AstraZeneca Corporate Responsibility - Our medicines - Pharmaceuticals in the environment

The environmental profile of AstraZeneca’s new pharmaceuticals is assessed prior to applying for government approval in a manner that is, at a minimum, consistent with applicable regulatory regimes. The science in this area is continuously evolving, and AstraZeneca is committed to conducting its assessments based upon the best available science. In light of this changing science, there has been much activity in a number of areas over the last few years. For example, the United Kingdom and Sweden have carried out major reviews of the scientific data relevant to the potential impact caused by pharmaceutical residues in the environment. New Environmental Risk Assessment Guidelines have now been introduced in the European Union and are being revised in a number of other regions, particularly in Canada and Japan. AstraZeneca continues to work with the relevant pharmaceutical industry trade associations to provide expert input to the current public consultations. In anticipation of these new guidelines, and as an element of our internal PIE-related initiatives, we have reviewed the environmental risk assessments for our existing products and, where appropriate, have carried out further studies to replace previous default values with measured data.

We make this environmental risk data, together with available information on our existing products, publicly available via the Swedish Doctors Prescribing Guide website using the voluntary disclosure system introduced by the Swedish Association of the Pharmaceutical Industry (LIF). The system was developed by LIF and a number of Swedish stakeholders, in conjunction with expert representatives from international pharmaceutical companies, convened and chaired by AstraZeneca. In association with the Association of British Pharmaceutical Industries we are also helping the Environment Agency for England and Wales to evaluate the risks of the existing medicines on their priority action list. We continue to investigate the potential application of green chemistry principles to our drug design process. In addition, we have introduced an Environmental Risk Management Plan that will accompany all new medicines through the development process and will enable all data relevant to the environmental risks associated with the use and disposal of medicines to be available at all key decision points.

Further data continues to be published on the presence of pharmaceutical residues in surface waters. This data is consistent with initial observations that, although variable, quantities present in the environment are likely to be several orders of magnitude below those that would pose any significant risk to human beings and are not high enough to cause immediate or short term (acute) harm to aquatic life. Nevertheless, a better understanding of the potential long term effects, if any, of pharmaceuticals in the environment continues to be a priority area of study for AstraZeneca’s environmental scientists, working both independently and in collaboration with other organisations to advance research in this area.

Although there is little evidence that the current concentrations of pharmaceuticals in the environment pose any significant risk the fact that they are present causes concern to some stakeholders. Complete elimination of such residues is unlikely to be possible. However, products in our development pipeline are likely to result in lower environmental residues than those in our current portfolio for two reasons. Firstly, the needs of the patient and the environment coincide, which means that changes in drug design aimed at improved treatment effectiveness will also improve the environmental performance. For example, the current treatment for tuberculosis requires the use of five different drugs over a period of 6-8 months, whereas the target for our TB research team in Bangalore is to produce a single drug that is effective within four months. If successful, this will lead to a significant reduction in drug released to the environment during the treatment of this widespread disease. Secondly, an increasing proportion of our pipeline consists of biopharmaceuticals and these types of molecule tend to be metabolised by the body or rapidly degraded in the environment.

AstraZeneca’s own scientists, located at our Brixham Environmental Laboratory, are at the forefront of research in this field, working both independently and in collaboration with other companies, leading academics and regulatory bodies to advance PIE-related research. We recently invested a further $24 million in new laboratories at the Brixham site to improve the facilities for the evaluation of environmental fate and persistence of pharmaceuticals.

Current work is concentrating on two areas of fundamental research. Firstly, improving our understanding of the processes leading to the breakdown of pharmaceutical residues by both biotic and abiotic processes, in the natural environment and in sewage treatment plants. This will improve our ability to model API concentrations in the environment, and promises to provide a better understanding of the fate of pharmaceuticals both in sewage treatment plants and in the wider environment. Secondly we are working to understand the potential for some APIs to exert atypical impacts on the biota in the receiving environment. In particular, we are investigating whether it is possible to predict ecological responses from the large amount of preclinical data that is already produced as part of the registration submission for all new drugs, thus reducing the need for additional animal testing. We expect the results to contribute positively to global efforts to continuously improve the overall state of scientific understanding in this area.

As the research moves forward, the understanding of some of the complexities of this issue improves. There was an initial concern that all pharmaceuticals might have long-term environmental effects that were not predictable, by extrapolation, from short-term studies. However, as evidence accumulates it appears that this may only be an issue for a small number of substances that demonstrate ‘atypical’ effects. For example, AstraZeneca has undertaken a fish full lifecycle study on tamoxifen that showed significantly less toxicity than might have been predicted for a hormonally acting compound. It also appears that even some closely related substances with the same mode of action can show very different environmental profiles. This has been observed with the beta-blockers, atenolol and propranolol, for example, where atenolol shows significantly lower toxicity to fish compared with propranolol. In addition, our research has demonstrated that natural photo-degradation, caused by sunlight, can be a powerful factor in the removal of pharmaceutical residues from the environment. For example, there is evidence that around 70% of propranolol can be destroyed this way. It seems, therefore, that all medicines should be evaluated on a case-by-case basis in these respects, rather than being grouped together as a single class or classes. We continue to publish our research in this area and a selection of our work is shown in the bibliography below.

Consistent with our commitment to product stewardship and sustainable production, AstraZeneca works continually to better understand the way in which our drug substances interact with the environment. One of our stated objectives is to pursue site-specific opportunities to minimise the amount of product lost to wastewater during our manufacturing activities. As far as practicable, through our process design and operating procedures, we aim to avoid the loss of product to the environment during manufacturing and ensure that any losses that do occur are unlikely to cause harm. To this end, we continue to develop and refine assessment tools that enable us to screen our discharges through application of available data and current scientific knowledge. During 2006, we introduced a new expert system to help our engineers to select the most appropriate effluent treatment technology. This system was used to verify the design of our new manufacturing facility in Egypt, commissioned during that year.

Based upon work conducted to date, we have no scientific basis for believing that our manufacturing discharges pose a significant threat to the environment. For example, a recent study monitoring the effluent arising from the AstraZeneca manufacturing facilities in Södertälje, Sweden, showed concentrations of APIs well below any effect thresholds of concern. This study will be published in early 2008. However, we will continue to conduct internal evaluations for purposes of identifying future research needs and guiding internal risk management decisions. In the longer term, we will continue to work to ensure that the development and application of our evaluation techniques remains consistent with the evolving science, and that our manufacturing activities remain protective of human health and the environment. One example of our commitment is our commissioning in 2005 of a $36 million state of the art biological treatment facility at our Avlon Works in Bristol in the UK as well as improving effluent treatment at other facilities.