Providing a bright future with cell therapies

Diseases for which there are frequently no effective treatments can potentially be treated and sometimes cured with cell therapies. Several different therapeutic modalities are covered by the term “cell therapy”, employing various cell types and manufacturing processes, and targeting a variety of conditions.

Image Credit: ShutterStock/Anusorn Nakdee

Consequently, cell therapy manufacturing is intricate, with processes and technologies still developing to meet specific requirements.

This article provides a general overview of the important factors to consider when producing cell therapies, the technologies being created and used, and, ultimately, how a therapeutic candidate transitions from research scale to clinical or commercial manufacturing.

Industry outlook

The market for cell therapy is robust and expanding on a global scale. According to market research, there will be an annual growth rate of 5.4%, or $8.83 billion, by 2027.

This unprecedented growth is attributed to the approval of new cell therapy products, the expansion of approved indications for existing products, and the rising awareness, acceptance, and use of these advanced biological products worldwide.

With 1,220 ongoing clinical trials worldwide, cell and gene therapies are moving forward in the clinical pipeline at the fastest rate so far.1 The need for manufacturing solutions has grown due to this market expansion, strong clinical outcomes, and recent regulatory approvals.

Providing a bright future with cell therapies

Image Credit: Corning Life Sciences

Indications

In particular, gene-modified cell therapies for cancer immunology, such as CAR T therapies, have received much attention recently.

Adoptive immunotherapy using chimeric antigen receptor T cells (CAR T) was named the most significant clinical cancer advancement of the year in the American Society of Clinical Oncology’s (ASCO) Clinical Cancer Advances 2018 report. Oncology and indications for the central nervous system are the two most common indications for cell therapy.2

Recent approvals have stimulated research and investment in the CAR T field. The FDA approved Kite’s Tecartus CAR-T therapy for patients with R/R (relapsed or refractory) mantle cell lymphoma in 2020.

Patient results have been revolutionary, with a response rate of almost 90%.1 Breyanzi, a CAR-T therapy developed by Bristol Myers Squibb, was given FDA approval in February 2021 to treat diffuse large B-cell lymphoma.

The first treatment authorized by the FDA under the Regenerative Medicine Advanced Therapy (RMAT) Designation was Breyanzi. Regenerative medicine therapies intended for serious conditions can be developed more quickly with the help of the RMAT designation.

Cell therapy manufacturing

Effective manufacturing is crucial in determining whether or not a cell therapy will be commercialized. To ensure speed to market and commercial viability, process development and manufacturing plans should be incorporated early in the product development process.

The designation of a cell therapy under a regulatory expedited timeline will impact development timelines and must be considered during process design and scale-up.

Autologous vs. allogenic

Examples of personalized medicine include autologous therapies. They are created in a single lot per patient using the patient’s cells as the starting point. Due to the necessity of manufacturing numerous small lots of unique products at once, autologous scale-up is frequently called “scaling out.”

On the other hand, allogeneic therapies use tissue from unrelated donors and are produced in large batches. As a single product used to treat many patients, allogeneic therapies are regarded as being “off the shelf.” Scaling up the manufacturing vessel volume is necessary for these therapies.

Process development

Process development aims to create a strong biomanufacturing process with additional key goals of increasing efficiency and consistency, lowering costs, maintaining quality and safety standards, and reducing overall risk.

Process development is an essential intermediate step between research and commercial manufacturing, although speed-to-market initiatives have compressed already short timelines.

The optimization achieved during process development is the foundation for producing a reliable and economical cell product at a scale that can meet patient needs.

The general cellular therapy workflow includes upstream and downstream unit operations such as cell isolation, cell culture media optimization, cell expansion, modification, purification, and characterization. However, the specific process steps can vary.

Providing a bright future with cell therapies

Image Credit: Corning Life Sciences

Media optimization

Since the therapeutic product in cell-based therapies is a cultured cell, cell culture media must be optimized to meet growth and productivity goals for cell production. Off-the-shelf media options can offer a quick and effective solution in the early stages of development. However, some specific scale-up requirements are challenging to meet with off-the-shelf media.

When switching from small-scale, small-volume static cultures to large-scale, large-volume vessels, several additional requirements arise that are difficult to handle with a ready-made solution.

Therefore, it is crucial for successful clinical and commercial manufacturing to develop and optimize media. Working with a contract media manufacturer can provide the knowledge and assistance required to smoothly transition from lab to commercial-scale media.

Scalability

Scale is one of the most important factors when designing the manufacturing process. This can be challenging to accomplish, particularly if a product’s approval process is sped up.

Knowing how much material is required to produce the therapeutic means deciding whether to scale up or out. No matter the manufacturing process, the cells must maintain their phenotype and functionality since they are the therapeutic product.

Allogeneic treatments are compatible with a more conventional, centralized manufacturing model in which a single therapeutic batch can treat many patients. On the other hand, autologous therapies demand a decentralized model, where manufacturing takes place close to the point of care as the therapy is patient-specific.

In this case, one patient equals one manufacturing batch, limiting batch volumes and related economies of scale.

Aseptic processing and closed systems

Aseptic processing is defined as: “Handling sterile materials in a controlled environment, in which the air supply, facility, materials, equipment, and personnel are regulated to control microbial and particulate contamination to acceptable levels.”3

Aseptic controls are crucial when producing cell therapies since there are frequently more open operations than traditional protein-based biologics. This increases the risk of contamination. Since the cell is the therapy, basic techniques for viral clearance and sterile filtration cannot be used with cell therapies.4

Contaminant risk can be eliminated in a closed system with no environmental exposure. However, this might not be possible given the nature of some production steps for cell therapies. As a result, a “functionally closed system” enables users to carry out unit operations safely, realistically, and reasonably.

In closing

Although manufacturing issues and potential solutions are developing, cell therapies present a significant opportunity to expand the medicinal arsenal. Suppliers are developing innovative, functional products to address the specific issues that cell therapy products raise. 

References

  1. Alliance for Regenerative Medicine. Advancing gene, cell, & tissue-Based Therapies-ARM annual report & sector year in review: 2019. Accessed Oct. 11, 2020: Retrieved from www.alliancerm.org/sector-report/2019-annual-report/
  2. Alliance for Regenerative Medicine. Growth & Resilience in Regenerative Medicines: 2020. Accessed May 1, 2021: Retrieved from https://alliancerm.org/sector-report/2020-annual-report/
  3. Parenteral Drug Association (2011). Process simulation for aseptically filled products PDA task force-2011. Accessed Oct. 11, 2020: Retrieved from https://store.pda.org/TableOfContents/TR2211_TOC.pdf
  4. Barone, P. W. et al. Viral contamination in biologic manufacture and implications for emerging therapies. Nat Biotechnol 38, 563-572 (2020).

About Corning Life Sciences

A division of Corning Incorporated, Corning Life Sciences is a leading global manufacturer of cell culture products and solutions that enable academic, biotech and biopharma scientists to harness the power of cells to create life-changing innovations. Corning supports a range of application areas including core cell culture, 3D cell culture, bioprocess, cancer research, primary and stem cell research, drug screening, cell and gene therapy, disease modeling, lab automation and more.

Whether your goal is stem cell expansion or viral vector production, Corning Life Sciences platforms, including HYPERStack® vessels that maximize cell growth area in a small footprint, the high-yield Ascent® Fixed Bed Reactor platform, microcarriers, and closed system solutions can help get you there. Choose from hundreds of vessels, the widest selection of cell culture surfaces, and custom media in a variety of single-use technology configurations. Learn more at www.corning.com/lifesciences.

Last updated: Nov 22, 2022 at 9:49 AM

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