Environmental Risk Assessment ERA
Environmental Risk Assessment ERA

Human Medicinal Products

Human Medicinal Products - ERA

Environmental Risk Assessment ERA (acc. EMEA/CHMP/SWP/4447/00 Rev. 1):

Four properties of your API (Active Pharmaceutical Ingredient) will decide, to what degree you will need to perform an Environmental Risk Assessment (ERA):

- Octanol-water coefficient (logPOW)

- Water solubility

- Ready Biodegradability

- Dissociation constant (pKA)

LAUS can provide these parameters, and together with the Predicted Environmental Concentration (PEC) of the API, you will be able to develop a detailed test strategy and budgeting.

The revised version of the guideline on the ERA of medicinal products for human use (EMEA/CHMP/SWP/4447/00 Rev. 1) requires the determination of the logPOW in phase I, which could trigger a PBT/vPvB assessment. The PEC could trigger phase II testing, where water solubility and pKA are key for the decision which ecotoxicological studies will be necessary.

The Environmental Risk Assessment (ERA) must be included in the dossier for a marketing authorization application (MAA) for medicinal products for human use (HMP). LAUS supports you with experimental data throughout the entire process of the Environmental Risk Assessment (ERA) according to the requirements of the European Medicines Agency (EMA). We also have a network to assist you with toxicological and regulatory work.

Risk assessment, Phase I:

Draft Guideline EMEA/CHMP/SWP/4447/00 Rev. 1. states that in Phase I the potential for environmental exposure of the active substance of the medicinal product needs to be analyzed and evaluated. The risk assessment according to Phase I consists of a decision tree (for details refer to the homepage of the European Medicines Agency (EMA)).

Risk assessment, Phase II:

Phase II risk assessment is based on the physico-chemical properties, environmental fate and toxicity of active substances. With help of these parameters important information about the drug in the environment can be obtained. In this context, we at LAUS GmbH carry out studies according to Phase II of ERA, which examine the physico-chemical properties, as well as the environmental fate and the ecotoxicity of the drug and enable an evaluation (EMEA/CHMP/SWP/4447/00 Rev. 1.).

Table 1: Mandatory and non-mandatory studies according to Phase II of ERA:

  • Physico-chemical properties (4.2.1.1)
    OECD 105 Water Solubilty
    OECD 107 or 123 Partition Coefficient (n-octanol/water) (#)
    OECD 112 Dissociation Constants in Water
    OECD 101 UV-VIS Absorption Spectra (*)
    OECD 102 Melting Point/Melting Range (*)
    OECD 104 Vapour Pressure (*)
  • Fate properties (4.2.1.2)
    OECD 106 Adsorption/Desorption using a Batch Equilibrium Method with 3 soils and 2 sludges
    OECD 301 Ready Biodegradability Test
  • Aquatic toxicity (4.2.1.3)
    OECD201 Freshwater Algae and Cyanobacteria, Growth Inhibition Test
    OECD 211 Daphnia magna Reproduction Test
    OECD 210 Fish, Early-life Stage Toxicity Test (Danio rerio)
  • Functioning of STP (4.2.5.1)
    OECD 209 Activated Sludge, Respiration Inhibition Test
  • Sediment toxicity (choose one of the tests below) (4.2.1.3)
    OECD 225 Sediment-Water Lumbriculus Toxicity Test Using Spiked Sediment
    OECD 218/219 Sediment-Water Chironomid Toxicity Using Spiked Sediment/Spiked Water

(*) Not mandatory

(#) Study also required for Phase I PBT screening.

All further studies could be provided by a partner lab, contact us, if you don’t find your study on the list.