Fulvestrant

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 Faslodex

Assessment report for Faslodex (fulvestrant) 12 October 2017 EMA/53381/2018 and 29 May 2017 EMA/490887/2017.

Hazard

Persistence: "DT₅₀, sediment = 23–29 d (20°C). DT₅₀, sediment = 41 d (12°C). DT₅₀, whole system < 14 d (20°C) % shifting to sediment > 10%. Comment: "Not persistent."

Bioaccumulation: Log K_ow (ph 7) = 7.67. "The octanol-water partition coefficient, Log P_ow, is > 4.5, however the measured assessment of bioaccumulation potential in fish, BCF < 357, demonstrates that fulvestrant is not bioaccumulative."

Chronic toxicity: There are data for 3 trophic levels, lowest NOEC for crustacean (D. magna) 0.78 microg/L.

Risk

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

Phase IIB refined PEC_SW = 0.0037 microg/L.

PNEC = Lowest NOEC, 0,78 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 0.078 microg/L.

PEC/PNEC = 0.0474 which gives the risk insignificant.

Assessment report Fulvestrant Mylan

Assessment report for Fulvestrant Mylan, 9 November 2017, EMA/CHMP/810299/2017.

Hazard

Persistence: OECD 308: DT₅₀ = < 14 days (Total System).

Bioaccumulation: Log K_ow = 7.67. BCF < 400.

Toxicity: No data.

Risk

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

PEC_surfacewater, default or refined (e.g. prevalence, literature) = 0.00113 microg/L.

The environmental risk assessment (ERA) shows that predicted concentrations in surface water are well below the action limit, and no Phase II studies are needed. Although fulvestrant is a potential endocrine disruptor, the applicant provided sufficient public domain data to support a scientifically sound risk assessment while avoiding unnecessary animal testing. Fulvestrant is fully degraded during wastewater treatment and has low potential for bioaccumulation. The ERA is considered acceptable, and the non-clinical sections of the SmPC align with the reference product.

Fass environmental information

Fass environmental information for Faslodex from AstraZeneca (retrieved on 2021-07-07).

Hazard

Persistence: OECD 308: DT₅₀ = < 14 days (Total System).... Based on the evidence of the OECD303A and 308 the phrase “Fulvestrant is degraded in the environment” is assigned.

Bioaccumulation: Log P = 7.67. "Bioconcentration (Whole Body-Based on Total Measured Radioactivity) steady state = 338, Kinetic BCF = 357."

Chronic toxicity: "Long-term tests have been undertaken for species from three trophic levels, based on internationally accepted guidelines." Lowest NOEC for fish (Pimephales promelas) 0.0057 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2021. PEC/PNEC = 0.60 which gives the risk low.