Sustainability by Design in the Context of Bioprocess Development

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Pharmaceutical TechnologyPharmaceutical Technology May 2025
Volume 49
Issue 4
Pages: 24-27

Incorporating sustainable practices into process designs as early as possible ensures optimal performance.

Protect environement | Image Credit: ©Y. L. Photographies -stock.adobe.com

Protect environement | Image Credit: ©Y. L. Photographies -stock.adobe.com

Drug developers face increasing pressure to accelerate process development and reduce costs while ensuring safety and efficacy of investigational candidates and marketed products. They must achieve these goals while minimizing the impact that development and manufacturing operations have on the environment. Given shorter development times and the challenges associated with making process changes in later development stages, the best approach for improving sustainability is to incorporate sustainable practices into process designs as early as possible.

Considering sustainability from the outset

Sustainability-by-design in bioprocess development, according to Adam Goldstein, senior director of R&D Collaborations at Thermo Fisher Scientific, involves integrating sustainable practices and principles from the very beginning of the development process, which includes considering environmental impacts, resource efficiency, and waste reduction during the design phase, to create processes that are not only efficient but also lower the environmental footprint.

Because 80% of a drug’s final environmental impact is determined during the early stages of process design (1), Kami Krista, CEO of Elio Technologies, adds that sustainability needs to be part of the decision-making process during the early R&D and chemistry, manufacturing, and controls (CMC) phases—particularly before changes become difficult due to regulatory constraints (e.g., once process inputs are defined in the regulatory dossier).

In addition, because 42–47% of a pharmaceutical company’s emissions profile can be attributed to purchased goods and services (2), Krista emphasizes the importance of considering both process inputs and conditions. That means employing more environmentally friendly chemicals and processes.

Incorporating sustainability-by-design into process development activities is most effectively achieved by integrating sustainable practices throughout design, construction, and operation of biopharmaceutical production sites, according to Jacob Skou, sustainability manager at FUJIFILM Diosynth Biotechnologies. Key elements that are considered include resource and energy efficiency, waste minimization, and use of less hazardous chemicals and processes. “Processes are designed that optimize the use of raw materials, energy, and water, and alternative renewable energy options such as solar and wind are used where possible to increase energy efficiency. Furthermore, strategies are implemented for reducing, reusing, and recycling waste material generated during bioprocessing,” he says.

Krista concludes that “to successfully integrate sustainability, it is essential that every scientist, process engineer, and other relevant stakeholders can easily assess the sustainability implications of their decisions—alongside technical and cost considerations—and weigh the associated trade-offs.”

Environmental, operational, and cost benefits

Adopting a sustainability-by-design approach in biopharmaceutical manufacturing offers a wide range of benefits in addition to reducing the impact of development and manufacturing operations on the environment. Skou highlights cost efficiency, compliance and risk management, innovation, and increased social responsibility as important benefits resulting from the integration of sustainability into bioprocess development activities.

“Reducing resource and energy consumption and minimizing waste reduction benefits the environment and contributes to cost reductions. Furthermore, as environmental standards become more stringent, adopting sustainable practices helps ensure continued compliance and reduces the risk of legal penalties and reputational damage. Taking a sustainability-by-design approach can also drive innovation that results in market-differentiating processes. Finally, sustainable practices emphasize ethical considerations; promote the health, safety, and well-being of employees and communities; and thus align with broader social responsibility goals,” Skou explains.

Goldstein emphasizes the importance of the innovations that result from adopting a sustainability-by-design approach because they can lead to improved product quality and process efficiency.“Driving higher titer in smaller volumes means yielding higher throughput of product in a smaller footprint. The benefits are lower cost of goods in manufacturing while simultaneously delivering the product in a much more sustainable fashion with regards to emissions reductions,” he comments.

Another important benefit of taking a sustainability-by-design approach for Krista is the fact that by integrating sustainability improvements from the outset, it is not only possible to dramatically reduce the impact of biopharmaceutical operations and the overall environmental footprint of the product and company, the high costs and challenges to making sustainability improvements during later stages are avoided.

There are marketing advantages as well. For contract development and manufacturing organizations (CDMOs), Skou believes having an improved sustainability profile is a competitive advantage.

