The importance of implementing greener chemical and engineering practices throughout every level of the pharmaceutical industry is gaining speed nowadays. By definition, green chemistry (environmentally benign chemistry or sustainable chemistry) is the design, development and implementation of chemical products and processes to reduce or eliminate the use and generation of substances hazardous to human health and the environment. On the other hand, green engineering is the design, commercialisation and use of chemical processes in ways that minimise pollution at source and reduce impact on health and environment.
In 2005, the ACS Green Chemistry Institute and global pharmaceutical corporations developed the ACS GCI pharmaceutical roundtable to encourage innovation, while catalysing the integration of green chemistry and green engineering in the pharmaceutical industry. Nine pharmaceutical companies, including Pfizer, Johnson & Johnson, AstraZeneca and GlaxoSmithKline (GSK), are now roundtable members. Each year, the Environmental Protection Agency's Presidential Green Challenges (EPAPGC) Awards recognise advances in green chemistry or environmentally favoured approaches in all fields of chemistry. The EPAPGC has recognised companies such as Pfizer, Merck, Bayer and Eli Lilly for finding green synthetic pathways and promoting green reactions.
The complexity of the pharmaceutical industry necessitates a holistic approach to greening its processes, starting with a paradigm shift from focusing only on waste management to an approach that encompasses manufacturing process efficiency, yield and economic gains for pharmaceutical companies. But unlike other sectors, the pharmaceutical industry must also comply with stringent current good manufacturing practice regulations. Decisions about green, sustainable and energy-saving opportunities cannot be based just on financial considerations alone. It is imperative that all systems, processes, equipment and facility designs be reliable and compromise not on drug efficacy and safety. Being green in the pharmaceutical industry begins at the intersection of business, innovation, compliance and the environment. As the environmental impact and costs associated with disposing of toxic solvents and waste products have come to the forefront, greater emphasis is being given to reducing waste streams and minimising energy input.
The process of developing a sustainability programme and incorporating it into a pharmaceutical operation should first identify the direct effect the operations have on the environment and establish a base line of the company's greenhouse gas emissions (often referred to as its carbon footprint). The pharma firms must realise that they affect the environment both directly (through the emissions from their buildings and processes) and indirectly (through the amount and type of power they consume). A key aspect of any green programme is to minimise or eliminate the use of particularly harmful or hazardous chemicals. Solvents represent one of the largest cost components in chemical synthetic processes when one combines the cost of solvents with the disposal of mixed aqueous/solvent wastes. They account for 75-80 per cent of the environmental impact and energy use in the life cycle of a pharmaceutical compound. In this wake, some companies have developed tables which list undesirable solvents and suggest suitable replacements, and such programmes have cut by almost two thirds the amount of dichloromethane used, while use of diisopropyl ether has been eliminated entirely. Similar tables of alternatives have been developed for common chemical transformations, such as the oxidation of alcohols to aldehydes.
Advances in enzymatic catalysis of synthetic reactions, solvent substitutions, and recycling of by-products and waste may not only reduce the environmental impact of pharmaceutical processes, but with the potential to have a positive effect on synthetic efficiency and overall productivity, can also decrease waste streams, lessen energy input, and minimise the need for hazardous reagents. And most importantly, these developments are also cost beneficial (it just has a perception that it is more expensive). The savings come about because efficient syntheses that avoid exotic reagents, minimise energy use and replace organic solvents are invariably cheaper to perform.
"It's important to consider the green option throughout the drug development process," according to GSK's Richard Henderson. "We try to get people think about what is the most efficient process throughout the lifecycle, so that it is already in a good state by the time it reaches manufacturing."
Industry observers also agree that drug makers must develop their active pharmaceutical ingredient manufacturing techniques with the environment in mind from the start, rather than focusing on solvent recovery later in the process. It is especially important for pharmaceutical companies to explore alternative processes early on, because once a drug and its associated manufacturing process receives Food and Drug Administration approval, it may be cost prohibitive to make changes and risk having to repeat the regulatory review process.
"Green chemistry and green engineering need to work hand-in-hand at the design stage," appraised Tracy Williamson, chief of the industrial chemistry branch of the EPA's Office of Pollution Prevention and Toxics (OPPT). "The best green chemistry might not be feasible at commercial scale and that needs to be considered upfront. Hence it is imperative for pharmaceutical industry to perform a green assessment of the manufacturing process during the drug development stage. Performing this assessment and incorporating sustainability early in development will yield benefits during the manufacturing process and for the company's triple bottom line which incorporates financial, social and environmental performance."
Although, process analytical technology initiatives, lean six sigma strategies and design of experiments are contributing to the adoption of engineering by design and improved operational efficiency, the potential to reap maximal rewards from the introduction of green chemistry requires that the constructs be an integral consideration and component in the initial design of complex synthetic processes. While substitution of a safer solvent or use of a biocatalyst to drive a reaction to completion more efficiently is a useful strategy, a top-down design-based approach that incorporates green chemistry and engineering concepts and techniques throughout a process would have a greater impact on these complex, multi-step synthetic processes.
Implementing green chemistry and engineering in the pharmaceutical industry is an evolutionary process. "A culture change takes a long time," says Dr. constable, director, EHS product stewardship, corporate environment, health and safety, GSK. Additional tools for implementing green chemistry and engineering will be developed as these concepts gain priority and a culture of green chemistry / green engineering gains ascendancy. The pharmaceutical industry, however, will definitely continue to realise incremental gains in the future. The labours of green chemistry and green engineering in pharmaceutical industry will eventually heal the environment - both upstream and downstream- in the real world.
(While Mrunali R Patel is with Indukaka Ipcowala College of Pharmacy, Sardar Patel University, Gujarat, Rashmin B Patel is with A R College of Pharmacy & G H Patel Institute of Pharmacy, Sardar Patel University, Gujarat)