	Environmental sustainability is a growing concern in many manufacturing industries, and the pharma industry is no exception. Facilities and operations that are designed to conserve resources, such as energy and water, can improve a company’s “green” image as well as reduce its manufacturing costs. Although there are some instances where GMP requirements may not be the most energy or water-conserving mode of operation, it is possible to attain both GMP compliance and efficiency, say experts (1, 2). Big Pharma companies have already made progress toward reducing water, energy, and waste, thus improving carbon footprint (3, 4).

	Drinking water, a crucial input to pharma manufacturing, is expected to become an increasingly limited resource, which means its cost will rise (2). Careful use, including repurposing discharge water from pharma processes for other uses (e.g., cooling towers or building sanitation systems) would help address this problem (2). Discharge of polluted water from some API manufacturing facilities, particularly effluents that could cause antimicrobial resistance, is also a growing concern that is beginning to be addressed (5).

	Although different types of pharmaceutical manufacturing processes use energy in different amounts, HVAC (heating, ventilation, and air conditioning) systems, used to control the air quality of the process environment, consume more energy than any other system across all types of manufacturing. In API manufacturing, for example, HVAC may account for 35–40% of manufacturing site energy use, and in drug product manufacturing, HVAC may account for 60–75%, says Keith Beattie, Life Science lead at EECO2, a UK-based energy efficiency consultancy. “Optimizing other utilities, such as installing a more energy-efficient chiller or implementing control strategies, can improve efficiency by a few percent, but improving HVAC is the quickest return on investment,” he adds.

	There are some straightforward methods for reducing HVAC energy use, often using existing systems and reengineering or optimizing them. “The first step is to minimize the quantity of air used,” suggests Beattie. “Cleanrooms often use higher air change rates than required to meet their classification, and reducing air flow by even a small amount can result in significant savings.” A second step is to minimize the energy going into conditioning of the air. Systems can be set back or even switched off when not needed, and widening the set points for temperature and humidity can allow the system to run more efficiently. Conditioning more efficiently-using high-efficiency motors and fans, for example-also creates energy savings. Finally, says Beattie, companies should maintain their systems by monitoring, optimizing, and not neglecting mechanical maintenance.

	EECO2 has developed an innovative approach to make cleanroom operations even more efficient using a control system that maintains a fixed air quality level (i.e., particulate count) by varying air flow rates, rather than the traditional method of fixed air change rate. The company has been able to reduce energy consumption by nearly 70% using this method of model predictive control in the company’s test facility, which is representative of a commercial cleanroom, says Beattie. He reports that this energy savings using the adaptive, demand-based system is measured from an already energy-efficient baseline traditional system. “Our adaptive system analyzes the data from particle counters in real time and uses these data to control the air change rate. From a compliance point of view, we are controlling the contamination level and we have data on the real performance of the cleanroom. This control system can thus assure quality and improve efficiency.” How to validate such a system is a question that needs to be answered, because the current validation methods were based on traditional methods, notes Beattie.

Single-use systems impact in biopharma manufacturing

	In biopharma manufacturing, single-use systems are considered beneficial for various reasons, including significantly reducing the water use required for cleaning of traditional stainless-steel systems. Another benefit is that, because they are closed systems, single-use systems can operate in a cleanroom with a lower grade classification, which corresponds to operational savings (6).

	To better understand the factors affecting the sustainability of a biopharmaceutical facility, the M+W engineering construction company conducted a lifecycle assessment (LCA) on a facility model. LCA is standard methodology used to evaluate environmental impact of a product, process, or service (or in this case, a facility), explains David Estapé, technology manager for Life Sciences in the Global Business Unit, Life Sciences & Chemicals, of M+W Group. An LCA can look at different environmental impact categories; this study considered climate change impact (i.e., carbon footprint in carbon dioxide equivalents). An LCA from “cradle to grave” takes into account not just the facility operation, but all materials and resources from construction to demolition of a facility. Facility operation, however, is the largest contribution to carbon footprint, the study confirmed (7). 

	Using a software program designed to evaluate LCA via mass and energy balances, M+W looked at process, building, and utility systems for a generic monoclonal antibody production process using single-use systems and modular construction for a manufacturing facility located in China.

