Cell and Gene Therapy: Current Challenges and the Benefits of Automation
Cell and gene therapy is a field of personalized medicine, driving the innovation of medicine and revolutionizing the way we treat disease.
Gene therapies use DNA or other genetic material to edit a patient's cells to treat inherited or acquired diseases, and cell therapies involve the transfer of whole cells into a patient which replace those affected by disease.
At the time of writing, the US Food and Drug Administration has approved the use of 25 cell and gene therapies, with many more under assessment in clinical trials.
To learn more about the field of cell and gene therapy and discuss some of the challenges facing the industry and the benefits that automation can bring, Technology Networks spoke with Nirupama Pike PhD, senior director of technical affairs at Thermo Fisher Scientific.
Anna MacDonald (AM): Which disease areas are set to benefit most from cell and gene therapies?
Nirupama Pike (NP): Cell therapies:
- Cell therapy involves the transfer of intact and live cells into the body in order to replace damaged or diseased cells, induce an immune response or deliver therapies to targets. In cell therapy, the cells are modified outside the body and then delivered to the patient.
- Cell therapies have made a significant impact on the treatment of blood cancers and hematologic conditions including lymphomas, leukemias and multiple myeloma.
- Cell therapies are also showing success in clinical trials for the treatment of solid tumors.
- Other potential applications of cell therapies include treating cancers, autoimmune diseases, urinary problems, infectious diseases, rebuilding damaged cartilage in joints, repairing spinal cord injuries, improving a weakened immune system and helping patients with neurological disorders.
Stem cell therapies:
- Specifically, stem cell therapies can treat spinal cord injuries, Type 1 diabetes, Parkinson's disease, amyotrophic lateral sclerosis, Alzheimer's disease, heart disease, stroke, burns, cancer and osteoarthritis.
- Gene therapy involves the use of genetic material for the treatment or prevention of disease by altering the genes inside the body.
- Gene therapy holds promise for treating diseases such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS as well as inherited disorders such as cystic fibrosis, alpha-1 antitrypsin deficiency, hemophilia, beta thalassemia and sickle cell disease.
AM: Can you describe some of the challenges faced by those working in cell and gene therapy development and manufacturing?
NP: Some of the challenges faced by those working in cell and gene therapy development and manufacturing are as follows:
- Shortage of raw materials, including starting materials. Many cell therapies require good medical practice (GMP)-grade raw materials such as plasmids and viral vectors. Due to the rapid acceleration of the cell therapy field, there is a bottleneck for the availability of critical GMP-grade raw materials. There is also a shortage of single-use parts critical for manufacturing, such as tubing sets and bags. Starting material (apheresis, blood, bone marrow etc.) is often single source (i.e., from the patient or donor). A slight disruption to any part of the supply chain can result in failure.
- Complex supply chain and cold chain logistics. Cell therapies have a circular supply chain process that begins with the delivery of the starting material from the patient/donor to the manufacturing facility and ends with the delivery of the final product back to the patient. Both the starting material and the final product have time and temperature specifications and need a process that monitors the chain of custody and chain of identity in an efficient manner.
- Recruitment and retention of a skilled workforce. Since cell therapy manufacturing is complex and lacks standardization, the workforce needs in this space are unique and specific. Manufacturers need to develop a strong technical workforce by assessing the current skills gap and developing and implementing strong training programs with regular competency assessments. Since skilled technical staff are in acute shortage and high demand, it is vital to create individual development opportunities and well-defined career paths for the staff in order to retain them.
AM: What benefits can automation offer this field?
NP: The recent commercial success of cell and gene therapies has garnered a lot of interest from investors and manufacturers, which in turn has resulted in increased regulatory approvals being obtained. Because of this intensification, there is an emerging and pressing need for the industrialization of the manufacturing process. Gaining process efficiency, reducing manufacturing costs and simplifying the regulatory requirements are some of the issues that need to be addressed before the industrialization of cell and gene therapies becomes standard practice. The use of automation can address these issues and pave the way toward commercialization. Automation can also play an important role in scaling up manufacturing, especially for allogeneic “off-the-shelf” therapies. Automation has the potential to address many of these existing challenges without compromising the safety and efficacy of such therapies.
