Pharma companies are ramping up integrating innovations in green technologies into their processes as sustainability becomes the watchword amidst mounting pressures to reduce carbon footprints.

With environmental concerns in the backdrop, the call is growing louder worldwide for action and accountability from the energy-intensive pharmaceutical industry—one of the biggest contributors of greenhouse gases (GHG).

Sustainability is a critical issue, according to CPHI’s Annual Industry Report 2023, “with 90% of executives citing ‘visibility on supply chain partner’s sustainability record’ as extremely important or important.’”

“With growing numbers of sponsors scrutinizing clinical trial operations against environmental, social, governance (ESG) frameworks, sustainability is no longer a buzzword in the background,” comments Lyn McNeill, supply chain solutions manager, Almac Clinical Services, a global CDMO headquartered in Craigavon, UK, and a member of the privately owned Almac Group. “Instead, sustainability is rapidly becoming a key performance indicator and a mechanism to lower the environmental impact of bringing new drugs to market, ensuring limited resources are ethically utilized to safeguard patient access, and drive more cost-effective operations.”

Contract manufacturers, constantly looking for ways to maximize efficiency, increasingly hold that sustainability must become a core value for everyone to have the greatest impact.

CDMOs that prioritize sustainability can differentiate themselves in today’s highly competitive market by enhancing brand value and attracting more contracts from companies seeking to minimize environmental impact in their supply chains, says Leonardo Magneschi, vice president, research and technology development at Ingenza Ltd., a contract research development and manufacturing organization (CRDMO) based in Roslin, UK. “By positioning sustainability as a core business model, CRDMOs can boost customer loyalty, increase revenues, and build resilience against future market shifts.”

Mariesa Coppola, general counsel and corporate secretary at Curia, a CDMO headquartered in Albany, NY, expresses a similar view. “The pharma industry is driving its own impactful sustainability requirements, largely from Big Pharma pushing commitments and expectations down to CDMOs,” she says.

Already, companies have started reviewing the longstanding methods in various aspects of the pharmaceutical supply chain, which accounts for 90% of the energy consumption of a company, to upgrade the infrastructure and support more eco-friendly practices. 

“Biopharmaceutical companies are facing several challenges, from helping develop treatments for complex diseases to reducing their environmental footprint and complying with newly implemented and upcoming environmental regulations around the world,” says John Puglia, senior director, research and development, Thermo Fisher Scientific.

With the increasing demand for biologics, it’s important for commercial manufacturers to select solutions that can help them maximize efficiency, save costs, and increase yield, as well as make strides toward their respective sustainability goals, Puglia adds.

The paradigm shift: From energy-intensive processes…

Thermo Fisher has recently launched a bio-based solution that features the same performance as the plastic polymer-based versions. Derived from plant-based materials, these films allow biopharma companies to maintain consistency in their manufacturing processes, all while helping reduce resin-based GHG emissions.

Studies suggest that manufacturing is the largest component of emissions attributable to a pharmaceutical company, contributing to around 80% of indirect emissions.

To help manufacturers reduce their environmental footprint, Thermo Fisher offers a selection of single-use solutions. This includes the DynaSpin single-use centrifuge, which enables a faster, cost-efficient cell culture harvesting process while helping reduce the usage of traditional depth filtration. It offers upwards of a six-fold reduction in material requirements, eliminating 70% of waste compared to traditional harvest systems.

Single-use bioreactors (SUB), such as the DynaDrive generate up to 27% less product and packaging waste compared to the 2,000L SUB traditional workflow, with the added benefit of helping to reduce the cost of consumables for manufacturers by up to 37% when compared to stainless steel bioreactors.

“Single-use technologies (SUTs) in bioprocessing boast several benefits over stainless steel for biopharmaceutical manufacturers and are becoming an increasingly popular choice due to their advantages in sustainability, flexibility, and scalability,” says Puglia.

One disadvantage of stainless-steel technologies is that they require users to follow strict sterilization and cleaning processes, which can exacerbate both water and overall facility energy usage. SUBs have also been proven to reduce the cost of consumables for manufacturers by 37% when compared to stainless steel bioreactors.

Magneschi of Ingenza also endorses the advantages of SUBs to reduce resource consumption, harsh chemical use, and waste generation while eliminating the need for extensive cleaning and autoclaving. Ingenza makes use of SUBs in the fermentation phase as one of the several ways to optimize their bioprocesses.

