Entacapone

Detailed information

EMA’s scientific discussion on Comtess and Stalevo

EMA’s scientific discussion on Comtess (entacapone) 21/10/2005. "Environmental risk assessment - The applicant provided sufficient information on ecotoxicity and environmental risk associated with the use of entacapone." No data are included in the document.

EMA’s scientific discussion on Stalevo (levodopa, carbidopa, entacapone) 30/10/2006. "Environmental risk assessment - The applicant provided adequate information on ecotoxicity and environmental risk associated with the use of entacapone." No data are included in the document.

Assessment reports on generic entacapone

There are several assessment reports on generic entacapone products containing similar information. The most recent is for Levodopa Carbidopa Entacapone Sandoz, dated 19 September 2013 (EMA/CHMP/707244/2013). As this is an informed consent application for a product intended to replace an already approved medicine (Stalevo) at similar doses and indications, no increased environmental risk is expected. Reference is made to the CHMP assessment report (MA no. EU/1/03/260/001-038). A disposal statement was added to the package leaflet to support environmental protection.

Statement regarding generic medicines

After the implementation of the latest European Medicines Agency (EMA) ERA guideline (1 September 2024), a generic company has the following options for Article 10 procedures under Directive 2001/83/EC:

i) to argue that a full ERA is not required because the pharmaceutical substance belongs to certain substance groups (e.g., so-called natural substances);

ii) to identify an official ERA from a previously accepted product and use it; or

iii) to develop its own ERA according to the latest EMA ERA guideline.

Arguments for not submitting an Environmental Risk Assessment (ERA) based on the claim that total environmental exposure has not increased (via total sales volumes) belong to the previous ERA guideline system (2006–2024) and are no longer applicable. Regarding option ii), it should be noted that if a reference ERA exists, the generic company must demonstrate that its conclusions remain technically relevant (since the latest ERA guideline introduced several new technical requirements absent in the previous ERA guideline) and in terms of exposure (showing that the estimated exposure used in the reference ERA remains reasonable). Regulatory authorities (national and EMA) recommend that generic companies attempt to obtain reference ERA documentation from other companies via a so-called Letter of Access (LoA). However, if this is not possible, it remains feasible to argue that the conclusions of an existing reference ERA are still relevant based on information gathered from public assessment reports (summarized descriptions of environmental risk assessments) and product information (to confirm that dosages, indications, etc., have not changed). It should be noted that in some cases, reference ERAs approved between 2006 and 2024 may need to be modified (e.g., with additional experimental studies). If no previous reference ERA can be identified or used, the generic company must commit to developing its own ERA.