Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Herbal Medicinal Products for Paediatric Population: Analysis of the Status quo in the European Union with Focus on Germany and Approaches to Improve the Situation ***

Simona Stratil (Abschlußjahr: 2015)

Summary
Language: English
The objective of this master thesis was to analyse the status quo Herbal Medicinal Products (HMPs) for paediatric population in the European Union with focus on Germany, as well as to present some obstacles and current approaches to improve the situation. The master thesis investigated Well-established Use Herbal Medicinal Products and Traditional Use Herbal Medicinal Products ((T)HMPs) as defined in the Directive 2001/83/EC.
The status quo of (T)HMPs was examined from the perspectives of three interested parties, which were the authorities (and the legislation), the paediatric HMP-users and the industry (by showing the (T)HMP-market exemplarily).
The Paediatric Regulation (EC) No 1901/2006 is applicable to all medicinal products in the EU, but it has been focused on applications of new pharmaceutical entities, which are obliged to submit a Paediatric Investigation Plan (PIP). Research funding in off-patent pharmaceuticals is limited to those medicinal products which are prioritised by unmet needs. (T)HMPs however are off-patent medicinal products commonly used for self-limiting illnesses. They are in no way unmet-need-medicines, however they are used or may be used by a considerable number of children and adolescents throughout the EU. The argument of the Paediatric Regulation that children should have access to properly assessed medicinal products applies as well to (T)HMPs as to any other class of medicinal products. The option offered by Paediatric Regulation to off-patent medicinal products, the Paediatric Use Marketing Authorisation (PUMA) application, has not yet been working.
One reason for excluding the (T)HMPs from the scope of Paediatric Regulation may have been that they have been used for a long time. Experiences as such of course do not meet the current requirements on sound scientific evidence and the bibliographical references on herbals used in children and adolescents are often of poor quality or lacking at all.
The lack of adequate data on paediatric use has been a rising concern, as the emerging legislation on paediatric use has set new standards. As a consequence the Committee on Herbal Medicinal Products (HMPC) and National Competent Authorities (NCAs) accepted paediatric indications in their monographs or in applications for (T)HMPs only if the use in each subset of paediatric population was well documented and complied with the requirements of the Guideline on Summary of Product Characteristics (SMPC). As frequently there was no sufficiently well documented evidence for the use of the specific herbals in children available, (T)HMPs and the corresponding HMPC-monographs were consequently recommended for older children or adults only.
The current situation is partly due to the fact, that there are no HMP-specific guidelines in place how to conduct (clinical) studies in paediatric population or how to collect data that consider the peculiarities of HMPs. Of course the HMPC has realised that there is an issue, and addressed it by the “Reflection paper on the necessity of clinical studies with HMPs in paediatric population” in the year 2011, but since then no further actions were initiated.
At the same time most users consider (T)HMPs to be safe and gentle, but nevertheless efficient remedies for children of any age and especially in Germany.
The paediatric HMP users, respectively their parents were identified as an inhomogeneous group. There are users who applicate the (T)HMPs as allopathic medicinal products according to package leaflet and would use as well chemical pharmaceuticals if needed, but on the other hand there are as well users who are extremely sceptical about chemical drugs and often use herbals as part of alternative therapies. Especially in this latter group herbals are often used in self-prescription and instead of “conventional medicine”. Moreover the users (or their parents) often do not inform the attending physician about the application (and vice versa the doctors do not ask), and subsequently the doctors as well often do not inform the NCAs about suspected adverse reactions of herbals.
It seems that the shares of the different user groups vary in the EU Member States, but actually the data are quite poor on this issue. At the moment not only there are very limited data on the actual use of (T)HMPs in the EU, but as well there is little communication between the users, the healthcare professionals and the authorities.
(T)HMPs are mostly used to relieve the symptoms of coughs and colds. The (T)HMP-market in Germany was therefore analysed by means of two examples of commonly used herbal substances (ivy and thyme). The analysis showed a very mixed picture of medicinal products recommended for very young children as well as medicinal products (containing the same substances) which were contraindicated for young children – however no comprehensible reasons for the varying recommendations were given.
The obvious solution to the current situation would be research and studies conducted by the applicants, but there is no obligation for (T)HMPs to file data on paediatric use with an application. As there are not even guidelines how to perform HMP-specific studies, the applicant would risk the investment in expensive studies which might not be accepted by the NCAs and which would not be subject to data protection.
An improvement of the current situation may be achieved by the implementation of the proposals made in the HMPC-Reflection paper, by providing appropriate guidelines and by promoting funding, even though it questionable if these options were used by industry. There are several proposals how to gain high quality information by bringing together data from different sources e.g. by pharmaco-epidemiological methods. A more vague approach may be the participation of patients and healthcare professionals.
However at the moment there are no new initiatives started at EU or national level.
When discussing the lack of information on HMPs in paediatric population in the EU, it must not be forgotten that this issue may not be equally important throughout the EU Member States. There are just a few Member States like Germany, France or Italy, where (T)HMPs play an important role. Thus the question remains, whether the problem will be judged as sufficiently serious to seek a solution.
Pages: 59,
Annexes: 2, pages: 62