- Email: [email protected]
Food or medicine? Decision time in Europe
Occasional Paper
Food or medicine? Decision time in Europe S. Y. Mills Complementary Health Studies, School of Education and Lifelong Learning, University of Exeter, Exeter, Devon, UK
narrow the amorphous “borderline” between medicines and foods into which most natural products fall. New Directives on herbal products and food supplements are aimed to force manufacturers to choose one category or another.
INTRODUCTION In the United Kingdom (UK) and other countries in Europe, members of the public who wish to use natural products for their own healthcare are faced with a bewildering range of legal categories and assurances. These products may be either:
THE DIRECTIVE ON HERBAL MEDICINAL PRODUCTS WITH TRADITIONAL USE
(1) fully licensed medicines with indications approved by the government medicines regulator and manufactured to pharmaceutical standards of purity and consistency (there are around 600 herbal products licensed as medicines in the UK, many more in other European countries); (2) (in the UK only) herbal medicinal products exempt from licensing and thus with no claims but also no confirmed standard of manufacture; (3) products sold under the laws that apply to foodstuffs, perhaps choosing the title “dietary supplement” in which “health maintenance” claims appropriate to foods are permitted; apart from not breaching laws on selling food fit for human consumption these products are not subject to verifiable manufacturing standards.
Simon Y. Mills MA, FNIMH, MCPP, Complementary Health Studies, School of Education and Lifelong Learning, University of Exeter, Exeter EX1 2LU, Devon, UK.
A medicine, or in EU-terminology a “medicinal product”, achieves its licensed status by satisfying the regulators that is has met formal requirements to assure its quality, safety and efficacy. This triad is unique. Foods and cosmetics need only to be safe for human use, with less formal quality requirements. In the case of a manufacturer hoping to licence a new medicine, he has to have demonstrated:
In the UK the only way to establish if a product is a medicine is a tiny “PL” and a licence number at the bottom of the container. Most consumers do not know that, and manufacturers may not even be able to say that it is a medicine! There are similar uncertainties in other countries around the world, each causing varying degrees of potential disquiet. For example, in the USA, the vast majority of natural products are sold as “dietary supplements” without assured manufacturing standards or other certifiable quality, yet able to make claims for effects on the structure or function of the body. Concerns about quality standards for these “supplements” have been persistent among the regulators and European industry ever since. There are obvious concerns about such confusion and exposure. New regulatory initiatives in Europe are intended to reduce the problem, in particular to
Complementary Therapies in Medicine (2002), 10, 176–178
© 2002 Published by Elsevier Science Ltd.
doi: 10.1016/S0965-2299(02)00078-X, available online at http:/ /www.idealibrary.com on
(1) auditable manufacturing processes to assure purity and consistency of the product, so-called pharmaceutical Good Manufacturing Practice (GMP), with verifiable markers of these quality standards (e.g. from a monograph in an official pharmacopoeia); (2) a range of preclinical and other studies (mostly involving laboratory animals) to establish its toxicological profile, and a surveillance mechanism after licensing to monitor its safety in use; (3) a range of preclinical and clinical studies (animals and then humans) to establish significant efficacy over placebo.
176
There have been exceptions negotiated before. A well-established medicinal product has usually been able to survive on the basis of evidence that it has already been used safely, rather than on new toxicological studies. However where an old familiar is found to raise new concerns—for example, aspirin or paracetamol—new toxicological studies can be called for. There is indeed a formal category of “medicines with well-established use”1 that in theory
Food or medicine? Decision time in Europe
allows a medicine to be licensed on the basis of sound bibliographic evidence of its efficacy rather than on new clinical trials. A new product based largely on senna for example could now be licensed on the grounds that there is generic evidence for efficacy that has been separately agreed as reliable, and the limits of its safe dosing are similarly generically agreed. When the “well-established” category came in there were hopes that it could be applied to some of the large range of otherwise unregulated herbal products that are available to the European public. In practice however this option is restricted largely to the German natural medicinal products industry, reflecting the enormous range of medicines used in that country. It was clear that something