Herbal medicinal products in the European Union - AESGP

(a) (ii) of Council Directive 65/65/EEC. No simplified proof of efficacy exists other than the
option of bibliographic applications.
Finland
The requirements for proof of efficacy have already been eased because these products fall
within the scope of “herbal medicinal products”. According to the existing legislation, the
efficacy (i.e., the proposed indication of the product) can be explained or proved by
information available in the scientific literature (bibliographic data). The requirements for
proof of efficacy cannot be simplified further, even when the manufacturer refers in the
indication to the “traditional use” of the herbal medicinal product.
France
The French Medicines Agency (AdM) grants marketing authorisations based on abridged
dossiers by making reference to traditional use. The shortened procedure requires limited or
no pharmacological, toxicological and clinical tests and is detailed in the Agency
Instructions No. 3 (“Cahiers de l’Agence No. 3”) [F 4]. The list of drugs with accepted
traditional uses was first published in 1985 by the Ministry of Health in a Notice to
Applicants (“Avis aux fabricants”). This list has been revised several times since 1985 i n
order to incorporate Community requirements and new scientific developments. The Agency
Instructions No. 3 include the most recent list. Traditional use has been recognised for
minor indications of approximately 200 herbal drugs as well as most of the preparations
derived from these drugs. Except for plant-based laxatives, indications are introduced by the
statement “Traditionally used in …” (“ Traditionellement utilisé dans … ”).
The abridged registration procedure may be used for herbal medicinal products if the herbal
drug or herbal drug preparation is included in the positive list of almost 200 herbal drugs
recognised by the AdM [F 4]. This list was compiled on the basis of available literature,
historical proof of widespread traditional use, safety, an optimum benefit-risk ratio,
chemical composition and well-established use in self-medication. The list may be updated
as new scientific data become available. It does not describe the preparations in detail.
Therefore, some flexibility concerning what constitutes innovation is left to the marketing
authorisation applicant. Generally, the AdM recommends that applicants justify the use of
any unusual preparation.
If the drugs and the indications claimed are on the positive list, the requirements for
pharmacological, toxicological and clinical data may be reduced or waived entirely.
When establishing the positive list, the AdM recognised that the available bibliographic data
do not meet the pharmaco-toxicological and clinical criteria required for a marketing
authorisation as defined in the EC Directives.
The Agency Instructions No. 3 also include a detailed description of the required contents of
the dossier, a list of toxicological recommendations by preparation and rules for labelling
and packaging of herbal medicinal products (with special recommendations for laxatives).
Chemical and pharmaceutical dossiers must be submitted in all cases.
The need for toxicological evaluation of a herbal drug or preparation depends on its
traditional use, pharmaceutical form and the presence of undesirable constituents in the
drug. With regard to the toxicological dossier, two cases are envisaged:
— Category 1: No study is required for most of the herbal drugs and herbal drug
preparations. This is the case in particular for herbal teas and laxative herbal drugs
— Category 2: A reduced toxicological study may be required for some herbal drug
preparations. This is the case in particular for most powdered drugs.
In certain cases, additional toxicological studies may be requested. This is particularly
likely for topical forms and for combinations of two plants included in the positive list
whose combination was not on the list.
With regard to clinical dossiers:
— Clinical data are not necessary if drugs and claimed indications are on the positive
list.
— Acceptability and/or bioavailability studies are generally not required.
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