Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Möglichkeiten und Grenzen der Vermarktung von pflanzlichen Produkten

Dr. Angelika Koch (Abschlußjahr: 2006)

Language: English

In recent years there has been increasing interest on consumers and patients in the use of herbal medicines from a number of different herbal traditions, notably western herbal medicine, traditional Chinese medicine (TCM) and Ayurveda.
Many people wish to take responsibility for their own health. This may entail buying a herbal remedy or suitable “health food” made up to meet their individual needs. This is part of a wider trend of increasing interest in complementary and alternative medicines (CAM) in the developed world. The public generally considers natural products to be safe and beneficial. But unfortunately, these substances are largely unregulated.
It has been widely recognised that there is an international trade in herbal products and ingredients of unreliable quality and doubtful provenance. Some of the
problems reported, for example, the accidental inclusion of toxic herbs of
similar name or appearance to the intended species, reflect clear weaknesses in systems of quality control.

The purpose of this thesis is to describe the changes for placing herbal products on the market and to stress (take into consideration) the differences and changes in the field of quality and safety assurence

A: Herbal substances as a herbal medicine
The main European legislation regulating medicines, Directive 2001/83 EC, requires of industrially produced herbal medicines placed on the market to have a marketing authorisation (this means quality and safety assurance of the product before placed on the market.
The Directive 2004/24 EC (a) on Traditional Herbal Medicinal Products and the Directive 2004/27 EC (b) which both amend 2001/83/EC, put in place a regulatory framework for manufactured (a) traditional herbal medicines and (b) herbals of "well established use".
These amendmenst take into account the peculiarity of plants to furnish proof of quality and safety of herbal remedies and therefore, allow the establishment of a simplified procedure for the registration of manufactured traditional herbal medicines and, in order to facilitate the procedure in the area of herbal medicinal products the HMPC proposes an Annex on herbal substances and monographs compiled by e.g. ESCOP or WHO.
The implementation of this new legislation into national law causes different difficulties in the Member States.
Germany

In order to meet the requirements of Article 8 of the Directive 2001/83/EC manufactures of (herbal) medicinal products had to (re)-evaluate and (re)-authorize their products.

According to (section) § 105 AMG manufactures had the choise

  • to reach the new (section) § 39a via (section) § 109 (3) - 109a,
  • switch to food supplements,
  • to withdraw their products from the market (section) § 31 (waiver).

Initially, the Commission E was set up to prepare (positiv) monographs, to which manufacturers might refer to. This commission is now replaced by the HMPC (see above).
 
In the UK there has for many years been an exemption allowing the sale
and supply of unlicensed herbal remedies. Most herbal remedies on the
UK market are unlicensed. Section 12 of the Medicines Act 1968 provides an exemption from various licensing requirements of the Medicines Act for certain herbal remedies that are not industrially produced.
Section 12(1) of the Medicines Act 1968, permits unlicensed herbal remedies to be made up to meet the needs of an individual patient following a one-to-one consultation. Herbal remedies supplied under Section 12 (1) have not been not subject to a regime of specific safety or quality requirements. Seriously, anyone irrespective of qualifications or experience - can practise herbal medicine can make a diagnosis and, can make up and supply an unlicensed herbal medicine under Section 12(1) of the Medicines Act.
The unlicensed herbal remedies which are supplied under Section 12(2) may be subject only to simple processes (drying, crushing or comminuting) and must be sold without brand names or written claims: manufactured unlicensed herbal remedies sold as OTC products. Though there is a transitional period for products beeing on the market as of 30 April 2004 the Herbal Medicine Regulatory Working Group (HMRWG), made proposals as to the statutory regulation of the herbalist profession.

Quality and safety
The evaluation of Herbal Medicinal Products is performed by the Committee for Herbal Medicinal Products (HMPC) at the EMEA.
The new European legislation for traditional herbal medicinal products will require manufacturers of products registered under new national schemes to comply with regulatory provisions on pharmacovigilance.
The European pharmacovigilance system is based on a decentralized collection and validation of safety data by member states and a centralized evaluation (EMEA) and decision making process at the European Agency .

The current model of pharmacovigilance and its associated tools have been developed in relation to synthetic drugs. But taking into account the peculiarity of plants, preparing a new model which meets all characteristics of herbals, challenges the authorities. Several problems to monitoring the safety of herbal medicines relate to the ways in which herbal medicines are named, sourced, manufactured and utilised.
There is an urgent need for a communication of national, European and international pharmacovigilance and food monitoring systems because in the USA and many other foreign countries herbals are marketed as (unregulated) food stuffs.

USA: Herbal remedies are defined as dietary supplements, and by this, are defined by the Dietary Supplemental Health and Education Act (DSHEA) of 1994. They do not fall under postmarket regulation by the FDA, but the FDA is responsible, however, for taking action against unsafe products once reported. - Patients and consumers have to report ADRs.