	The study concluded (7) that transportation of the building modules (by ship) had a small percent of the total environmental impact of the facility (only 1%). The building systems (particularly HVAC) had a significant impact that varied by facility output (28–38%). Surprisingly, the production and disposal of single-use components accounted for only 9–11% of the total impact, while transportation of the consumables to the facility site accounted for 25–30% of the total. “The waste generated by consumables has been raised as a possible concern for single-use systems, but we found that waste was, in reality, a relatively small component. For a facility located at a long distance from the single-use system source, air transportation of the consumables was the biggest impact,” reports Estapé. Optimizing the supply chain for consumables is thus important. “Facility location is significant for transportation as well as for the ‘greenness’ of the energy source used in the LCA,” he adds.

	“Sustainability of facility design is increasingly important, and programs like LEED [the United States Green Building Council’s Leadership in Energy and Environmental Design] certification are desired,” notes Estapé. “It is necessary, however, to understand what exactly contributes to the environmental impact for a particular facility, given its location and all aspects of its operation, not only factors such as energy-efficient lighting and HVAC. We can design the best facility but not truly solve the problem, if the majority of the impact is outside the facility, in transportation, for example. Looking at the LCA is crucial to addressing the real impacts.”

	1.     PharmTech, “Energy Management in Bio/pharmaceutical Facilities,” (Feb. 20, 2013), 

www.pharmtech.com/energy-management-biopharmaceutical-facilities

	2.     J. Markarian, “Considering Water Use in Pharma Manufacturing,” (Oct. 18, 2017), 

www.pharmtech.com/considering-water-use-pharma-manufacturing

	7.     D. Estape, “Sustainable Facilities: Global Environment Impact of a Biopharmaceutical Facility,” presentation at 2017 ISPE Annual Meeting & Expo (San Diego, Oct. 30, 2017). 

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Optimizing water and HVAC systems can reduce resource use in all pharma facilities, and, for biopharma manufacturing, the supply chain of consumables should be evaluated.  

Improving Sustainability in Pharma Manufacturing

	FDA Commissioner Scott Gottlieb, MD, said that reducing the overall exposure to opioid drugs is a crucial part of preventing addiction, and that FDA is exploring further how opioid drug products are packaged, stored, and disposed of. “The FDA is committed to exploring our existing authorities to find new and impactful ways of regulating these product features to improve patient safety,” said Gottleib, in an Oct. 30, 2017 

	He noted that FDA is considering solutions: “For example, it’s possible that a defined, short-term supply of medication could be packaged in a manner that limits the number of pills dispensed. This might be achieved, for example, through a blister pack that has a defined duration of use that might be for only a limited number of doses. Other packaging innovations could make it easier to track the number of doses that have been taken. Still other options could work to improve storage and encourage prompt disposal to reduce the available supply and reduce the risk for third-party access, such as a child accidentally ingesting pills they found in a medicine cabinet. There are also technologies that could allow health care providers, pharmacists, or family members to monitor patient use of prescription opioids.”

	Gottlieb said that the Opioid Policy Steering Committee, established in May 2017, is considering what steps the agency should take regarding opioid prescription packaging, and an internal task force is conducting additional research to inform the agency’s policies and decision-making. FDA participated in a 

workshop convened by the Duke-Margolis Center for Health Policy

 in June 2017 on opioid packaging, storage, and disposal, and on Oct. 31, 2017, FDA announced a 

, to be held Dec. 11–12, 2017 in Silver Spring, MD.

	The workshop, “Packaging, Storage, and Disposal Options To Enhance Opioid Safety-Exploring the Path Forward” will, said Gottlieb in the statement: “advance this issue by working with a broad set of federal, state, and other stakeholders who are also addressing the challenges of balancing pain management with the critical need to address the opioid epidemic. Our goals at this scientific workshop encompass three key areas. First, we need to define the specific problems that these types of packaging and disposal solutions can help address. Second, we want to more clearly define the guiding principles that the scientific community should consider in designing product features that achieve these possible solutions. Finally, we’ll better define the types of data needed in order to evaluate how these solutions are working.”

FDA announced a public workshop to explore strategies for addressing the crisis of opioid addiction through innovations in packaging, storage, and disposal.

Equipment and Processing Report-11-15-2017

Improving Sustainability in Pharma Manufacturing

FDA Commissioner Says Packaging Innovations Can Help Address Opioid Crisis