Emmanuel Abate, president Genomic Medicine and head of Sustainability, Cytiva, reflects on the developments of the biotech industry in 2022 and despite the manufacturing challenges that remain, the focus on sustainable solutions must not be ignored.
Key insights:
- mRNA manufacturing has not yet been standardised, leading to challenges with operations, personnel, process, quality control, and contamination.
- Sustainability should be built into the product lifecycle from the start through to end of life, one example is advanced recycling.
- In gene therapy, implementing an integrated solution is important to not only optimise each unit of operation, but could reduce process steps.
2022 was another major year for the biotechnology industry. Although nations were slowly starting to emerge from two years of public health measures related to COVID, the science and innovation never stopped. In 2020, the scientific community cracked the code on mRNA technology and has since been applying that knowledge to try and solve other global health challenges.
The US FDA approved two gene therapies in 2022, giving hope to patients who historically had few options. However, advancing and accelerating the development of mRNA-based therapeutics, vaccines, and gene therapies can only be done if manufacturing challenges are addressed. As the industry works to develop the tools and technologies needed solve these issues, we can’t lose sight of environmental concerns. Solutions must be sustainable.
Overcoming the challenges of mRNA manufacturing
mRNA was catapulted into the spotlight during the COVID-19 pandemic as an exciting technology that could change the future of medicine. While we may not have another breakthrough for some time, the scientific community must now address the process and manufacturing challenges for any potential mRNA vaccine or therapeutic to reach its potential.
Adapting the process remains one of the key hurdles, as most current processes are designed and optimised for other molecules. mRNA manufacturing has not yet been standardised, leading to challenges with operations, personnel, process, quality control, and contamination. mRNA is on a much smaller scale than traditional cell-based modality manufacturing which presents another challenge for its development. While this results in considerable space and cost savings, it does require manufacturers to think differently about their space.
Another key challenge is DNA linearisation and purity at various stages of the process. Due to their size and varying impurity profiles, traditional chromatography resins don’t always interact well with mRNA molecules. Greater flexibility in purification technologies and allowing process development scientists to mix and match media, based on the specific characteristics of the molecule, are two ways to deal with this challenge.
The key to success for mRNA manufacturing is flexibility. Ensuring equipment is scalable and supporting the transfer from process development to GMP manufacturing will be a crucial success factor in building out the mRNA manufacturing ecosystem.
Gene therapy is here to stay, but manufacturing isn’t there yet
There are many gene therapy candidates in clinical development and more global regulatory approvals anticipated over the coming years. However, we are not yet in a place where the industry could manufacture to meet patient demand.
Most gene therapy products are manufactured using individual steps that are manual and involve open operations. As such, efficiency is affected, and the risk of product contamination increases significantly. The solution to reducing these risks is scalable, automated, and closed platform manufacturing.
Through adding single use technologies to the closed system, this can further save time, reduce risk, and lower overall manufacturing costs. By reducing cleaning and validation time, set-up time, and in process hold steps for an operator to oversee equipment, has led to anywhere from a couple of days to a couple of weeks being saved. Closed systems are also more compatible with automation, which can further reduce timelines and cost, and, perhaps most importantly, ensure consistent product quality.
Implementing an integrated solution involves all the unit operations working together in a continuous manner resulting in all consumables being compatible. It is important to not only optimise each unit of operation, but also to consider how all these units fit together and could reduce process steps. This solution will also ensure the process will run the same way each time.
Accelerating therapeutics sustainably
While we work to address manufacturing challenges, we must do this sustainably. The use of plastic is integral to accelerating therapeutics. While there continues to be a need for plastic, one solution doesn’t fit all applications. As such, it’s essential that the biotechnology industry considers its approach on how to create more sustainable alternatives.
The industry’s dependence on plastic can impact the environment, and so starting to introduce circular models into product design processes can help. Sustainability should be built into the product lifecycle from the start through to end of life. To ensure that this is a reality, companies need to implement a framework that engages teams to think of ways to reduce, reuse, and recycle throughout the design process. For example, could recycled plastic be used instead of virgin plastic when sourcing materials? Or could the product be recycled at the end of its life? If the industry can learn to look at product design through a sustainability lens, then the environmental benefit could be huge.
There are also sustainable opportunities to be pursued in advanced recycling, where technologies are currently being developed to meet rising demand. This process enables the transformation of used plastics into new products that can be repeatedly recycled. Although there’s a high demand for this type of solution, there’s a limited availability of advanced recycling facilities. This restricts the speed of implementation. Ultimately, the biotechnology industry will need to accelerate its sustainability efforts, and start to support academic institutions researching advanced recycling of contaminated plastics.
The adoption of smart logistics is another solution which can reduce environmental impact. This could look like a rethink of packaging materials, using more direct and shorter routes, as well as changing transport modes. Through smart logistics companies can cut carbon emissions and transportation costs.
The big picture
The world needs advanced therapeutics to solve some of the greatest health threats from potential pandemics to cancer to rare diseases. Addressing the manufacturing challenges they pose, is only part of the solution. Developing technologies that can advance therapeutics sustainably will help preserve the planet while providing patients with the medicines they need.