From Laboratory to Community: Is Point-of-Care Manufacturing Cell and Gene Therapy's Future?

Cell and gene therapies are redefining modern medicine landscape, by delivering life-changing results across a wide range of chronic conditions such as cancer. But despite their promising outcome, patient access remains a critical barrier both in terms of geography and affordability. To bridge this gap and bring breakthrough treatments to more patients, the industry is turning to innovative solutions such as point-of-care manufacturing.

Recently, researchers from the Singapore-MIT Alliance for Research and Technology (SMART) created a novel microfluidic chip that is roughly the size of a deck of cards and can produce clinical doses of CAR-T cells for cancer treatment in a closed, automated, and minuscule system.

Current Pulse of the Industry

• Today, point-of-care manufacturing for gene and cell therapy is a disputable and much discussed topic. The decision between point-of-care and centralized manufacturing in cell and gene therapy is not simple.
• Even if point-of-care manufacturing is implemented, centralized production will remain essential for cell and gene therapy. This is due to the fact that not all illnesses and treatments will benefit from point-of-care manufacturing.
• Wherein a third model decentralized manufacturing comes into picture which exists between the point of care and centralized manufacturing, involving multiple GMP-compliant facilities across different locations.

Thus, the emergence of point of care manufacturing for cell and gene therapy as a viable option is exciting yet controversial development in the field.

Unlocking the Future: Innovations Powering Point-of-Care Manufacturing

There are four main technical improvements that are crucial to enable point of care manufacturing:

1. Fresh, On-Demand Therapies:

• The use of fresh product is one of the primary distinctions between centralized manufacturing and point-of-care. In order to help manage the logistics of scheduling manufacture and administering the therapy to the patient's need, centralized manufacturing typically uses cryopreserved cells at the beginning and conclusion of the manufacturing process.
• A University of Pennsylvania study found that functional CART cells may be produced in less than 24 hours without requiring T-cell ex vivo expansion, making them ideal for point-of-care manufacturing.
• However, there is undoubtedly a trade-off here between the time and expense savings in producing the cell therapy and the possible cost rise for quick quality control and release testing, as well as the expense and work involved in arranging the delivery of a non-cryopreserved (fresh) treatment.

2. Power of Miniaturization:

• Manufacturers' adaptation of equipment to create cell processing systems for use in point-of-care manufacturing for gene and cell therapy will heavily rely on miniaturization. Only when working with a far smaller number of cells than what is needed for a therapeutic dose can this procedure be effective.
• Microfluidics and lab-on-a-chip technology are being used by companies like Sarcura and Indee Labs to further reduce the equipment footprint, which poses challenges, especially when choosing materials for cell contact components.
• Although some manufacturers are actively implementing these technologies, many are still overcoming obstacles relating to materials, scalability, and regulatory compliance. Miniaturization is generally acknowledged as the future of point of care cell and gene therapy production.

3. Seamless Integration & Smart Automation:

• Over the past 10-15 years, cell therapy manufacturing has evolved from manual open systems to single use technologies, somewhat similar to biologics manufacturing,
• Single use technologies offer benefits for point of care manufacturing by enabling the use of lower grade cleanroom space, reducing facility costs.
• Moving away from centralized manufacturing requires integrated and automated solutions to simplify operations and maintain product quality.
• Companies such as Cellares leads in automation with a fully integrated, robotic platform that minimizes human intervention, ideal for decentralized sites.
• However, tech transfer to new sites is time-consuming and costly due to the need for process re-validation.

4. Digitization and analytics:

• For point-of-care manufacturing, digitization is crucial, especially for release testing, in-process quality control, and chain of custody.
• The industry is already moving toward digital batch records, replacing traditional paper-based systems.
• “Advances across in-line analytics will be necessary for point-of-care manufacturing to guarantee quality and comparability across facilities” according to FDA's Kimberly Schultz during an ISCT webinar.
• Key areas needing innovation or tech adoption in point of care manufacturing for cell and gene therapy:
  • Rapid sterility testing - possible through molecular diagnostic assays.
  • Potency assays – vary based on therapy-specific requirements.
• According to Patrick Hanley, Director of the Children's National Hospital's Cell Therapy Program, “QC testing is difficult and will require highly qualified staff, which is an important consideration.”
• Thus, GMP compliance and uncertainty around how quality and control processes will be managed at point of care manufacturing sites are major reasons for industry caution in adopting point of care manufacturing.

Transforming Accessibility: Bringing Cell Therapies to the Front Lines of Care

Cell and gene therapies are transforming care but are hampered by high expense and complicated logistics. Point-of-care manufacturing has the potential to turn that around by localizing production near patients, reducing delays and costs. That could turn personalized therapies into first-line care available at a nearby hospital, initiating a new age of faster, more affordable cancer care.