Product environmental improvement

We aim to integrate environmental considerations into a medicine’s complete lifecycle – from discovery and development, through manufacturing, marketing, use and ultimately disposal.

Our responsibility begins in discovery, where we are starting to explore the feasibility of predicting the environmental properties of drugs at an early stage, and continues through development, manufacture, launch and lifecycle management of a new medicine. We have environmental risk management plans for new products, and apply green chemistry principles to our manufacturing processes to maximise resource efficiency. We use non-ozone depleting propellants wherever possible, and are reducing the amount of packaging in our products. Once our medicines are on the market, we provide healthcare professionals with information on their appropriate use and we work with national and local authorities to make appropriate guidance available to patients about how to dispose of unused medicines. Finally we are starting to develop our ideas for ‘ecopharmacovigilance’ to support our Environment Risk Management Plans once a product is placed on the market.

Underpinning all of this activity is our commitment to environmental research.

Towards greener drugs

We are looking at ways to improve the environmental sustainability of our future product pipeline. Green drug design per se is extremely challenging and the needs of the patient will always come first. However, if there is a choice between two compounds, our aim is to determine whether mechanisms exist, or can be developed, to decide which one is ‘greener’.

Taking into account the many regulatory frameworks that we work within, we have a vision of what a ‘greener’ drug could look like. This vision considers the environmental hazard and risk profile of a candidate drug, together with the likelihood of it reaching the environment in an unchanged active form. The computer and laboratory-based tools that are available to assess these potential hazards and risks are being evaluated to determine whether they can be used earlier in the drug discovery and development process to inform decision making and candidate drug selection. Work conducted to date suggests that existing computer-based tools are unlikely to be predictive enough, but a number of laboratory screening tools have been identified that could potentially be used to inform decision-making at an earlier stage. These tools will be subject to further scrutiny and experimental validation to determine their predictability of environmental hazard and risk. The proactive development of greener drugs is still a long way from being realised but we currently remain committed to exploring this area further.

Environmental Risk Management plans

Our Environmental Risk Management Plans, introduced in 2008, now accompany new medicines along the path to launch. These plans enable all available environmental data to be taken into account at key decision points during drug discovery and development, and to provide early warning of medicines that could pose a potential risk to the environment. They also provide a framework for updating our risk assessments after a new product is launched, taking into account any new information that may be available.

Green chemistry

The main pillar used to ensure the sustainability of new active pharmaceutical ingredient (API) manufacturing processes is our 'SHE Triggers' model, which enables potential safety, health and environmental issues to be identified and designed out at the earliest possible stage. We apply ‘SHE Triggers’ to the full manufacturing process, including steps developed on our behalf by our suppliers. The model incorporates an environmental risk assessment tool to enable our scientists to prioritise environmental issues for their projects. The 'SHE Triggers' concept is now also used in the development of secondary manufacturing processes and pharmaceutical products, including environmental assessment of packaging and devices.

Our ‘Green Chemistry Network’ links environmental specialists, Pharmaceutical Development chemists and chemical engineers, and medicinal chemists to help promote the principles of green chemistry and engineering. All scientists in our Global Pharmaceutical Development function have the opportunity to attend training to raise awareness of how they can minimise the environmental impact of the manufacturing processes they are developing.The training includes practical and theoretical advances in the application of Green Chemistry, an appreciation of the environmental hazards associated with commonly used solvents and reagents and demonstrations of the tools that our Green Chemistry Network has devised, as outlined below.

• Solvent Selection Guide: This guide provides information to promote the selection of solvents with the minimum SHE impact when developing our processes.
• Acid/Base, Alkylating Agent and Amide Formation Reagent Selection Guides: These guides provide environmental information to promote careful consideration of environmental impact when reagents are chosen.
• Substance Avoidance Database: This tool lists all substances on relevant regulatory lists from around the world to highlight substances that should be avoided when developing manufacturing processes. For the most problematic substances, alternative choices are offered for the process development scientists. The database is continually updated.
  Active Pharmaceutical Ingredient (API) Removal Technology Selection Tool This tool aids selection of the most appropriate treatment technology for effluent streams containing APIs generated from manufacturing processes.

