Tofacitinib

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 reports on Xeljanz

There are several assessment reports containing environmental information on Xeljanz (tofacitinib). The 2018 report is presented below, as the applicant submitted a complete Environmental Risk Assessment (ERA) in support of the line extension and the change in therapeutic indication. In addition, the 2022 report is included, providing the most recent data on PEC_{surface water} to calculate the environmental risk.

Assessment report Xeljanz 2018

Assessment report for Xeljanz, Pfizer Limited, 31 May 2018, EMA/414633/2018.

Hazard

Persistence: DT₅₀ values and ready biodegradability were calculated using Modelmaker 4.0. For Brandywine Creek (freshwater), the DT₅₀ at 12 °C was 29.9 days in water, 350 days in sediment, and 70.2 days for the total system. For the Choptank River (freshwater), the corresponding values were 65.7 days in water, 273 days in sediment, and 135.7 days for the total system. Based on these results, the substance is classified as P in water and vP in sediment.

Bioaccumulation: Log D = 1.19 (pH 7).

Toxicity: There are data for 3 trophic levels, most sensitive fish NOEC 2.9 microg/L.

Risk

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

PEC_{surface water} = 0.10 microg/L.

PNEC = Lowest NOEC, 2.9 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 0.29 microg/L

PEC/PNEC = 0.34 which gives the risk low.

Assessment report Xeljanz 2022

Assessment report for Xeljanz, for a new indication, Pfizer Limited, 19 May 2022, EMA/CHMP/623552/2022.

Hazard

Persistence: No data are presented here, but they are available, for example, in the 2018 assessment report.

Bioaccumulation: Log D value < 4.5.

Toxicity: No data are presented here, but they are available, for example, in the 2018 assessment report.

Risk

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

PEC_{surface water} alla indications = 0.058 microg/L.

PNEC = Lowest NOEC, 2.9 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 0.29 microg/L

PEC/PNEC = 0.2 which gives the risk low.

According to the assessment report: The PEC/PNEC values for surface water (2 × 10⁻⁴), groundwater (3.1 x 10⁻⁵), microorganisms (5.8 x 10⁻⁶) and sediment dwelling organisms (1.9 x 10⁻²), are all significantly below the respective action limits, therefore it may be concluded that tofacitinib will not present an environmental risk following patient use. No environmental concerns are apparent.

There are differences in the PEC/PNEC ratios, but the calculations point more or less to the same conclusion: the risk is considered low.