A specialized CDMO, Ingenza has capitalized on the innate benefits of microbial hosts by engineering a range of micro-organisms, including Bacillus subtilis and Pichiapastoris, with enhanced growth rates and protein yield per liter.

Microbial hosts, including bacteria and yeasts, can grow on simpler and more cost-effective media than mammalian cells which are traditionally used for recombinant protein expression. They also display faster growth rates and the ability to reach very high cell densities. This means that less water and energy are needed to produce higher protein yields.

Ingenza’s proprietary machine learning gene design algorithm can predict and further boost recombinant protein expression levels. These highly productive, engineered hosts can help bio-pharmaceutical manufacturers improve process efficiencies and overcome production bottlenecks. The higher productivity of microbial lines also helps manufacturers simultaneously lower their bioreactor volume requirements, consequently reducing waste generation for greater sustainability.

With over two decades of experience, Ingenza has also demonstrated how the shift towards continuous manufacturing and automated control strategies further reduces environmental impact by successfully redesigning recombinant processes for antimicrobial peptides and intensified semi-continuous processes for B Domain Deleted Human Factor VIII (BDD-FVIII).
Ingenza combines biological and chemical approaches by incorporating enzymes into production, wherever possible, explains Magneschi. “This allows us to develop more environment-friendly biocatalytic methods capable of replacing expensive and resource-heavy chemical catalysis.” This is particularly relevant in the synthesis of chiral synthons and pharmaceutical intermediates, which can be highly energy-intensive and may generate significant volumes of waste material.

…to greener methods

“The substitution of chemical synthesis processes by fermentation green routes constitutes a very efficient bioprocess both from the industrial and environmental point of view,” concurs Jose Luis Barredo, GM and head of global fermentation at Curia.

Scientific advances now enable the use of microorganisms to create part or all of any desired molecule. In some cases, fermentation can be utilized to produce molecules that are not amenable to traditional synthetic organic chemistry. Biocatalysts are now used to modify current commercial molecules as well.

Contrary to chemical synthesis, fermentation processes do not need exotic metals, hydrocarbon solvents, etc., and they typically proceed near to room temperature and pressure. In addition to being sustainable, fermentation avoids the handling and disposal of hazardous waste, and as such, this green approach is safer for both manufacturers and the environment, Barredo explains.

Curia has recently made significant investments in sustainable solutions across its network including the non-thermal water for injection (WFI) generation system at the CRDMO’s Albuquerque, NM site. “This system uses reverse osmosis (RO) plus ultrafiltration technology to generate WFI instead of traditional methods involving boiling and recondensing water, significantly reducing energy consumption in our drug product manufacturing process,” says John Valley, vice president, engineering and technical services at Curia.

Curia has also installed thermal oxidizers at selected sites, achieving a minimum 98% removal efficiency of air emissions.

“Additionally, we have implemented solvent recovery systems at different sites, including Origgio, Italy, which reduce the need for incineration and external disposal besides a trigeneration plant that enhances energy efficiency and reduces CO2 emissions, at our Origgio site,” adds Elena Ponta, maintenance at Curia (Origgio), Italy.

Alternatives to traditional production methods have almost become a forte of many CDMOs to optimize processes and reduce costs, especially for compounds requiring energy-intensive processes.

Cell and gene therapies (CGTs), for example, require significant energy to manufacture, transport, and store at extremely low temperature ranges with the cost for manufacturing one batch of CGT product typically varying between $500,000 and $1 million.

“For CGTs, Almac’s Just in Time Manufacturing service can help create optimized and adaptive supply chains that promote enhanced product viability and reduced product waste—just one of our options to effect substantial impact on both ESG credentials and a sponsor’s bottom line,” says Lyn McNeill of Almac.

Meanwhile, active pharmaceutical ingredient (API) makers like Olon believe partnerships with institutions and universities are essential drivers for innovation.

Olon runs a scholarship program with the University of Milan’s Department of Chemistry for a PhD in the development of new photochemistry-based processes applied to the production of APIs.

The goal of the project is to develop new alternative routes of synthesis based on photochemistry—a highly innovative, sustainable process that can be systematically applied to industrial-scale production.

Olon is working on cutting-edge R&D processes applied both to chemistry, in terms of flow chemistry, photochemistry, and electrochemistry, and to biotechnologies.

“Innovation is embedded in Olon’s business model, enabling the company to be more agile in sharpening the focus on core business and optimizing the phases of research, while maintaining high standards of product quality and safety, ensuring product accessibility to a wide range of people and reducing their environmental footprint,” says Paolo Tubertini, CEO, Olon Group.

