Legislation relating to nutraceuticals in the
European Union with a particular focus on
botanical-sourced products
PREAPRED BY:-THAKKAR
PRIYANSHU
[Link] PRA Sem:-2 Department of pharmaceutical
Enrollment no:-222050827015 regulatory affairs
Roll no:-15 Anand pharmacy collage
Guided by:-Assistant professor
Ms. Hemangini Patel
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TABLE of contents:-
• 1. Introduction:-
• 2. Nutraceutical concept in European Union:-
• 3. Regulatory frame work including regulatory
status of botanicals in different EU countries:-
• 4. Quality aspects:-
• 5. Safety studies:-
• 6. Efficacy studies:-
• 7. Conclusions:-
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1. Introduction:-
• Nutraceutical is defined as a food or part of it that provides the
body with medical or health benefits, including the prevention
and treatment of a disease.
• Nutraceuticals is a term coined to describe substances which are
not traditionally recognized nutrients (e.g. vitamins and minerals)
but which have positive physiological effects on the human body.
• The term was originally used by Defelice in 1995.
• As they have defined physiological effects nutraceuticals do not
easily fall into the legal categories of food or drug but inhabit a
grey area between the two.
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Food
Nutraceutical
Drug
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• Within European Union (EU) law the legal categorization of a
nutraceutical is, in general, made on the basis of its accepted
effects on the body. Thus, if the substance contributes only to
the maintenance of healthy tissues and organs it may be
considered to be a food ingredient. If, however, it can be shown
to have a modifying effect on one or more of the body’s
physiological processes, it is likely to be considered to be a
medicinal substance.
• The development of foods and food components that provide
benefits beyond their traditional nutritional value has created
tremendous academic, commercial, regulatory and public
interest. These products in broad sense cover health promotion,
“optimal nutrition” and concept of enhanced performance –
both physically and mentally – and reduction of disease risk
factors.
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• The challenges ahead relate to quality, safety and efficacy. In
many cases there are still a number of unknowns such as the
identification of specific active components, their absorption
and metabolism in the human body and the effects of processing
on the products containing them. Botanical materials represent a
large segment of nutraceuticals and present additional problems
relating to the complex nature and composition of botanical
ingredients. Botanicals in this context represent whole,
fragmented or cut plants, algae, fungi, lichens and botanical
preparations from these materials involving extraction,
distillation, expression, fractionation, purification,
concentration and fermentation. Botanical substances are
defined by the botanical name of the plant according to the
binomial system (genus, species, variety and author) and the
part used (e.g. leaf, root and fruit).
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• In this chapter the focus will mainly be on legislation
governing botanical-sourced nutraceuticals in the European
Union.
• Within Europe, the regulatory status of nutraceuticals is
diversified due to differences in tradition, historical and
cultural backgrounds and different legislation and
enforcement practices at national level within the 25
member states.
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2. Nutraceutical concept in European Union:-
• Much of the early development of the nutraceutical concept and
products was driven from the United States of America where,
since its introduction in 1994, the Dietary Supplement and
Health Education Act (DSHEA, 1994) has allowed considerable
flexibility and blurred the boundaries between foods and
medicines found in other parts of the world.
• Under DSHEA a dietary supplement may contain ‘an herb or
other botanical’ or ‘a concentrate, metabolite, constituent,
extract or combination of any ingredient from the other
categories’. This is subject to very little qualification and as a
consequence a wide variety of botanicals and other substances
have been sold as dietary supplement ingredients, including
many that are considered to be medicinal substances under most
regulatory regimes in EU countries.
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• This liberalism in the interpretation has not been reflected
within the EU. In 1998 a report on a study carried out on
behalf of the European Commission by the AESGP, the
European Association of the SelfMedication Industry
concluded that several EU member states seemed to face
problems in applying identical rules to all medicinal
products in a uniform manner. The report which has the
title ‘Herbal Medicinal Products in the European Union’
found that there was no consistency between the 15
member states in the interpretation of the medicines
Directive 65/65/EEC with respect to herbs (AESGP, 1998).
