Febuxostat

Detailed information

General information about assessment reports

Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data are available in the public assessment report (PAR/EPAR for centrally approved medicines). Environmental considerations are not included in the benefit-risk assessment for human medicines. If new data emerge after approval that necessitate an update of the environmental risk assessment, a variation application (“type IB C.I.z variation”) must be submitted to the regulatory authority.

The PEC (predicted environmental concentration) values used to calculate risk in the manufacturers' assessment reports are based on the estimated use of the medicinal product to which the assessment report relates, as well as possibly other products from the same company, not all medicinal products containing the same active substance.

Assessment report Adenuric 2008

Assessment report for Adenuric (febuxostat), Doc Ref : EMEA/258531/2008.

"An environmental risk assessment including Phase I was carried out. The Applicant calculated a Phase I PEC_SURFACEWATER of 0.006 μg L ^-1 using the default values specified in the CHMP/SWP/4447/00 draft guideline. However, the Fpen used by the Applicant was 0.01 % rather than the default of 1 %. The use of an Fpen of 0.01 % was not supported by appropriate references. The correct PEC_SURFACEWATER is 0.6 μg L -1 which is well above 0.01 μg L^-1 and a Phase II assessment was requested by CHMP.

A Phase II investigation according to the Guideline on the environmental Risk Assessment of Medicinal Products for human use (EMEA/CHMP/SWP/4447/00) was performed, as requested in the CHMP LoOI), which included the following tests: Activated sludge respiration inhibition test (OECD 209), Assessment of ready biodegradability by measurement of Carbon Dioxide Evolution (OECD 301B), Activated sludge adsorption isotherm (OPPTS 835.1110), Inhibition of growth to the alga Pseudokirchneriella subcapitata (OECD 210), Fish toxicity testing to Pimephales promelas (OECD 203 and 210) and acute and chronic effects to Daphnia magna (OECD 211). As requested by CHMP the applicant commits to perform a study on aerobic transformation in aquatic sediment systems (OECD 308) for febuxostat to complete the Phase II environmental fate and effect analysis and to prove that febuxostat is unlikely to be a concern for the environment." No such data were found in the search of the EMA website (30 June 2025).

Assessment report Adenuric 2015

Assessment report Adenuric 2015, type II variation, 26 February 2015, EMA/CHMP/176388/2015 – corr.2.

The environmental risk assessment (ERA) for the initially approved indication showed that febuxostat is unlikely to pose an environmental risk when used as prescribed. For the new indication (Tumor Lysis Syndrome), which involves short-term treatment in a small patient population, the added environmental burden is expected to be less than 10%. This increase is considered insignificant, and febuxostat is still regarded as unlikely to represent an environmental risk.

Assessment report Febuxostat Mylan 2017

Assessment report Febuxostat Mylan 21 April 2017, EMA/368110/2017.

"No Environmental Risk Assessment was submitted. This was justified by the applicant as the introduction of Febuxostat Mylan manufactured by Mylan S.A.S is considered unlikely to result in any significant increase in the combined sales volumes for all febuxostat containing products and the exposure of the environment to the active substance. Thus, the ERA is expected to be similar and not increased. The CHMP agreed with this justification."

Assessment report Febuxostat Krka 2019

Assessment report Febuxostat Krka 31 January 2019, EMA/123663/2019.

No environmental risk assessment (ERA) studies were initially submitted. During the review, the applicant was asked to provide data supporting their claim of no expected increase in environmental exposure. An updated ERA with recent EU consumption data was submitted, but as the total exposure exceeded the Phase II trigger value, a Phase II ERA was deemed necessary. The applicant committed to conducting these studies by the end of 2021. No such data were found in the search of the EMA website (30 June 2025).

Comments on generics

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.