Guest Column | January 17, 2025

Cell & Gene Therapy Manufacturing: Considerations For Early-Stage Companies

By Brian Harrison, managing director, biopharmaceutical product development and manufacturing

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The manufacture of advanced medicines such as cell and gene therapies is complex and requires a different approach and thinking when compared with pharmaceuticals (chemical-based) and biopharmaceuticals (originating from live cells such as CHO cells). These pharma and biopharma products are generally made in large manufacturing facilities, stored in large warehouses, and then distributed to large pharmacy organizations that provide these products to pharmacies and hospitals.

Cell and gene therapies, especially autologous cell therapies (cells from a patient, modified or boosted, then administered back to the same patient), require a significantly different manufacturing and supply approach to ensure the product can be manufactured and returned to the patient in the short timeline required.

Develop And Manufacture Internally

From the initial approvals of Kymriah (CAR-T) and Luxturna (gene therapy for inherited vision loss) in 2017, there have been many cell and gene therapies approved and many more in the process of being developed.1 In the early years, the companies developing these products raised funds to build their own internal manufacturing for the clinical and potential commercial manufacture of these products. This focus on internal manufacture, which was driven by the concept of “process is the product” and the assertion that the companies’ own scientists and engineers need to control the manufacture of the product, has dissipated.

Develop And Manufacture Locally

The advanced therapies industry has become aware that the capital required to build cleanrooms is only part of the funds needed and that once built, there are very high operating costs for GMP manufacturing cleanroom facilities. These GMP facilities need to be staffed and GMP licences need to be obtained and then maintained, even if there is little ongoing manufacturing, as clinical trials often do not meet their initially defined timelines. While some advanced therapy medicinal product (ATMP) companies are investing in their own cleanrooms, most new spinout companies are not being funded by their investors to build their own cleanrooms but are encouraged to work with partners to bring their products into clinical trials. Some companies are working with CDMOs for the manufacture of clinical trial batches.

Currently, there are many different providers of cleanroom space for the manufacture of early-stage clinical materials, including:

  • university cleanrooms
  • hospital cleanrooms
  • other government supported investment such as CCRM in Canada, Australia, and the Nordics; and Catapult in the U.K.
  • CDMOs

Maximizing Patient Access To Advanced Medicines

Many advanced medicine product developers focus on getting into clinical trials in the country where their research is centred and where their manufacturing is based close to their company HQ. The U.S. is leading the way in terms of number of trials and level of investment.1 As many advanced medicines such as cell and gene therapies are developed by startups4 or university spinouts, their focus is more localized. Multinational biopharmaceutical companies have a focus on developing products for patients around the world and in general submit regulatory dossiers in many countries and regions at the same time.

To advance cell and gene therapies and make them standard of care, it is important that more of these cell and gene therapy products are developed and launched on a global scale. The more patients that can be treated will require a larger volume of cell and gene therapy products to be manufactured and supplied and should, in general, lead to costs of manufacturing being reduced.

Select A CDMO Partner Based On Capability, Not Location

From a manufacturing perspective, if product developers have a global view, this should lead to these companies not just looking at local manufacture but selecting CDMO partners that meet predefined criteria that can be outlined in a request for proposal (RFP) document. This approach will ensure that the company developing a new cell and gene therapy will select a partner based on its capability to develop, manufacture, and supply the new therapy rather than proximity to the developer. Local manufacture is the default decision at present, especially in Europe and the U.K., where government funding is providing access to low-cost cleanrooms to support local startups, as outlined in cleanroom space options above. Of course, local manufacturing must occur where a cell or gene therapy product with a short shelf life requires manufacture and patient treatment in a matter of hours or days.

However, many cell and gene therapy products are manufactured and cryogenically stored before the patients are treated. In these cases, the partner CDMO should be selected according to capability using defined criteria such as:

  • experience with cell type
  • experience with specialized equipment
  • access to biomaterials
  • capacity availability

The availability of specialist couriers, transportation equipment, and tracking systems enables manufacture of stable and cryopreserved products at a CDMO partner that is selected based on its capability. These supply chain experts and technical advances can provide assurance that products can be manufactured in the quantity and quality required at a preferred CDMO, rather than only at a site close to the developer.

Advanced medicines are known to be very expensive, and access to these medicines is uneven across countries.3 While pricing is a complex subject and includes comparative value of the advanced medicine to the current standard of care, the cost of manufacture and supply of these medicines continues to be a key cost driver. To make advanced medicines available to patients who need them, there is a need for cell and gene therapy developers to gain approval for their medicines in as many countries as possible so that the number of available patients increases and, then, the cost of manufacturing and supply should reduce, given that cleanrooms and equipment will have higher utilization and unit costs can therefore decline. Regulators also have a part to play as, for example, CAR T treatments are largely considered the third line of treatment,2 and this limits the number of patients that are available and, hence, will continue to ensure that costs remain high.

Summary

The manufacture and supply of advanced medicines is on a journey from internal and local manufacturing to a partnering approach. As more of these cell and gene therapies hit pivotal clinical trials (higher volume) and global approvals, there will be a move to defining the correct partnerships based on technical and supply chain needs, aligned with the partner capabilities to best meet these needs. Manufacturing costs will continue to fall as more advanced medicines are developed and approved. However, further alignment by regulators, product developers, and payers can accelerate cost reduction by increasing the number of potential patients that can be treated. It is critically important that clinical trials are set up to allow regulatory submissions on a global basis.

The key goal is to make these novel and life-changing medicines available to the patients who need them, no matter where the patient is located around the world.

References

  1. Industry snapshot: https://alliancerm.org/sector-snapshot-august-2024/
  2. CAR T treatments status: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10629745/
  3. Access to ATMPs: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10715052/
  4. Health technology startups: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10668566/