Sustained interest? Biopharma’s green manufacturing gains traction

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Sustainability remains a priority across industries, including biopharma. While some sectors achieve greener operations through simpler changes such as switching energy suppliers or reducing packaging waste, large molecule drug manufacturers face more complex challenges.  

Verena Ahnert, Partner at L.E.K. Consulting, notes, “Sustainability has long been a growing focus in biopharma manufacturing. Although the sector initially trailed other industries in setting emissions targets, mounting regulatory and customer expectations have steadily elevated its commitment to greener practices.”

Despite this focus on sustainability, biopharma remains a major source of carbon emissions. According to recent analysis, drug production generates some 4.4% - 260 million tCO₂ – of global carbon emissions each year. 

Biopharma’s carbon footprint reflects the energy and materials-hungry nature of its production processes according to the authors, who cite monoclonal antibodies (mAbs) as an example. 

“A typical mAb manufacturing process has a processes mass intensity (PMI) of 7700 kg/kg, with macromolecular medicines using 100 times more water than small molecule pharmaceuticals."

“Adopting sustainable methods in the development and manufacture of current and future products can therefore have significant impact on net global emissions,” they conclude.

The complexity of biopharmaceutical manufacturing - combined with the high level of regulatory scrutiny under which the industry operates - makes it difficult and costly to change existing processes. 

As a result, most sustainability efforts take place in the development lab. The idea is to create processes that have minimal environmental impact, through an approach known as sustainability-by-design (SbD). 

Like quality-by-design (QbD) – which puts product quality at the heart of process development – SbD, makes sustainability a consideration that informs everything from technology selection through to facility design. 

For example, protein therapeutics companies are increasingly taking sustainability into account when choosing expression systems according to a recent study by researchers at Merck KGaA. 

“Selecting an expression system regarding sustainability means striking a balance between the key criteria of expression yield, resource efficiency, and the required product quality and manufacturing scale."

“Expression yield directly impacts process mass intensity (PMI), a sustainability metric defined as the total mass of materials used divided by the mass of the final product. Thus, increasing yield or reducing material consumption can improve sustainability,” they write.

Sustainability concerns are increasingly being factored into the production technologies firms choose, according to a study by researchers at Imperial College London’s Sargent Centre for Process Systems Engineering. 

“The choice and optimisation of the modus operandi have been traditionally led by product purity, functionality, process operability and yield considerations, without explicitly considering the environmental footprint. This could be partially attributed to the fact that the industry’s positive impact on society has, so far, outweighed the environmental footprint of the sector."

“However, net zero initiatives are now at the heart of the broader Life Sciences sector, with concrete commitments in place by as early as 2030. It is, therefore, timelier than ever to address how sustainability can be integrated into bioprocess design and optimisation,” the authors write. 

And there are other reasons why focusing sustainability efforts on new processes makes sense. According to another study*3, 80% of a biopharmaceutical’s environmental impact is determined during process design. 

The authors write:“Development is the most powerful and cost-effective point to address the resource footprint of future products, with early development having the most impact on possible changes, followed by late development. This highlights the importance of embedding sustainability in pharmaceutical research and development in line with the chemistry, manufacturing, and controls (CMC) timelines.”

Biopharma has used single-use plastics (SUP) in manufacturing for decades. For example, the tubing used to transfer the process stream from one unit operation to the next is typically plastic and typically replaced after each production run.  

However, in the past two decades the amount of disposable plastic used in drug manufacturing has increased significantly as more companies choose single-use bioprocessing systems rather than traditional, stainless-steel reactors.

According to one study, since 2005, single-use bioreactor capacity has grown from 1% to 13%. In addition, the proportion of single-use reactors has risen from 30% to 46% of all installed capacity.

What impact the increased use of single-use systems has had on sustainability is unclear. According to the authors, “the disposal of approximately 30,000 tons of SUPs annually through landfilling or incineration presents largely unquantified environmental and health challenges."

However, while the volume of plastic waste may have increased, the reduced energy and cleaning requirements associated with single-use systems are also a factor.

“Life-cycle analysis (LCA) of SUPs suggests a lower environmental footprint compared to traditional stainless-steel systems, primarily due to the high energy intensity and embodied carbon of the latter. There are notable reductions in in-process energy and water requirements associated with SUT,” the authors write.

This take is in keeping with the conclusions of a separate 2023 study, which indicated that the environmental “cost” of disposing of single use technologies is offset by the reduction in water and energy consumption associated with such systems.

“The results of this study indicate that the single-use process train exhibited lower environmental impacts compared to the traditional fixed-in-place process train in each environmental impact category studied."

“This is primarily due to a reduced need for the energy intensive water-for-injection, process water and clean steam that are required to perform cleaning and sterilization between batches for traditional fixed-in-place equipment,” the authors write.

Another major obstacle for sustainability efforts is the complex nature of biopharmaceutical supply chains.  

Making a biopharmaceutical typically involves a large network of raw materials and technology suppliers as well as, potentially, manufacturing, formulation and logistics contractors – all of which have their own production practices that impact the overall sustainability of the finished product.

Understanding these dynamics is a challenging, but vital part of making production more sustainable, Ahnert says.

“In order to reduce upstream and downstream emissions, pharma companies need greater visibility into their supply chains."

“A related co-benefit of more supply chain visibility is greater oversight of supplier behaviours; with more insight into suppliers’ activities, pharma companies are better able to partner with them and hold them accountable for their actions.”

Whether sustainability remains a top concern for biopharma in the long-term remains to be seen. However, there are positive signs, according to Ahnert.

“Thirteen of the top 20 pharma companies by revenue have committed to net zero, and among these, over half made their commitments in the past three years. In line with the growing focus on the connection between climate and health, stakeholders in the healthcare industry are increasingly seeking to decarbonise.”

And, says Ahnert, the public nature of such commitments are a sign the industry is finally taking sustainability seriously, pointing to Sanofi’s 2023 “road to net zero” document to support the argument.

“The factsheet acknowledges that, ‘environmental awareness has significantly increased among customers, investors, and society in general. Not complying with sustainability expectations and requirements bears severe financial and reputational risks for Sanofi.”