Docetaxel

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.

Docetaxel 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 docetaxel (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.

Assessment report for Taxotere 2010

Assessment report for Taxotere (docetaxel) London, 20.05.2010, Doc. Ref No.: EMA/355802/2010.

The CHMP assessed that environmental exposure to docetaxel, even with the extended indication, remained below the threshold value (0.01 µg/L). However, the data submitted by the MAH (Marketing Authorisation Holder) were questioned, particularly regarding the substance's degradability, bioaccumulation potential, and environmental toxicity. The CHMP found the tests to be insufficient, lacking relevant detail, and not in line with the guideline. The MAH was therefore requested to supplement its data, including a bioaccumulation study if the log K_ow exceeds 3, and to provide clearer statistics demonstrating that the new indication does not increase environmental exposure. If this cannot be done, a Phase II environmental risk assessment is required. No such data were found during a search of the EMA website (2025-06-25).

Assessment report for Taxotere 2019

Assessment report for Taxotere, type II variation, 19 September 2019, EMA/647024/2019.

The estimated annual consumption of docetaxel for all indications in the EU is 165.4 kg, based on expected use in patients with metastatic prostate cancer. This results in a predicted environmental concentration (PEC) in surface water of 0.000442 µg/L, below the regulatory threshold of 0.01 µg/L. Therefore, a Phase II environmental risk assessment is not required. Docetaxel is administered in small quantities under controlled hospital conditions and is therefore not expected to cause any significant environmental impact.

Assessment reports for generic versions of docetaxel

Assessment report for Docetaxel Kabi 15 March 2012, EMA/305675/2012. Assessment report for Doxetaxel Accord 15 March 2012, EMA/339179/2012. From the latter. "No Environmental Risk Assessment was submitted. This was justified by the applicant as the introduction of Docetaxel Accord manufactured by Accord Healthcare Ltd. is considered unlikely to result in any significant increase in the combined sales volumes for all docetaxel containing products and the exposure of the environment to the active substance. Thus, the ERA is expected to be similar and not increased."

Comment on generics in accordance with the ERA Guideline of 1 September 2024

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.