Ibrutinib

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.

Assessment report Imbruvica 2014

Assessment report for Imbruvica (ibrutinib) 24 July 2014, EMA/CHMP/645137/2014.

Hazard

Persistence: In OECD 308 studies using sediments from Calwich Abbey Lake and Swiss Lake, ibrutinib showed DT₅₀ values of 4.2–9.5 days in water, 54–62 days in sediment, and 38–41 days in the total system. Since more than 10% of the substance partitioned to sediment, a sediment risk assessment is triggered.

Bioaccumulation: Ibrutinib has a log K_ow of 4.0 at pH 7. In an OECD 305 study, BCF values were 13.5 (low dose) and 68.0 (high dose). The substance is not considered bioaccumulative (not B).

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish (Fathead minnow) NOEC 15.5 microg/L.

Risk

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

PEC_surfacewater, refined (e.g. prevalence, literature) = 0.012 microg/L.

PNEC = Lowest NOEC, 15.5 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 1.55 microg/L

PEC/PNEC = 0.00774 which gives the risk insignificant.

Assessment report Imbruvica 2020

Assessment report for Imbruvica the most recent Type II variation was submitted in 2020, dated 23 July 2020 (EMA/CHMP/452512/2020).

"No new data for the environmental risk assessment were provided with this application. A complete ERA has been provided in previous procedures and considered acceptable. The MAH has provided a justification statement for not submitting an ERA. The proposed modification of the existing ibrutinib CLL indication does not extend the target patient population, and therefore there is no increase in environmental exposure versus the existing approved CLL indications. The justification provided is acceptable."

Fass environmental information

Fass environmental information for Imbruvica from Janssen-Cilag (retrieved on 2025-07-08).

Hazard

Persistence: Ibrutinib is not readily biodegradable according to OECD 301F. In OECD 308 simulation studies using aquatic sediment systems (Calwich Abbey Lake and Swiss Lake), the substance showed slow degradation, with DT₅₀ values of 4.2–9.5 days in water, 54–62 days in sediment, and 38–41 days in the total system. A significant portion of the substance became non-extractable in sediment after 100 days. Overall, ibrutinib is considered to degrade slowly in the environment.

Bioaccumulation: Ibrutinib has a log K_ow of 4.0 at pH 7 (OECD 107). In an OECD 305 study, BCF values were 13.5 (low dose) and 68.0 (high dose). The substance is not considered bioaccumulative (not B).

Chronic toxicity: There are data for 3 trophic levels, most sensitive fish (Fathead minnow) NOEC 15.5 microg/L.

Risk

PEC (0.01232269 μg/L)/PNEC is based on sales data in Sweden in year 2023. PEC/PNEC = 0.007950122 which gives the risk insignificant.