Over the past 15 years, a substantial amount of work has been done to determine the occurrence, fate, effects, and resulting risks of APIs in the environment. Regulations have also been developed regarding the assessment of environmental risks of APIs (e.g., CDER 1998; EMEA 2006; WHO 2011) and the pharmaceutical industry has done a vast amount of testing to meet these regulatory requirements. Currently, environmental assessments of APIs are typically performed at the end of the development process, i.e. when the API is close to an application for market approval. Concerns have been raised over whether the standard OECD testing methods for examining chronic effects on organisms (CDER 1998; CHMP 2006; CVMP 2000, 2004) will identify ecologically important effects of specifically acting APIs (Boxall et al., 2012; Brooks et al. 2009; ECETOC 2008). The effect of the nonsteroidal, anti-inflammatory compound diclofenac on vulture populations (Oaks et al. 2004) is one example of an affected non-target organism that would not have been predicted from standard studies.
The challenge is to identify potential environmental risks of new APIs during the early stages of the development process, such that intelligent and efficient testing strategies can be defined. This can be realized by developing predictive models based on preclinical and clinical pharmacological and toxicological data for existing APIs or by using Quantitative Structure-Activity Relationships for environmental endpoints. For example, knowledge of the presence or absence of API targets across a wide range of taxa could be invaluable in identifying those organisms and life stages of organisms that are most likely to respond to exposure to an API and which should therefore be specifically targeted in the risk assessment process (Ankley et al. 2007; ECETOC 2008; Gunnarsson et al. 2008; Huggett et al. 2003; Seiler 2002; Trudeau et al. 2005). Comparative biochemistry, genomics, and other “omic” technologies also offer potential tools for early identification of APIs of potential concern, as well as the most sensitive and vulnerable species.