else was needed for the growing herbal sector elsewhere. In 1995 the Council of Ministers had called on the European Commission to study the existing situation of herbal medicinal products in the European Union.2 The European association representing the interests of proprietary medicine manufacturers, was asked to survey the landscape and duly published its report.3 This confirmed that across Europe, herbal products were poorly regulated with very variable approaches to their position under medicines law. The report in fact called for the well-established use provisions to be applied to this group. It was when this proved inappropriate that the momentum for more change grew, and the UK Medicines Control Agency (MCA) was asked to provide the first draft of such legislation in September 2000. After a number of redrafts, final proposals for a new Directive on Herbal Medicinal Products with Traditional Use were published in January 2002. They are likely to be included in wider EU medicines legislation to take effect in 2004. The legislation proposes that manufacturers of herbal products (and only herbal products) who can show evidence that these have been used for a certain purpose for 30 years, can substitute that evidence for efficacy studies, provided that claims for such use are restricted to minor indications (suitable for self-diagnosis and treatment) and accompanied by suitable qualifiers and disclaimers. They also have to meet every other requirement for the supply of medicinal products, that is, pharmaceutical standards of quality and formal procedures for monitoring safety. In return they will be able to “register” these products as medicinal products, a stage short of a full licence. Concerns have been expressed on a number of fronts. Surprisingly perhaps there is little sign of disquiet on the principle of granting traditional use the status of medicinal efficacy. The pragmatic principle has predominated: if the public insists on choosing to use herbal remedies it is better to regulate them for quality and safety at least than leave the public exposed to inferior goods. On the other hand some in the herbal sector have been less content. There is currently a significant media campaign claiming that the new legislation will clear the shelves of herbal products and that it
177
is draconian for the small enterprises that provide many of the products. The concerns concentrate on a number of key points. Small-scale manufacturers will not be able to meet pharmaceutical GMP (this needs very expensive factories, facilities and licensed staff). The regulators admit that, if they cannot adapt, manufacturers may go out of business. Some in the sector worry that pharmaceutical standards cannot be applied to herbs. The experience of the licensed herbal medicine sector however is that pragmatic application to plant drug manufacture is possible. The new Directive covers only herbal products. There are many new combination products where herbs are mixed with food supplements (especially from the USA where they are all “dietary supplements”), which may have no legal home. There are also many formulations from Ayurvedic and Chinese medicine that are mixtures of herbs, mineral and animal products. Industry assessments are that most natural remedies in the UK would actually fall outside the legislation.4 These are already being supplied in, at best, an unregulated “grey area” between medicines and food, and, at worst, actually outside current law in the UK and Europe. There may be scope in future for a limited application of traditional use measure to ethnic medicines where safety can be agreed. The Directive states that a ‘traditional use’ means at least 30 years use in the European Union, or 15 years if there is at least 30 years attested use for that product and indication outside Europe. This has been seen to discriminate against non-European cultures, a view shared by the MCA on behalf of the ethnic populations in Britain, who argue that it is the quality rather than the provenance of the evidence that is important. There is however almost no sympathy for this argument among regulators or industry in continental Europe. The new medicine category may turn out to be a ghetto where research and development will wither because there are few incentives or opportunities to apply for full licensing. The existence of an essentially similar product that is licensable may bar registrations, and there is a view for example that current licensed herbal medicines will be demoted to registration in due course. This is a concern of many with the long-term interests of herbal medicine at heart. Those making the latter argument also hope that the new Directive will be enforced by the MCA better than previous law: there are still too many flagrant breaches of the current law, in effect penalising the responsible sector. Such concerns notwithstanding, the new measures are likely to be enacted in 2004 and fully in force 5 years later.
