The Royal Pharmaceutical Society's Pharmaceutical Sciences Group and the School of Health, Biological and Environmental Sciences at Middlesex university jointly presented a two-day symposium on traditional Chinese medicine at the Royal Pharmaceutical Society on October 25 and 26. Topics covered at the meeting included quality and authentication of Chinese herbal medicines, safety aspects, the views of the Medicines Control Agency on these medicines and their use in clinical practice
Mrs CHRISTINE GLOVER (President, Royal Pharmaceutical Society) welcomed delegates and said that this was "a ground-breaking meeting for the Pharmaceutical Sciences Group".
Traditional Chinese medicine (TCM) was a topical subject and complementary medicine in general was the subject of a House of Lords inquiry to which the Society had submitted evidence. Mrs Glover hoped that the Medicines Control Agency (MCA) would think about organising a new category of medicines which would cover, for example, traditional Chinese medicines, and that the Society could work with the MCA on that. She went on to say that it was good that pharmacognosy was "back on the agenda".
A Western perspective on TCM was provided by Professor DAVID PHILLIPSON (emeritus professor, centre for pharmacognosy and phytotherapy, School of Pharmacy, University of London). Answering the question "What is TCM?", Professor Phillipson said it was a holistic, ancient form of medicine with a strong philosophical background. It included not only the use of Chinese medicinal herbs, but also acupuncture, massage, dietary advice and other treatment modalities. In China, most patients had the opportunity to choose whether they wished to use Western medicine or TCM. It was also popular outside China, for example, in Japan and south-east Asia, and was embraced by many Western countries following President Nixon's visit to China in the 1970s.
Pot pourri Professor Phillipson said there were around 8,000 traditional Chinese medicines, but that only around 1,000 were commonly used. TCM prescriptions were multicomponent and could contain up to 15 or more different herbs - "there is a pot pourri of drugs in any Chinese herbal prescription", he said. According to the principles of TCM, each prescription contained the following components:
Referring to the development of plant-derived medicines, Professor Phillipson said that the Western approach with clinically effective plant extracts was to ask "what is the active principle?", and then to isolate, purify, determine its structure and produce a standardised dosage form. This was completely different to the TCM approach.
Research interests Professor Phillipson went on to describe some of his own research interests in TCM - quality was one of these.
Professor Phillipson and colleagues had analysed 12 commercial samples, purchased in London, of Paeonia lactiflora, a herbal ingredient of the TCM treatment tested in clinical trials in atopic eczema at Great Ormond Street hospital in London. The Chinese Pharmacopoeia's monograph for P lactiflora stated that the paeoniflorin content should be not less than 2 per cent. However, content ranged from 0.01 to 4.57 per cent in the 12 samples tested, and, in nine of these, it was at the lower end of the range. Other work had centred on the analysis of nine samples of "fangji", all of which had been found to contain aristolochic acids.
Dr CHRISTINE LEON (Royal Botanic Gardens, Kew) described the development of the Chinese Medicinal Plants Authentication Centre at Kew. Working with the Institute of Medicinal Plant Development, Beijing, the centre aimed to offer an authentication and quality assurance service for all Chinese herbs available on the Western market.
Around 400 to 500 different species of loose herbs were on the UK market, although this represented only a small proportion of those available in China. According to Dr Leon, there were around 20 traders and importers of Chinese herbs in the UK, yet not all plants entered the country via this route, since practitioners might bring in some herbal material directly. "Quality assurance takes place at the discretion of the importing company", Dr Leon said. The extent to which tests were carried out to confirm whether the plant was the correct one, and to detect heavy metals, pesticides and antimicrobial contamination was "variable". The main tests done were "naked-eye" tests where the herbal material was examined by smell and appearance. Analytical and chemical tests were less common, but were beginning to be introduced.
Suppliers association founded Dr Leon described the formation of the Chinese Medicine Association of Suppliers (CMAS), set up in April, 1999, as "a great step forward among suppliers to pick up the gauntlet and lay down standards (for Chinese herbs)". The CMAS required that its members abided by the association's code of practice to uphold both quality and safety in the supply of Chinese herbs.
In China, every province had its own authentication centre for herbal material, which strictly adhered to the Chinese Pharmacopoeia, and hospitals and clinics could not use herbs that were not included in this pharmacopoeia. However, in the UK, many species were available which were not in the Chinese Pharmacopoeia.
Dr Leon referred to the "tremendous variability" in the quality of Chinese herbal material in the UK. The authentication centre at Kew was developing reference materials and validated authentication tests based on the pharmacopoeia for all Chinese medicinal herbs on the market. A key part had been the putting together of reference libraries, which included:
The centre's authentication service had recently become operational. Dr Leon listed potential users of the service as including importers/suppliers, manufacturers, practitioners, researchers, regulators, health authorities and the pharmaceutical industry.
