Cell and Gene Therapies (CGT) are revolutionizing modern medicine by offering potential cures for previously untreatable diseases. However, the effective delivery of these advanced therapies poses unique challenges. Herein, we explore five key challenges associated with CGT products that need to be considered for effective treatment and discuss how innovative Drug Delivery Devices for Cell and Gene Therapies can address these issues.

Challenge 1: The CGT product needs accurate delivery to a hard-to-reach location in the body.

Drugs are frequently taken orally or administered via injection for systemic treatment in the body. However, many CGT products must be delivered to a specific location in the body to realize their therapeutic benefit, and often, these locations in the body are hard-to-reach. For example, there are several CGT products that require delivery to the brain for the treatment of Parkinson’s disease and other neurodegenerative conditions, such as ALS, both areas that we have direct product development experience. In these instances, without adequate targeting of the cell or gene therapy, the treatment is not effective.

Challenge 2: CGT products are often administered as complex formulations.

Many CGT products are formulated in complex, often high-viscosity solutions, making them difficult to administer through conventional delivery systems. For example, hyaluronic acid (a naturally occurring polysaccharide) is often used in cell therapy formulations due to its favourable biocompatibility profile and cell suspension/dispersion properties. The viscosity of these types of formulations is highly dependent on the molecular weight and concentration of the hyaluronic acid used but is generally orders of magnitude higher than simpler water-based formulations.

Depending on the nature of the final formulation, off-the-shelf drug delivery systems may not be available for precise and accurate injection of the CGT product. Especially when a large volume of a viscous cell therapy product needs to be administered, a custom delivery solution may be required. Fortunately, a variety of novel drug delivery devices have been engineered with suitable fluid injection mechanisms capable of handling viscous formulations. Advanced wearable syringe pumps and auto-injectors with high-force delivery capabilities (e.g., the Ypsomed YpsoMate auto-injector) are examples of Drug Delivery Devices for Cell and Gene Therapies that can effectively administer these viscous solutions without compromising the integrity of the therapeutic agents or causing significant discomfort to the patient.

Challenge 3: CGT products are sensitive to fluid flow conditions.

CGT products are composed of large, conformation-specific biomacromolecules and/or particles that are almost always sensitive to mechanical stress, such as fluid shearing forces.  These forces can deform and degrade the CGT products by inducing changes to their native structures, reducing or altering their efficacy. That is why the fluid flow dynamics of any CGT delivery device must be well understood and controlled as a key parameter of the device design and development process.

Challenge 4: CGT products are often stored in cryoprotectants that must be removed post-thaw, before administration.

Typically, non-CGT drug products are stored in their final formulation before administration to the patient. This is purposeful because it minimizes processing of the drug at the patient’s bedside. However, CGT products often require cryoprotectants for long-term stability and viability during storage at -80°C. These cryoprotectants must be removed immediately before administration, necessitating aseptic processing—such as filtration or centrifugation—post-thaw.

Ideally, the preparation and administration of CGT products, including the removal of cryoprotectants, should occur outside the constraints of dedicated GMP clean rooms. Therefore, the entire workflow, from preparation to administration, must be carefully considered when designing an aseptic drug delivery system. Post-thaw processing of CGT products may also introduce additional testing requirements to ensure the safety and efficacy of the final product after cryoprotectant removal.

An optimal Drug Delivery Device for Cell and Gene Therapies should facilitate a robust and streamlined CGT preparation and administration process, enabling these critical steps to be performed safely and effectively at the patient’s bedside.

Challenge 5: CGT products need expensive infrastructure for drug administration.

In addition to needing expensive specialized, complex manufacturing processes, CGT products also often depend on highly specialized infrastructure for effective drug administration. This presents a significant challenge to scaling these therapies.