Recent Developments in Risk Assessments of Herbal Medicinal Products: Unlimited limitation?

Recent risk assessments for compounds of toxicological concern in herbal preparations involved new approaches and tools for risk minimization such as safety factors, the Margin of Exposure (MOE) or Threshold for Toxicological Concern (TTC) method. These methods are now regularly applied to assess the toxicological properties of isolated single compounds, and to extrapolate the results to herbal preparations containing this constituent. Thus, dose limitations for herbal extracts are regularly proposed even when the toxicological properties of the single compound are not known from the extract preparation as such.

The methods for risk minimization originate from environmental toxicology and were created to minimize contact to toxic impurities with no pharmacological benefit. Their use highlights a need for scientifically sound approaches to risk assessment for herbal medicinal preparations:

• In accordance with the recent EMEA concept paper [1], risk assessments must not be made on extrapolated suspicions which are not based on signals of adverse events.

• The safety factor, MOE and TTC methods are unsuitable for medicinal plants. They lead to random results which are obviously not in accordance with clinical experience.

• Metabolic factors and the scope of dietary exposure must be taken into consideration.

• Recently applied practises of risk assessment may lead to arbitrary and inadequate regulatory actions which may affect an in principle unlimited number of herbal preparations, regardless of the observation of adverse events.

References: [1] Concept paper on the development of a guideline on the assessment of genotoxic constituents in herbal substances/preparations (2006) EMEA/HMPC/413271/2006.