178
Complementary Therapies in Medicine
DIETARY PRODUCTS While pharmaceutical quality standards are being imposed on the medicinal side of the borderline, there are much tighter regimes in prospect for the nutritional side. A recent Directive5 defines the relevant products as “food supplements”, which are foodstuffs “the purpose of which is to supplement the normal diet”, and “which are concentrated sources of nutrients or other substances”. The term “nutrients” here is restricted solely to vitamins and minerals. The Directive aims to regulate the content of nutrients in food supplements as a first step; further measures to regulate other ingredients (including amino acids, essential fatty acids, fibre and plants and herbal extracts) are said to be following. The Directive sets up a positive list of nutrients that may be used in the manufacture of food supplements. Other nutrients already on the market may stay there until formal review in 2007; attaining the list in future will require approval from the European Food Safety Authority (EFSA). Most contentiously, upper safe limits of nutrients are published, based on a multiple of the Recommended Daily Allowances, and manufacturers will no longer be able to market supplements which give higher doses, taking account also of intake from other dietary sources. These rules will take effect in 2005. There are a number of products on the market containing nutrients at levels that are likely to exceed published safe maximum limits. These may follow research on the pharmacological properties of nutrients, often in animals and at high doses. The Directive is clear: if a nutrient is being taken outside its normal dietary range it may be pharmacologically active and should be regulated as a medicinal product, not as a food. The outcry from the industry has been noisy. The European Community has also adopted tighter rules on labelling. Another recent Directive6 again prohibits attributing to foods any properties of prevention, treatment or cure of a human disease, although now accepting that foods may be able to contribute to “a significant reduction of a major disease risk factor”. However some specific claims for nutritional products were not well covered by these measures and in 2002 new proposals were
published.7 These extend the definition of nutrients from the above to “other substances with a nutritional or physiological effect”, for example anti-oxidants and lactic bacteria. It proposes that any claims for a significant reduction of a major disease risk factor may only follow publication of these in a register by the EFSA. The role of calcium as an “aid to the development of strong bones and teeth” is widely acceptable; claims that “sufficient calcium intake may reduce the risk of osteoporosis” would need formal confirmation. Various vague and non-verifiable marketing terms such as “helps support your body’s natural defences”, “helps your body resist stress”, “purifies your organism”, will be discontinued. With the new measures anticipated for nonnutrient ingredients in food supplements it is likely that the border line in Europe between foods and medicines will be more sharply defined. The contrast with the one-size-fits-all policy in the USA will be stark, raising potential issues at the World Trade Organisation. Another risk is that the definitions will be drawn so tightly that innovation and research will be stifled. Small manufacturing companies will definitely face major adaptation or demise and the multinationals will dominate. However if the measures lead to fewer inferior or misleading products lurking in the unregulated grey area between food and medicine then the public may conclude the prices are worth paying.
REFERENCES 1. Proposal for a Directive on Herbal Medicinal Products with Traditional Use, http://europa.eu.int/. 2. OJ No C350, http://europa.eu.int/. 3. Herbal medicinal products in the European Union ETD/97/501336, AESGP http://www.aesgp.com. 4. Survey by the Herbal Registration Forum (personal correspondence). 5. Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements, http://europa.eu.int/. 6. Directive 2000/13/EC of the European Parliament and of the Council relating to the labelling, presentation and advertising of foodstuffs, http://europa.eu.int/. 7. Draft proposal for Regulation of the European Parliament and of the Council on Nutrition, Functional and Health Claims made on Foods. Working Document SANCO/1832/2002 http://europa.eu.int/.
Food or medicine? Decision time in Europe S. Y. Mills Complementary Health Studies, School of Education and Lifelong Learning, University of Exeter, Exeter, Devon, UK
narrow the amorphous “borderline” between medicines and foods into which most natural products fall. New Directives on herbal products and food supplements are aimed to force manufacturers to choose one category or another.
INTRODUCTION In the United Kingdom (UK) and other countries in Europe, members of the public who wish to use natural products for their own healthcare are faced with a bewildering range of legal categories and assurances. These products may be either:
THE DIRECTIVE ON HERBAL MEDICINAL PRODUCTS WITH TRADITIONAL USE
(1) fully licensed medicines with indications approved by the government medicines regulator and manufactured to pharmaceutical standards of purity and consistency (there are around 600 herbal products licensed as medicines in the UK, many more in other European countries); (2) (in the UK only) herbal medicinal products exempt from licensing and thus with no claims but also no confirmed standard of manufacture; (3) products sold under the laws that apply to foodstuffs, perhaps choosing the title “dietary supplement” in which “health maintenance” claims appropriate to foods are permitted; apart from not breaching laws on selling food fit for human consumption these products are not subject to verifiable manufacturing standards.
Simon Y. Mills MA, FNIMH, MCPP, Complementary Health Studies, School of Education and Lifelong Learning, University of Exeter, Exeter EX1 2LU, Devon, UK.
A medicine, or in EU-terminology a “medicinal product”, achieves its licensed status by satisfying the regulators that is has met formal requirements to assure its quality, safety and efficacy. This triad is unique. Foods and cosmetics need only to be safe for human use, with less formal quality requirements. In the case of a manufacturer hoping to licence a new medicine, he has to have demonstrated:
In the UK the only way to establish if a product is a medicine is a tiny “PL” and a licence number at the bottom of the container. Most consumers do not know that, and manufacturers may not even be able to say that it is a medicine! There are similar uncertainties in other countries around the world, each causing varying degrees of potential disquiet. For example, in the USA, the vast majority of natural products are sold as “dietary supplements” without assured manufacturing standards or other certifiable quality, yet able to make claims for effects on the structure or function of the body. Concerns about quality standards for these “supplements” have been persistent among the regulators and European industry ever since. There are obvious concerns about such confusion and exposure. New regulatory initiatives in Europe are intended to reduce the problem, in particular to
Complementary Therapies in Medicine (2002), 10, 176–178
© 2002 Published by Elsevier Science Ltd.
