“This is very important news for the market in the United States,” Rick Kingston, president of regulatory and scientific affairs and senior toxicologist at SafetyCall International told NutraIngredients-USA. Kingston is also a clinical professor of pharmacy at the University of Minnesota.
The article, published in ABC’s HerbalEGram online newsletter, was authored by Mathias Schmidt, PhD, a pharmacist with intimate knowledge of kava (Piper methysticum) and the German market. Botanical ingredients are regulated differently there than they are in the United States, as they are classified as herbal drugs. Hence, the questions surrounding the way in which kava was first banned there and the subsequent decision to lift the ban differ from how such an action would proceed in the US.
Liver injury reports
The nitty gritty details: Almost 12 years ago kava was banned in the German market after a series of liver injury adverse event reports. On June 11 of this year, the German Administrative Court in the city of Cologne reversed that decision, saying there was not enough evidence to ban products containing kava. The administrative body that first banned the botanical, the Federal Institute for Drugs and Medical Devices (Bundesinsitut für Arzneimittel und Medizinprodukte, BfArM), has appealed the decision, so it may be several years yet before the legal issue is finally put to rest.
According to Schmidt, the ban was actually a withdrawal of marketing authorizations for medicinal products containing kava extracts. Kava as an ingredient has been shown to have calming properties, and in Germany had often been used as a alternative to benzodiazepines, a family of anti-anxiety drugs. The case features a complex regulatory history with BfArM changing in midstream some of the data requirements to prove safety and efficacy.
The initial ban rested on a small number of adverse events that connected kava use to liver injury. There were 26 cases of liver damage referred to in the original ban, but after closer investigation, only three could be definitely linked to ingestion of a kava containing product. Manufacturers of the products claimed in their appeal to the court that this represented a vanishing level of risk, when ranged against the approximately 450 million yearly doses of the product consumed in Germany prior to the ban in 2002.
Disproportionate response
“There certainly were questions about the safety, but the response was disproportionate to the risk,” said Kingston. “It seemed as if the decision to ban kava was politically driven on a number of fronts.”
Kingston said the German kava case points out once again the difficulty of evaluating adverse events reports in connection to herbal products. Formulations differ in the amount of actives they contain as well as in other ingredients, and patients have individual histories. Better data collection could aid both regulators and manufacturers, he said.
“The risk presented by the use of kava products is generally very low, but even kava proponents admit that it is not zero,” Kingston said. “Our challenge is to monitor for any new alleged cases of kava-associated liver damage and make sure they are properly documented, investigated and medically vetted. Additionally, if a case is identified, analysis and characterization of the kava will be important. Thus a robust post market surveillance effort should be put in place in those markets where it will be sold. This is especially true in the US where kava will likely also see resurgence due to the German news. Since kava products in the US are taken at consumer discretion, companies should prepare to conduct their own safety surveillance to confirm the safety of their products.
“Another aspect that hasn’t been brought up is that researchers at the University of Minnesota may have identified a mechanism for those rare instances of adverse liver effects, and they may also have identified how those rare adverse liver effects can be further reduced or eliminated with new kava formulations,” Kingston said.
Poised for greatness?
Kingston said that he believes that the German ban (and a subsequent ban on kava in the UK) has had a chilling effect on the US market, where kava-containing products can legally be sold, even though FDA put out a consumer advisory on kava in 2002. Kingston said he believes that kava is poised for super-stardom in the herbal market, not only for its anxiety-relieving properties but also because of promising cancer research conducted by his colleague Chengguo Xing, PhD.
“I think this is really good news for those individuals looking for an overall low risk product in the (anxiety) category, especially as compared to alternative drug products in the market,” he said.
To read the full ABC article, click here.