Herbal medicinal products in the European Union - AESGP

is justified. Certain combinations defined in the Agency Instructions No. 3 do not need to be
examined on a case-by-case basis.
Some herbal drugs may be added in order to improve the taste or other aspects. For
combinations of plants intended for use as herbal teas, the Agency allows a maximum of ten
different plants (and a maximum of five herbal drugs as active principles).
Germany
For medicinal products containing more than one active ingredient, Section 22 Paragraph
3a of the German Medicines Law must be respected. According to this legislation, it must be
justified that each active ingredient contributes to the positive assessment of the medicinal
product. In this context Paragraph 5 of the Guidelines for Medicines Testing
(“Arzneimittelprüfrichtlinien”) describes the documents that must be submitted and
differentiates between new and well-known combinations. For a combination of new active
ingredients, pharmacological-toxicological as well as clinical data are required. The same
principle applies to new combinations of well-known ingredients. However, well-known
combinations of well-known substances (assumed to make up the largest proportion of herbal
combination products) are assessed using bibliographic data.
The specific characteristics of the medicinal products in question must be evaluated using a
graduated risk assessment. Preparations with a low risk, including many herbal medicinal
products, might benefit from this approach if the requirements for the justification of the
combination are lower.
The Federal Institute for Drugs and Medical Devices (BfArM) has published a Commission
E working document “Assessment Criteria for Fixed Combinations” which is based on the
idea that the single ingredients contribute to a positive assessment of the preparation by
contributing to safety or efficacy. The dosage of the single ingredients must be appropriate
with regard to efficacy. Fixed combinations may be assessed positively if the ingredients
have an additive or potentiating effect, if side-effects can be reduced or if a simplification of
therapy or an improvement of therapeutic safety is provided by the combination.
Greece
For combination herbal medicinal products that have not previously been used
therapeutically in this particular combination, the results of studies on the actual
combination must be submitted. Studies on each single herbal ingredient are not required.
Ireland
With regard to combination medicinal products in general, guidelines published by the
National Drugs Advisory Board (NDAB) in 1984 [IRL 6] stated that evidence was required i n
support of the following criteria for assessment:
1. Each active ingredient should make a relevant and reasonable contribution to the
therapy.
2. The quantity of each active ingredient must be effective, safe and appropriate to the
recommended use and range of dosage.
3. Adverse interactions should not occur between the active ingredients at the
concentrations to be used. Such interaction would include diminished
reduced biological availability and altered excretion.
efficacy,
4. Each of the active ingredients should have an appropriate duration of action relative to
the other constituents.
5. The active ingredients should not have widely different therapeutic benefit-risk ratios.
6. The fixed combination product should not be recommended for use in the treatment of
disease in which careful individual adjustment of dosage is required.
Insofar as herbal medicinal products are treated in the same way as other medicinal
products, it would appear likely that the NDAB guidelines on fixed product combinations
would be applied to the licensing of combinations of several herbal ingredients. There are no
guidelines dealing specifically with combinations of herbal products
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