AM: How can automated solutions be incorporated into workflows to transform cell and gene therapy development? In particular, what role could automation play to advance the development of autologous/allogeneic cell therapies?
NP: The established biomanufacturing sectors (such as biologics, small molecules and monoclonal antibodies) have demonstrated that reducing hands-on time through automation offers a way to reduce human error, obtain more reproducible results, achieve standardization and improve the critical quality attributes of the final product. These benefits could be achieved through the automation of a single step, multiple automated steps integrated together in a workflow or through completely automated workflows.1 Ideally, fully automated platforms would offer an end-to-end solution from donor to product with continuous validation and monitoring for ongoing process optimization activities.1 These systems could be fully closed, eliminating user contact to reduce the chance of contamination and human error.1 Unfortunately, automation platforms designed for biologics and monoclonal antibodies lack the versatility and flexibility required for cell and gene therapy (CGT) applications.1 Cell therapies that are living pharmaceuticals require altered, fit-for-purpose manufacturing solutions.
It is important to note that cell therapies are “living pharmaceuticals” and therefore, will require altered, fit-for-purpose manufacturing solutions in order to address challenges such as inherent donor variability, cell heterogeneity, insufficient scalability and batch-to-batch discrepancies.
Efforts to enhance automation during manufacturing are ongoing, and the industry is now beginning to see the emergence of platforms that incorporate bioreactor and scaffold technologies to provide complete automation for both adherent and suspension cell cultures.1 The next step for system developers is to identify the many factors that contribute to enhancing a bioprocessing strategy and to implement these into their workflows.2 For CGT, the differences between autologous and allogeneic therapies must also be considered. Autologous therapies can benefit from a decentralized approach or a hybrid approach, while allogeneic therapies are more compatible to centralized manufacturing, which is easier to scale up and will make the initial investment in automation solutions more cost-effective.3
AM: How has the COVID-19 pandemic encouraged the industry to adapt, including the use of automation?
NP: The COVID-19 pandemic has undoubtedly amplified the pre-existing challenges in the CGT manufacturing space. During the pandemic, CGT manufacturers have faced issues related to shortage of raw materials, strained manufacturing capacity, overburdened supply chain logistics and interruptions in research and clinical development. In light of these issues, CGT developers have felt the pressure to optimize processes and streamline activities in order to ensure the clinical and commercial success of these critical therapies. The need for automation and reduction of human touch points in CGT development has been at the forefront of the collective industry mind for some time, and the CGT sector has witnessed the benefits that other biopharmaceutical sectors are enjoying from automating their workflows and modernizing into the digital era. Now CGT development must follow the same path. As we look ahead to a post-COVID world, optimizations such as digital connectivity technology and automation can not only reduce the human intervention necessary in the workflow but alleviate regulatory challenges and improve scalability.
AM: What has so far held back greater adoption of automation in cell and gene therapy workflows?
NP: Cost – cell therapies are very expensive due to the complex manufacturing process. While automation can eventually reduce costs, the costs associated with establishing automation and robotics can be very expensive.
Currently, several diverse manufacturing platforms are being used to manufacture cell therapies, each with its own set of distinct parameters. It would be expensive to implement automation for each of them due to a lack of standardization.
Many manufacturing processes are being developed at academic medical centers that do not have the expertise or funds to incorporate automation. Such academic centers can benefit from creating partnerships with pharmaceutical companies that have adopted automation or organizations that excel in building automation steps in the manufacturing workflow.
- Spielvogel CP, Stoiber S, Papp L, et al. Radiogenomic markers enable risk stratification and inference of mutational pathway states in head and neck cancer. Eur J Nucl Med Mol Imaging. 2022. doi: 10.1007/s00259-022-05973-9
- Ball O, Robinson S, Bure K, Brindley DA, Mccall D. Bioprocessing automation in cell therapy manufacturing: Outcomes of special interest group automation workshop. Cytotherapy. 2018;20(4):592-599. doi: 10.1016/j.jcyt.2018.01.005
- Automation is key in cell and gene therapy manufacturing | Reuters Events | Pharma. Accessed October 26, 2022. https://www.reutersevents.com/pharma/clinical/automation-key-cell-and-gene-therapy-manufacturing
Dr. Nirupama Pike was speaking to Anna MacDonald, Science Writer for Technology Networks.