Krista also notes that in Europe, many hospital procurement systems (i.e., England’s National Health Service and the Joint Nordic Procurement system) are including sustainability performance as a decision criterion when selecting drug products. For public companies and early-stage firms seeking specific investors, having a good sustainability rating (often based on product stewardship, sustainable raw material selection, or similar ecodesign criteria) can attract more investors. Sustainability is also increasingly featured as a decision criterion by Big Pharma companies when making merger and acquisition decisions, according to Krista.

From cell line to waste management

All aspects of biopharmaceutical manufacturing should be considered when taking a sustainability-by-design approach to bioprocess development, starting with the choice of cell line through methods for waste processing, according to Goldstein.

“High-titer cell lines are more productive, while chemically defined media reduce contamination risks and allow for sourcing of materials from sustainability-minded suppliers. Using centrifugation rather than depth filtration can reduce waste and processing times while improving yields, and higher-capacity chromatography resins can reduce buffer usage,” explains Goldstein.

Intensified processing both upstream and downstream can, meanwhile, reduce manufacturing footprints and resource consumption while reducing waste generation and improving facility throughput.

Upstream intensification examples highlighted by Goldstein include the use of high-density cell banking to skip long drawn-out seed expansions (reducing the six to eight days of standard good manufacturing practice [GMP] expansion) saving time, money, and resources (plastic, water, and media) by employing the use of single-use bioreactors (SUBs) that have high turndown ratios, which allows seeding at very low operating values and the growth of cells to high densities as the volume is expanded in the same unit operation SUB step. Downstream opportunities include the use of membrane separations.These technologies replace larger chromatography columns that use large volumes of buffers and take entire shifts to run.

Real-time monitoring of processes via inline sampling, often an important component of process intensification and continuous processing, also helps ensure more robust and high-quality processes and products, according to Goldstein. “Additional efficiencies are gained using ballroom designs vs. traditional costly, broken-up manufacturing suites, allowing for greater use and flexibility of manufacturing space, while funneling of waste into circular waste streams via collaborations with waste-stream recyclers add further benefits,” he notes.

The choice of water purity for certain activities can also have a significant sustainability impact. Highly purified water (like water for injection) is extremely costly and resource laden from a carbon footprint perspective, due to the vast number of steps (steam evaporation, filtration, heating, cooling) that are involved in its creation per liter, Goldstein explains. Specifying a lower quality of purified water (like reverse osmosis quality water Type 2 vs. Type 1) can and should be considered in the makeup of media, cleaning of equipment, and the creation of general early-stage purification buffers (until the process is in the final formulation stage). “Careful consideration and selection of the standard of water used for many manufacturing operations can drive large impactful improvements,” he states.

Involving the entire supply chain

Collaborating across the entire supply chain is, in fact, an essential component of a sustainability-by-design approach to bioprocess development, according to Ann-Cathrine Rosendahl, global sustainability manager with FUJIFILM Diosynth Biotechnologies. “When we talk about sustainability-by-design in bioprocess development, it’s not just about what happens on the factory floor—it’s about embedding sustainability into every step of the journey, from raw materials to the end-of-life of a product, to build a more resilient and responsible supply chain,” she notes.

Given that a significant part of bioprocess emissions comes from upstream activities (92%), engaging suppliers early is essential, Rosendahl says. “The sustainability of suppliers should be evaluated early, and we are working towards ensuring that partners who prioritize environmentally friendly practices—such as responsible sourcing and transport—are prioritized in our selection process,” she states. FUJIFILM Diosynth Biotechnologies is also committed to reducing environmental impact by working closely with suppliers to improve energy efficiency, adopt cleaner technologies, and explore innovative solutions that lower emissions. “By integrating sustainability into our business reviews and setting clear expectations, we are building stronger partnerships focused on continuous improvement,” Rosendahl remarks.

Sustainability aspects for final product management must also be considered. Where possible, packaging and logistics should also be optimized to reduce waste and emissions, according to Rosendahl. Promoting transparency and accountability is equally important to her, which she observes can be achieved by developing metrics for assessing sustainability performance and reporting progress to stakeholders. That, Rosendahl underscores, requires access to accurate data to ensure a clearer understanding of the Scope 3 footprint for biopharmaceutical manufacturers (indirect greenhouse gas emissions generated outside the company across its value chain).

