Medicinal products containing estragole
The committee on herbal medicinal products (HMPC) of the European Medicines Agency (EMA) published the revised Public Statement on the use of herbal medicinal products1 containing estragole (EMA/HMPC/137212/2005 Rev 1, https://www.ema.europa.eu/en/use-herbal-medicinal-products-containing-estragole-scientific-guideline). Estragole is a genotoxic carcinogen. For medicinal products the most important sources of estragole are fennel, fennel oil, aniseed, anise oil, star anise and star anise oil.
The CMDh stated in the meeting report from February 2022 (EMA/CMDh/78976/2022, „Medicinal products containing estragole as active substance or excipient“, https://www.hma.eu/human-medicines/cmdh/press-releases.html), that all medicinal products have to comply with the revised Public Statement within 2 years, which is March 2024.
Marketing authorisation / registration holders should check whether their medicinal products comply with the guidance value for estragole. If necessary, appropriate regulatory action should be undertaken. Excipients should be replaced if possible. The MAH/RH should justify if replacement of these excipients is not considered possible.
Changes in the composition (excipients) of the finished product fall under category B.II.a.3 of the Variation Classification Guideline. If the estragole containing excipient is a flavouring agent, a variation type IA is required, for excipients with other functions, a variation type IB is required to replace or reduce these excipients. Changes in the specification parameters and/or limits of an excipient fall under category B.II.c.1, e.g. B.II.c.1 f) “as a result of a safety issue” (type IB).
Changes in the composition (excipients) as well as changes in the posology and/or method of administration (incl. age limits) of nationally registered traditional herbal medicinal products and of registered pharmacy-owned medicinal products should be submitted according to AMG §24(2), changes in a specification according to AMG §24(5).
The BASG reserves the right to request the product specific risk assessment in case of any regulatory activity concerning medicinal products containing estragole.
