Are you ready for the environmental risk assessment of your products?
After years of discussion on the environmental assessment of medical products, the EMEA Directive has come into force (Source: EMEA /GHMP/SWP/4447/00).
An environmental risk assessment of all medical products is required. With just a few exceptions, all newly registered medical products with new and established active ingredients are affected.
The risk assessment includes the use, storage and destruction, but does not include synthesis.
Special situation for substances with log Kow >4.5 or "endocrine disruptors"
Substances, which bond strongly to organic substances and fat (limiting value log Kow >4.5) or which can interfere with hormonal control in organisms, are potentially dangerous and must be assessed independently from the quantity produced. If APIs are persistent, tests must be carried out to allow for assessment of bioaccumulation and toxicology in the environment.
Procedure for examining the risk of all other active pharmaceutical ingredients
The exposure in the environment is first calculated in a phased process and, if limiting concentrations are exceeded, studies will be required in Phase II, which enable a risk analysis to be carried out. The examination of exposure extends to the active pharmaceutical ingredient and relevant metabolites and includes all forms in which it is administered.
Phase 1: Examination of exposure in surface water
Human excrement and washing water are the main ways in which residues of medical products find their way into the environment. The concentration in surface water is therefore of particular importance.
The possible concentration in surface water is initially estimated in Phase I (Predicted Environmental Concentration = PEC). If the calculated value exceeds the precautionary value for the surface water (0.01 µg/L), then laboratory investigations are required (Phase II A and possibly Phase II B studies).
The calculation includes the maximum daily dose, the consumption data of the medicine, the influx of waste water and a dilution factor.
Source: EMEA / GHMP / SWP / 4447/00 Medicine
Input variablesMax. daily dose per inhabitantmg / (person*day)
Consumption per 100 persons0.01 = 1%
Waste water influx per inhabitantL/(person*day)
Output resultLocal conc. in surface watermg/L
Local conc. in surface waterµg/L
0,010,050,5Trigger for further risk assessmentPEC µg/L
AssessmentStopPhase IIAPhase IIA Table: Examination of exposure for medical products
In this example, the permissible environmental concentration for a medicine (AAA) with a market share of 1 % has already been reached with a maximum daily dose of 2 mg/person. With a daily dose of only 10 mg, the limiting value is already exceeded by a factor of 5. Because of the initially low dose and the low consumption value, it must be assumed that further studies relating to the environmental behaviour are required for all active ingredients.
The basic data record to be compiled in Phase II A involves studies relating to sorption and desorption in soils/sediments, rapid biological degradability, conversion in water/sediment systems under aerobic and anaerobic conditions, and a range of toxicological studies on algae, crustaceans (Daphnia spp), and early development stages in fish. Information on the environmental behaviour is provided by further studies into the inhibition of the degradation processes in waste water treatment plants.
The results are used to estimate a risk to the surface water, the groundwater and the soil. If further critical characteristics appear during this initial examination, further investigations may follow (Phase II B).
CriterionDirectiveEndocrinedisruptorsTGD 93/67/EEClog Kow>4.5 PersistenceTGD 93/67/EEC BioaccumulationTGD 93/67/EEC ToxicityTGD 93/67/EECPhase IIA Adsorption/DesorptionOECD 106, 121 BiodegradabilityOECD 301 Degradation; water/sedimentOECD 308 Algae, growth inhibition testOECD 201 Daphnia sp. reproduction testOECD 211 Fish, Early Life Stage TestOECD 210 MO, respiratory inhibitionOECD 209Phase IIB Degradation in the soilOECD 307 MO, N-transformationOECD 216 Plants, growth testOECD 208 Earthworm, acute tox.OECD 207 Collembola, reproduction testISO 11267MO = Micro-organisms Table: Studies relating to the environmental assessment of medical products
The investigation methods for the risk assessment of pesticides and chemicals have been developed and standardised in the last 15 years and are now applied to the active ingredients of medical products.
SGS INSTITUT FRESENIUS has established the required tests as part of its routine and has experts for assessing the environmental behaviour of medical products in surface water, soil and groundwater.
SGS INSTITUT FRESENIUS supports its risk analysis by carrying out tests in GLP certified laboratories, giving advice relating to a test strategy, and supplying globally applicable reports as well as expert statements.
If you are looking for assistance, inquire under e-mail or speak to our experts.
Dr. Eberhard Knoch – Environmental behaviour, metabolism, Tel.: 06128 744 158
E-mailDr. Ralph Weyandt – Degradability and ecotoxicology, Tel.: 06128 744 772
E-mailDr. Andreas Zumdick – Risk assessment of medical products, Tel.: 06128 744 730
E-mail SGS INSTITUT FRESENIUS GmbH, Im Maisel 14, D-65232 Taunusstein, Germany