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Achieving Large-Scale Cell and Gene Therapy Manufacturing

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Initial clinical successes with cell and gene therapies have driven significant investment in these next-generation technologies by both large bio/pharma companies and start-up specialist firms backed by venture capital dollars. Many of these companies are eager to advance beyond early clinical trials to phase III and commercial products, but lack the manufacturing capability.

There is a significant need for contract manufacturing partners with the specialized expertise necessary to innovate and implement novel manufacturing solutions that will help accelerate the commercialization of these advanced treatments that have tremendous potential to improve patient lives.

The cell and gene therapy industry is in the growth phase of its economic life cycle. Significant research and development expenditure by large pharma / biotechs and cell and gene therapy-focused biotechs is driving new product development. More than 500 companies have been identified by Jain PharmaBiotech to be involved in cell therapy alone, and the gene therapy market is estimated by Roots Analysis to be growing at 48.8% per year to reach $11billion by 2025. There is a rich pipeline of over 500 cell and gene therapy products in the clinic, which will drive significant capacity needs as the pipeline matures and progresses to commercial supply.

The early clinical successes that have been achieved are driving significant in- vestment in cell and gene therapy technologies. Larger bio / pharma companies are either developing in-house expertise or partnering with smaller, specialized companies focused on cell and gene therapies, many of which have been established with funding from venture capital groups and some of which have already completed successful initial public offerings (IPOs). As a result, there are numerous companies facing mounting pressure from investors to move into late-stage clinical trials and on to commercial launch. Most, however, do not have the capabilities required to manufacture cell and gene therapy products on the commercial scale.

Successful realization of commercial cell and gene therapies is thus predicated on the ability of these innovators to establish partnerships with contract development and manufacturing organizations (CDMOs) with the specialized expertise required to facilitate the progression of their products from the clinic to the market. At present, however, the contract development and manufacturing capacity dedicated to supporting the cell and gene therapy market is limited, and most capabilities can be described as immature.

Entirely New Technology

Cell and gene therapies, while biopharmaceuticals, are quite different from existing biologic drugs, such as blood factors, interferons, recombinant proteins and mono- clonal antibodies. Because these products comprise whole viruses or living cells, manufacturing processes are designed to maintain their potency. Product characterization (strength, identity, viability, purity, potency, viral safety) and release testing are particularly challenging, and require the use of novel analytical methods. Process development and validation, establishment of process reproducibility and alignment with current Good Manufacturing Practices (cGMP) also require innovative solutions for large-scale production. As with any new treatment platform, both safety concerns and regulatory uncertain- ties must be addressed. For example, with large patient populations, the logistics of extracting cells from patients, sending them to a site for processing and then delivering them back to the same patient, while feasible, does add additional layers of complexity.

Successful growth and maturation of the gene and cell therapy sector requires the application of existing process optimization and commercial manufacturing expertise to these emerging technology platforms, as well as the development of novel processing and analytical solutions. Consequently, scientists highly experienced in current state-of-the-art technologies for small-scale gene and cell therapy production and who are capable of innovative problem-solving, must be united with a leadership team that brings deep manufacturing and commercial expertise combined with knowledge of facility design, quality and regulatory systems.

Successful realization of commercial cell and gene therapies is thus predicated on the ability of these innovators to establish partnerships with contract development and manufacturing organizations (CDMOs)…

Applying Experience To Emerging Technologies To Meet A Significant Market Need

Recognizing the critical need for contract manufacturing organizations with this unique set of capabilities, Brammer Bio was founded with the goal of establishing a best-in-class CDMO dedicated to sup- porting the development of cell and gene therapies from early phase clinical studies to phase III and beyond. The company has been designed from the start to enable accelerated process development, and clinical and commercial manufacturing, as well as guide the industry in maturing to a robust supply base.

Brammer Bio brings together the wealth of industry experience in biologics development and clinical / commercial manufacturing of its cofounders — and previously cofounders of Gallus Biopharmaceuticals — with a 10-year track record in cell and gene therapy development, early-phase manufacturing and analytical testing services of Florida Biologix. An additional cell and gene therapy manufacturing facility in Massachusetts enables the company to provide support from discovery through commercial launch to customers, in accordance with global standards.

The Opportunity: Four Technology Platforms

The CDMO opportunity can be divided into four technology platforms:
[1] Autologous cell therapy

[2] Allogeneic cell therapy
[3] Ex vivo gene therapy
[4] In vivo gene therapy

[1] Autologous cell therapies are based on cells that are harvested from the patient. The cells are shipped to a manufacturing site where the cells with the desired properties are isolated and then expanded. The cells are then shipped back to the patient for reintroduction. Such patient-specific therapies have a low risk of adverse immune reactions, but are expensive due to the inability to scale the process.

[2] Allogeneic cell therapies have the ad- vantage of being derived from universal donor cells, which allows for greater scale. The cells are harvested from the donors and shipped to the processing facility for isolation, expansion and banking of multiple doses. Cell types that do not elicit immune responses upon implantation are used for these treatments, and therefore a single product has the potential to treat hundreds or thousands of patients.

[3] Ex vivo gene therapies are autologous cell therapies in which the cells harvested from the patient are genetically modified, typically using a viral vector to introduce new genetic information, and then reintroduced into the patient. The greatest focus is on chimeric antigen receptor T-cell (CAR-T) therapies, which contain special cell-surface receptors that recognize specific proteins on tumor cells. After infusion into the patient, the T cells multiply, recognize the cancer cells containing the antigen and kill them, and also reactivate components of the immune system that are suppressed by cancer cells.

[4] In vivo gene therapies involve the direct delivery of genetic information into patients using viral vectors with the goal of enabling patient cells to effectively ex- press missing or deficient proteins.

Conclusion

Cell and gene therapies are showing success in the clinic for the treatment of cancer, nervous system disorders, cardiovascular diseases and many rare disorders. The challenge faced by the industry today is the scale-up of manufacturing to achieve robust production of high-quality, safe and efficacious medicines that will have a significant impact on patient lives. CDMOs dedicated to supporting the commercialization of these promising treatments must have the ability to translate existing expertise in small-scale gene and cell therapy production and in large-scale biologic drug manufacturing into novel, efficient and reliable processes suitable for commercialization. Brammer Bio has been designed with this unique set of capabilities in order to support cell and gene therapy companies to rapidly move their autologous and allogeneic cell therapies and ex vivo and in vivo gene therapies into the clinic and to the marketplace.

 

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