Many patients take herbs in addition to medical treatment mostly without telling their practioners.The doctors have to learn that detailed questions about use of herbal drugs must form a part of taking a medical history.
Herbal - Drug interactions arise when they are given simultaneously. The impact on the metabolism of the medical agents may not be known.
Recently, many researchers have evaluated herbal-drug interactions and now continue to quantify the role of demographic, physiologic, and genetic factors that influence the activity of the drug metabolising systems in patients.
The enzyme cytochrome P450 is the most important herb/drug-metabolizing system.
The isoenzymes responsible for the largest part of drug metabolism are CYP3A (50%), CYP2D (25%), and CYP2C (20%).
Herbs may also induce enzymes and transporters in tumor cells and cause resistance to some cytotoxic agents or lessen therapeutic responses to other cytotoxic agents.That is why the concurrent use of some herbs with cytotoxic drugs may have clinical and toxicologic implications (e.g.Garlic).

The FDA, the EMEA and other agencies have developed websites containing enormous amounts of information on pharmacovigilance in general and on specific drugs in particular.

  • The FDA has begun to accept ADRs from healthcare providers and consumers directly on line using an electronic version of its MedWatch form,
  • in UK the Yellow Card Scheme was expanded on herbals,
  • a Herbal ATC Index was established in Uppsala in cooperation with WHO and the Royal Botanic Gardens in Kew.
Most ADRs reports refer to unlicensed herbal "remedies" , caused by counterfeited, contaminated or not properly identified plant sources in combination with a switch to food supplements because of easy marketing.
Fortunately, there are signs of a rapprochement between the two legal -drug and food frameworks.
In the longer term, improvements in safety monitoring of herbal medicines must include modifications to existing methodology, patient reporting and greater consideration of pharmacogenetics and pharmacogenomics in optimising the safety of herbal medicines and herbal foods.

The Codex Alimentarius Commission was created in 1963 by FAO and WHO to develop food standards, guidelines and related texts such as codes of practice under the Joint FAO/WHO Food Standards Programme. The main purposes of this Programme are protecting health of the consumers and ensuring fair trade practices in the food trade, and promoting coordination of all food standards work undertaken by international governmental and non-governmental organizations.
The food and consumer goods legislation (Regulation EC/178/2002) regulates the manufacture and handling of food and consumer goods. The Regulation establishes the principles of risk analysis in relation to food and establishes the structures and mechanisms for the scientific and technical evaluations which are undertaken by the European Food Safety Authority (EFSA).

Foodstuffs can be produced and sold in Germany without any special permission as long as it does not exert any damage on consumers health and meets the general standards(Codex Alimentarius and Weissbuch zur Lebensmittelsicherheit) set by legislation. However, manufacturers, importers and retailers are responsible for the quality and safety of the food they put into circulation.
They are bound by law to ensure and document the safety and quality of their food gained by internal control (retraceability). The competent authorities of the Federal States (Bundesländer) carry out regular controls and upon suspicion, take specimens for examination. The Food Monitoring Programme is a system of repeated representative measurements and evaluation of the content of pesticides, heavy metals and other contaminants in foodstuffs.
The entry of foodstuffs as e.g. food supplements, dietetic f and functional food into the market must be reported to the BVL. The BVL passes this information onto the competent authorities of the Bundesländer and to the Federal Ministry of Consumer Protection, Food and Agriculture.

Herbal substances in the "health diet" area

  • Food supplement: Directive 2002/46/CEimplemented into German law by theNemV regulates the labeling, presentation and advertising of these products. Nutritional supplements must not ascribe to therapeutic properties nor the ability to prevent or treat human illnesses, nor must they make any reference to similar properties. Ingredients such as vitamins, minerals and their sources have been extensively harmonized by the NemV but herbal extracts have not yet been regulated.
  • Among those foodstuffs that may state any health claims are foods for special medical purposes (Directive 89/389 EEC "Dietetic Food") Germany : DiätV).
    Dietetic food must fulfil strict criteria to meet the required health-related standards of specific groups of persons with special nutritional needs. Directive 2001/15/EC regulates substances that may be added for specific nutritional purposes in foods for particular nutritional uses. Botanicals/herbals become more popular as a source of nutritional additives.
  • Functional food or medicinal food is any fresh or processed food claimed to have a health-promoting and/or disease-preventing property beyond the basic nutritional function.The term was first used in Japan in the 1980s where there is a government approval process for functional foods, called "Foods for Specific Health Use" (FOSHU). The number of herb-related health foods have recently increased. Presently, however, there is no particular law that systematically controls or regulates health foods in Europe or Germany, that is why functional food is located at the borderline of food and novel food.
  • Novel foods are foods and food ingredients that have not been used for human consumption to a significant degree within the Community before 15 May 1997. Regulation Nr. 258/97 EC (directly implemented into the German Novel Food VO) lays out detailed rules for the authorisation of novel foods and novel food ingredients. In the course of the licensing proceedings, they are subjected to an extensive health-related assessment for the protection of consumers. The BVL(Germany) receives applications, prepares an initial test report which is then transmitted to the European Commission and the other Member States.
    On the other hand "Novel foods" or novel food ingredients may follow a simplified procedure, only requiring notifications from the company, when they are considered by a national food assessment body as "substantially equivalent" to existing foods or food ingredients (as regards their composition, nutritional value, metabolism, intended use and the level of undesirable substances contained therein).
Again, there is also an urgent need to resolve the issue of borderline products in collaboration with all parties involved.

Pages: 61
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