Features
March / April 2018

# Reining in Consumption for Sustainable Manufacturing

Scott Fotheringham, PhD

The word “sustainability” is both overused and abused: We hear about sustainable development in a sustainable economy that uses sustainable packaging for a sustainable future. But it’s an important concept, especially for the pharmaceutical industry as it transitions from manufacturing in stainless steel facilities to single-use technology (SUT) in much smaller plants. This shift has revolutionized pharmaceutical manufacturing and is producing results that go far beyond the financial. Corporate examples that measure results using the triple bottom line∗ can help us define and understand sustainability more clearly.

Derek Mullins, Senior Manager, Corporate Facilities and Engineering at Amgen, described the results he’s seen. “The process change from large fixed stainless steel facilities to smaller single-use systems has allowed us to rethink how we design and operate these plants,” he said. “It’s also led to significant environmental benefits in terms of energy and water consumption.”

Amgen’s biologics plant in Singapore, opened in 2014, is only one-quarter the size of other facilities that produce the same volume of drug substance. “The big benefit is flexibility,” Mullins continued. “We can configure a plant like this to make more products, in smaller batches.

“The capital costs are less than for a stainless steel plant, time to build is shorter, and the equipment can be run parallel with the facility. You can actually start building the facility while you’re still specifying, designing, and procuring the manufacturing equipment. For a large facility, the equipment is built in as the building is constructed.”

Mullins found that energy and water savings went hand in hand with these benefits. By shrinking core manufacturing capability, ancillaries got smaller. The purified water system is smaller, as is the steam-in-place system, since the need for steam is reduced. Mullins calculates that when the Amgen facility is compared to a stainless steel facility producing a similar amount of product, it uses 69% less energy, consumes 45% less water, and emits 69% less carbon dioxide (CO2).

Since a heating, ventilation, and air-conditioning (HVAC) system and its associated utilities account for more than 60% of the energy used at a traditional facility, this is where Amgen sees the greatest rewards. “We were sensible in sizing the equipment and built it to the size we needed, taking the Singapore climate into consideration,” Mullins said. “Had we been cautious, we would have oversized everything and put in the standard HVAC design, with large boiler systems and large reverse osmosis plants. If we had, the facility would have been as inefficient as a stainless plant.”

* A concept that expands the financial bottom line to include a company’s degree of social responsibility, economic value, and environmental impact.

## THE CASE FOR SUSTAINABILITY

Pharmaceutical manufacturing relies on resources such as energy and water that can be expensive and generate costly amounts of waste. Companies that minimize waste while using natural resources and energy efficiently can see benefits.

“There is increased interest in the benefits of continuity in most of its forms—continuous manufacturing and processing, generally—which inevitably leads to smaller, more technologically controllable facilities,” said Robert Bowen, an architect and director of facilities integration in the United Kingdom (UK). He specializes in the design and development of sustainable pharmaceutical facilities in the UK and the rest of Europe.

“We are in the middle of a revolution in data-based tech that affects the way and the scale at which we work. It offers the potential for increased throughput with significantly reduced footprint and huge significance in terms of ownership and capability. These are the fundamentals of sustainability in this industry.”

Governments, market regulators, investors, and industry groups are mandating, promoting, and otherwise encouraging corporate sustainability practices in pharmaceutical manufacturing.1 Many companies already recognize the benefits of limiting greenhouse gas emissions, reducing energy and water use, using waste to generate electricity or heat, and decreasing or recycling waste. These advantages were apparent to Ethicon’s facility in Puerto Rico, the 2016 winner of ISPE’s Facility of the Year Award for Sustainability.2 The following year, two other pharmaceutical corporations were named winners of the Presidential Green Chemistry Challenge awards: Merck, for its sustainable manufacturing processes, and Amgen, for greener reaction conditions to improve solid-phase peptide synthesis.3

“We are in the middle of a revolution in data-based tech that affects the way and the scale at which we work”

Innovation in sustainable facility design, construction, and maintenance are another industry focus. Many companies, including Genzyme, GlaxoSmithKline (GSK), Alexion, Johnson & Johnson, and Pfizer have embraced LEED certification for new construction and building renovations.4 Others have adopted similar environmental assessment methods such as BREEAM, or national methods, which often require a defined level of classification to obtain a permit, such as CASBEE in Japan and Green Mark in Singapore.

