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Feature Articles : Sep 1, 2010 (Vol. 30, No. 15)

Biopharma's Going Green

Drivers Include Sustainable Design, Technology, and Novel Bioprocessing Strategies
  • Vicki Glaser

Genetic Engineering & Biotechnology News’' first “GreenBioPharma” conference represented an important step in the trend toward making operations at life science companies and organizations more sustainable. That was the opinion of most of the presenters and attendees who gathered at the meeting, which took place in July in Philadelphia.

Experts from academia and industry, including architects, engineers, researchers, process specialists, facility managers, and design and operations management consultants, discussed and brainstormed over innovative strategies for building in green  processes and practices.

Topics ranged from environmentally sensitive building design, air-quality monitoring systems, building automation, energy efficiency, water-reduction strategies, biocatalysis to optimize process dynamics, and waste reduction and recycling.

Many of the presentations emphasized the operational efficiencies and sustainable advantages of switching to disposable technologies across the process stream, including savings in labor, energy, water, chemical use, and overall costs.

The speakers stressed the importance of robust metrics, pre- and post-implementation, to document these savings, both as proof-of-principle and to demonstrate the potential cost and efficiency advantages of sustainable initiatives to corporate management, staff, vendors, and customers.

Recurring themes throughout the two days of talks, roundtable discussions, and networking included the following: looking beyond the low-hanging fruit for ways to save energy and water can yield big payoffs; incentives and education should increase buy-in across an organization; and justifying and reaping the benefits of going green depends on quantifiable results.

Commitment Is Key

Across industry and research organizations, the speakers seemed to concur that a commitment to sustainability and eco-consciousness initiated from the top of the corporate/administrative ladder and allowed to filter downward is optimal.

Companies were encouraged first to incorporate sustainability into their own operations and then to expand those principles and practices to internal development and manufacturing processes, and ultimately export up and down the pipeline to suppliers and customers alike.

Beth Junker, Ph.D., senior scientific director in bioprocess R&D at Merck, encouraged companies to assess the environmental footprints of their chemical processes—such as the aquatic toxicity of heavy metals—early in the product life cycle.

“Biopharmaceutical processes are 80% defined at Phase IIb,” she said. Emphasizing the need to quantify and minimize the amount of waste produced, she pointed to the process mass index (PMI) as the “term du jour.”

PMI is composed of a direct (mass of waste/mass of product) and an indirect ([mass inputs-mass outputs]/mass products) component. The E-factor, defined as kg byproduct/g product, is “very high” in pharmaceutical manufacturing compared to many other industries, she said.

Junker identified three main opportunities for waste (including energy) reduction: process intensification, easing of purification bottlenecks, and a shift in focus in purification from product capture to contaminant removal. “We need formal tracking of environmental measures,” including PMI and E-factors, “so we can quantitatively demonstrate progress in environmental footprint reduction,” she said.

The Numbers Don't Lie

Tina Larson, director of technical development engineering at Genentech, led off the meeting with a keynote address titled, “Lean and Green: Sustainability in Development and Manufacturing.” Referring to sustainability in process development and manufacturing operations, Larson said, “I passionately believe we can do better.”

She described Genentech’s voluntary participation in the EPA’s Climate Leaders program, its in-house, grassroots Green Genes organization and ECOmpetitions, and the company’s annual EcoFairs, in which employees participate in environmentally oriented community service projects such as beach cleanups.

These activities and a strong commitment to reducing the carbon footprint, minimizing hazardous waste production, and other environmental initiatives are not only the right thing to do and can yield cost savings, but they can also have a positive impact on employee recruiting and retention.

Even though water and energy are “relatively cheap” at the company’s South San Francisco headquarters, parent company Roche, which espouses “a very top-down commitment,” voluntarily set aggressive targets for greenhouse gas reduction and modified the valuation factors used to assess engineering projects aimed at improving sustainability to justify their return on investment (ROI), “so it looks much more financially favorable to do the right thing,” said Larson.

Gathering metrics on day-to-day operations is essential, she asserted, citing the example of water use in one of the company’s pilot plants. Whereas water consumption for a typical 14-day production run was estimated to be about 300 gallons, the actual use was 14,500 gallons. By switching to an existing glycol system for process temperature control, water use was reduced to near zero, saving approximately 565,500 gallons of water per year in this one plant.

Switching from stainless steel tanks to single-use processing bags for buffer and final product storage and from glass bottles with stainless steel caps to disposable sampling containers in one of the company’s clinical manufacturing facilities also had “a clear impact,” said Larson, yielding a savings of about 20 metric tons of CO2 annually.