The criteria used to differentiate between medicinal and
food herbs varied widely.
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• To further complicate the problem it was found that in terms of
indications and efficacy there was also no agreement between
the countries. For example, garlic (Allium sativum) is used for
colds and coughs in the United Kingdom whereas in Germany it
is sold for the prevention of arteriosclerosis. In the UK there are
some garlic products licensed as medicines whilst in the same
market there are a number of garlic products being sold as
supplements under food law. In Germany the law prevents
garlic being sold in unit dose form as supplements.
• Within European Medicines law a nutraceutical can be defined
as a medicine for two reasons:
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• 1. if it presented for the prevention, treatment or cure of a
condition or disease, or
• 2. if it can be administered with a view to restoring, correcting
or modifying physiological functions in human beings.
• Over the years the interpretation of the second part of the
definition if a medicine has been based on the accepted function
of the substance. Thus, a vitamin at levels around the daily
requirement (Recommended Daily Allowance) is considered to
maintain the function of healthy organs and tissues and is
regarded as a food ingredient. However, if a substance can be
demonstrated to modify the functions, or to restore or correct
the functions, the substance or the product containing it may be
considered medicinal.
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3. Regulatory frame work including regulatory
status of botanicals in different EU countries:-
• As already discussed there is currently no consistency in
the legal status of some botanicals across the EU. In some
EU countries, botanical products are sold as foods, or
incorporated in functional/fortified foods or as food
supplements, meaning that no medicinal claims are made,
whereas in other EU countries these preparations are seen
as herbal medicines registered by full or simplified
registration procedures. In some countries, the medicinal
product status is automatically linked to pharmacy-only
status.
• [Link] the definition of a medicine is given in EU
legislation
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• has been interpreted differently by member states in the
context of products containing botanicals.
• The definition is in two parts and a product falling into the
scope of either part is considered a medicinal product under
law.
• The first part of the definition relates to the presentation of
the product and any statements or implications that the
product can prevent treat or cure a human condition or
disease can make the product medicinal. Under EU food
law it is illegal for a food product to make such expressed
or implied statements (i.e. prevention, treatment or cure).
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• The second part relates to the function of one or more
components in the product. The text in the legislation
states, “Any substance or combination of substances
which may be used in or administered to human beings
either with a view to restoring, correcting or modifying
physiological functions by exerting a pharmacological,
immunological or metabolic action, or to making a
medicinal diagnosis” can be a medicinal product. Thus, if
any of the components have a pharmacological effect on
the human body the product can be considered medicinal,
even though no ‘medicinal’ statements are made in its
labelling or presentation. A product falling into the scope
of the second part is described as being ‘medicinal by
function’.
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• It is the precise interpretation of the second part that has led
to the inconsistencies of interpretation between member
states.
• 2. If medicinal claims are made based on its traditional use
as defined in Directive 2004/24/EC on traditional herbal
medicinal products, or the herb is considered medicinal by
function the product may be categorized as a traditional
herbal medicinal product, provided the time-related criteria
are met (i.e. 30 years use).
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• 3. If it is categorized as food or food ingredient. Article 2
of Regulation (EC) No. 178/2002 giving the definition of
a food ingredient must be taken into consideration. For
whole foods with benefits beyond basic nutrition (for
example, whole grain oats for cholesterol lowering
effect), the material must be well identified and
characterized.
• 4. Novel Food Regulation (EC) No. 258/97 defines a
novel food as foods or food ingredients, which have not
been used to a significant degree for human consumption
in the EU before 15 May 1997. (For example, Noni juice.
Lycopene derived from Blakeslea trispora.) A
comprehensive safety evaluation is required before
approval for use in foods is given.
