The excitement about cell and gene therapies is almost tangible within the biotech and pharma industry. Over 950 companies are actively developing advanced therapies, which are expected to make exceptional improvements to peoples’ lives in the next decade. Although hopes are high, the industry still faces a number of challenges in cell and gene therapy manufacturing, mainly around being able to deliver these often difficult to make, complex treatments at the scale needed to meet patient demand.
The unprecedented growth of the industry, alongside the need to develop scalable manufacturing strategies, has led to a number of challenges that need to be addressed urgently. Previously, patient numbers were so small that processes were highly manual and required numerous skilled operators. However, the recent success of early gene therapy trials means upscaling now needs to be considered right from the start.
Facing the challenges in cell and gene therapy manufacturing
“In the early days the aim was just to get to the clinic,” said Lindsey Clarke, Head of Cell and Gene Therapy EMEA at Bio-Techne. “Scale didn’t come into it so much, but now the conversations we are having focus much more on making these complex therapies at a scale needed for a commercial medicine. There are increased efforts on finding solutions that don’t just work for trials with 10 patients, but will still work at 1000 times that scale.”
Life science tools and technology provider, Bio-Techne, has made it its mission to further support the cell and gene therapy industry by channeling its expertise into developing technologies that can help to scale manufacturing processes. The company’s commitment is highlighted by its recent investment into a new good manufacturing practice (GMP) manufacturing facility in St Paul, Minnesota, US, that will focus on producing raw materials for use in cell and gene therapy applications.
“We have realized that if all our customers are to be successful with their therapies then there will be a huge demand for raw materials,” Clarke explained. “So we’ve started building that capability, ahead of time. But it’s not just about supply, we are also innovating, from simple things like looking closely at the format our products come in and making them more compatible with large-scale manufacturing to whole new product ranges.”
Complex supply chains and logistics
Bio-Techne’s investment in the new GMP manufacturing facility is a solution to meet the growing demand for raw materials needed for cell and gene therapy manufacturing. But it’s just one piece of a large puzzle: cell and gene therapy developers also need to consider the complex logistics required to deliver their therapies to the clinic, particularly when it’s an autologous therapy.
The process from the patient to the clinician, to the apheresis collection, to the manufacturing site, then the complex manufacturing process and then delivery back to the patient is highly complex.
Another key challenge closely related to upscaling is the great risk of human error in manual processes. Many of the cell and gene manufacturing processes currently in place have been developed with small patient numbers in mind and involve manual steps.
“Humans are an excellent source of error and risk,” explained Clarke. “When you’re manufacturing in a GMP environment, you need highly-skilled, trained operators and there is a shortage of them out there. Automation is going to be key to address this issue. Not only does it reduce the manpower that is required, but it can also streamline the processes and make them less risky, more scalable, and reproducible as well,” Clarke added.
With cell and gene therapy products, various analytical methods are used to assess critical quality attributes during development and manufacturing. These reflect the identity, potency, purity, safety, and stability of the product. However, such methods are frequently complex, non-standardized, time-consuming, and performed manually by trained operators.
Organizations such as Cell and Gene Therapy Catapult have called for the development of new analytical solutions for quality testing of advanced therapies throughout the manufacturing process. More automated analytical technologies have the potential to increase facility throughput and make quality control (QC) faster, less error-prone, more reproducible, and more GMP compliant.
Although Bio-Techne has a long-standing history of developing quality proteins, antibodies, small molecules, and immunoassays, it has expanded into automated protein analytical technologies in recent years.
For viral and non-viral vectors, Bio-Techne’s ProteinSimple branded platforms are rapidly being adopted by cell and gene therapy developers for assessment of vector identity, purity, and stability. Compared to traditional methods like Western blot, SDS-PAGE, and ELISA, ProteinSimple’s technology platform is based on capillary electrophoresis and microfluidics and provides a fully automated and accurate quantitative analysis of vectors.
“We are also seeing Micro-Flow Imaging (MFI), a more common image-based analytical platform in biologics, used to characterize subvisible particles for quality control of cell and gene therapy products,” explained Kamar Johnson, Commercial Development Manager in Cell and Gene Therapy at Bio-Techne. “These automated platforms offer ease of use, rapid time to result, enhanced reproducibility and software that meets GMP requirements.”
Collaboration lies at the heart of successful innovation. “It is especially important at the interface between process development and manufacturing,” said Johnson.
“Not everyone is an expert in everything, we all have our particular niches of expertise,” added Clarke. “We believe that we need to collaborate to get the innovation that will help change the way we manufacture cell and gene therapies. Collaboration is the key to solving the challenges of the cell and gene therapy industry.”
On that note, Bio-Techne recently partnered with Fresenius Kabi and Wilson Wolf to form a new joint venture that provides manufacturing technologies and processes for the development and commercialization of new cell and gene therapies.
The collaboration combines Bio-Techne’s expertise of proteins, reagents, media, and gene editing technologies with Fresenius Kabi’s Lovo® cell processing system and the bioreactor expertise from Wilson Wolf with its G-Rex® technology that is designed as a scalable and practical platform for personalized cell therapies.
The future of the cell and gene therapy landscape
As processes develop and technologies evolve, the cell and gene therapy space will be confronted with new challenges. At Bio-Techne, the team is keeping an eye out for interesting trends that might affect the industry.
“I see the induced pluripotent stem cell (iPSC) therapy field continuing to grow with more allogeneic cell therapies being developed,” says Johnson. “Allogeneic manufacturing is potentially less complicated than autologous manufacturing due to the ability to provide off-the-shelf products when patients need them.”
Although the challenges in cell and gene therapy manufacturing remain a problem, companies like Bio-Techne are establishing quicker, simpler, and more automated options within quality control, manufacturing, and process development.
“Wherever we go, we see newer technologies supporting cell and gene therapy manufacturing,” says Clarke. “Within our industry, changes come so rapidly and the treatments have shown so much promise that there is a lot of focus on cell and gene therapies. This puts a lot of pressure on us as an industry to provide these treatments. I believe that collaboration is the key to tackling this problem.”