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Pharmaceutical Technology Europe
The amount of water used by industry, including pharma and biotech manufacturing, amounts to 23% of the world's supplies
Clean water is an increasingly precious resource, and there are huge inequities in water use around the world; for example, 700 L for domestic use per individual per day in the US, compared with 7 L a day in Senegal. Meanwhile, according to the World Water Council, more than 1 billion people lack access to clean drinking water while 2.6 billion do not have access to adequate sanitation. However, the main consumers of water are industry and agriculture. The amount of water used by industry, including pharma and biotech manufacturing, amounts to 23% of the world's supplies on average, which ranges from 5% to as much as 80%, depending on the nation and its level of development.
The pressure is on to save water in all areas of life. This means not only fixing that dripping tap, but making sure that industries use the smartest technologies and best designs possible to optimize water use.
These efforts could learn from a relatively new concept known as water footprint, which has been introduced by Arjen Hoekstra and Ashok Chapagain of the University of Twente (The Netherlands). Water footprint is similar to the idea of carbon footprint, and the two are connected because energy is used to produce purified waters, such as those used in pharma and biotech manufacturing, and to process wastewater effluents. The water footprint is defined as the amount of freshwater a nation uses in production of goods and services, including its medicines. The total global water footprint is, on average, 7450 Gm3/year, which is equivalent to 1240 m3/year/head, varying from 2480 m3/year per head in the US, to 700 m3/year per head in China. These figures include the volume of industrial water drawn both within and outside the nation.
Water footprint is closely linked to the concept of 'virtual water', which is the water used to produce a good or service (according to Hoekstra and Chapagain, the virtual water content of a microchip is 32 L, and 8000 L for a pair of shoes).1 So far, this concept of water 'price' has mainly been applied to agriculture. Industrial products are said to have an average virtual water content of 80 L per dollar used in their production, which varies from 100 L in the US, to 50 L in Germany and The Netherlands, and only 10–15 L in Japan, Australia and Canada. These concepts have not been widely applied to the pharma and biotech industry.
Pharma and biotech industries rely on water — and expensive purified sterile water at that — for processing, as their products are intended for human consumption. Biologics manufacturing relies on water even more because microbial and mammalian cell culture require a carefully controlled aqueous medium for productivity, and water quality and availability are key issues. If this industry is to grow, it must get the water it needs, and this can be a major contributing factor in determining the location of a plant. A large facility uses millions of litres a day and cannot afford to be affected by interruptions in supply. For instance, Amgen (CA, USA) had extensive discussions with the local water authority in 2004 regarding whether enough water would be available to manufacture its drug Enbrel at its Rhode Island plant in the US. The talks resulted in the company introducing many water conservation measures in-house to safeguard its supplies. This was not just, the company said, self-interest, but about trying to set an example as a corporate citizen.
Water is also a necessity for biotech industries for downstream processing, formulation and cleaning, with the latter application accounting for approximately 60–80% of water usage in a manufacturing plant. Energy and costs of producing the different grades of water, which are used in the operations that go into making a biological medicine, must also be considered. According to Simon Routledge, cGMP production manager at the UK's National Biomanufacturing Centre in Speke, the water requirements of a plant largely depend on the dosage form and purity requirements of the final product, and this is also true for pharma. If the product will be introduced orally, water quality requirements are not as high as those required for a parenteral product, Routledge explains.
Water used in manufacturing ranges from simple, reverse osmosis-treated water, which has undergone one filtration pass through a membrane, to highly purified water for injection (WFI). Different types are classified according to their level of microbial contamination (colony forming units [CFU] per mL). United States Pharmacopeia purified water is subject to various purification processes, such as filtration, reverse osmosis and ultraviolet (UV) treatment, and has less than 100 CFU/mL.
Drinking water is often the source of purified water for manufacture, but chlorine content interferes with cell culture and corrodes stainless steel. Therefore, the UV stage is used to kill bacteria, which grow more rapidly once the chlorine has been removed. WFI is the purest water used in manufacturing and should be fit for the purpose that the name implies. It is virtually sterile, with fewer than 0.1 CFU/mL, and is free of bacterial endotoxins, which is a key requirement of regulatory authorities. It is then kept at 80°C, preventing microbial contamination. It is used in downstream processing operations, in the formulation of parenteral products, and in the final rinse of the washing of stainless steel pipes and vessels in the plant.
The middling grade of water is known as 'highly purified water' and can sometimes be used in certain cleaning operations. In many respects it is equivalent to WFI, but is cheaper to produce because it does not have to be distilled.
Water quality requirements tend to increase for the purification stage of a manufacturing process as you near the final dosage form of a product, says Routledge. This is because impurities have a bigger impact on product quality at these later stages.
The demand for WFI is increasing, partly because of more stringent regulatory demands for purity in the final pharmaceutical product. As WFI is so costly to produce, manufacturers are looking at ways of optimizing its use in manufacture.
There are many ways to decrease water consumption in biopharma manufacturing. Smart engineering and design can create plant water supply systems that can easily switch between grades of water for different operations. Where a lower grade is acceptable, it can rapidly be supplied by such a system. PAT, with its emphasis on a deeper and better understanding of the whole manufacturing process, will also make a big contribution by revealing the optimum use of water in the various operations involved.
There are also alternatives to water, such as ozone, for cleaning and the trend towards disposables promises to cut water use dramatically. Wherever a disposable component replaces stainless steel — be it in a pipe, valve or vessel — cleaning is eliminated, along with resulting wastewater, which must also be considered as it involves further energy costs. Typically, more water will be used in steam injection to decontaminate the water used in a biotech process. Chemical content must be neutralized so it is harmless and the water will then, perhaps, enter public drains. Recycling wastewater is increasingly an option for many companies. The water can be used for cooling to save drawing more water for this purpose from the local supply.
Hoeskstra and Chapagain suggest many ideas for reducing water footprint that could be applied to pharma and biotech. First, adopt production techniques that use less water per unit of product. Second, raise awareness across the board about the water requirements involved in manufacturing and, finally, consider locating production in areas of higher water productivity.
Biotech products can be lifesaving, but so too can access to clean water. Minimizing water use in production will not only cut the costs of these medicines, but make a small, yet significant, contribution to easing the global water crisis.
1. A.Y. Hoekstra and A.K. Chapagain, Water footprints of nations: Water use by people as a function of their consumption pattern (2007).