3 Strategies For A Successful Journey Toward Cell And Gene Therapy Commercialization

By Amy Hay, CBO, CTMC

Cell and gene therapies have introduced unprecedented therapeutic possibilities into the clinical landscape, but their implications for operational and regulatory frameworks are as unique as the treatments themselves. Cell and gene therapies by their nature require the patient to not only receive the therapeutic but also function as the main component of the supply chain for its development. The diverse and complex nature of these therapies presents an opportunity to develop and implement purpose-fit development and manufacturing processes that include close collaboration across regulatory bodies, scientific innovators, and technical manufacturers. In these times of volatility and uncertainty in the cell and gene therapy market, such as the decrease in federal funding for the FDA and potential pending pharmaceutical tariffs, co-development and partnerships at all levels are essential.

This article provides strategic recommendations for teams focused on the journey toward cell and gene therapy commercialization. We will discuss the complexities of regulatory requirements, logistical considerations, and best practices essential for successfully navigating the regulatory process. By following these recommendations, teams may enhance their preparedness, develop the right strategic partnerships, and improve their chances of successful drug approval.

Strategies For Success

1. Be Intentionally Fit-for-Purpose

In cell and gene therapy, uncertainty and complexity behave like a virus within the system. Initially subtle, they swiftly cause disruption once widespread and can result in serious consequences. To protect against this viral infection, biotechnology companies should intentionally create an ecosystem purposefully designed to meet the challenges of diversity and complexity that often add time and cost to the commercialization process.

Developing key strategic manufacturing and service relationships is critical. Following these steps will help identify the right partners to support the journey to commercialization.

• Partner to Complement and Enable: Identify a manufacturer and service provider that complements your team. If capital efficiency is the highest priority, identifying a manufacturer that has expansive capabilities across development, regulatory, and logistics may be critical to avoid costly overhead. If speed to clinic and patient accruals is a driving force, then choosing a manufacturer aligned with a large academic provider to streamline clinical trials might be the right fit. By understanding your strengths and weaknesses, you can develop strategic partnerships that add value and reduce complexity.
• Align Incentives: Not all cell and gene therapy manufacturers are the same, and often, contracts do not align the correct incentives between the organizations; such as accelerating the timeline or obtaining an IND. Business constructs that align incentives can instill a team-oriented approach. For example, it is traditional for a manufacturer to contract with an early stage bio-tech company in a fee for service mechanism rather than tying fees to important milestones such as timing acceleration, product releases, or FDA approvals. Engaging the manufacturer to accelerate a program by aligning payment to milestones such as these, creates a relationship in which all parties are focused on a clear goal. , shifting from a pure fee-for-service model to a milestone-based model may be the right recipe for alignment. When discovery and manufacturing co-develop and agree on tangible outcomes, there is a clear pathway for joint success.
• Regionalize for Optimal Operations: In cell and gene therapy, the patient is the critical part of the supply chain. Engaging with a manufacturing team that works closely with, or is adjacent to the clinical provider, can reduce risk and eliminate potential delays. Having the opportunity to work with a manufacturer that can in house identify potential clinical trial locations and investigators eliminates the need to source first in human and early phase trials. Identifying the right investigator to bring your trial into the clinic rapidly with access to a large volume of potential patients, will reduce the risk of delays and accelerate the timeline to clinical proof of concept. 

2. Get CMC Squared Away

When developing cell and gene therapies, it is essential to prioritize chemistry, manufacturing, and controls (CMC) from the very beginning. CMC encompasses a product's entire life cycle, including its composition, manufacturing processes, quality control measures, and regulatory compliance. A strong CMC framework ensures the product is consistently produced and tightly controlled according to quality standards.

In recent years, several promising therapies have encountered regulatory delays due to incomplete CMC frameworks, underscoring the need to embed regulatory rigor early in development. If the CMC elements are not adequately addressed early on, it can result in significant delays in obtaining regulatory approvals from the FDA. Delays can arise from identified deficiencies in documentation, manufacturing practices, or product quality – all of which must be rectified before moving forward in the regulatory approval process.

