Efavirenz

Detailed information

Fass environmental information

Fass environmental information for Stocrin (efavirenz) from MSD retrieved on 2025-06-26).

Hazard

Persistence: "Biotic degradation. Biodegradation Simulation Screening (FDA 3.11) ... Test results showed 12% biodegradation to CO₂ by Day 28.
Abiotic degradation. Photolysis (EPA 795.70) ... Test results indicate 85% photo-degradation over 16 days.
Justification of chosen degradation phrase: Efavirenz is degradable in biological systems and via photolysis, however the criteria for classification as degradable was not met. The phrase “Efavirenz is potentially persistent” is thus chosen."

Bioaccumulation: "Bioconcentration Factor (OECD 305). ... Measured BCF values were 439 for low concentration (0.9 µg/L) and 454 for high concentration (9 µg/L) Justification of chosen bioaccumulation phrase: Since measured BCF < 500, the substance has low potential for bioaccumulation."

Toxicity: There are data for 3 trophic levels, most sensitive algae NOEC 26 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2022. PEC/PNEC = 0.0088 which gives the risk insignificant.

EMA’s scientific discussion on Stocrin

EMA’s scientific discussion on Stocrin dated 3 November 2005. "Environmental risk assessment does not foresee any toxicological risk for the environment with efavirenz."

Assessment reports for generic versions of efavirenz

There are several assessment reports for generic products containing efavirenz with similar information. The most recent is for Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, dated 14 December 2017 (EMA/846772/2017). "The applicant submitted a statement that this combination product of efavirenz, emtricitabine and tenofovir DS does not contain any genetically modified organisms. Since efavirenz, emtricitabine and tenofovir has already been present on the European market with the originator's product for several years with recognized efficacy and an acceptable level of safety, the introduction of the generic product onto the market is unlikely to result in any significant increase in the environmental exposure and would thus not be expected to have an adverse effect upon the environment. With this regard and on the basis of CHMP Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use (EMEA/CHMP/SWP/4447/00), a formal environmental risk assessment for efavirenz, emtricitabine and tenofovir DS was not considered necessary by the Applicant and this is acceptable to the CHMP."

Statement regarding generic medicines

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.