“Having better data helps companies identify where the biggest impacts are and explore opportunities with suppliers to make processes more sustainable over time,” Rosendahl adds. “By addressing these aspects, companies can move toward an approach to sustainability that considers not just the products themselves but also the surrounding processes, infrastructure, and practices, leading to a holistic and effective sustainability strategy,” she concludes.

As an example, Goldstein highlights a program his company has established to connect customers with recyclers that can recycle single-use bioprocess containers (BPCs) after use. “This program helps biopharma manufacturers divert waste from landfills or carbon-intensive incineration, advancing their sustainability goals through a convenient recycling service that turns BPCs into high-quality plastic lumber. Approximately 400,000 pounds of plastic waste has been diverted from landfills or incineration since initiation of the program,” he observes.

Work is now focused, Goldstein says, on identifying recyclers that can accept mixed waste from biomanufacturers and convert those materials to bio-oil, which can then be recycled into new polymers. These new polymers can be used either in the biomanufacturing environment or in entirely separate recycled products, such as faux wood, fillers for roads, etc.

Comprehensive assessment is important

The key to successful pursuit of a sustainability-by-design approach to bioprocess development is effective assessment of the environmental impacts of each unit operation. The first step, emphasizes Krista, is to equip scientists, process engineers, and all others involved in process development with tools that allow them to understand the sustainability impact of the decisions they are making.

Those tools must then be employed to thoroughly assess process development activities and identify opportunities for incorporating more sustainable practices, adds Goldstein.

Growing adoption, but several hurdles to overcome

The adoption of sustainability-by-design is growing, driven by regulatory pressures, consumer demand for greener products, and corporate environmental sustainability goals, according to Goldstein.

As environmental responsibility continues to become a major focus, the bioprocessing industry is transforming its approach to sustainability, with a major driver being requests from customers and investors to deliver on this agenda, evidence that strong sustainability strategy and actions is good business, adds Peter Skals, director of global sustainability for FUJIFILM Diosynth Biotechnologies.

In fact, based on 2024 data, nine of the top 10 pharma companies by revenue have ecodesign targets and activities embedded into their sustainability strategies, Krista observes. “The breadth of these ecodesign targets and activities vary from specific targets like green chemistry to programs that cover the entire value chain. In addition, while Big Pharma companies are leading the charge on ecodesign, due to pressures from customers, investors, and regulators, biopharma service providers, small and emerging biotechs, and suppliers are all stepping up activities focused on improving sustainability,” he comments.

Reaching aggressive sustainability targets requires overcoming some notable challenges, however. For instance, broader application in the bioprocessing sector is inhibited by inherent limitations of the bioprocess itself, which requires a different approach due to quality and safety restrictions, according to Skals. In addition, Goldstein notes that designing in sustainability for process development must begin in the pre-clinical phase, with the capability of selected raw materials demonstrated via qualification early in the development stage.

Sustainability also needs to be integrated into pretty much every design decision, leading to a very high volume of decisions that it must be seamlessly embedded into, Krista says. In addition, he notes there are inherent trade-offs to be made, with each right decision context-dependent, increasing the complexity of the decision-making process because more parameters must be considered.

Other important challenges noted by Krista include the lack of available “clean” data for performing sustainability assessments and the time- and cost-intensive nature of current assessment methods. “A lot of the data that [are] required to assess the sustainability impact of process design and process input selection [do] not exist or [are] hard to get,” he says. Much is based on responses to supplier surveys, which are not in sufficient quantity to support effective decision-making. Traditional lifecycle assessments, meanwhile, require weeks to months to complete, and can cost in the hundreds of millions for typical processes if you include the assessments for each of the different process-design and process-input variations at the relevant decision points (3).

Further increasing the challenge is the fact that most technical staff in bioprocessing plants are not sustainability experts. “Upskilling people in sustainability to the level that would be necessary to complete sustainability assessments is not feasible, which means straightforward guidance is needed,” Krista says.

Finally, Krista emphasizes the importance of not only quantifying and naming the sustainability pressures driving ecodesign today, but assessing those that will be present 10 years from today when investigational candidates eventually reach the market. “The most sophisticated pharma companies in the context of ecodesign are considering this impact lag and extrapolating in order to assess sustainability pressures beyond the response of a particular political party in power today, but where the longer arc of history is bending towards,” he contends.

