Deferasirox

Detailed information

EMA's scientific discussion Exjade

EMA's scientific discussion for Exjade (deferasirox), 2007-04-17.

"The PEC was 178-fold below the action limit (PEC >10 µg/kg soil) recommended in the draft guideline [EMEA, Released for consultation January 2005 (http://www.emea.eu.int/pdfs/human/swp/519902en.pdf) #8] on environmental risk assessment of medicinal products for human use. Therefore, no further analysis was performed. [...] Based on the results of the environmental risk assessment report, deferasirox is expected to be of negligible risk to the environment."

Assessment reports Exjade

Due to a type II variation and new formulations, environmental data is revisited in assessment reports. From the latest assessment report addressing environmental information for Exjade, 14 September 2017, EMA/639290/2017.

"According to the guideline on the Environmental Risk Assessment (ERA) of medicinal product for human use (EMEA/CHMP/SWP/4447/00 corr2), the evaluation of the environmental impact should be made if there is an increase in the environmental exposure. The molecule in this application is similar to the marketed one. Consequently environmental exposure with deferasirox is not expected to increase. The justification provided by the MAH for not submitting an updated ERA is considered acceptable. Therefore, deferasirox formulated as granules is not expected to pose a risk to the environment different from those identified for the initial market approval."

General about 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exposure has not increased (via total sales volumes) belong to the previous ERA guideline system (2006–2024) and are no longer applicable.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.

Assessment report Deferasirox Accord

Assessment report Deferasirox Accord 14 November 2019, EMA/659255/2019.

"No Environmental Risk Assessment studies were submitted. This was justified by the Applicant as the introduction of Deferasirox Accord manufactured by drug substance manufacturer is considered unlikely to result in any significant increase in the combined sales volumes for all deferasirox containing products and the exposure of the environment to the active substance. Thus, the ERA was expected to be similar."

Assessment report Deferasirox Mylan

Assessment report Deferasirox Mylan 25 July 2019, EMA/CHMP/509090/2019.

"No Environmental Risk Assessment studies were submitted. This was justified by the applicant as the introduction of Deferasirox Mylan manufactured by Mylan S.A.S is considered unlikely to result in any significant increase in the combined sales volumes for all deferasirox containing products and the exposure of the environment to the active substance. Thus, the ERA is expected to be similar."