ADVENTURE INTO HOODIA/XHOBA PATENTING IN SOUTHERN AFRICA.

BACKGROUND: Africa is being described as the wretched of the earth, despite this, the continent is endowed with natural resources, dynamic ecosystem, and different species of plants and animals, and species derivatives. This paper area of departure is to focus on Hoodia, a plant that is being a source of food, medicine and water for the San and Khoe indigenous peoples before the advent of Europeans into southern Africa. South African Council for Scientific and Industrial Research (CSIR) dubiously patented Hoodia without observing the basic indices of geographical indications (GIs), indigenous knowledge (IK), novelty, access sharing benefit (ASB), prior informed consent (PIC) and sustainability of ecosystem before the rights was sold to Phytopharm pharmaceutical company. MATERIALS AND METHODS: This article adopts neoliberal thesis with emphasis on complex interdependence theory of organic linkages between developing and developed countries. Secondary sources of information taken into account of qualitative and critical discuss content analyses dominate this paper. RESULT: The paper recommends a linkage between developed and developing states based on endowment theory and comparative advantage with the notion of adhering to the Convention on Biological Diversity (CBD) which has three objectives: the conservation of biodiversity; the sustainable utilisation of indigenous biological resources (IBR); and fair and equitable benefit sharing. CONCLUSION: The paper recommends that there is a need to follow CBD and other relevant international regimes that promote equal exchange in exploitation of Africa resources as against the present skewed arrangement that is in favour of multinational corporations (MNCs).

What risks do herbal products pose to the Australian community?

Traditional herbal products are widely used in Australia to treat a broad range of conditions and diseases. It is popularly believed that these products are safer than prescribed drugs. While many may be safe, it is worrying that the specific effects and harmful interactions of a number of their components with prescription medications is not well understood. Some traditional herbal preparations contain heavy metals and toxic chemicals, as well as naturally occurring organic toxins. The effects of these substances can be dire, including acute hepatic and renal failure, exacerbation of pre-existing conditions and diseases, and even death. The content and quality of herbal preparations are not tightly controlled, with some ingredients either not listed or their concentrations recorded inaccurately on websites or labels. Herbal products may also include illegal ingredients, such as ephedra, Asarum europaeum (European wild ginger) and endangered animal species (eg, snow leopard). An additional problem is augmentation with prescription medications to enhance the apparent effectiveness of a preparation. Toxic substances may also be deliberately or inadvertently added: less expensive, more harmful plants may be substituted for more expensive ingredients, and processing may not be adequate. The lack of regulation and monitoring of traditional herbal preparations in Australia and other Western countries means that their contribution to illness and death is unknown. We need to raise awareness of these problems with health care practitioners and with the general public.

The legislative and regulatory framework governing herbal medicine use and practice in Kenya: a review.

Complementary and alternative medicine is an integral component of primary healthcare in Kenya. This is because the infrastructural health setup in the country is inadequate in catering for all the medical needs of the population. This particularly holds true in the rural areas where many rural folk rely on products of herbal origin to offset their healthcare needs. More often than not these products are an elaborate cacophony of several different substances of biological origin and thus need personnel adept in their preparation. Sadly, due to loopholes in legislation and regulation, quacks have a field day in the practice. Moreover, the process of planting, harvesting, preparation and storage of herbs and related products dictates that a significant number of people will ultimately be involved in the whole process. This is likely to set the stage for manipulation and compromise of the safety, quality and efficacy of these products. This state of affairs appears unabated especially in the context of the current legal and regulatory framework governing herbal medicine use and practice in Kenya. Not only are these laws inadequate, they are shrouded in ambiguity, open to interpretation and the authorities mandated to implement them often end up performing duplicate roles. The aim of this review is to critique the legal and regulatory provisions governing herbal medicine use and practice in Kenya. In conclusion, laws and regulations meant to control herbal medicine use and practice in Kenya are wanting. Clear and definitive legislation on herbal medicine use and practice coupled with effective implementation by mandated institutions will go a long way in inspiring confidence to all stakeholders of herbal medicine.

An overview of herb and dietary supplement efficacy, safety and government regulations in the United States with suggested improvements. Part 1 of 5 series.

