Paclitaxel

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 Abraxane 2008

Assessment report for Abraxane (paclitaxel), Abraxis BioSciences, EMEA/47053/2008.

"A revised Environmental Assessment Report (EAR) is provided based on the drug paclitaxel. The PEC_surfacewater value for paclitaxel in Abraxane is 0.0001 microg/L, based on peak (maximum) projected consumption at Year 2017 (projected figures provided from Year 2008 to 2017). This value is significantly below (100 times) the 0.01 microg/L Phase I action limit, as stipulated in the Guideline EMEA/CHMP/SWP/4447/00.It is concluded that Abraxane offers a negligible risk to the environment following its prescribed usage in metastatic breast cancer patients and from its storage and disposal. The applicant has provided ISM Health data to address the potential emission to the environment after use of Abraxane. Abraxane was estimated to take a 35% share in the estimated use of taxanes to treat the indicated health condition. Under this assumption the PEC is 0.1 ng/L. Even for a 100% share in the group of patients treated with taxanes, the PEC would not be surpassed." No further data are presented.

Assessment report Abraxane 2013

Assessment report for Abraxane for a new indication, Celgene Europe, 21 November 2013, EMA/CHMP/627629/2013.

Hazard

Persistence: No data.

Bioaccumulation: No experimental data are available for the partition coefficient (log K_ow) of paclitaxel, but estimated values in the literature indicate that the substance may have bioaccumulative properties (data not shown).

Toxicity: No data.

Risk

The applicant has submitted an ERA in accordance with the EMEA/CHMP/SWP/4447/00 guideline. Based on prevalence data, dosing and refined Fpen values, the combined PEC for paclitaxel is calculated to be 0.007 µg/L, which is below the 0.10 µg/L trigger value.

The environmental risk assessment cannot be finalised as the PBT assessment cannot be concluded. The log K_ow study must be evaluated. Available data indicate that albumin‑bound paclitaxel is not expected to pose an environmental risk. The CHMP recommends evaluating log K_ow, if necessary through a dedicated study.

Assessment report Abraxane 2015

Assessment report for Abraxane for a new indication, Celgene Europe, 22 January 2015, EMA/76768/2015.

Hazard

Persistence: No data.

Bioaccumulation: Log K_ow = 3.31.

Toxicity: No data.

Risk

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

PEC = 0.011 microg/L.

PNEC = No data.

As the total PEC_surfacewater exceeds the 0.01 μg/L action limit, a Phase II assessment has been initiated by the MAH. The available data do not allow a definitive conclusion on the environmental risk of paclitaxel. The CHMP recommends further investigation, including a Phase II assessment with a refined Fpen. No such data have been found on the EMA website for Abraxane (2026-02-24).

Assessment report Pazenir

Assessment report for Pazenir (paclitaxel), Teva, 28 February 2019
EMA/202215/2019.

"No Environmental Risk Assessment studies were submitted. This was justified by the applicant as the introduction of Pazenir is considered unlikely to result in any significant increase in the combined sales volumes for all paclitaxel containing products and the exposure of the environment to the active substance."

Assessment report Naveruclif

Assessment report for Naveruclif (paclitaxel), Accord Healthcare, 9 November 2023, EMA/535209/2023.

Hazard

Persistence: No data.

Bioaccumulation: No data.

Toxicity: No data.

Risk

PEC_surfacewater does not exceed the 0.01 µg/L threshold.

"In conclusion, the data package submitted includes adequate justification for not providing a complete ERA and thus indicates that Naveruclif is likely to pose a minor risk to the environment when used as recommended as well as during storage and disposal."

Assessment report Apexelsin

Assessment report for Apexelsin (paclitaxel), Whiteoak Pharmaceutical, 30 May 2024, EMA/283170/2024.

No Environmental Risk Assessment studies were submitted. This was considered acceptable as the introduction of Apexelsin by Whiteoak Pharmaceutical B.V. is unlikely to increase overall sales of paclitaxel products or environmental exposure. The ERA is therefore expected to remain unchanged.

Comment on generics

After the implementation of the latest European Medicines Agency (EMA) ERA guideline (1 September 2024), a generic company has the following options for Article 10 procedures under Directive 2001/83/EC:

i) to argue that a full ERA is not required because the pharmaceutical substance belongs to certain substance groups (e.g., so-called natural substances);

ii) to identify an official ERA from a previously accepted product and use it; or

iii) to develop its own ERA according to the latest EMA ERA guideline.

Arguments for not submitting an Environmental Risk Assessment (ERA) based on the claim that total environmental exposure has not increased (via total sales volumes) belong to the previous ERA guideline system (2006–2024) and are no longer applicable. Regarding option ii), it should be noted that if a reference ERA exists, the generic company must demonstrate that its conclusions remain technically relevant (since the latest ERA guideline introduced several new technical requirements absent in the previous ERA guideline) and in terms of exposure (showing that the estimated exposure used in the reference ERA remains reasonable). Regulatory authorities (national and EMA) recommend that generic companies attempt to obtain reference ERA documentation from other companies via a so-called Letter of Access (LoA). However, if this is not possible, it remains feasible to argue that the conclusions of an existing reference ERA are still relevant based on information gathered from public assessment reports (summarized descriptions of environmental risk assessments) and product information (to confirm that dosages, indications, etc., have not changed). It should be noted that in some cases, reference ERAs approved between 2006 and 2024 may need to be modified (e.g., with additional experimental studies). If no previous reference ERA can be identified or used, the generic company must commit to developing its own ERA.

Fass environmental information

Fass environmental information for Paclitaxel Fresenius Kabi (retrieved on 2026-02-24).

Hazard

Persistence: Paclitaxel is readily biodegradable, showing 68.1% mineralisation within 14 days. Hydrolysis occurs slowly (DT50 65.6 days at pH 5; 18.6 days at pH 7; 13.9 days at pH 9). As paclitaxel passes the ready biodegradation test, the phrase "paclitaxel is degraded in the environment" is applied.

Bioaccumulation: Paclitaxel shows low bioaccumulation potential, with a BCF of 1.59 and a log P of 3.5 at pH 7.

Acute toxicity: There are data for 3 trophic levels, most sensitive green algae EC₅₀ 1234 mikrog/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2021.

PEC = 0.001 microg/L.

PNEC = Lowest EC₅₀, 1234 microg/L/1000 (Assessment Factor (AF) for 3 acute studies = 1,234 microg/L.

PEC/PNEC = 0.00081 which gives the risk insignificant.

The statement in Fass "PNEC (μg/L) = 1234/100, where 100 is the assessment factor used" is inconsistent, as the reported result "PNEC = 1.234 µg/L" corresponds to the assessment factor 1000 rather than 100. In the calculation here, an assessment factor of 1000 has been used.