Pyrrolizidine alkaloids in herbal medicinal products - update.
Since toxic pyrrolizidine alkaloids (PAs) were detected in high concentrations in herbal medicinal products produced from plants that do not biosynthesize PAs themselves, in March 2016 BASG published risk-minimizing measures that were to be implemented by all affected marketing authorization / registration holders (<link news-center/news/news-detail/article/pyrrolizidinalkaloide-in-arzneimitteln-1125/>http://www.basg.gv.at/news-center/news/news-detail/article/pyrrolizidinalkaloide-in-arzneimitteln-1125/).Based on current data, the list of plants subject to mandatory testing must be expanded. Marketing authorization / registration holders of (traditional) herbal medicinal products containing active substances or excipients derived from- St. John's wort (Hyperici herba), - Passion flower herb (Passiflorae herba), -chamomile (Matricariae flos), - lady's mantle herb (Alchemillae herba), - licorice root (Liquiritiae radix), - balm (Melissae folium), - peppermint (Menthae piperitae folium), -sage (Salviae folium), - dandelion herb with root (Taraxaci herba cum radice),- thyme (Thymi herba), - horsetail herb (Equiseti herba), NEW-Nettle root (Urticae radix), NEW-Nettle herb, leaves (Urticae herba, Urticae folium), NEW-and preparations thereof (essential oils are provisionally excluded), must be registered by 1.7.2017 implement adequate changes in the dossier. Release specification: a limit of 1 µg toxic PA per maximum daily dose is to be included in the release specification of the finished product. Guidance on the analytical method and selection of PAs to be tested can be found in the HMPC Public Statement(http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2016/06/WC500208195.pdf). The dossier update must contain the description and validation of the analytical method.The actual testing can also be performed on the active substance, and in justified exceptional cases possibly on the starting material (e.g., medicinal teas). The results can be converted mathematically to the finished product.
Authorized herbal medicinal products, traditional herbal medicinal products (MRP/DCP):Change in the specification: IB-Variation application, B.II.d.1.g) Change in the specification parameters and/or limits of the finished product. Addition or replacement (excluding biological or immunological product) of a specification parameter with its corresponding test method as a result of a safety or quality issueMeasures to reduce PA exposure:IB variation application, B.I.a.2z) Changes in the manufacturing process of the active substance - other changeSkip testing (optional if sufficient batch analyses from the same raw material supplier are available):IB variation application B.II.d.1z) Change in the specification parameters and/or limits of the finished product - other change
Traditional herbal medicinal products (national registrations): A notifiable change according to §24(5) (change in the pharmaceutical-chemical documentation) has to be submitted. Despite the classification as a notifiable change, the BASG reserves the right to ask questions and / or demand improvement measures, if necessary.
