10/11 March 2021
The Herbal Medicinal Products Committee (HMPC) of the EMA has published the draft of the updated public statement on pyrrolizidine alkaloids (PAs). The statement contains, among other things, the limit values for the daily maximum intake of PAs and can be commented until 15 November 2020.
The document is an update of the public statement published in 2014, which contained 0.35 µg PAs per day as maximum intake level. This limit is also specified in the Ph. Eur. draft for the new chapter 2.8.26. Contaminant pyrrolizidine alkaloids. At the same time, the USP is currently developing a new chapter on <1567> Pyrrolizidine Alkaloids.
In 2016, the German Federal Institute for Drugs and Medical Devices (BfArM) had asked pharmaceutical companies to check the risk of contamination in a product-specific way, to determine the content of pyrrolizidine alkaloids and to take measures if necessary. The aim of this BfArM measure was to avoid an exposure to PAs above 1 µg per day.
The revised HMPC document now comes to the following limit values:
Oral use of medicinal products (with PA-containing herbal starting materials/herbal preparations):
Topical application of medicinal products (with PA-containing herbal starting materials/herbal preparations):
Recommended strategy for the risk management of possible PA contamination
The basic procedure for risk management of PA contamination in herbal medicinal products should be based on the ALARA concept ("As Low As Reasonably Achievable", i.e. the risk should be as low as possible). According to the HMPC, contamination of herbal source materials with PA-containing herbs should not occur at all due to pharmaceutical product quality requirements and compliance with GACP and GMP.
With regard to the quality of herbal medicinal products, two main aspects should be considered:
The "HMPC Public Statement on the use of herbal medicinal products containing toxic, unsaturated pyrrolizidine alkaloids (PAs) including recommendations regarding contamination of herbal medicinal products with pyrrolizidine alkaloids" can be viewed on the EMA website.