In 2008, Bayer initiated a climate check footprint initiative that assessed the CO2 footprint (defined as pounds of CO2 produced/pounds of product) for each of its sites and products, expanding early assessments of electricity and natural gas use for production activities to include raw materials and transportation.

A case study focused on fermentation processes at Bayer Healthcare’s Berkeley, CA, site, where Bayer’s factor VIII is produced, identified “quick wins” in utility use reduction, followed by process changes using technology to increase efficiency and reduce cost-of-goods, according to Thomas Daskowski, Ph.D., head of Bayer Technology Services.

These included increasing the height of chromatography columns (but staying within established process specifications to avoid the need for re-evaluation), which is predicted to increase yield by 5%, saving millions of dollars and reducing the carbon footprint of this unit operation by about 3%.

Similarly, changing from a fed-batch fermentation process to a three-month, continuous process using a hybrid membrane module, with increased aeration and cell density capacity, is expected to yield 60% more product from the same fermentation volume and reduce CO2 emission by at least 90%.

Mark Butler, a senior vp with Integrated Project Services, provided a real-world example to demonstrate that it is not necessary to build a new facility to take advantage of significant cost and energy savings possible by incorporating sustainable equipment and operating practices.

A biopharmaceutical client that chose a $30 million renovation project over building a $300 million new production plant was able to achieve a 300% increase in yield with the same amount of energy usage.

Butler described the concept of “retro-commissioning,” which involves assessing whether an existing facility is operating according to its design and intended use and identifying potential areas for improvement to optimize performance. This can result in typical energy savings of 5–20%, with a payback of less than two years.

Life Technologies’ internal energy-efficiency efforts will save the company a projected $25 million between 2004 and 2012, reported Cristina Amorim, vp of global EHS and citizenship.

Little things add up, and big savings can come from unexpected places. For example, historically Life Technologies had shipped its Applied Biosystems TaqMan® assays to customers in Styrofoam coolers. Looking for ways to reduce waste, the company performed stability tests and determined that the reagents could safely be shipped in regular packaging, eliminating the use of 100,000 coolers per year and saving the company $1.5 million/year.

Breathing Easy

Joe Monahan, a principal planning engineer at the University of Pennsylvania, described a three-year pilot program of active air-quality monitoring and feedback control in a laboratory and a vivarium facility on campus.

Constant air volume change rates are traditionally built into the design of research and animal containment spaces to ensure sufficiently low levels of contaminants and particular matter. But this type of passive engineering approach is energy intensive, and Monahan presented the “need to go to a more active control system,” sampling the air in real-time and basing air exchange rates on the resulting measurements, rather than replacing clean air with clean air.

“No one ventilation rate is right all the time,” he said. If a spill occurs in a lab, for example, an active air sensing and ventilation system could adjust air flow accordingly.

Automatic air-sampling units installed as part of this project periodically route air samples to a centralized sensor suite that measures carbon monoxide, carbon dioxide, total volatile organic compounds, and particulates. Based on these readings, the system instructs the building control system whether or not to increase the air flow to the area sampled. To benefit from this capability the building must have a variable air flow system.

Monahan reported an energy cost savings of $15,000/year (from $95,000 down to $80,000, or 17%) for the research lab, with an ROI of 2.45 years, and a 42% drop in energy costs for the vivarium, with an ROI of 1.71 years.

Illustrating the benefits of a top-down corporate commitment to sustainability, Paul Lukitsch, worldwide energy manager for Millipore, described the company’s goals for reducing energy and water use from baseline measurements collected in 2006. He described a 15% drop in greenhouse gas (GHG) emissions, 15% reduction in electricity use, and a 22% decline in water use achieved by year-end 2009.

This would not have been possible without “a robust energy-management program,” said Lukitsch. “You need to invest in energy metrics.” Measure what you use, capture your energy costs and demand, perform intensive energy audits, identify fast ROI, low capital projects, execute scalable projects, and, above all else, “meter everything,” before and after making changes, he urged.

Take a multipronged approach and consider your options, he advised. Improving the efficiency of existing energy resources is likely to have a five times greater impact than switching to renewable sources such as solar energy.

“We are now starting to design our products with sustainability in mind,” added Lukitsch. 

Demetri Petrides, Ph.D., president of Intelligen, producers of SchedulePro and SuperPro Designer software for process manufacturing, design, simulation, and scheduling, spoke on the impact of single-use systems on cleaning materials, cost of goods, and the environment.

He presented a case study involving a clinical manufacturing facility that produced 2 g/L of a mAb in four 2,000 L bioreactors over a 12-day period. Fixed (reusable, requiring CIP/SIP) bioreactors were replaced with disposables for product manufacturing, capture, purification, and storage (not including buffer preparation). The change reduced infrastructure needs from six equipment skids to three, water for infection (WFI) demand from a daily maximum of 35,000 L to 16,000 L, and a required WFI tank volume from 25,000 L to 15,000 L.