Despite all these challenges and uncertainties, Skals believes that industry innovations and the inclusion of sustainability practices in the design phase is where the big wins can be achieved. But the incremental improvements of traditional designed bioprocess are important as well, he adds, and reduce waste without compromising product quality, stability, or safety.

Increasing role for digital technologies

Advances in digital technologies are making those assessments easier to perform and providing more valuable insights. Advanced technology facilitates access to reliable process monitoring data, allowing identification and prioritization of potential areas of improvement and implementation of appropriate process adjustments, according to Skals.

Technologies such as automation, real-time monitoring, and advanced analytics help in achieving precision and efficiency, adds Goldstein. He comments that innovations in materials science also contribute to more sustainable bioprocesses.

Machine learning (ML) can help overcome many of the challenges that exist in applying sustainability-by-design today, Krista contends. “At Elio, we believe ML is critical to ensuring sustainability-by-design can be adopted as widely as possible, as early as possible, and thereby have the biggest impact. Specifically, it can help with the challenge of insufficient, high-quality data,” he says.

ML models, Krista explains, in combination with data engineering, can help fill in data gaps with sophisticated estimations using data about the specific product, supplier, and/or specific process aspects from a wide variety of data sources that are available publicly (freely or through a license). “Using this approach can enable bypassing of the data bottleneck coming from relying on supplier surveys,” he adds.

“Pharma companies are already making decisions based on very crude generalizations, such as based on product category (e.g., all alcohols have the same footprint) or other characteristics (e.g., a chemical with a higher molecular complexity has a higher environmental footprint),” Krista observes. “ML models can simply be trained on a much higher dimensionality of data and thus can make higher accuracy predictions,” he contends. Using ML tools thus also addresses the time and cost issues associated with sustainability assessments, as the calculations can be completed much more quickly and at scale.

Fundamental shift

The biopharmaceutical industry does not typically have a first-mover mentality due to stringent regulatory requirements and the need to ensure patient safety. However, Skals believes there is potential for even more intelligent sustainability solutions in the future, particularly through incorporation of improvements in greenfield designs.

It will be necessary, though, Krista emphasizes, to move away from a desire to wait to get enough of the “best” data, which pharma professionals Elio Technologies has spoken to estimate will not be available for another 5–10 years. “Fortunately, sustainability leaders in pharma companies and even pharma suppliers are recognizing that making decisions based on imperfect data earlier is key,” he comments (4,5).

Most importantly for Goldstein is the fact that sustainability-by-design is not merely a passing trend but a fundamental shift in how bioprocesses are conceptualized, developed, and ultimately transferred to commercial operations. “Goals are defined not just in yield and cost, but also by sustainability in delivering a socially responsible product. Collaborative efforts across the supply chain are underway, with companies across the industry committed to driving continuous improvement in sustainability performance,” he asserts. “Ultimately, driving sustainability into the design of our process development strategies ensures that we continue to innovate in a responsible manner while delivering high quality products for our customers,” Goldstein concludes.

References

  1. Barle, E.; Melton, T.; Judge, E. Sustainability by Design for Pharmaceutical Products. Pharm. Engin. 2023 March/April.
  2. Elio Technologies. Analysis using data from: My Green Lab, The Carbon Impact of Biotech & Pharma. November 2022.
  3. Elio Technologies. Interviews with pharma companies and internal Elio Technologies research and analysis.
  4. Cytiva. 2024 Global Biopharma Sustainability Review.
  5. D’Souza, N. and Fava, J. Episode 13: Merck’s Jeffrey Whitford on Why Optimisim is Opportuity and How to Use Serendipity to Become Systematic. Five Lifes to Fifty. Podcast. Nov. 21, 2024.

About the author

Cynthia A. Challener, PhD, is a contributing editor to Pharmaceutical Technology®.

Article details

Pharmaceutical Technology®
Vol. 49, No. 4
May 2025
Pages: 24-27

Citation

When referring to this article, please cite it as Challener, C.A. Sustainability by Design in the Context of Bioprocess Development. Pharmaceutical Technology 2025 49 (4).

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