With an expanding and increasing ageing population worldwide, there will be a substantial demand for medicines that will necessitate an increase in production in the pharmaceutical sector while adopting sustainable approaches.

A 2019 study by researchers revealed that the pharmaceutical segment is more emission intensive than the automobile sector and the excessive production would further impact the environment, stressing the ecosystem and adversely affecting long-term health¹. As put rightly by the McMaster University Eco-entrepreneurship Chair and Associate Professor Lotfi Belkhir, “Helping people is no justification for killing the planet”. It has therefore become imperative for the pharmaceutical manufacturing industry to adopt sustainable approaches to comply with the environmental regulations and to achieve cost-effectiveness².

Several strategies such as modification of existing manufacturing processes, usage of greener excipients, effluent treatment, better in silico and in vitro testing and predictive models, and establishing correlation between in vitro and in vivo results can be sought to achieve sustainability goals. Exploring sustainable options can bring positive outcomes for the pharmaceutical industry even though the path can be tortuous. Although some initiatives like modification of existing equipment and facilities will incur a heavy initial investment, they can prove to be economic holistically when considering the long-term benefits of reducing process and operational expenditures, the cost savings from increased efficiencies and from reducing resources. On the other hand, replacing existing raw materials with greener alternatives is an easy approach. A zero-emission product cannot be produced without a zero-emission raw material. Leading excipient manufacturers across the globe are thus investing in innovative excipients that are produced in a cleaner way with minimum impact to the environment, providing sustainable solutions to the pharma industry.

Global sustainability action

The United Nations has provided a list of 17 sustainable development goals (SDGs) that aim to end poverty and provide everyone peace and prosperity by 2030. In an endeavour to be aligned with the SDGs, the top pharma companies have put in place corporate sustainability goals as a part of corporate social responsibility. Many of the top players are aiming to achieve a target of zero carbon dioxide emissions by 2050. There are two goals in the framework to which the pharmaceutical industry can contribute. Goal 3 as defined by UN aims at ensuring healthy lives and providing good health for everyone at all ages, while goal 12 caters to ensuring sustainable consumption and production patterns.

The pharma sector is putting concerted efforts to meet goal 3 through developing low-cost generic medicines and through their CSR initiatives. The challenge lies in achieving sustainable production, as it requires finding, financing and implementing eco-friendly solutions – especially where processes and infrastructure is concerned. An easier alternative is to use sustainable raw materials in production, boosting production efficiency and minimising resource consumption and waste generation. Excipients are the inactive ingredient that make up most of the dosage form and often aid in providing a specific functionality. The formulation parameters and processes largely depend on the excipients that are selected by the manufacturers. A proper choice of these raw materials can aid the scientist in building a sustainable formulation. Some production facets that can be explored to achieve sustainability are described below.

Approaches to sustainability

1. Reduce carbon footprint There has been a heavy focus on environmental footprint created during API synthesis in drug discovery, resulting in the adoption of green chemistry approaches to lower emissions and promote use of safe chemicals. Use of green solvents replacing the traditional solvents and applying aspects of green chemistry to improve reaction efficiency can in part contribute to diminish environmental impact. Both suppliers and manufacturers are exerting vigorous efforts to meet SDGs through the use of green excipients and designing efficient production processes to produce those excipients. Using clean energy in production and supply chain and switching to biodegradable alternatives are other options that can be explored. As an example of how process modification can curtail carbon footprint, the IMCD Mumbai Pharmaceutical Technical Centre (PTC) developed a one-pot melt granulation approach using specialised lipids (polyoxyethylene mono and diglycerides) to prepare an ODT formulation of an anti-histaminergic agent. The right choice of excipients (lipidic granules adsorbed into calcium silicate and a particle-engineered DC excipient) helped in the preparation of granules, which was followed by direct compression. This resulted in a solvent-free, one-step green process, making it amenable to continuous manufacturing.
2. Reduce production waste Manufacturing generates numerous by-products in API synthesis and in formulation that filter out into the environment and have implications on human health. By reducing the number of unit operations that are needed to produce a tablet, for example, yields can be improved and lead to a reduction in pharmaceutical waste. To further promote this objective, one of our partners provides specific aqueous-based cleaning solutions to effectively remove APIs from equipment change parts and machinery. The cleaning solutions can be selected based on the chemistry of the API or the excipient and aid in reducing the number of cleaning cycles and man hours, as well as being non-corrosive to the equipment and thereby extending its shelf life. Minimising the volume of the cleaning solution with fewer cycles also leads to lower water consumption and a reduction in the toxic pharmaceutical waste generated. This also eliminates the use of alcohol-based solvents that are frequently employed for cleaning, further making the process green.
3. Use of sustainable excipients and improved processes Sustainability is being applied slowly in pre-formulation and formulation development. Using excipients from renewable resources that are multi-functional and of high quality is opening an arena that is only recently being explored. Although multi-functionality may result in a higher cost for the raw material, this is compensated by an improvement in the production economy through minimised processing steps, a reduction in the number of formulation variables, and better formulation stability. The result is an enhanced formulation development approach in a short time frame. As a model to this approach, the IMCD Mumbai PTC developed an alternative direct compression process for a low dose anti-coagulant that was traditionally formulated using dry granulation, utilising a multi-functional co-processed excipient that was comprised of a diluent, a disintegrant and a lubricant. The steps of roller compaction, followed by milling and blending were essentially eliminated, thereby improving the process. The tablet was further coated using a PEG-PVA-based coating polymer that allowed high solid content suspensions to be sprayed without the use of a plasticiser, thus reducing coating times and improving overall efficiency.
4. Data and digital initiatives The pharma domain is aggressively focused on getting data and digital solutions for R&D and manufacturing on board, and rightly so, as this eliminates paper, speeds up the process and renders the process green. A quality by design approach, together with simulation software and statistical modelling can minimise laboratory experimentation, saving resources and time in development. Electronic records help in quick capture of data, reducing the paperwork and labour to support data integrity. IMCD uses digital solutions in the way of cloud-based electronic lab notebooks that can be accessed globally and help to capture the data contemporaneously and with accuracy, thereby enabling faster development of products and improving overall efficiency.

Conclusion                                                                                                             

Although major pharmaceutical companies across the globe are moving towards sustainable development, the mid- and small-scale companies must also place emphasis on this aspect. It is only a matter of time when sustainability goals become a part of regulations and GMP, and it becomes imperative for the pharma industry to be in accordance with the UN objective. For newer products, the industry can start exploring the existing sustainable solutions right from the start, so systems are embedded with the sustainability strategy.  A strong collaboration between the API and excipient suppliers and customers is indispensable to unearth novel opportunities that provide cost-effective medicines to patients.

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1. Belkhir L, Elmeligi A. Carbon footprint of the global pharmaceutical industry and relative impact of its major players. Journal of Cleaner Production. 2019 Mar 20;214:185-94.
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3. https://www.pharmasalmanac.com/articles/sustainability-in-pharmaceutical-manufacturing-a-cdmos-contribution
4. https://pharma-trends.com/2021/04/08/towards-a-sustainable-future/
5. https://pharma.nridigital.com/pharma_apr20/turning_pharma_green_an_eco-wish_list_for_the_industry
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8. Belkhir L, Elmeligi A. Carbon footprint of the global pharmaceutical industry and relative impact of its major players. Journal of Cleaner Production. 2019 Mar 20;214:185-94.