Designing greener active pharmaceutical ingredients: Insights from pharmaceutical industry into drug discovery and development.

Active pharmaceutical ingredients (APIs), their metabolites and transformation products (TPs) are found as pollutants in the environment. They can impact human and environmental health. To address this issue, an efficient, long-term prevention strategy could be the design of APIs that have less impact on the natural environment, i.e. the design of greener APIs, by the implementation of environmental parameters into the drug discovery and development process (also abbreviated R&D for 'research and development'). Our study aimed to evaluate the feasibility of the design of greener APIs based on insights from drug design experts working in large, research-based pharmaceutical companies. The feasibility evaluation also identified needs and incentives for process modification. For this purpose, 30 R&D and environmental experts from seven globally active pharmaceutical companies were interviewed along a structured questionnaire. Main findings are that the interviewed experts saw manifold opportunities to include properties rendering APIs greener in different stages along the R&D process. This implementation would be favoured by the fact that the pharmaceutical R&D process is very flexible and relies on balancing multiple parameters. Furthermore, some API properties that reduce environmental risks were considered compatible with common desirable properties for application. Environmental properties should be considered early during R&D, i.e. when molecules are screened and optimized. It has been found that availability of suitable in silico models and in vitro assays is crucial for this environmental consideration. Their attributes, e.g. throughput and costs, determine at which process stage they can be successfully applied. An intensified exchange between R&D and environmental experts within and outside companies would push the industrial application of the benign by design approach for APIs forward. Collaboration across pharmaceutical companies, authorities, and academia is seen as highly promising in this respect. Financial, social, and regulatory incentives would support future design of greener APIs.

Design of greener drugs: aligning parameters in pharmaceutical R&D and drivers for environmental impact.

Active pharmaceutical ingredients (APIs) in the environment, primarily resulting from patient excretion, are of concern because of potential risks to wildlife. This has led to more restrictive regulatory policies. Here, we discuss the 'benign-by-design' approach, which encourages the development of environmentally friendly APIs that are also safe and efficacious for patients. We explore the challenges and opportunities associated with identifying chemical properties that influence the environmental impact of APIs. Although a straightforward application of greener properties could hinder the development of new drugs, more nuanced approaches could lead to drugs that benefit both patients and the environment. We advocate for an enhanced dialogue between research and development (R&D) and environmental scientists and development of a toolbox to incorporate environmental sustainability in drug development.

Three methods for integration of environmental risk into the benefit-risk assessment of veterinary medicinal products.

Veterinary medicinal products (VMPs) require, as part of the European Union (EU) authorization process, consideration of both risks and benefits. Uses of VMPs have multiple risks (e.g., risks to the animal being treated, to the person administering the VMP) including risks to the environment. Environmental risks are not directly comparable to therapeutic benefits; there is no standardized approach to compare both environmental risks and therapeutic benefits. We have developed three methods for communicating and comparing therapeutic benefits and environmental risks for the benefit-risk assessment that supports the EU authorization process. Two of these methods support independent product evaluation (i.e., a summative classification and a visual scoring matrix classification); the other supports a comparative evaluation between alternative products (i.e., a comparative classification). The methods and the challenges to implementing a benefit-risk assessment including environmental risk are presented herein; how these concepts would work in current policy is discussed. Adaptability to scientific and policy development is considered. This work is an initial step in the development of a standardized methodology for integrated decision-making for VMPs.