N. Schultz (corresponding author), G. Franck-Karl, J. Schilk, N. Rose
Since Hahnemann's time preparations of materials of animal origin have played an important role in homoeopathy, such as snake venoms (Lachesis), honey bee (Apis), or cuttlefish (Sepia) as well as parts of slaughtered animals such as cattle or pigs. These preparations are therapeutically used in homoeopathy and anthroposophic medicine as single remedies or in combination with others in complex remedies.
Due to their natural origin, it is possible that such preparations of animal raw materials could be contaminated with pathogens from the animal and potentially harmful by transmitting these infectious agents to man. Therefore the safety of such preparations is of great concern. The European Pharmacopoeia monograph on ‘Homoeopathic Preparations’ requires pharmaceutical companies to take steps to minimise the risk of infection, e. g. by the choice of the raw material or the preparation method.
In particular, the question of how to demonstrate viral safety of animal raw materials was and is still a great challenge to pharmaceutical companies as well as to the authorities.
How to demonstrate viral safety
In this context the ‘Viral Safety Group’ was established, a working group of German pharmaceutical companies, all ECHAMP members, supported by the two major German pharmaceutical associations. All manufacturers have to follow the same legal regulations and use the same raw materials and production methods, so by combining efforts, the companies were able to share their pharmaceutical, veterinary and regulatory expertise and avoid the costly challenge of meeting the pharmacopoeial requirements alone. The aim of the collaboration was to elaborate a viable strategy on how to demonstrate the viral safety of homeopathic and anthroposophic preparations of animal origin as required by the Monograph ‘Homoeopathic Preparations’ of the European Pharmacopoeia.
Specifications were developed for each animal or human raw material, derived from detailed assessment reports about the risk of contamination with and transmission of pathogens by the material and/or its preparations. The assessments identify the risk associated with the various materials. The specifications cover the animals’ origin and living conditions, e.g. breeding conditions, housing, food and where applicable slaughtering conditions. Animals that are usually intended for human consumption must meet the EU food hygiene regulations (‘fit for human consumption’).
In order to show how different homeopathic methods of preparation can minimise or remove a potential virus load, as identified in the assessment reports, the working group initiated a validation study of the homeopathic manufacturing processes of mother tinctures and dilutions in terms of virus reduction or removal in accordance with the relevant European Medicines Agency Guidance on Virus Validation Studies.
In principle, one validation study would have to be performed for each animal preparation in homoeopathy or anthroposophy. Since there are about 100 different animal starting materials, some of them differently prepared, it was necessary to combine them into groups based on the assumption that materials with similar properties would show a similar behaviour against viruses. The criteria for the classification were the zoological taxonomy and the type of tissue as well as the pharmacopoeial preparation methods and the content of the alcohol with which the preparations were made.
Six main groups of fluid preparations were established, briefly characterised as follows:
|Preparations of poisons||glycerol 85% (m/m)|
|Preparations of small entire animal||ethanol 62% and ethanol 86% (m/m)|
|Preparations of excretions||ethanol 43% and ethanol 30% (m/m)|
|Preparations of components of slaughter animals||glycerol 85% (m/m) and glycerol + NaCl - sol|
|Preparations of animals with very simple material composition|
|Preparations with heat treatment|
Virus inactivation in solid preparations i.e. triturations of water or ethanol insoluble materials, cannot be tested. The risk assessment must be done individually.
Each group in the study was represented by an appropriate number of test preparations. Additionally, blank samples of all vehicles of the test preparations were tested as well as ethanol 15% and a 1+9 mixture of glycerol 85%/ethanol 43%, which is used for processing higher dilutions of snake venoms.
The publication describes the study procedure: the test preparations were spiked with four test viruses, representing the entire range of viral contaminants (RNA/DNA and enveloped/non–enveloped A reduction rate of 10-4 within the given time period was defined as effective.
The outcome was positive for the companies: all preparations and blank samples with ethanol concentrations of 30% (m/m) or higher and all glycerolic preparations/blank samples with sodium chloride effectively reduced three of the four test viruses, regardless of the animal material processed. Two tables illustrate these results.
None of the animal raw material showed an inhibitory effect on the virus inactivating capacity. This observation was of great importance because it justified the classification of the materials into groups. Therefore, the study results of one preparation apply to others within the same group and a large number of homeopathic and anthroposophic preparations benefit from the results of the test preparations.
Only a limited number of preparations were not effective in reducing or removing viruses. For these preparations, it is necessary to ensure viral safety in another way. For example, according to the risk assessment, toga viruses, enveloped RNA-viruses, may occur naturally in snakes. Preparations of snake venoms are prepared using glycerol 85% (m/m) without sodium chloride as a vehicle. Such preparations were not effective against enveloped RNA-viruses. Consequently, a cost intensive batch specific analysis on the absence of toga viruses is necessary.
This applies to low dilutions (≤ D6) of the snake venoms. Dilutions higher than D6 are prepared with ethanol 43% (m/m) according to the German Pharmacopoeia (HAB). An as yet unpublished supplementary validation study of the preparation of the dilution D7 was performed as an alternative to the batch-to-batch analysis.
The essay concludes that the work of the ‘Viral Safety Group’ provides a viable solution to ensure viral safety of homeopathic and anthroposophic preparations based upon Pharmacopoeial requirements. Moreover the results have been well accepted by the German Federal Institute for Drugs and Medical Devices (BfArM). Other approaches may be possible, but information is lacking.
This work was published as an essay, 'Viral Safety in Homoeopathic Medicinal Products,' in Pharmeuropa Bio & Scientific Notes (2011-1), a periodical publication of the European Directorate for the Quality of Medicines and HealthCare (EDQM).