† LEED: Leadership in Energy and Environmental Design, a green building rating system developed by the United States Green Building Council
BREEAM: Building Research Establishment Environmental Assessment Method, a system that determines a building’s social, economic, and environmental sustainability performance
CASBEE: Comprehensive Assessment System for Built Environment Efficiency, the green building management system in Japan
Green Mark: an initiative launched in 2005 by the Singapore Building and Construction Authority to encourage and reward an environmentally friendly and sustainable built environment

Companies are also harvesting green energy sources such as wind and solar. GSK, Novartis, Janssen, and DePuy Synthes collaborated to build and maintain wind turbines that could generate electricity and reduce CO2 emissions at their facilities in Cork, Ireland.5 The Janssen facility in Titusville, New Jersey, which received LEED Gold certification, generates almost 85% of its electricity from a giant array of solar panels.6 AstraZeneca, Biogen, Novo Nordisk, and Johnson & Johnson belong to RE100, an industry initiative comprised of companies committed to sourcing 100% of their electricity from renewable sources.7

Johann Bonnet, Vice President, Business Development, Pharma & Cosmetics at Veolia Water Technologies, believes that a robust focus on corporate sustainability in four areas benefits pharmaceutical manufacturers:

• Regulatory compliance: A sustainability strategy that focuses on managing risks associated with water use, energy consumption, and waste can prevent FDA warning letters.
• Design: Including environmental footprint reduction to reduce life cycle costs in the design of plastic products (such as medical devices, inhalers, and packaging) can curb unnecessary waste and provide a source of reusable materials.
• Innovation: Original thinking can reduce waste and boost profitability—by reusing solvents as secondary raw material, for example.
• Spending: Scale down investments in infrastructure; rent, share, or outsource manufacturing facilities instead.

## CONSERVING AND REUSING WATER

Access to a good source of clean water is a main area of concern in pharmaceutical manufacturing. In addition to being potable, pharmaceutical water must comply with international laws, pharmacopoeia, and regulatory guidelines.

“Legislation is there and companies have sustainability policies, but what drives them to consider water efficiency is economics,” said Nik Krpan, president of Cheme Engineering, a consultancy based near Toronto, Canada, that offers process engineering services to the biopharmaceutical industry. “It depends on the jurisdiction. At some sites in the developing world there is little or no municipal infrastructure for drinking water or sewage treatment. In these cases, facilities need to be prepared to treat their own waste, which provides an incentive to do so in an economically feasible way. They can implement groundwater recharge, greenwater harvesting and recharge, rainwater harvesting, and reclamation of water. Here we see this as sustainability, but there it’s a necessity and sometimes legally mandated.”

Bonnet and Veolia work with companies in Europe, including Roche, Bristol Myers-Squibb, AstraZeneca, and Pfizer. They have undertaken projects that include the construction of a sewage-treatment plant to reduce the environmental footprint, biogas production, chemical use minimization, water-use management, electricity cogeneration that reduces carbon emissions, as well as water reuse and purification.

“The biggest consumers of water are boilers and coolers, and the payback on these systems can be significant,” Bonnet said. “Changing from an open-loop to closed-loop system increases efficiency. Water can be recycled, since the grade of water does not need to be as high as for process. The goal is not [necessarily] to recover all the water, but companies are looking at what makes sense in terms of economics and the environment.”

In North America, the incentive to conserve water is caused by the rising cost for water and sewage services, which is increasing two to three times faster than for other utilities.8 “The situation in North America is caused by a history of under-recapitalization of municipal infrastructure and now we are playing catch-up,” Krpan said. “Because there’s a lack of appetite to increase taxes, local governments increase water rates instead.”

Nissan Cohen, owner of Start-Up Business Development and a specialist who consults on industrial water issues, says that “North American companies could realize cost savings by paying more attention to water.” He likes to refer to the four Rs of sustainability—reduce, recycle, reuse, and reclaim. He says that 25%–35% percent of the water that goes down the drain should be reclaimed. “For a US company that dumps 100,000 gallons of water a day, that’s about $800 down the drain every day. I estimate that the industry is wasting a lot more than$50 million per year on water.”

Krpan believes the trend for manufacturing facilities is to reuse water, despite an esthetic stumbling block. “There is an ‘ick factor’ to reusing water for human consumption,” he says, “so generally reclamation at pharma sites involves using it in cooler towers or boiler feeds, or for nonproduction uses such as gray water.” In some cases it is used for aquifer recharge.

One country that has overcome the distaste for reusing water is Singapore. While the densely populated island imports some of its drinking water from Malaysia, its Public Utilities Board (PUB) reclaims its branded NEWater from sewage wastewater, using a three-step purification process of microfiltration, reverse osmosis, and disinfection with UV light. NEWater supplies 40% of the country’s needs.9

“Water is a constrained resource in Singapore,” said Amgen’s Mullins, whose facility in the country relies on NEWater for industrial uses, such as cooling water, that don’t require potable water. “The local PUB regulations are tight and they expect large water users like us to put in place sensible water management processes to conserve water.”

“The process change from large fixed stainless steel facilities to smaller single-use systems has allowed us to rethink how we design and operate these plants”

Where possible, Amgen uses recovered water for its cooling towers instead of using drinking water. In a region where potable water is scarce, the company also collects condensate from the HVAC cooling coils. This is a significant source in a tropical climate, amounting to about 24 cubic meters of water per day, which contributes to significant water savings. Amgen believes it can further improve the water intensity of this facility and the company has its sights on its facilities around the world, even in regions where water is plentiful.

“We always ask ourselves if it’s OK to use drinking water in a cooling tower,” Mullins said. “We recover water in all our plants and use reverse osmosis so it can be reused, or collect clean condensate. An example is our eight-story building in Cambridge, Massachusetts, where we collect cooling condensate from all the air handlers and it gets recycled into the cooling towers.”