Ms DEBBIE SHAW (medical toxicology unit, Guy's and St Thomas's hospital NHS trust) described some of the work of the traditional remedies surveillance project, established in 1991, which monitored the adverse effects of traditional remedies, food supplements and herbal remedies. The biggest cluster of cases reported had related to liver damage associated with the use of Chinese herbal medicines for skin conditions, including psoriasis and eczema. Other causes had been excluded, and it was concluded that the reaction was probably an idiosyncratic one.
Outlining problems in investigating cases, Ms Shaw listed the multi-herb prescription, the lack of practitioner regulation and the lack of quality control of herbs and herbal products. Another key problem was the variability in case information provided by the patient, the practitioner and the patient's doctor - usually there were several versions of the story, a phenomenon described by Ms Shaw as "Chinese whispers".
Australian approach Turning to the Australian approach to regulating herbal remedies, Ms Shaw explained that, in that country, products were either "listed" or "registered". Listed products were of certified quality and were required to have supporting evidence of safety from the literature. No claims regarding efficacy could be made. Registered products equated to those with a licence in the UK. She also referred to a report, "Towards a safer choice", published in 1996, which resulted from a review of the practice of TCM in Australia. This had concluded that there needed to be regulation of Chinese herbal medicine and acupuncture practitioners, and had led to the Chinese Medicine Regulation Act 1999, which set out statutory regulation for such practitioners in the state of Victoria. The intention was that regulation would eventually be brought in on a national scale. Ms Shaw emphasised that this was being done for the benefit of the public, not practitioners.
Summing up, Ms Shaw listed five elements for improving the safety of Chinese herbal medicines:
Dr LINDA ANDERSON (Medicines Control Agency) addressed the question "where do traditional Chinese medicines fit into the current regulatory framework?" and what the problems with these medicines were from a regulatory viewpoint.
Traditional Chinese medicines were a major growth area in this country. However, there were no TCM products licensed in the UK. Many fell outside the current exemptions related to herbal remedies, as some contained non-herbal active ingredients, or herbal ingredients restricted by the POM order or SI 2130. Also, many products made medicinal claims.
Particular safety concerns with regard to traditional Chinese medicines were that some contained intrinsically toxic herbal ingredients, such as Aconitum, Croton or Aristolochia. Others concerns included the risk of serious idiosyncratic reactions, potential interactions with conventional medicines, and use in pregnancy, lactation, older people and children. Quality-related safety concerns included:
The UK experience The UK experience with problems caused by traditional Chinese medicines included two cases of renal failure reported in 1999, which had led to an emergency ban on all Aristolochia species. Other examples were a case of arsenic poisoning in a patient who had taken a Chinese herbal mixture containing up to 10 per cent arsenic disulphide, instances of Chinese "herbal" skin creams containing dexamethasone, and a TCM mixture containing foreign matter which was identified as larvae of Hymenoptera parasitica (parasitic wasps).
Dr Anderson went on to outline the steps that MCA was taking to resolve problems with TCM. These were reviewing controls of potentially toxic plants, looking at regulatory options for ensuring that harmful substitutions were avoided, consulting importers and practitioner groups, extension of the yellow card scheme (in October, 1996) to cover unlicensed herbal remedies, and playing an active role in current European discussions on developing a suitable regulatory framework for herbal medicines.
Concluding, Dr Anderson emphasised that the MCA had a responsibility to safeguard public health. Current procedures for licensed products offered protection but not enough choice, whereas the unlicensed regimen offered public choice but not enough protection. The challenge was to balance consumer choice with consumer safety, she said.
On day two of the symposium, Dr AMALA RAMAN (lecturer in pharmacognosy, Department of Pharmacy, King's College London) described how her group was using mechanism-based in vitro bioassays as a method of evaluating extracts and isolated compounds from plants used in traditional medicine. In vitro systems utilising cells and enzymes were a relatively easy and rapid method of evaluating extracts, said Dr Raman, but there were several inter-related problems - expense, clinical relevance and efficiency.
The group had chosen the SVK-14 cell line, a rapidly dividing immortalised human keratinocyte cell line that mimicked hyperproliferation of the epidermis, to investigate the potential of traditionally used medicinal plants in the treatment of psoriasis. The method was applied to aqueous extracts from plants used in TCM. According to Dr Raman, an extract of the root bark of Paeonia suffructicosa was the most active, producing a marked inhibition of cell growth compared with control. Further studies were now required to determine the active constituents.
Dr SHOUMING ZHONG (director of research and development, Oxford Natural Products Plc) reviewed clinical trial evidence for the use of TCM in patients with hepatitis C virus (HCV) infection.
