Melphalan

Detailed information

Fass environmental information

Fass environmental information for Alkeran (melphalan) from Aspen Nordic (retrieved on 2025-11-10).

Hazard

Persistence: There is no biodegradation data available for melphalan. However, due to its rapid hydrolysis (DT₅₀ < 24 h) and extensive metabolism, melphalan itself is considered non-persistent. Still, persistence of its degradation and metabolic products cannot be excluded, so the phrase “The potential for persistence of melphalan cannot be excluded, due to lack of data” is applied.

Bioaccumulation: Log D_ow = -0,52 at pH7.4.

Toxicity: There are data for 1 trophic levels, crustaceans > 10000 microg/L (OECD 202). Comment: Values reported as greater than are not according to the guidelines. The actual value may be lower.

Risk

PEC/PNEC is based on sales data in Sweden in year 2024.

PEC = 3.2*10^-5 μg/L.

According to the European Medicines Agency guideline on environmental risk assessment of medicinal products (EMA/CHMP/SWP/4447/00), use of melphalan is unlikely to represent a risk for the environment, because the predicted environmental concentration (PEC) at the time of registration was below the action limit 0.01 µg/L.

Since enough ecotoxicity data of relevance for the PNEC calculation is not available, the statement “Risk of environmental impact of melphalan cannot be excluded, since no ecotoxicity data are available” is used.

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 Phelinun (melphalan), 17 September 2020, EMA/CHMP/624882/2020.

Log K_ow is well below 4.5, indicating low bioaccumulation potential. PEC_sw exceeded the threshold, triggering Phase II studies. The applicant submitted an updated ERA with toxicity endpoints based on melphalan. OECD 121 was accepted as a substitute for OECD 106, but OECD 308 remains required. Toxicity is likely due to hydrolysis products, and further studies on degradation products are recommended. CHMP approves certain adjustments and accepts post-approval completion of remaining studies. No additional data for the requested studies were found during a search of the European Medicines Agency (EMA) website on 10 November 2025.