Posaconazole

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 reports Noxafil

Data from the assessment report for Noxafil (posakonazole) 24 Juli 2014 EMA/CHMP/75051/2015 and 20 Februari 2014 EMA/159150/2014.

Hazard

Persistence: "The half-life of the parent posaconazole in two river sediments was calculated to be 20.4 and 21.1 days. The half-lives of the two major transformation products in in two river sediments were calculated to be 38 and 106.7 (metabolite M2) and 358.1 and 108.1 (M3). The Applicant states that the metabolites (M2 and M3) could not be named according to chemical nomenclature as their definitive structures are unknown. However, different half-lives for the fate of the major transformation products (elucidated structure) of posaconazole in water/sediment systems have been calculated. Nevertheless, all three transformation products show persistence in sediment with half-lives >120d. Posaconazole is therefore classified as being persistent."

Bioaccumulation: "The Phase I screening for persistence, bioaccumulation and toxicity (PBT) indicates that further evaluation of posaconazole is not warranted due to a log K_ow < 4.5." "Based on the Phase II–Tier A assessment, posaconazole is unlikely to represent a risk to surface water, ground water micro-organisms and sediment dwelling organisms. Posaconazole is not likely to bioconcentrate in aquatic organisms and is not a PBT compound (BCF < 2000), indicating little risk to the aquatic and sediment environments."

Toxicity: No data.

Risk

The risk, PEC/PNEC, from a European perspective:

PEC = 760 microg/kg.

PNEC = 8.06 microg/kg. It is not clear how PNEC has been calculated.

PEC/PNEC = 0.01 which gives the risk insignificant.

Assessment report generics posakonazole

Assessment report for Posaconazole Accord, 29 May 2019, EMA/354142/2019, and assessment report for Posaconazole AHCL, 29 May 2019, EMA/354180/2019. Similar wording is provided in both assessment reports. The following text is taken from the latter: "No Environmental Risk Assessment studies were submitted. This was justified by the applicant as the introduction of Posaconazole AHCL manufactured by Accord Healthcare S.L.U. is considered unlikely to result in any significant increase in the combined sales volumes for all posaconazole containing products and the exposure of the environment to the active substance. Thus, the ERA is expected to be similar."

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 Noxafil

Fass environmental information for Noxafil from MSD (retrieved on 2026-07-07).

Hazard

Persistence: "Posaconazole has a half-life less than 32 days.The phrase “Posaconazole is degraded in the environment is thus chosen."

Bioaccumulation: "Posaconazole has a measured bioconcentration factor (BCF) of 20 (OECD 305)."

Chronic toxicity: There is NOEC for 3 trophic levels, lowest NOEC for algae (Selenastrum capricornutum) 41 microg/L.

Risk

PEC/PNEC is based on sales data in Sweden in year 2024.

PEC = 0.0038 microg/L.

PNEC = Lowest NOEC, 41 microg/L/10 (Assessment Factor (AF) for 3 chronic studies) = 4.1 microg/L.

PEC/PNEC = 0.00094 which gives the risk insignificant.