Raloxifene

Detailed information

General information about raloxifene

Raloxifene is a selective estrogen receptor modulator. According to the new guidelines for environmental risk assessments, Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use 22 August 2024, EMEA/CHMP/SWP/4447/00 Rev. 1- Corr., a specific assessment strategy for endocrine‑active substances is included.

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.

EMA’s scientific discussion on Evista

EMA’s scientific discussion on Evista (raloxifene) from Substipharm, 2005‑10‑21.

Calculations of multiple safety factors showed very large safety margins for surface water and soil, and the use of raloxifene was concluded not to pose an environmental hazard. No data were presented.

EMA’s scientific discussion on Optruma

EMA’s scientific discussion on Opruma (raloxifene) from Eli Lilly, 2005-10-21.

Calculations of multiple safety factors showed very large safety margins for surface water and soil, and the use of raloxifene was concluded not to pose an environmental hazard. No data were presented.

Assessment report for Raloxifene Teva

Assessment report for Raloxifene Teva, Doc Ref: EMA/231873/2010, London, 29 April 2010. No environmental information was presented in the assessment report.

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.

Pharmaceutical residues in the aquatic environment in Region Stockholm

Raloxifene has previously been measured and detected in effluent from wastewater treatment plants and in sewage sludge in Sweden.