Stability Testing

The AAHP office just received a copy of an article, Stability Testing of Medicinal Products According to Homeopathic Principles; this appeared in Pharmaceutical Industry (71, Nr. 12). The article was co-written by 8 colleagues of European companies, of which 5 are members, or related to members, of the AAHP. The article addresses the implementation, in daily practice, of stability testing requirements. However, due to the unique characteristics of homeopathic products, the authors note that such testing should be restricted only to those circumstances when appropriate. While the regulations cited in the article apply to the European Community, the same concepts are universally applicable for homeopathic products everywhere.

The authors indicate stability testing shows how the quality of an active substance varies over time due to the influence of environmental factors, such as temperature and humidity. Retest periods are defined based on systematic stability studies. But, the authors state, homeopathic products have a more complex relationship to retest periods, as they can be final products or an intermediate product for further processing.

Thus, the attenuation “… of the most concentrated preparation [to a higher attenuation] is a manufacturing step resulting is a new active substance or a new finished product, in line with the definitions of Article 15 of Directive 2001/83. Therefore always the individual manufacturing step is the start of a new re-rest period or new shelf-life.”

The authors go on to give examples of the implementation of stability testing requirements; these examples are based on the actual practices of companies manufacturing homeopathic medicines. For the most concentrated homeopathic preparations (e.g. tinctures), stability over time would be assured so long as the monograph specifications continue to be met. The article discusses assays and microbiological testing and addresses circumstances when these are not relevant tests based on the characteristics of the homeopathic products.

Addressing intermediate products, the authors divide these into two groups: those for which definitive substances are present and can be tested, and those for which there aren’t such substances present (either due to the source material or the degree of attenuation). In the latter case, general stability relevant properties are sufficient, for which the authors propose appropriate parameters. Likewise, finished products could fall into the same two categories, and the authors provide similar justifications and parameters.

In conclusion, the authors state stability testing should be restricted to those situations for which it is appropriate and “… the following principles should apply:

• “Stability testing of the most concentrated homoeopathic preparations should be performed if they are stored and if they are not re-tested immediately before use.
• “If the most concentrated homoeopathic preparation is not stored/storable, stability testing is performed on the first stored/storable dilution.
• “For intermediate products the re-test period can be deduced either from the re-test period of the most concentrated/first stored preparation or from [its’] own stability studies.
• “In the latter case, the re-test period of less concentrated preparations may exceed the re-test period of the more concentrated preparation.
• “For intermediate and finished products in which substances can be identified, identification is usually possible up to D3 [3X attenuation] depending on the method.
• “If substances cannot be identified, testing of the general stability-relevant properties is considered sufficient. In this case, the principle of a “group stability” according to chapter 3.2.3 can be applied, usually from D4 [4X attenuation]”

The full article can be obtained from the publisher at: http://www.ecv.de/suse_item.php?suseId=Z|pi|5137&susePattern=homeopathic