The prevalence of HCV infection in China was around 3 per cent, according to Dr Zhong. Since there was a lack of effective treatments, attention in China had focused on the potential use of traditional medicine in patients with HCV infection. Almost 1,300 patients had taken part in 18 clinical trials, with some encouraging results. However, while a few studies had used a set formula of Chinese herbs, the majority of clinical trials had used individualised treatments, and hence it was not yet possible to make specific statements about efficacy.
Dr Zhong said he believed that knowledge of the use of TCM, its chemistry and pharmacology, together with the application of modern scientific technology would enable the rationalisation of TCM formulae, and lead to a reduction in the number of herbal ingredients in order to make the final product commercially and therapeutically viable for the treatment of HCV in Western countries. In discussion following his presentation, Dr Zhong agreed that in order to produce convincing evidence of efficacy, better protocols to test TCM needed to be designed. He said that the reason for reducing the number of herbs in a TCM formula would in part be to produce a formula that was acceptable to regulatory authorities.
Ms CATHERINE MARTIN (Sino-European Clinics) said there had been several barriers to the entry of TCM to Western countries. These included a different cultural understanding, that medical dialogue in the West was not appropriate for TCM diagnosis and treatment, and that there was a lack of research funding in the area. "TCM could be one of China's great contributions to the West," she said, but first the issues needed to be addressed and proper clinical research needed to be carried out in the UK. She referred to "a plethora of [Chinese] herbal take-aways" which reflected poorly on the image of all TCM clinics. The majority of patients attending Sino-European clinics self-referred or attended on the recommendation of a relative or friend. Skin conditions, particularly eczema and psoriasis, were those most commonly treated, according to Ms Martin. The clinics had now treated over 10,000 patients, but outcome data had not yet been evaluated.
The way forward required co-ordinated international development in the research field, dialogue between the MCA and the Chinese regulatory authorities, and the regulation of the quality of exported herbs. Referring to the Chinese Medicinal Plants Authentication Centre at Kew, described by Dr Christine Leon, Ms Martin said: "I cannot emphasise enough how important that is." Closing her presentation, Ms Martin stated that Chinese medicine was not a fringe health care system and put out a plea for more medical tolerance.
Mr ANDREW FLOWER (Register for Chinese Herbal Medicine [RCHM]) told the audience that the RCHM was the main register for practitioners of Chinese herbal medicine in the UK. Established in 1987, it now had around 400 members. Importantly, an increasing number of Chinese doctors were registering. The main aims of the RCHM were:
Looking to the future, Mr Flower believed that "top of the agenda must be quality assurance", but improved training, new herbal licensing laws, statutory self-regulation, research, good product development, and integration into the National Health Service were also important. "People should be allowed access to basically what is a very effective form of medicine," Mr Flower declared.
Professor KELVIN CHAN (school of pharmacy and chemistry, Liverpool John Moores university, and Zayed Complex for Herbal Research and Traditional Medicine, United Arab Emirates) said that there was a general lack of randomised controlled trials in Chinese medicine.
He described the Kotzting TCM hospital in Munich, Germany, which utilised both Chinese and orthodox medicine to treat a broad range of conditions. The hospital had data on 7,585 inpatients who were treated between 1991 and 1998 and who were assessed before and after treatment. Touching on safety aspects of Chinese herbal medicines, Professor Chan pointed out that there was a potential for drug interactions to occur between Chinese herbal medicinal products and orthodox drugs; however, not all interactions would be harmful.
The development and applications of Phytotrack, an electronically based integrated audit trail that allowed "comprehensive and detailed recording of information and analytical data relating to a crop and its growth as it passes from field to formulation" was described by Professor MICHAEL FOWLER (University of Sheffield and Phytotrack Ltd, Oxford).
The interest in herbal medicines and related products had led to increasing pressure on raw materials suppliers and "less than careful" choosing of materials going into herbs. Professor Fowler referred to the "tortuous path" from field to formulation - checks along the trail were few and the system was open to a variety of abuses, such as substitution of other materials and addition of potentially dangerous bulking agents.
There was a need for a system that could provide for tracking of the fate of individual batches of raw materials from the grower to the manufacturer and, in Professor Fowler's view, Phytotrack provided such a system. The system was designed for data input and information recording at all stages during growing (eg, use of pesticides), harvesting, post-harvest treatments (eg, washing and drying), storage and processing. The audit trail could be linked to the licence requirements for a particular product (eg, concentration of active constituent, residue concentrations) and would not allow the input of data or criteria outside those of the licence. It also incorporated a tamper-proof system linked to a secure server.
Field trials with the system had been carried out with Digitalis and feverfew. The company was developing a hard copy, waterproof, scannable version for use in countries like China where many raw materials were grown by small farmers. - from Jo Barnes (centre for pharmacognosy and phytotherapy, School of Pharmacy, University of London).