This is the first of five review articles investigating dietary supplements (DS; includes herbs) that now exceed over 50,000 in the Office of Dietary Supplement's "Dietary Supplement Label Database." Four review articles follow summarizing published medical case reports of DS related to liver toxicity, kidney toxicity, heart toxicity, and cancer. The most popular DS were vitamin or mineral supplements (43%) followed by specialty supplements (20%), botanicals (20%; herbs), and sports supplements (16%). The 2013 Annual Report of the American Association of Poison Control Centers revealed 1692 fatalities due to drugs, and zero deaths due to DS. Less than 1 percent of Americans experience adverse events related to DS, and the majority was classified as minor, with many of these related to caffeine, yohimbe, or other stimulant ingredients. The number one adulterant in DS is drugs, followed by New Dietary Ingredients (NDI) not submitted to the FDA - both are illegal and not DS, but rather "tainted products marketed as dietary supplements." The three main categories of DS prone to medical problems are those for sexual enhancement, weight loss, and sports performance/body building. DS are regulated in the U.S. by several federal agencies with overlapping jurisdiction - the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC); enforced by the State Attorneys General Offices (AGO) and Department of Justice (DOJ); and monitored (not regulated) by the Centers for Disease Control and Prevention (CDC). The FDA can remove a DS from the market for phase IV post-marketing surveillance adverse event reports, adulteration (drugs, NDI, synthetic substances), contamination, misidentification, mislabeling or false claims, and not meeting good manufacturing practices (GMP). The FTC and state AGO can also enforce laws against deceptive marketing practices. Suggested improvements to current regulatory requirements are included along with online DS Toxic Tables in the series to forewarn consumers, clinicians, corporations, and governments of possible serious adverse events. They may also quicken the response rate during Phase IV post-marketing surveillance, in which governments could then exercise their regulatory powers.

The legislative and regulatory framework governing herbal medicine use and practice in Kenya: a review

Complementary and alternative medicine is an integral component of primary healthcare in Kenya. This is because the infrastructural health setup in the country is inadequate in catering for all the medical needs of the population. This particularly holds true in the rural areas where many rural folk rely on products of herbal origin to offset their healthcare needs. More often than not these products are an elaborate cacophony of several different substances of biological origin and thus need personnel adept in their preparation. Sadly, due to loopholes in legislation and regulation, quacks have a field day in the practice. Moreover, the process of planting, harvesting, preparation and storage of herbs and related products dictates that a significant number of people will ultimately be involved in the whole process. This is likely to set the stage for manipulation and compromise of the safety, quality and efficacy of these products. This state of affairs appears unabated especially in the context of the current legal and regulatory framework governing herbal medicine use and practice in Kenya. Not only are these laws inadequate, they are shrouded in ambiguity, open to interpretation and the authorities mandated to implement them often end up performing duplicate roles. The aim of this review is to critique the legal and regulatory provisions governing herbal medicine use and practice in Kenya. In conclusion, laws and regulations meant to control herbal medicine use and practice in Kenya are wanting. Clear and definitive legislation on herbal medicine use and practice coupled with effective implementation by mandated institutions will go a long way in inspiring confidence to all stakeholders of herbal medicine

The legislative and regulatory framework governing herbal medicine use and practice in Kenya: a review

Complementary and alternative medicine is an integral component of primary healthcare in Kenya. This is because the infrastructural health setup in the country is inadequate in catering for all the medical needs of the population. This particularly holds true in the rural areas where many rural folk rely on products of herbal origin to offset their healthcare needs. More often than not these products are an elaborate cacophony of several different substances of biological origin and thus need personnel adept in their preparation. Sadly, due to loopholes in legislation and regulation, quacks have a field day in the practice. Moreover, the process of planting, harvesting, preparation and storage of herbs and related products dictates that a significant number of people will ultimately be involved in the whole process. This is likely to set the stage for manipulation and compromise of the safety, quality and efficacy of these products. This state of affairs appears unabated especially in the context of the current legal and regulatory framework governing herbal medicine use and practice in Kenya. Not only are these laws inadequate, they are shrouded in ambiguity, open to interpretation and the authorities mandated to implement them often end up performing duplicate roles. The aim of this review is to critique the legal and regulatory provisions governing herbal medicine use and practice in Kenya. In conclusion, laws and regulations meant to control herbal medicine use and practice in Kenya are wanting. Clear and definitive legislation on herbal medicine use and practice coupled with effective implementation by mandated institutions will go a long way in inspiring confidence to all stakeholders of herbal medicine

Innovation in Phytotherapy: Is a New Regulation the Feasible Perspective in Europe?

Classical multicomponent preparations mostly derived from traditional usages in Western and Eastern phytotherapy have been under-evaluated for a long time as potential new pharmaceutical products. The regulatory scenario, in particular at the European level, has only recently considered these aspects proposing harmonized guidelines for the pharmaceutical registration of traditional herbal products. Nevertheless, a specific regulation for innovative products based on the combination of precious knowledge arising from traditional usages and modern scientific advancements is still missing. In this paper, we propose a critical review of the current situation with the specific aim of contributing to create a more favorable regulatory environment for the pharmaceutical registration of new and innovative herbal medicinal products.

Herbal Medicine in Mexico: A Cause of Hepatotoxicity. A Critical Review.

In Mexico, herbal products are commonly used as therapeutic tools. The analysis of several publications reveals that there are dozens of different herbs and herbal products used for different reasons, some of which have been implicated in causing toxic liver disease. However, methodological aspects limit the attribution of causality, and the precise incidence and clinical manifestations of herb-induced liver injury have not been well characterized. This review outlines the history of traditional herbal medicine in Mexico, critically summarizes the mechanisms and adverse effects of commonly used herbal plants, and examines the regulatory issues regarding the legal use of these products.