For a single production batch, Petrides reported declines in use of WFI by 51%, of caustic cleaning agents by 68%, of acids by 64%, and of clean steam by 52%. As a result, the cost of goods for antibody produced in disposables dropped to $352/gram, compared to $415/gram in fixed equipment.

The cost-saving benefits of disposables diminish as scale increases, noted Petrides. Whereas a manufacturer will “definitely save money for a 1,000–2,000 L scale facility,” by switching to disposable processing equipment, the turning point for savings is about 8,000 L, he said.

AIEX

Replacing anion exchange column chromatography (AIEX) in the polishing step of a mAb product with Sartorius Stedim Biotech’s disposable Sartobind Q Membrane Adsorber technology allows for higher flow rates (0.1 CV/min for a column vs. 10–20 MV/min for the membrane), smaller devices (200 L resin column vs. 2 L membrane device), higher load density (up to 100 g/L of mAb on a column vs 10 kg/L on the membrane), and a 95% reduction in buffer consumption, according to case studies presented by Natalie Fraud, Ph.D., a senior process development scientist in purification technologies.

Use of a disposable membrane in place of AIEX chromatography for product polishing eliminated the need for column cleaning and yielded a savings of about 4% in the overall cost-of-goods and a savings of 3% in water usage.

Cleaning capacity was the largest bottleneck at one facility evaluated by Hyde Engineering + Consulting. Peter Watler, Ph.D., the company’s CTO, described a case study in which optimization of cleaning processes for one bioreactor resulted in 79% less water use, a 63% savings in cycle time, and 81% less CO2 production.

By combining multiple process vessels into a cleaning circuit, those figures declined further to 88%, 90%, and 90%, respectively, with an overall reduction from 7 to 2 cleaning cycles requiring 6 rather than 30 hours. This resulted in increased plant capacity, a savings of 12 million L of water per year, and annual cost-of-goods savings of $2.4 million.

Describing the current trend in bioprocessing toward smaller scale, reduced process volumes, and higher expression titers, Vincent Pizzi, global product marketing group leader at GE Healthcare, suggested that replacing reusable systems with single-use equipment from start to finish can provide the throughput needed to alleviate the growing pressure on downstream processes.

Replacing one 500 L stainless steel reactor with a single-use reactor over 40 production batches would save about 1,300 hours/year in CIP/SIP time and about $4,000 per batch on WFI.

Other talks at the conference focused on procurement and materials management to minimize inventories and create a centralized store of stock chemicals for better control of purchasing and disposal, solvent-sparing techniques in chromatography, and the use of biocatalysis to optimize chemical processes.

GEN is planning to hold its second “GreenBioPharma” meeting in Princeton, NJ, in 2011.

Sidebar: Sustainability by Design

Buildings account for 48% of U.S. energy consumption and roughly half of greenhouse gas emissions,” Donald Schmitt, an architect and principal at Diamond & Schmitt Architects, told the “GreenBioPharma” attendees.

Schmitt described several of the firm’s recently constructed laboratory facilities, including a 22-story research tower for Sick Children’s Hospital in Toronto, designed to house a 2,000-person staff and featuring a range of sustainable design concepts, building materials, and operational characteristics. These features are not only eco-friendly but will reduce operating costs by 30–40% and enhance the work environment, according to Schmitt.

This and similar projects incorporate an efficient exterior building envelope designed to minimize the perimeter. The envelope includes large window surfaces that allow natural light to be harvested and pushed deep in the building interior, connects those working inside to the surrounding landscape, creates common areas that encourage interaction among research teams, and recovers heat generated in the building by lab equipment and computers, for example.

Innovations such as “biowalls” create living biofilters to clean the air within the facility. Ceramic frits embedded in windows protect against UV rays. High-efficiency plumbing systems and reuse of gray water contribute to reduced water consumption. And green roofs can help mitigate stormwater damage and minimize heat island effects. The use of reflective roofing materials can limit heat build-up.

Paul Todd Merrill, director of sustainable construction at Clayco, provided a general contractor’s perspective and described the challenges inherent in finding the sweetspot in design and construction, trying to balance project costs, operations, and sustainability. He emphasized the importance of buy-in among the decision makers in a company or organization, and the need for education, baseline measurements, and well-defined sustainability goals.

“We emphasize early energy modeling on projects,” said Merrill, to enable an analysis of costs and to predict the ROI for each option. He estimated a three-year payback for daylight-harvesting strategies, five years for a more energy-efficient HVAC system, and five to ten years for improvements to the building envelope.