Written by:
Daniel Pappas
Executive Director, BioPharmaceuticals Development, AstraZeneca
Cell therapies are actively being developed and hold great promise to treat a multitude of disease indications. However, there are immediate and long-term challenges that create obstacles during the manufacturing process of these therapeutics. In response, we have pursued collaboration and innovation, ensuring the best chance of bringing cell-based treatments, and one day even cures, to the patients who need it most.
Cell therapies are currently in development with the aim to halt and reverse disease, restore damaged organs, and ultimately, cure many life-threatening conditions. We aim to do this by placing new, healthy cells into the body to replace diseased or damaged ones, or by removing disease causing or dysfunctional cells using immune cells.
Though these treatments represent a tremendous opportunity, we need to be able to turn research discoveries into clinical grade products, and in such a novel and continuously evolving field, this can add additional challenges. Like a tangled web, biological, manufacturing and regulatory challenges are intimately connected and these need to be effectively navigated throughout the cell product delivery process.
Cell therapy manufacturing process
- Choose starting materials and adequate reagents
- Assess feasibility of production and expansion
- Assess viability and functionality of product
- Define ways to characterise and release the final product
- Assess feasibility of master and working cell banks
- Identify activity and safety of product
- Define how the product will be stored, shipped and delivered to the patient
The cell therapy manufacturing process is continually refined to increase product yield, batch size, purity, reproducibility, potency and stability while striving to decrease manufacturing time and cost.
Key challenges with cell therapy manufacturing
Manufacturing stands between the research of cell therapies and the eventual delivery of these medicines to patients. As part of the manufacturing process, we need to consider both ends of product development, including biological and regulatory needs. For instance, early in the research phase, scientists must isolate the correct cell type and determine its mechanism of action to ensure the cell therapy has the intended profile. Determining this mode of action requires extensive research and use of specific assays to create an efficacious product that can be delivered safely to patients and be approved by regulatory authorities.
Like other drug modalities, cell therapies are also affected by well-established challenges that current drug products face on a large-scale. To reach millions of patients, drug products need to be produced at scale, depending on the process and disease that is targeted. The processes also need to be refined simultaneously to increase the yield, batch size, purity, reproducibility and potency. But cell therapies also bring their own unique set of challenges. Due to their novelty, their production typically requires the use of non-conventional raw materials which may result in an inconsistent supply of products, along with issues related to logistics surrounding low-temperature storage and shipping. Personnel also often require specialised training to handle these materials.
Manufacturing cell therapies that utilise a patient’s own cells have the additional challenge of adhering to a condensed manufacturing timeline. This type of cell therapy, needs cells to be collected from a patient, biologically altered, and transplanted back to the patient in a short window – right now, the goal is to go from vein to vein in just 21 days. To achieve this and optimise the development and manufacturing of all cell therapies alike, scaling and commercialisation are considered in parallel with product development, sometimes even before the first dose is made.
Cell therapy manufacturing bridges disease areas
Cell therapy is a new space with unique logistic and manufacturing challenges, but we continue to invest in processes and approaches to address these challenges. Specifically, we are building on our existing biological manufacturing infrastructure by welcoming talented cell therapy scientists with specific skill sets, alongside partnering with academic, non-academic and cell industrialisation centres. In addition, we are investing in building specialised facilities to support early cell therapy product development and manufacturing.
From repairing damaged cardiac cells in the heart after heart attack to modifying a patient’s own T cells to target solid tumours, we are proud of our progress and confident that in the next five to 10 years, cell therapy will help improve the outlook for patients with some of today’s most serious and life limiting diseases.
