By Michael Heinrich, PhD
In 2004 the European Union (EU) established a simplified registration procedure for traditional herbal medicinal products (THMPs) for human use (Directive 2004/24/EC), which requires all such products to be registered nationally. Many EU member countries have had registration and/or licensing procedures in place that covered most or all herbal medicinal products, the United Kingdom (UK) has had a largely unregulated market. On February 27, 2007, the School of Pharmacy at the University of London hosted a one-day symposium titled “Traditional Herbal Medicines: Opportunities and Challenges for the Future.” The purpose of the symposium was to discuss the implications of these recent changes to the British regulations for herbal medicinal products. It featured nine presentations delivered by experts from the regulatory authorities, academia, and industry.
The symposium was organized by this writer and Richard Middleton, PhD, from the British Herbal Medicine Association, in collaboration with the Association of Pharmaceutical Sciences of Great Britain, the Society for Medicinal Plant Research, and the International Society for Ethnopharmacology. William Ransom & Sons, a manufacturer of nutraceuticals and phytomedicines, sponsored the event. About 180 delegates more or less equally drawn from academia and industry attended, with delegates mainly from the UK but also from other countries including Canada, Finland, Germany, Ireland, Spain, Switzerland, and Thailand.
According to Middleton, herbal medicines have long existed as a popular health care choice in the UK. In recent years, their safety and efficacy have come under increased scrutiny. Under the new Directive, all manufactured THMPs are required to be registered under the Traditional Herbal Medicines Registration Scheme (THMRS, European Directive 2004/24/EC).
This has important implications for the UK’s healthcare sector. Producers, wholesalers, and retailers have until 2011 to register products under this new framework, and products that do not have a registration by then will have to be withdrawn from the market. Thus, the UK’s largely unregulated market for herbal medicinal products will be transformed to one that regulates the quality and safety of such products and also requires appropriate procedures for pharmacovigilance (adverse event reporting). In the opinion of this writer, the future of the UK herbal industry is positive, provided that companies adapt to the new framework, plan and choose service providers wisely, and implement their registration programs expeditiously. Only about four years are left until the end of the transition period, and thus the industry not only needs to ensure that the relevant studies for specific products are initiated (e.g., on product stability) but also that these studies comply with the regulatory requirements.
Richard Woodfield from the Medicines and Healthcare products Regulatory Agency (MHRA) focused his presentation on legal and administrative matters. The new Directive is now legally binding and a registration scheme is in place. The THMRS requires manufacturers, importers, and wholesale dealers to obtain product registration for all herbal medicinal products available in the UK. Applicants must provide evidence to prove that the product (or an equivalent product) has been in use as a traditional medicinal product in the EU for a period of at least 30 years (or, alternatively, 15 years in the EU plus 15 years outside of the EU). It is not possible to make claims about the product’s efficacy but only about its traditional use. A company must submit a bibliographic review of safety data, justification for the application under this procedure, and a dossier describing quality assurance. Pharmacovigilance is a legal requirement. Importantly, this process establishes that the quality of a medicinal product is independent of its traditional use. In short, all general principles of quality control, good manufacturing practice, and good distribution practice now apply to traditional medicinal products for human use. Two product registrations have already been granted: (1) an arnica (Arnica montana, Asteraceae) gel for topical application and (2) a devil’s claw (Harpagophytum procumbens, Pedaliaceae) root extract for use in chronic pain and inflammation. An advisory committee has been established at the MHRA to give independent expert advice. However, Mr. Woodfield raised concerns that some sectors of the UK’s herbal industry are not yet engaged in the legislative changes and that the MHRA faces a huge challenge to change the culture in a medicines sector that has become accustomed to operating in a largely unregulated environment.
According to Linda Anderson, PhD, also from the MHRA, while many current herbal medicinal products are already assessed and monitored appropriately, others exist that are not of an acceptable quality, giving the products in general a bad name. Examples of poor quality medicines include products that contain, in addition to the herbal product, heavy metals or pharmaceutical drugs like glucocorticoids or sildenafil. Clearly one needs to be concerned about the potential impact on public health of such poor quality products in an unregulated market. However, ensuring the quality of herbal medicinal products (HMPs) presents a number of unique challenges compared with conventional pharmaceutical formulations. At their simplest HMPs will contain one herbal substance or herbal preparation but this in turn will consist of a complex mixture of phytochemical constituents. Also, as is the case with many traditional HMPs, especially in Ayurvedic and Traditional Chinese Medicines, the product contains a mixture of different herbal materials. Mixtures of six or more ingredients are not uncommon.
New responsibilities are being placed on phytomedicinals, a point stressed by all speakers. There are implications for the entire production and distribution process, from growing botanical materials, processing, extraction, formulation, storage and use, an area covered by Keith Helliwell, PhD, from William Ransom & Son plc and by Colin Newbould, PhD, from Essential Nutrition Ltd. The legislation will also influence the health profession’s continuous professional development initiatives.
According to Dr. Romanus Lehnfeld from Phytolab GmbH & Co, pharmacovigilance is difficult in a sector dominated by small- and medium-sized companies; one option is the outsourcing of monitoring of the relevant literature. In Germany, the largest European market for herbal medicinal products, two products have so far been registered under the new procedure: (1) a bitter aromatic carminative/digestive (Klosterfrau® Melissengeist) and (2) a hawthorn (Crataegus spp., Rosaceae) tea for the supplementary treatment of mild cardiac problems. This was pointed out by Professor Werner Knoess from the German regulatory authority, the Federal Institute for Drugs and Medical Devices. Professor Knoess stated that the interpretation of the Directive differs in the various member countries and a continued dialogue between the interested parties in all member countries is needed.
Professor Philip Routledge from the University of Cardiff placed the current regulatory practices into a broader historical context. Regulation of medicines in general (many of them initially containing herbal ingredients) was first stimulated 100 years ago by concerns in the United States about problems in the manufacture and sale of so-called patent medicines. In 2003, 53 of 141 responding World Health Organization member states had regulations relating to herbal medicine and half the remainder stated that these regulations were in development.
In summary, the new Directive and associated registration process has an impact on many aspects of pharmacy and other professions, and obviously, the phytomedicine industry. The symposium highlighted the opportunities and challenges for all health-related professions and the relevant industries. From the perspective of academic pharmaceutical sciences and patient care, it is essential that the public has access to high quality herbal medicinal products, and this regulation moves towards ensuring the safety and continued availability of these products.
Michael Heinrich, PhD, is a professor at the Centre for Pharmacognosy and Phytotherapy, School of Pharmacy, University of London. Email: firstname.lastname@example.org.
Editor’s note: For more information on this subject, please refer to the previously published HerbalGram article: Brinckmann J, McIntyre M. Proposed Quality Control Guidelines for the EU Directive on Traditional Herbal Medicinal Products: Implications for Small- to Medium-Sized Enterprises. HerbalGram. 2006;70:62.66.