Cladribine

Detailed information

Fass environmental information

Fass environmental information for Mavenclad (cladribine) from Merck (retrieved on 2025-09-24).

Hazard

Persistence: No data.

Bioaccumulation: Log K_ow = 0.0595 at pH 7 (guideline OECD 107).

Acute toxicity: There are data for 3 trophic levels, most sensitive algae EC₅₀ 1100 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2022.

PEC = 0.000004439 microg/L.

PNEC = Lowest EC₅₀, 1100 microg/L/1000 (Assessment Factor (AF) for 3 acute studies) = 1,1 microg/L.

PEC/PNEC = 0.000004035 which gives the risk insignificant.

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

Assessment report for Mavenclad, 22 June 2017, EMA/435731/2017.

Hazard

Persistence: No data.

Bioaccumulation: OECD 107: 0.0595.

Toxicity: Not data.

Risk

PEC_surfacewater = 0.00027 microg/L. "Cladribine PEC_surfacewater value is below the action limit of 0.01 µg/L and is not a persistence, bioaccumulation and toxicity (PBT) substance as log K_ow does not exceed 4.5. Therefore cladribine is not expected to pose a risk to the environment."

Comment

Cladribine has only undergone a phase I study in accordance with regulatory requirements for environmental risk assessments (Guideline on the environmental risk assessment of medicinal products for human use, EMEA/CHMP/SWP/4447/00 Rev. 1- Corr.) A phase I study includes data on bioaccumulation and an estimation of the environmental concentration of cladribine (PEC_{Surface water}). If the specified threshold values are not exceeded, the company is not required to conduct a Phase II study, which includes data on toxicity, persistence, and risk assessment based on PEC/PNEC.

EMA’s scientific discussion

EMA’s scientific discussion for Litak (cladribine) from Lipomed GmbH 2005-10-21.

The applicant calculated a crude predicted environmental concentration (PEC) of cladribine in the aquatic environment based on a worst-case scenario, resulting in a value as low as 0.0008 mg/L. An environmental risk assessment was conducted with focus on the aquatic compartment, which is considered appropriate given cladribine’s water solubility, low vapour pressure, and octanol-water partition coefficient. Since the PEC is well below the threshold of 0.1 µg/L, no further testing is deemed necessary.