Tox by Design ERA reports are developed in compliance with current EMA guideline and follow a stepwise procedure:
Step 1 − Phase I: Estimation of exposure to the drug substance
§ For drug substance with logKow > 4.5: Screening for Persistence, Bioaccumulation and Toxicity following ECHA guidance
§ For drug substance with logKow < 4.5:
- Calculation of the Predicted Environmental Concentration (PEC) restricted to Aquatic compartment:
The penetration factor Fpen represents the proportion of the population being treated daily with a specific drug substance and is calculated as follows:
- Actions limits:
=> If PECSURFACEWATER < 0.01 µg/L and no other environmental concerns are apparent: the medicinal product is unlikely to represent a risk for the environment following its prescribed usage in patients
=> If PECSURFACEWATER ≥ 0.01 µg/L: a Phase II environmental fate and effect analysis should be performed
Step 2 − Phase II: Environmental fate and effects analysis
Tier A: Initial environmental fate and effect analysis
Tier A is based on the drug substance: identified hazards, physico-chemical properties and fate of the substance in the environment.
- Calculation of the Predicted Non Effect Concentration (PNEC) by applying an assessments factor to the no-observed-effect-concentration (NOEC)
=> If PEC/PNEC < 1: the risk is adequately controlled
=> If PEC/PNEC < 1: further evaluation is required in Tier B
Tier B: Extended environment fate and effect analysis
The risk assessment may be refined using the refined PEC and the PNEC for the parent compound, as well as using the dedicated PEC and PNEC for the relevant (≥ 10% of amount excreted) metabolites.
- PECSURFACEWATER may be refined with information from STP modelling using the SimpleTreat model (EUSES, http://ecb.jrc.it)
- Analysis of the extended effects on water sediments and microorganisms
- Outcome: Information from the refined data set is available comprising:
=> Information on route(s) of excretion and qualitative and quantitative information on excreted compounds
=> Additional long-term toxicity data
=> Additional data on microbial inhibition
=> Additional information on the biodegradability of the substance
Step 3 − Precautionary and safety measures to be taken for administration, disposal and labelling
When the possibility of environmental risks cannot be excluded, precautionary and safety measures may consist of:
- An indication of potential risks presented by the medicinal product for the environment.
- Proposals for labelling (SPC, PL) giving an outline of the information that applicants could provide on precautionary and safety measures to be taken.
Labelling should generally aim at minimising the quantity discharged into the environment by appropriate mitigation measures
You can check Tox by Design methodology for Environmental Risk Assessments, which are duly validated and signed by an European Registered Toxicologist expert.
In the event you are performing this exercise for innovative compounds GMP scale up manufacturing, please be noted that Tox by Design is duly accredited for the French Research Tax Credit CIR.
Feel free to contact us using the Quotation Request below to receive a quotation for Environmental Risk Assessment of your drug products.