Intentional integration of regulatory teams will foster a shared understanding of the regulatory landscape, enabling teams to anticipate potential challenges and address them early. Regularly reviewing guidance updates and participating in FDA-hosted webinars or workshops can help teams remain aligned with evolving expectations. The following key strategic approaches will enable this integration and reduce costly and time-consuming rework while also setting the tone of regulatory awareness and compliance.

• Integrate regulatory expertise within core technical teams from the earliest stages of therapeutic development to create a continuous feedback loop, ensure seamless collaboration, and support proactive problem-solving. By having your regulatory lead involved in core team meetings, you can ensure that the best decisions for development also are aligned with the regulatory process and requirements.
• Embed regulatory considerations into the development process from the start, rather than treating them as an afterthought. For example, currently in cell therapy there is a lot of discussion around the requirement needs of potency assays in TIL therapy. By addressing this up front during the development of the manufacturing process, you can align a plan that addresses this need with the FDA up front and enables early discussion to ensure alignment.

3. Create scientific innovation within regulatory restraints to foster a shared understanding of the regulatory landscape to enable teams to anticipate potential challenges and address them early. This will allow you to address regulatory restraints upfront and therefore encourage creativity and innovation in addressing them. For example, in some cases the FDA is requiring increased visual inspection of cell therapy products. If the team understands this constraint early, then they have the ability to identify technology  or develop new processes to accommodate this requirement.

Collaborate Closely With Regulators

Engaging with regulatory bodies, such as the FDA, is a vital step in drug development. Early interactions are invaluable and allow sponsors to gain insights into the expectations, requirements, and any specific considerations that may need to be addressed. By understanding the FDA's current perspective, sponsors can better align their development strategies with regulatory expectations, setting the foundation for a smoother review process and building a collaborative partnership. The following activities will build credibility and trust with the FDA.

• Engage with the FDA early and through pre-IND meetings to present IND plans when sufficient data is available and a comprehensive working draft is ready. For example, if your clinical trial includes a new technology in the planned product, then one  tool for early engagement is the INTERACT (INitial Targeted Engagement for Regulatory Advice on CBER/CDER ProducTs) meeting. This allows sponsors to obtain preliminary, informal feedback on chemistry, manufacturing, and controls, non-clinical, and clinical aspects of their investigational product. 
• Focus your application on a clear, compelling story that demonstrates safety and feasibility in the most efficient way possible. Remember the quote from Ira Glass, the host of the National Public Radio show This American Life, “Great stories happen to those who can tell them.”
• Prepare contingency plans for any concerns and prepare key questions in advance of the meeting about trial design and endpoints.  One area that is often an area of focus in early-stage cell therapy products is safety monitoring, due to its often single-dose nature.  The FDA often requires significant patient safety monitoring during and after treatment including long term follow-up. Ensuring that you have not only a detailed plan to address this data need, but also additional methods to determine long-term delayed adverse effects will provide the FDA confidence in your approach.

Fueling Continued Therapeutic Progress

Strategic, fit-for-purpose partnerships and a well-executed regulatory strategy are essential to transforming scientific breakthroughs into real-world patient outcomes. Strategic partnerships will complement and enable your team, align incentives, and optimize clinical trial operations. This, coupled with a regulatory strategy grounded in proactive engagement and collaborative interaction, will accelerate your path to commercialization.

About The Expert:

Amy Hay is a strategic leader focused on transforming global oncology care. In her role as chief business officer at the Cell Therapy Manufacturing Center (CTMC), a joint venture between National Resilience and MD Anderson Cancer Center, she is responsible for developing and executing the overall business strategy for the company, focusing on market penetration, strategic partnerships, revenue generation, and long-term growth. She leverages her deep understanding of comprehensive oncology care, innovation, and digitalization to navigate the market dynamics and complex business models from discovery to commercialization of cell therapy to optimize and democratize its global utilization for patients. Amy earned her B.A. in psychology from Southwestern University in Georgetown, Texas and her M.S. in healthcare administration from Houston Baptist University in Houston, Texas.