Pharmaceuticals

The occurrence of medicinal products (e.g. drugs) and their metabolites in the environment is of increasing concern and one main focus of current environmental research (e.g. Halling-Sørensen 1998, Dietrich et al. 2004, Aga, 2007, Kümmerer, 2008). Indeed, the German Medical Law requires the submission of „ documents to assess potential environmental risks”. The European Medicines Agency (EMA) published several guidelines for the evaluation of such risks. For this, a distinction between human and veterinary medical products is made.

Human medicinal products

The directive 2001/83/EC of the European Parliament and of the Council related to medicinal products for human use demands that applications for marketing authorisations shall include, where necessary, an assessment of possible environmental risks due to the use and/or disposal of medicinal products.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has drafted a guideline for suitable ecotoxicity test strategies and for environmental risk assessment, which will be the basis for the future authorisation of human medicinal products.

Guideline on the environmental risk assessment of medicinal products for human use (July 2006). For the interpretation of the CHMH-guideline the EMEA has adopted a background document: Questions and answers on 'Guideline on the environmental risk assessment of medicinal products for human use (June 2010) EMA/CHMP/SWP/44609/2010.

The current status can be followed up on the website of the European Medicines Agency (Öffnet externen Link in neuem FensterHuman medicines - non-clinical general guidelines).

The CHMH guideline on environmental risk assessment of human medicinal products consists of two phases: Phase I assesses the exposure of the environment to the active substance and/or its metabolites. A predicted concentration in the environment (surface water) above 0.01 microgram per litre is assumed as criterion for the initialisation of Phase II (Risk assessment). Phase II is a tiered approach divided into level A and B, where the following ecotoxicity tests are required besides data on degradability and physical-chemical properties:

Phase I Tier A

(aquatic effects)

OECD 301 Ready biodegradability test  
OECD 201 Algae, growth inhibition test
OECD 211 Daphnia sp. reproduction test
OECD 210 Fish, early life stage test (FELS)
OECD 209 Belebtschlamm-Activated sludge, respiration inhibition test

Phase I Tier B

(terrestrial effects)

OECD 208 Terrestrial plants, growth test
OECD 207 Earthworm, acute toxicity test
ISO 11267 Collembola reproduction
OECD 216 Soil microorganisms, nitrogen transformation test

As one can see, the main focus is on the investigation of chronic effects. Hydrotox GmbH is offering all the aquatic ecotoxicity tests mentioned above.

Veterinary medicinal products

Similar as for human medicinal products the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) has published three guidance documents on suitable ecotoxicity test strategies and on environmental risk assessment:

  • Environmental Impact Assessment for Veterinary Medicinal Products Phase I (final 2000)
  • Environmental Impact Assessment for Veterinary Medicinal Products Phase II Guidance (final 2005)
  • Environmental Impact Assessment for Veterinary Medicinal Products in support of the VICH guidelines GL6 (Phase I) and GL38 (Phase II) (final September 2007)

The CVMH guideline on environmental impact assessment for veterinary medicinal products consists of several phases. Phase I assesses the exposure of the environment to the active substance and/or its metabolites and defines the further proceeding by using a decision tree. In Phase II Tier A, assessment of the acute aquatic and terrestrial ecotoxicity follows, and in Phase II Tier B the chronic ecotoxicity is assessed.

The current status can be followed up on the EMEA website (Öffnet externen Link in neuem FensterVeterinary medicines safety and residues).

Hydrotox GmbH offers all acute and chronic aquatic tests with algae, daphnia and fish.


References:

  • Aga, D. S. (2007). Fate of Pharmaceuticals in the Environment and in Water Treatment Systems. CRC Press, USA
  • Dietrich, D. R. et al. (2004). Hot Spot Pollutants: Pharmaceuticals in the Environment. Advances in Pharmacology, Elsevier Academic Press, USA
  • Halling-Sørensen B, Nors Nielsen S, Lanzky PF, Ingerslev F, Holten-Lützhoft HC, Jorgensen SE. 1998. Occurrence, fate and effects of pharmaceutical substances in the environment - a review. Chemosphere 36:357-393
  • Kümmerer K.(Third Edition) 2008. Pharmaceuticals in the Environment. Springer Verlag, Germany.