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• 5. Directive 89/398/EEC defines foods for particular
nutritional use (PARNUTS) as foods, “which, owing to
their special composition or manufacturing process are
clearly distinguishable from food stuffs for normal
consumption, which are suitable for claimed nutritional
purposes, and which are marketed in such way as to
indicate such suitability”. This category covers the dietetic
foods. Examples are: infant formulae, baby foods for
infants and young children, slimming foods, foods for
special medical uses, sports foods, food for diabetics, etc.
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• [Link] 89/107/EEC defines food additives as
substances that are intentionally added to foods to perform
certain technological functions such as to colour, or to
preserve. Processing aids are not, as yet, regulated as food
additives and flavourings are the subject of specific
legislation.
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• 7. Food supplements are defined in Article 2 of Directive
2002/46/EC, as “Food stuffs the purpose of which is to
supplement the normal diet and which are concentrated
sources of nutrients or other substances with a nutritional
or physiological effect, alone or in combination, marketed
in dose form namely forms such as capsules, pastilles,
tablets, pills and other similar forms, sachets of powder,
ampoules of liquids, drops dispensing bottles and other
similar forms of liquids and powders designated to be taken
in measures small unit quantities”. Examples are
Pycnogenol® (French maritime pine bark extract), green
tea extract or grape seed extract.
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• [Link] is a regulation in progress for frame work
legislation on “Nutritional and Health Claims for Food”
and this is likely to be adopted early in 2006. The proposal
of European Commission (EU Commission, 2003a) was
made on 16.07.2003
• 9.A regulation on food fortification (EU Commission,
2003b) with the formal title of “The Addition of Vitamins,
Minerals and Certain other Substances to Foods” is at
present under consideration by the European Parliament
and the Council and could be adopted early in 2006.
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• [Link] as a cosmetic agent as perDirective 76/768/EEC
would put the herbal product into cosmetic category, as
defined in the legislation.
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Regulatory status of botanical nutraceuticals
as food supplements in the EU:-
• Even after the introduction of the Food Supplements
Directive 2002/46/EC, there is still very little harmonisation
across the EU, particularly with regard to substances which
are neither vitamins nor minerals. Botanicalsourced
supplement ingredients are:-
• Belgium has introduced both positive (permitted) and
negative (prohibited) lists for plants, their derivatives and
fungae. This list was amended in early 2005 to introduce
maximum levels of active constituents or marker substances
for a number of herbs and their extracts
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• In Germany almost all botanicals sold in unit dose form
(i.e. as supplements) are considered medicinal and require
medicines authorisation.
• In the United Kingdom a concession to sell certain
medicinal herbs without licensing (Section 12.2 of the UK
Medicines Act 1968) was removed from the 1 May 2004.
From October 2005 only those botanicals officially defined
by the British authorities as not being medicinal by
function will be permitted in supplements and foods. Other
products will require either registration under the
Traditional Herbal Medicinal Products Directive or full
medicines authorisation.
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• France has officially only 34 botanicals permitted for use
in foods with a further list of over 100 which can be
registered under a procedure similar to that required from
2005 for traditional herbal medicinal products. 80 O.P.
Gulati, P. Berry Ottaway / Toxicology 221 (2006) 75–87.
• The Netherlands is now regarded as having the most
liberal regulatory regime with the only controls currently
being a relatively short negative list of dangerous herbs.
• Italy has a list of notified herbal food supplement
products and another list of herbals prohibited to be
incorporated in food supplements.
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4. Quality aspects:-
• The botanical product should be well identified and
characterized. Identification, standardisation and
specification are of paramount importance in considering
the safety of botanicals. Here are few points to consider for
reference:-
• [Link] source:-
• identity, scientific name, common name;
• part of the plant used;
• geographical origin;
• contamination with other plant species: species
identification is a critical factor, where related or toxic
species/genera are known;
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2. Growth conditions:-
• good agriculture practice;
• wild or cultivated;
• site of collection;
• time of harvest;
• stage of growth;
• storage conditions post-harvest; pre- and post-harvest
treatments (use of pesticides, etc).