## ZERO LIQUID DISCHARGE

“I like to show companies where the water is and where it goes, what are the costs, and how they can reclaim and reuse this water and, in so doing, become better corporate citizens,” Cohen said. He’s an advocate of zero liquid discharge (ZLD), a process that purifies and recycles wastewater, leaving behind solid waste that can be recovered, incinerated, or disposed of (see his editorial) “I absolutely recommend that companies reclaim water. Water can be taken back to source water if the conductivity is low enough; depending on the results, it can be used for irrigation outside, for sanitary applications in urinals and toilets, or in cooling towers for AC systems.”

Many effluent waters can also be reclaimed and reused elsewhere at the facility, he says. The simplest example is to feed gray water into an external irrigation system.

One place where ZLD makes sense is India, where seasonal rains make it difficult to find sources of clean water. The Indian Pharmacopoeia mandates that municipalities chlorinate water to make it potable for pharmaceutical applications, but during monsoon season water comes in at such a rate that it outstrips the 20-minute contact time required to purify the water.

“Pharmaceutical companies are adding chlorine to the water, but it’s not doing anything, especially during monsoon season,” said Cohen, who recently visited the country. “The amount of pathogens, microbials, and organics in the water cannot be treated properly. I recommended to the Indian Pharmacopoeia that they change from chlorine dioxide to any purifying agent that would be effective on the front end, such as ozone. Ozone oxidizes bacteria, pathogens, and organics efficiently and is 36 times more effective than chlorine.

“The biggest consumers of water are boilers and coolers, and the payback on these systems can be significant”

“If you can clean it up on the front end, you can reuse the water. Ozone can reduce bacteria and other pathogens to zero, which is important. The water can be reused in cooling towers or makeup water for the source water. The quality of the treated water is actually better than the source water coming in. Why isn’t it being reused? Ozone generators are used extensively to clean up water and waste in the bottled water industry,” Cohen continued. “The bottled water has to have an ozone residual to prevent bacterial growth and maintain its shelf life of two years. Not many pharma companies are using it, though.”

## HOW DOES PHARMA COMPARE?

“When you consider that the cement industry was the first worldwide adopter of a sustainability policy in the early part of this century,10 the pharmaceutical industry has been late in the game,” Bowen said. “That was a part of the driver for ISPE to publish its Sustainability Handbook.”

Bowen, who is the global Co-Chair of the ISPE HVAC and Sustainable Facilities community of practice, and Nicholas Haycocks, Senior QA Specialist at Amgen, recognized the need for a sustainability guide for the pharmaceutical industry. They led the task team that produced the handbook in 2015,11 which provides a global perspective on legislation, regulation, and policy development. Among the topics it covers are the design and engineering of sustainable energy processes, HVAC systems, electricity and utilities, waste management, and water use. Bowen is positive about what companies are doing.

“Some companies are extremely proactive in their response to sustainability, both in terms of climate change and the recognition that the supply chain and operation can provide significant returns when a sustainable policy is adopted,” he said. “These accrue through manufacturing efficiencies, operational benefits, and staff welfare gains. Sometimes this awareness has been influenced, from a board perspective, by early adopters.

“It tends to show most when there is the opportunity for a new plant and the chance to showcase. The EU Directive about climate change goals is 15 years old, and its expectations about tougher building standards and aggressive time targets are well embedded in the culture. In some ways that takes the onus o the companies, as they have to comply.”

In the European Union, there is usually a separation between legislation concerning buildings, and legislation dealing with processes and equipment. For buildings, architects and building engineers (e.g., mechanical/HVAC, electrical, civil/structural) have mandated targets, even for retrofits. “Companies have little choice but to follow,” Bowen said. “Of course, there is a latitude divide at play. If you have sun all year, it’s relatively easy to take advantage of solar power. That is, it’s easier in Texas than in Ireland. In straight build terms, a small retrofit in an older building is less likely to be built to sustainable standards, unless legislated, than a new build.

“In terms of legislation dealing with processes and equipment, the pressure is on only where there is a company commitment. Big pharma is in the vanguard here as well, as they have the investment opportunities and most have taken a board commitment to investigate green options. Where these have been adopted, the benefits have become clear and self-sustainable. Likewise, in the drive for improved production methods and the use of datatech, the potential efficiencies of continuous manufacturing are beginning to show great gains that support sustainability and carbon reduction through plant-size reduction, asset reduction, reduced energy, and material usage.”

Bowen returns to the triple bottom line. “There are intangibles that drive our interests, other than the pure cost to sustainability. We strive for simpler, more sustainable operations, more satisfied employees, and a greater return on investment. It is a case of practicing what you preach—creating a manufacturing and operational environment that supports health, increases life expectancy, well-being, and a better environment. The pharmaceutical industry is the grunt end of the health care industry and only works if it’s sustainable. The health care industry only works if it cares about its environment and its patients, for whom it is there to improve things and to provide cures.”