The German Legal and Regulatory Environment and the History and Background of Commission E
In contrast to other countries in Europe, herbal medicines have a special status in Germany, beginning with the Imperial Decree of 1901 that permitted the trade of many botanical drugs outside pharmacies. This was incorporated into Articles 29 - 31 of the First Medicines Act (AMG) of 1961 (Schilcher, 1998b).
The legal basis for modern drug laws in Germany is based on European Community Directives 65/65/EEC issued in 1965, plus Directives 75/318/EEC and 75/319/EEC, issued in 1975. Under the terms of these directives all member states of the European Community pledged to establish a formal review of all medicinal products on the market at that time and to assure that they met appropriate standards for quality and purity. Products were to be reviewed for safety and efficacy and re-registered by 1990 in Germany.
Consequently, on August 24, 1976, Germany passed the Second Medicines Act ( Arzneimittelgesetz 1976, or AMG 76), which went into effect January 1, 1978, and required that the entire range of medicines in the pharmaceutical market (including conventional drugs, as well as medicinal plants and phytomedicines) be reviewed by scientific committees. AMG 76 includes special sections on phytomedicines: Article 22 Abs. 2 Nr.2, Section Article 25 Abs., Article 36, Article 44, and Article 45.
In 1978 the Minister of Health established a series of commissions to review various categories of drugs, including an expert committee for herbal drugs and preparations from medicinal plants, Commission E. These commissions were situated at the Bundesges-undheitsamt (BGA), the Federal Health Agency, charged with reviewing and approving the safety and efficacy of all drugs. In 1994 the BGA became the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), the Federal Institute for Drugs and Medical Devices.
According to the AMG 76, for preparations that were already on the market at that time, a transition period of 12 years was allowed, following European guidelines. During this time, the products remained on the market, but evidence of quality, safety, and effectiveness still required validation. The regulations were designed so that the manufacturer had to provide proof of pharmaceutical quality for traditional herbal ingredients, whereas evaluations of safety and effectiveness were relegated to the monographs to be published by Commission E (Steinhoff, 1997b).
However, all drugs that came into the market after the law went into effect (1978) had to be evaluated according to the procedures for new drug approvals. This applied to herbal and conventional drugs alike. The manufacturer must apply every five years for an extension of the drug registration. Proof of quality, safety, and effectiveness applied equally; however, for safety and effectiveness, reference to bibliographic evidence was allowed for herbal drugs (Steinhoff, 1997b).
Table 11: The Commissions of the German Federal Institute for Drugs and Medical Devices (BfArM)
Area of Expertise
||Angiology, cardiology, nephrology|
||Gastroenterology, metabolism, urology|
||Infectious diseases, oncology, immunology, pulmonology|
||Infusion and transfusion medicine|
||Radiology and nuclear medicine|
||Anthroposophic therapy and substances|
||Homeopathic therapy and substances|
||Phytotherapy and herbal substances|
|109a AMG 76
These commissions scientifically evaluated the following number of medicines: from 1978 until September 1994: 1,369 conventional drugs, 360 herbal drugs, and 187 veterinary drugs (Busse, 1997a). By the end of 1995, the total number of herbs evaluated by Commission E was 360, whereas the number of herb parts reviewed as preparations was at least 391. This seeming discrepancy is because in some cases there is a monograph for each of several parts from the same plant (e.g., Senna fruit and Senna leaf; Hawthorn leaf with flower, Hawthorn fruit, leaf, or flower respectively).
Composition of Commission E
According to the Second Medicines Act the members of the scientific committees must have experience in the respective therapeutic area.Commission E was composed of 24 members proposed by associations of the health professionals (physicians, pharmacists, non-medical practitioners (Heilpraktiker), pharmacologists, toxicologists, and biostatisticians) and by representatives of the pharmaceutical industry (Keller, 1992). Fifty percent are experts from the clinical or therapeutic field (Busse, 1996). Scientists and physicians serving on the Commission have authored over 1,000 scientific publications, not only in phytotherapy, but also in medicine, pharmacology, dentistry, health care delivery, and medical ethics. One longstanding member has written that the interdisciplinary nature of the Commission is unique in the entire world (Schilcher, 1997b). The Commission will be appointed every three years by the Minister of Health. The Commission is headed by a Chairman (Dr. Oelze) and a Vice President (Prof. Dr. H. Schilcher). The contact to the BfArM is Dr. K. Keller, who is considered the Referee (Berichterstatter). For a list of the current members of the Commission, please see page xvii.
For old herbal products already on the market that could not meet Commission E standards, a Traditional Medicine status was introduced in January 1992 that permitted the re-registration of traditional medicines without requiring rigorous studies and scientific data on a specific product (Steinhoff, 1993/4b). According to Article 109a of the AMG 76, these traditional products must be safe and meet standards for quality. The challenge of proving efficacy can be overcome by using traditional use as a criterion for effectiveness " drugs that have proven useful for many years." (Steinhoff, 1997b.)
These "traditionally used preparations" also must pass the review and control of the new Commission to 109a AMG 76, established in August 1996. This commission makes lists for traditional medicines (not limited to herb-based products) to include specific products mentioned in Article 44(1) AMG 76. Medicinal claims must be limited to minor conditions and preventive statements, and the phrase traditionally used in must be on the label. They can be intended only for indications such as strengthening, invigorating, or supporting the body (possibly not unlike a structure-function claim under DSHEA in the U.S.), but they cannot be intended to cure or treat a disease. Phyto-medicines approved by this commission do not qualify for reimbursement from medical health plans (Shilcher, 1998c). This commission is also composed of an interdisciplinary group of experts. Prof. H. Schilcher is Vice President of both this commission and Commission E (Schilcher, 1997b).
In sum, although these products must still meet standards for quality manufacture, their historical uses are not documented by plausible scientific data. Thus, there is a distinction between the standards for the approval of Traditional Medicines and the scientific standards for herbal drugs approved by Commission E (Busse, 1997; Steinhoff, 1993/4b, Schilcher 1998).
Regarding the standards for quality, the pharmaceutical quality of Traditional Medicines must be documented. As of the fall of 1997 the Commission to 109a AMG 76 has listed over 800 substances (many herbal) that the manufacturers have petitioned for inclusion. The BfArM does not inspect the manufacture of these medicines, but the pharmaceutical manufacturer must provide a statutory declaration for the herb ingredient, dosage form, and intended use. (Steinhoff, 1997b).