Imatinib

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 Glivec

Assessment report for Glivec (imatinib), 30 May 2013, EMA/CHMP/161314/2013.

Hazard

Persistence: Under aerobic and anaerobic conditions in aquatic sediment systems, the transformation of the substance was evaluated according to OECD 308 guidelines. The dissipation half-life (DT₅₀) for the whole system ranged from 83 to 137 days, while the time required for 90% dissipation (DT₉₀) ranged from 309 to 552 days.

Bioaccumulation: Bioaccumulation potential – log K_ow OECD 107: 3.5.

Toxicity: There are data for 3 trophic levels, most sensitive algae NOEC 960 microg/L.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC_{surface water}, default or refined (e.g. prevalence data, literature) = 3 microg/L.

PNEC = Lowest NOEC, 960 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 96 microg/L.

PEC/PNEC = 0.03125 which gives the risk insignificant.

Assessment report for generics

There are assessment reports for the generics Imatinib Teva and Imatinib Accord with similar environmental information. From the assessment report for Imatinib Accord dated 25 April 2013, EMA/389694/2013.

No Environmental Risk Assessment (ERA) was submitted. This was justified by the applicant on the grounds that the introduction of Imatinib Accord by Accord Healthcare Ltd. is not expected to significantly increase the overall sales volume of imatinib-containing products or the environmental exposure to the active substance. Therefore, the environmental risk is considered unchanged.

In accordance with EMA guideline (EMEA/CHMP/SWP/4447/00), the justification for not submitting a new ERA is considered acceptable.

Comment 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.

Fass environmental information

Fass environmental information for Glivec from Novartis (retrieved on 2025-07-09).

Hazard

Persistence: Imatinib shows low biodegradability. In a ready biodegradability test according to OECD 301B, only 9–12% degradation was observed after 28 days, indicating that the substance is not readily biodegradable (NOTOX Project 270258). In simulation studies conducted according to OECD 308 (NOTOX Project 486002), the dissipation time (DT) for the total system ranged from 82 to 111 days. Upon addition of imatinib mesylate to the water phase, the substance partitioned between the water and sediment layers. After 29 days of incubation, radioactivity in the water phase had decreased to less than 5% of the applied amount. No mineralisation occurred, and bound residues accounted for a maximum of 30–40% of the applied dose. No relevant metabolites were detected. According to the pass criteria for OECD 308 studies, imatinib can be classified as "slowly degraded in the environment," as the DT for the total system is ≤ 120 days.

Bioaccumulation: The partition coefficient log D at pH 7.4 is 2.34, indicating a low potential for bioaccumulation. Since log P is < 4, imatinib is considered to have a low bioaccumulation potential.

Toxicity: There are data for 3 trophic levels, most sensitive algae NOEC 960 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2021.

PEC = 0.25 microg/L.

PNEC = Lowest NOEC, 960 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 96 microg/L

PEC/PNEC = 0.00264 which gives the risk insignificant.