Navigating cell therapy's maze of risks

The number of cell therapies in development continues to grow, rising from 150 investigational new drug applications in 2018 to more than 2,460 active cell therapy trials currently underway, according to ClinicalTrials.gov. This growing sector could revolutionize the treatment of cancers, autoimmune disorders, and more. However, the field’s rapid expansion continues to highlight challenges in the efficient development and eventual commercialization of these groundbreaking products.

The FDA’s 2024 approval of the first tumor infiltrating lymphocyte (TIL) therapy for solid tumors marks a major milestone, especially considering that solid tumors account for approximately 90% percent of cancers. While this approach encountered many delays, there is now a path forward to FDA approval for other companies. To avoid setbacks and ensure cell therapies can reach their full potential, biopharma companies must adopt a deliberate, informed strategy to navigate the unique scientific, technical and regulatory challenges ahead.

The patient-specific nature of autologous cell therapies introduces complexities in the development and manufacture of these products from preclinical to clinical and commercial stages. While the efficacy of autologous therapies is a priority, manufacturing drugs that begin and end with the patient also requires reliable, efficient and carefully coordinated logistical processes. For developers new to the cell therapy space, navigating this complex maze of risks can threaten the ultimate success of their therapy and, above all, the positive impact it could have on patients.

Biopharma companies advancing cell therapies must confront a range of key considerations and risks. A strategic, collaborative approach can accelerate product development and ultimately ensure patients reliably access safe and effective cell therapy products.

Minimizing risk to maximize success

Even on a small scale, cell therapies are the most complex drug to develop and manufacture. Minimizing the risk of errors, contamination or delays that lead to a failed cell therapy batch is uniquely challenging, and the gravity of these mistakes is especially great.

Process failure rates in autologous cell therapy manufacturing range between 5-10%, far exceeding typical biopharma standards. Each failed batch is estimated to cost over $100,000 to manufacture. However, the greater cost is the impact on the patient who often endures a grueling collection process, the demands of travel to a major cancer center, and suspension of other therapies. The consequences of a delay can be both emotionally and clinically devastating.

Product loss also presents significant short- and long-term financial consequences for drugmakers, along with negative public perception of a drugmaker. Patients, families, and providers pursuing cell therapy treatment place trust in the promise to receive a safe and timely product. A low failure rate, for a product that is often a last resort, is essential to delivering on this promise.

Leveraging process development experience

Despite the field’s growth, cell therapy remains a young, demanding modality. Success requires knowledge and experience — not just in biologics but specifically in autologous cell therapies.

Unlike monoclonal antibodies which involve fairly simple, off-the-shelf manufacturing and administration, autologous cell therapies start with patient cells that vary depending on treatment history, disease state, and other biological variables. The process of taking living cells from patients to a manufacturing site, through processing, and back to patients as a therapy is a logistical puzzle that must be completed within strict time and temperature constraints. Rigid, standardized manufacturing processes developed with healthy donor leukopaks can thus fail to translate into clinical- and commercial-stage manufacturing with highly variable patient samples. Experienced scientists and associates factor in these nuances to build robust, safe, scalable therapies.

Balancing speed with quality

The delicate balance of reaching clinical proof of concept quickly without compromising patient safety or impacting commercial readiness is tricky. While the potential of new cell therapies is a great motivator, moving too quickly can undermine a company’s ability to establish scalable, reliable manufacturing processes and, in turn, increase the risk of batch failure. For patients in desperate need of therapies, delays can be fatal; an estimated 20% of patients on waitlists for CAR-T cell drugs die before receiving treatment.

Biopharma companies entering the cell therapy space can and should aim to reach clinical proof of concept as quickly as possible. However, this shouldn’t come at the expense of commercial readiness. New companies often over-engineer processes, duplicate steps, or invest in unnecessary steps due to inexperience. This inefficiency leads to delays in cost, time, capital, and patient access. A well-designed strategy utilizing digitalization, predictive analytics, and experienced scientists and technologists can help companies move quickly without compromising quality or commercial readiness.