Promoting green chemistry and engineering

In addition to our internal efforts we are an active partner in the American Chemical Society Green Chemistry Institute (ACS GCI) Pharmaceutical Roundtable. This coalition between most of the world’s largest ethical pharmaceutical manufacturers has a mission to catalyse the implementation of green chemistry and engineering in the pharmaceutical industry globally. The group is active in process intensity benchmarking, the development of common green chemistry tools and funding academic research around the world.

Sustainable packaging and devices

We are committed to improving the sustainability of our packaging and have a target to reduce the amount of packaging we use per medicinal dose in our key products.

Packaging plays a critical role in protecting products as they transit through the supply chains. Making packaging more sustainable includes minimising on the amount of material used; using materials from recycled or renewable sources and using materials that can be recycled. Unnecessary packaging wastes energy and materials.

Environmental considerations are taken into account at an early stage of packaging and device development. We evaluate packaging of new projects at four critical stages of their development from idea generation to launch. At each stage projects are challenged to use less packaging and to minimise the use of hazardous materials, with appropriate consideration to the end user.

For established products we also continue to review our packaging requirements and identify improvements.  For example, we have a project looking at global standardisation which aims to reduce the complexity of packaging that is used for our products.

The principal impact of our inhalation therapy product portfolio is in the potential for the propellant gases contained in specific devices known as pressurised Metered Dose Inhalers (pMDIs) to contribute to climate change. These issues, and how we are managing them, are discussed in the Climate Change section.

Excretion from patients is recognised as the major source of pharmaceuticals in the environment, but inappropriate disposal of unused medicines is also a factor.

As part of our everyday business activity, we work through product packaging innovations and other initiatives to encourage patients to complete their course of medication.

The main aim is to make sure that they get the full benefit from the medicine by taking the full course, but improving patient adherence to a treatment regime also reduces the amount of medicines that are not used.

When medicines have to be discarded, patients should have the information they need to do so in an environmentally sensible manner. We work with national and local authorities to make appropriate disposal options and guidance available, and to discourage disposal to the drain or directly to sewage systems. We support the use of approved, voluntary ‘take-back’ programmes where these are available and the promotion of safe disposal by patients. Where schemes do not exist, then the only option is for the patient to take precautions to ensure that the medicines are made unpleasant and unrecognisable by mixing with undesirable household waste such as cat litter.

In the EU, for example, we are following the EU Directive recommendation to include a statement on the patient information leaflet about how to handle the waste product. We support the European Federation of Pharmaceutical Industries and Association’s (EFPIA) approach to reduce the waste of medicines and encourage and support the development of schemes to ensure the proper disposal of unused medicines. The situation is different in each EU country, but as an example AstraZeneca France supports Cyclamed, a non-profit organisation responsible for collecting unused medicines for human use returned by consumers to pharmacies.

In the US, the world's largest pharmaceutical market, we support the prescription drug disposal guidelines from the White House Office of National Drug Control Policy and the SMARxT Disposal Guidelines developed by the US Fish and Wildlife Service and the American Pharmacists Association in partnership with the US pharmaceutical industry association, PhRMA. These guidelines are designed to raise awareness of the potential environmental impact from improperly disposed of medicines and to provide proactive guidance through proper disposal alternatives.

The Environmental Risk Assessment (ERA) of a medicine is part of the registration submission to the EU and US markets. The ERA may discover potential environmental effects of the medicine before launch. However, until recently, there has not been a structured way of monitoring environmental risks of our medicines after launch. To fulfil this requirement, we have developed procedures to support ongoing ‘ecopharmacovigilance’.

Ecopharmacovigilance has been defined as; ‘the science and activities associated with the detection, evaluation, understanding and prevention of adverse effects of pharmaceuticals in the environment’. This is close to the WHO definition of pharmacovigilance, the science aiming to capture any adverse effects of pharmaceuticals in humans after use.

Our procedures aim to identify and manage any potential environmental risks, current or future, associated with our launched products. In practice, this is done via routine literature monitoring for any newly published information which may be relevant to understanding the potential environmental risks associated with our products. Such information may include any ecotoxicological information which could impact the Predicted No Effect Concentration (PNEC) and any information on fate and exposure which might impact on the Predicted Environmental Concentration (PEC). This information, together with knowledge gained from our own research on pharmaceuticals in the environment, is then used to refine the ERA as necessary. If potential risks are identified options for further risk refinement or risk management can be considered and an Environmental Risk Management Plan will be developed for the product in question.