Daunting agenda

Clearly, companies themselves have committed to reducing their own scope 1 (everything within the company’s production and buildings) and scope 2 (supplied energy consumption) emissions for several years. But the biggest chunk of their emissions is found in scope 3—emissions up and down the external supply chain.

According to a recent report from global consulting firm Oliver Wyman, the two biggest barriers to implementing environmental changes within the pharma manufacturing industry today include measuring and reducing scope 3 and the upfront cost and difficulty in creating a financial business case.

Scope 3 emissions are particularly difficult to quantify due to challenges in identifying indirect emissions from third-party contributors. Therefore, engaging with the external supply chain on how they can also measure and reduce their own emissions is central to achieving decarbonization, reports say.

Many pharmaceutical CDMOs maintain that they do keep systems to ensure that the third-party supplies are compliant with the expected standards.

“We work with third parties to monitor quality metrics like extractables and leachables, particulate values and making sure that our current levels are compliant with customer expectations and future products will outpace the standards that are being forecasted for the future,” says Puglia of Thermo Fisher Scientific.

Leaching of APIs to the environment is a problem in manufacturing, particularly for highly potent drugs.

Puglia adds that while the CDMOs play a role in providing instant capacity to the pharmaceutical industry and have to be prepared to pivot from one drug substance to another in short order, they have pushed their suppliers to increasingly concentrate on more sustainable solutions for the consumables they utilize. 

It is through routine supplier due diligence that Curia ascertains the site of manufacture for direct materials supplied to its manufacturing facility. The CRDMO’s procurement department undertakes the due diligence in the form of a checklist/questionnaire that covers safety, quality, production, environmental, social, and governance aspects, says Coppola.

Ingenza, meanwhile, seeks to manage compliance-related risks through a multi-faceted approach. “We establish clear contracts outlining compliance expectations, and regularly review and update our list of trusted partners based on feedback and performance,” says Magneschi.

Surveys also revealed a lack of investment in expertise and technology, a key challenge to achieving environmentally sustainable manufacturing. Life cycle assessments (LCA) are not yet a common practice in the pharma industry. Identifying a drug’s environmental impact early in its lifecycle could help improve pharma manufacturing’s environmental footprint as the environment has been identified as the most important of the three ESG sustainability concerns to pharma manufacturing.

Further, stringent regulations related to product safety and market pressures are being listed among the challenges hindering the adoption of sustainable practices in the industry.

On the other hand, regulation around sustainability in the pharma industry is distinctly lacking. The absence of guidance to encourage the reporting of a company’s emissions is leading to reduced accountability and huge data gaps.

However, several companies think ahead to become industry leaders in more sustainable drug manufacturing and packaging solutions.

Besides using ingenious techniques and green processes to cut down the demand for energy in some of the most energy-intensive operations and eliminate emissions in manufacturing, many companies utilize the principles of green chemistry to substitute processes with alternative solvents that lead to a reduced carbon footprint, cold-chain shipping by increasing the amount of green fuels, prioritizing water-saving policies and water/waste recycling, etc.

To increase transparency and reporting on targets, more companies are joining external initiatives like the Science-Based Targets initiative (SBTi). When validated, SBTi publishes shared targets in an annual report for stakeholders.

Curia, which has recently made a public commitment to SBTi for near and long-term targets as well as committed to a net zero target in 2050, provides an example. Curia has a focused responsibility on making meaningful contributions without strict regulation, remarks Coppola.

Industry reports say that public disclosures, external validation, and working with rating agencies to ensure credible targets are being set and progress is captured accurately is an important way of tracking real impact.

Upfront costs, as the Oliver Wyman survey pointed out, continues to be yet another major barrier. Many companies are still hesitant to implement decarbonizing strategies considering the cost to business.

However, the number of pharmaceutical CDMOs that believe they can still succeed economically while achieving ambitious sustainability goals looks to be growing by the day.
Ingenza, for example, has found that as a CRDMO, sustainability, and economic viability go hand in hand.

“By integrating sustainability into process design—whether batch, fed-batch or continuous—we align economic success with environmental goals, providing a competitive advantage and reinforcing long-term business viability,” affirms Magneschi. 

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Soman Harachand is a pharmaceutical journalist based in Mumbai and a regular contributor to Contract Pharma. He can be reached at harachand@gmail.com.