Minimizing regulatory delays

Manufacturing, logistics, and science are not the only challenges biopharma companies face — they must also navigate a complex and ever-evolving regulatory landscape. Proactive engagement with the FDA at the start of development is essential. Missteps in preclinical design, CMC strategy, or submission timing can delay IND clearance and add months and hundreds of thousands of dollars to development timelines while also losing investors’ confidence.

Partnering with regulatory experts with a strong track record of clearing several IND applications each year can offer timely and relevant guidance informed by those varied experiences. This insight guides biopharma companies with stage-appropriate, scientifically based risks and keeps them informed of evolving regulatory requirements.

Making efficient use of manufacturing infrastructure

As companies approach the clinic, they are faced with another pressing decision: build internal manufacturing capabilities or engage with an external service provider. While building in-house capacity maintains a level of control, it also requires heavy investments of capital, resources, and time.

Sourcing specialized and experienced talent is also difficult in a rapidly growing field. Startups who pursue in-house manufacturing often rely on inexperienced staff, investing significant time and energy into training, and can encounter high turnover rates due to the demands of the job.

Additionally, contending with the logistical uncertainty of just-in-time manufacturing, which often requires 24/7 staffing even when demand is inconsistent, can be a significant drain on resources. For even well-funded companies, this is often not the most efficient way to bring a product to market, nor is it sustainable.

Partnerships can drive progress

By fostering collaborative partnerships with CDMOs, research organizations, suppliers, equipment manufacturers, and other experienced leaders in the field of cell therapy, companies can access infrastructure, knowledge, and services to reduce their burden.

For example, building a process development team with experience specific to TIL or CAR-T processes and patient variability in cellular starting material shortens timelines and reduces risks. Building strong relationships with medical research institutions can drive patient-centric innovation and increase access, ensuring that the end goal remains helping patients.

Efficient use of capital is especially prudent in the current bearish market. Rather than spending $80 to $100 million to build a facility and another $20 to $50 million in annual operating costs, it is more efficient for early-stage companies to invest in new innovations to advance the pipeline. Leveraging collaborative relationships with manufacturing partners eliminates the need for upfront investment in specialized equipment, clean room space, consumables, and resources and is a far better return on investment.

Helping cell therapies reach full potential

Cell therapy brings new hope for treating previously intractable diseases. However, progress is not guaranteed as development, operational, and regulatory challenges persist. The African proverb rings true here: “If you want to go fast, go alone. If you want to go far, go together.” For companies looking to go far and fast, strategic partnerships can open doors.

By collaborating with experienced players, companies can reduce risk, use resources more efficiently, and accelerate development and manufacturing timelines. Efficiency for individual companies improves efficiency for the entire field, helping to bring better therapies to patients quickly, safely, and reliably.

Since patients should remain the top priority, every decision must be well-planned and executed with zero waste. With this priority, great progress can be made toward a collective goal of furthering the fight against cancer by innovating in the cell and gene therapy field, and bringing lifesaving treatments to the thousands of people hoping for a last shot at survival.

References

Capra, E., et. al. (2019, Oct). Gene therapy coming of age: Opportunities and challenges to getting ahead. McKinsey & Company.

ClinicalTrials.gov. National Library of Medicine. [accessed: July 2025]

Melocchi, A. et. al. (2025, May). Automated manufacturing of cell therapies. Journal of Controlled Release. 381, 113561.

Lopes, A., et. al. (2018, March). Cost Analysis of Cell Therapy Manufacture: Autologous Cell Therapies, Part 1. BioProcess International.

Tomtishen, J. (2023, Jan). Automated Manufacturing Will Deliver More—and Better—Cell Therapies. GEN.

Osborne, A. (2023, June). The cell and gene therapy CDMO bottleneck isn’t capacity – it’s capability. EPR.