doi: 10.1016/S0965-2299(02)00078-X, available online at http:/ /www.idealibrary.com on
(1) auditable manufacturing processes to assure purity and consistency of the product, so-called pharmaceutical Good Manufacturing Practice (GMP), with verifiable markers of these quality standards (e.g. from a monograph in an official pharmacopoeia); (2) a range of preclinical and other studies (mostly involving laboratory animals) to establish its toxicological profile, and a surveillance mechanism after licensing to monitor its safety in use; (3) a range of preclinical and clinical studies (animals and then humans) to establish significant efficacy over placebo.
176
There have been exceptions negotiated before. A well-established medicinal product has usually been able to survive on the basis of evidence that it has already been used safely, rather than on new toxicological studies. However where an old familiar is found to raise new concerns—for example, aspirin or paracetamol—new toxicological studies can be called for. There is indeed a formal category of “medicines with well-established use”1 that in theory
Food or medicine? Decision time in Europe
allows a medicine to be licensed on the basis of sound bibliographic evidence of its efficacy rather than on new clinical trials. A new product based largely on senna for example could now be licensed on the grounds that there is generic evidence for efficacy that has been separately agreed as reliable, and the limits of its safe dosing are similarly generically agreed. When the “well-established” category came in there were hopes that it could be applied to some of the large range of otherwise unregulated herbal products that are available to the European public. In practice however this option is restricted largely to the German natural medicinal products industry, reflecting the enormous range of medicines used in that country. It was clear that something else was needed for the growing herbal sector elsewhere. In 1995 the Council of Ministers had called on the European Commission to study the existing situation of herbal medicinal products in the European Union.2 The European association representing the interests of proprietary medicine manufacturers, was asked to survey the landscape and duly published its report.3 This confirmed that across Europe, herbal products were poorly regulated with very variable approaches to their position under medicines law. The report in fact called for the well-established use provisions to be applied to this group. It was when this proved inappropriate that the momentum for more change grew, and the UK Medicines Control Agency (MCA) was asked to provide the first draft of such legislation in September 2000. After a number of redrafts, final proposals for a new Directive on Herbal Medicinal Products with Traditional Use were published in January 2002. They are likely to be included in wider EU medicines legislation to take effect in 2004. The legislation proposes that manufacturers of herbal products (and only herbal products) who can show evidence that these have been used for a certain purpose for 30 years, can substitute that evidence for efficacy studies, provided that claims for such use are restricted to minor indications (suitable for self-diagnosis and treatment) and accompanied by suitable qualifiers and disclaimers. They also have to meet every other requirement for the supply of medicinal products, that is, pharmaceutical standards of quality and formal procedures for monitoring safety. In return they will be able to “register” these products as medicinal products, a stage short of a full licence. Concerns have been expressed on a number of fronts. Surprisingly perhaps there is little sign of disquiet on the principle of granting traditional use the status of medicinal efficacy. The pragmatic principle has predominated: if the public insists on choosing to use herbal remedies it is better to regulate them for quality and safety at least than leave the public exposed to inferior goods. On the other hand some in the herbal sector have been less content. There is currently a significant media campaign claiming that the new legislation will clear the shelves of herbal products and that it
177
is draconian for the small enterprises that provide many of the products. The concerns concentrate on a number of key points. Small-scale manufacturers will not be able to meet pharmaceutical GMP (this needs very expensive factories, facilities and licensed staff). The regulators admit that, if they cannot adapt, manufacturers may go out of business. Some in the sector worry that pharmaceutical standards cannot be applied to herbs. The experience of the licensed herbal medicine sector however is that pragmatic application to plant drug manufacture is possible. The new Directive covers only herbal products. There are many new combination products where herbs are mixed with food supplements (especially from the USA where they are all “dietary supplements”), which may have no legal home. There are also many formulations from Ayurvedic and Chinese medicine that are mixtures of herbs, mineral and animal products. Industry assessments are that most natural remedies in the UK would actually fall outside the legislation.4 These are already being supplied in, at best, an unregulated “grey area” between medicines and food, and, at worst, actually outside current law in the UK and Europe. There may be scope in future for a limited application of traditional use measure to ethnic medicines where safety can be agreed. The Directive states that a ‘traditional use’ means at least 30 years use in the European Union, or 15 years if there is at least 30 years attested use for that product and indication outside Europe. This has been seen to discriminate against non-European cultures, a view shared by the MCA on behalf of the ethnic populations in Britain, who argue that it is the quality rather than the provenance of the evidence that is important. There is however almost no sympathy for this argument among regulators or industry in continental Europe. The new medicine category may turn out to be a ghetto where research and development will wither because there are few incentives or opportunities to apply for full licensing. The existence of an essentially similar product that is licensable may bar registrations, and there is a view for example that current licensed herbal medicines will be demoted to registration in due course. This is a concern of many with the long-term interests of herbal medicine at heart. Those making the latter argument also hope that the new Directive will be enforced by the MCA better than previous law: there are still too many flagrant breaches of the current law, in effect penalising the responsible sector. Such concerns notwithstanding, the new measures are likely to be enacted in 2004 and fully in force 5 years later.
