Piero Iamartino
Although the impact of medicines on the environment has been highlighted since the 70s of the last century with the emergence of the first reports of pollution in surface waters, it is only since the beginning of the 2000s that specific regulatory interventions have been designed to promote the identification of the different sources of pollution and the determination of possible actions to be taken.
The obligation to submit the result of an environmental risk assessment of a medicinal product at the same time as the application for marketing authorisation was introduced only after the publication of the Environmental Risk Assessment (ERA) guideline issued by EMA in 2006, which sets out the guidelines and describes a series of standard tests to be performed. However, this first piece of legislation immediately highlighted limitations as it was applied only to the marketing of medicines from that moment on, without considering the contribution of medicines with the same active ingredient and neglecting the evaluation of those already authorised and on the market.
Over the following years, the problem of the environmental impact of medicines was tackled more extensively with the launch of several projects promoted by the European Commission in partnership with the EFPIA (IMI: Chem21, iPiE and Premier) which have deepened the characterisation of environmental risks, with the identification of priority criteria to be assigned to interventions and the development of models and tools to measure the sustainability of the processes of manufacture, in particular of active substances.
These important projects in recent years have been added to the initiatives undertaken at the European level with the publication in 2020 of the new European pharmaceutical strategy which defines some specific objectives for the mitigation of the environmental impact of medicines that will be reflected in the upcoming revision of European pharmaceutical legislation and which are part of the broader regulatory acts for the ecological transition envisaged by the Green Deal European.
In light of the above, a gradual transformation of some processes and operating methods carried out by the European pharmaceutical industry is envisaged, starting from the development of a new medicinal product to its distribution and, similarly, adequate regulatory interventions will have to be envisaged on the management of the correct use and disposal of medicinal products since the environmental impact of this last phase of the life cycle of a medicinal product is predominant.
Although these changes involve all professionals working in the pharmaceutical industry, a key role is played by the industrial pharmacist who, due to his professional profile dictated by his university curriculum, has the fundamental knowledge bases to occupy different positions in the industry, covering the entire path of medicine from its conception and manufacture as an active ingredient, its development as a medicinal product and its distribution on the market.
With this in mind, EIPG has started the preparation of a document that analyses the main critical areas of the entire production process of a medicinal product and sets out its position on the interventions considered a priority in a perspective of changes that will lead to the inclusion of new methods alternative material resources and will require new skills.
The first critical area examined is the manufacture of the active ingredient, both for its impact as such on the environment and for the process applied to its manufacture. The problem is particularly relevant for small molecules, while it is substantially insignificant for large molecules and even less so for products based on the use of cellular tissues or biological structures (ATMPs). The fundamental parameters to be considered are the environmental toxicity and the bio-degradability of the product. The problem is how to reconcile these two parameters with the chemical-physical and biopharmaceutical characteristics that an active ingredient must possess to be administered, absorbed and then carry out the desired pharmacological activity. The effort required in the design and screening phase of a new small molecule is the identification of a structural parameter that makes it more eco-friendly without compromising its purpose. Although this criticality does not arise in the case of large molecules and ATMPs, for these active ingredients the environmental impact due to higher energy consumption attributable to the need for low-temperature storage conditions may prevail.
About the production process of small molecules, which today still represent the largest percentage of active ingredients in development and on the market, it is essential to definitively introduce the application of the principles of Green Chemistry, as highlighted by the most recent studies (IMI Premier Project). The prospect is that of a progressive change in the synthesis processes with the use of reagents and less toxic solvents that are entirely recyclable and reusable, as well as the development of a synthesis route that allows the least number of operations, generating the least amount of waste and maintaining the best possible efficiency. It is desirable to increase biocatalysis processes as well as the introduction of more incisive treatments in the management of industrial wastewater to accentuate chemical degradation before their transfer to eternity.
A second large critical area where important changes are expected is the manufacturing processes of the medicine from the active substance to its availability for distribution on the market. Also in this area, interventions can be identified to optimize the use of the resources used, with particular reference to energy consumption and the use of water. These two parameters are already the subject of numerous studies for the development of new energy containment processes with the introduction of innovative plant solutions, and further improvements are expected considering the benefits that derive from them in terms of efficiency and therefore costs.
Among the parameters closely linked to the medicinal product that shows a significant environmental impact, attention must be paid to the packaging materials used in the pharmaceutical industry. A priority intervention must focus on certain widely used plastic materials that are difficult to dispose of and not recyclable, identifying alternative materials with the consequent need to study their compatibility with the medicinal product, especially if used in direct contact, and their impact on the stability profile of the same, as required by the reference standards. Other objectives should be the choice of secondary packaging materials that can be easily recycled by the end user, as well as the reduction of their volume, also favoured by the digitization of the information materials related to them. The implementation of these interventions will require adjustments both to the packaging lines used in the pharmaceutical industry and to the alternative ways of managing products in the transport and distribution phase, with a marked increase in studies for the reuse of packaging materials in line with the principles of the circular economy.
The prospects of the expected changes in the path from the active substance to the medicine will have to be accompanied by an assessment of the possibilities of intervening in the supply chain used by the pharmaceutical industry involving suppliers of active ingredients, materials and medicines. The regulatory guidelines and commitments on actions to improve environmental sustainability will require a progressive review in the management and evaluation of suppliers according to their ability to apply the ecosustainability criteria of their processes, giving preference to those who take this path.
The above analysis, limited to the areas of greatest environmental criticality, highlights the transformations that are expected in the pharmaceutical industry in the coming years with the implementation of the provisions that will be progressively adopted at the European level. We think there should be good coordination between the impositions for environmental sustainability and the need to adhere to pharmaceutical regulatory requirements to facilitate the implementation of changes. This coordination is essential as innovation will be the guiding criterion for the introduction of the required changes to meet the sustainability objectives.