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[Link] material:-
• specifications according to standard method
(Pharmacopoeia) or validated standard method;
• quantitative test to determine constituents relevant to
their biological significance;
• stability data.
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4. Raw process applied to starting material:-
• extraction process;
• solvents;
• methods used;
• specific precautions (light temperature sensitivity).
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5. Safety studies:-
•In vitro safety data:-These include isolated cells,
microorganisms, subcellular components (enzymes,
receptors and DNA). These models are rapid, less
expensive and reveal mechanisms of actions. Guiding
Principle for the in vitro study data can: serve as signals
of potential harmful effects in human, but not 84 O.P.
Gulati, P. Berry Ottaway / Toxicology 221 (2006) 75–87
as independent indicators of risk unless an ingredient
causes an effect that has been associated with harmful
effect in animals or human and there is evidence that the
ingredient or its metabolites are present in physiological
sites where they could cause harms. Alone, in vitro study
should serve only as hypothesis generators and indicators
of possible mechanisms of harm when the totality of the
data from different key factors is considered. 30
In vivo animal safety data:-
• Animal studies serve as important signal generators and in
some cases, may stand alone as indicators of unreasonable
risks. These include acute, sub-chronic, chronic toxicity,
reproduction toxicity, in vivo genotoxicity and safety
pharmacology studies. Knowledge of an ingredient’s
pharmacokinetics and in vivo metabolism will allow most
appropriate interpretation of relevancy of the dose used in
the in vitro tests. All cells react differently to its unique
biochemical pathways.
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. Clinical safety data:-
• Vulnerable sub-groups: vulnerable subpopulations can be
defined as groups of individuals who are more likely to
experience an adverse event related to the use of a food
supplement or ingredient or an individual in whom such
events are more likely to be serious in comparison with
the general population.
• Characteristics of such vulnerability may be:-
• Physiological (capacity of digestion, metabolism and
excretion). Elderly population, children, age related
changes, pregnancy.
• • Disease related (hepatitis, renal disease may alter
xenophobic clearance, hypertension, diabetes).
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[Link] studies:-
• It is anticipated that for long-established and
noncontroversial science, e.g. health claims that describe
the role of a nutrient or another substance in growth,
development and normal physiological functions of the
body, the assessment and approval prior to their use, will
result in the compilation of an approved list within a 3-
year period of the entry into force of the regulation (and
O.P. Gulati, P. Berry Ottaway / Toxicology 221 (2006) 75–
87 85 that the EU will develop a register of such health
claims (generic health claims).
• For all other “product-specific health claims”, an
authorization procedure will be developed based on
substantiation by generally accepted scientific data.
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7. Conclusions:-
• The addition of botanical-sourced nutraceuticals to food
supplements and functional foods encompass a number of
issues. The predominant one is the status of the food or
ingredient in relation to EU legislation covering both
medicines and foods, as many of the ingredients are very
close to the borderline between the two classifications.
Although new legislation covering traditional herbal
medicines is now in force, the work on the control of
botanically derived substances and particularly herbs, in
food supplements and other foods has barely started and
controls of these ingredients in food supplements are now
unlikely to be in place before 2012. In the meantime
companies wishing to market products in the EU will have
to continue to assess their regulatory status in each member
state.
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References:-
• AESGP (Association of the European Self-Medication
Industry), 1998. Herbal medicinal products in the European
Union. ETD/97/501336, Brussels.
• Dietary Supplement Health Education Act (DSHEA) of
1994. Public Law 103–417, available at FDA Website:
[Link]
• Diplock, A.T., Aggett, P.J., Ashwell, M., Bornet, F., Fern,
E.B., Roberfroid, M.B., 1999. Scientific concepts of
functional foods in Europe—consensus document. Br. J.
Nutr. 81 (Suppl. 1), S1–S27.
• Ministry of Agriculture, Fisheries and Food (MAFF),
1995. Food standards and labelling division discussion
paper on functional foods and health claims. MAFF
Publications, August. 35
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