178
Complementary Therapies in Medicine
DIETARY PRODUCTS While pharmaceutical quality standards are being imposed on the medicinal side of the borderline, there are much tighter regimes in prospect for the nutritional side. A recent Directive5 defines the relevant products as “food supplements”, which are foodstuffs “the purpose of which is to supplement the normal diet”, and “which are concentrated sources of nutrients or other substances”. The term “nutrients” here is restricted solely to vitamins and minerals. The Directive aims to regulate the content of nutrients in food supplements as a first step; further measures to regulate other ingredients (including amino acids, essential fatty acids, fibre and plants and herbal extracts) are said to be following. The Directive sets up a positive list of nutrients that may be used in the manufacture of food supplements. Other nutrients already on the market may stay there until formal review in 2007; attaining the list in future will require approval from the European Food Safety Authority (EFSA). Most contentiously, upper safe limits of nutrients are published, based on a multiple of the Recommended Daily Allowances, and manufacturers will no longer be able to market supplements which give higher doses, taking account also of intake from other dietary sources. These rules will take effect in 2005. There are a number of products on the market containing nutrients at levels that are likely to exceed published safe maximum limits. These may follow research on the pharmacological properties of nutrients, often in animals and at high doses. The Directive is clear: if a nutrient is being taken outside its normal dietary range it may be pharmacologically active and should be regulated as a medicinal product, not as a food. The outcry from the industry has been noisy. The European Community has also adopted tighter rules on labelling. Another recent Directive6 again prohibits attributing to foods any properties of prevention, treatment or cure of a human disease, although now accepting that foods may be able to contribute to “a significant reduction of a major disease risk factor”. However some specific claims for nutritional products were not well covered by these measures and in 2002 new proposals were
published.7 These extend the definition of nutrients from the above to “other substances with a nutritional or physiological effect”, for example anti-oxidants and lactic bacteria. It proposes that any claims for a significant reduction of a major disease risk factor may only follow publication of these in a register by the EFSA. The role of calcium as an “aid to the development of strong bones and teeth” is widely acceptable; claims that “sufficient calcium intake may reduce the risk of osteoporosis” would need formal confirmation. Various vague and non-verifiable marketing terms such as “helps support your body’s natural defences”, “helps your body resist stress”, “purifies your organism”, will be discontinued. With the new measures anticipated for nonnutrient ingredients in food supplements it is likely that the border line in Europe between foods and medicines will be more sharply defined. The contrast with the one-size-fits-all policy in the USA will be stark, raising potential issues at the World Trade Organisation. Another risk is that the definitions will be drawn so tightly that innovation and research will be stifled. Small manufacturing companies will definitely face major adaptation or demise and the multinationals will dominate. However if the measures lead to fewer inferior or misleading products lurking in the unregulated grey area between food and medicine then the public may conclude the prices are worth paying.
REFERENCES 1. Proposal for a Directive on Herbal Medicinal Products with Traditional Use, http://europa.eu.int/. 2. OJ No C350, http://europa.eu.int/. 3. Herbal medicinal products in the European Union ETD/97/501336, AESGP http://www.aesgp.com. 4. Survey by the Herbal Registration Forum (personal correspondence). 5. Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements, http://europa.eu.int/. 6. Directive 2000/13/EC of the European Parliament and of the Council relating to the labelling, presentation and advertising of foodstuffs, http://europa.eu.int/. 7. Draft proposal for Regulation of the European Parliament and of the Council on Nutrition, Functional and Health Claims made on Foods. Working Document SANCO/1832/2002 http://europa.eu.int/.