Overcoming the Challenges in Bringing Cell & Gene Therapies to Market – Part 2

As cell and gene therapies (CGTs) continue to enter the market, treatment centers have become the primary gatekeepers to patient access. Capacity limitations, operational burden, financial exposure, and increasing competition—both from other approved therapies and ongoing clinical trials—are forcing centers to be increasingly selective in what they adopt and sustain.

In this four-part blog series, we will address four major challenge areas manufacturers face in bringing cell and gene therapies to market, and the best practices to follow in overcoming them. Challenges and solutions discussed include:

1. Treatment Center Capacity Constraints
2. Operational Complexity and Workflow Burden
3. Financial Concerns and Reimbursement Exposure
4. Market Competition in Clinical Trials and Commercial Applications

Challenge 2 – Operational Complexity and Workflow Burden

The very premise of cell and gene therapy presents a staggering challenge to both the manufacturer and the treatment center, whether the therapy is autologous or allogeneic. The product process is inordinately complex with many stakeholders who must navigate and uphold the processes to keep them moving smoothly. Think of it like many moving gears at work. Each must interact exactly as intended to achieve the result.

Consider that there can be multiple clinical trial and commercial products in the same center at the same time. Each of these products requires its own specific ordering, training, documentation and reporting needs.

Within the product process, there is often task redundancy as well as a significant load on the individuals responsible for these tasks. Good planning for your product process and its potential eventualities is critical to avoid bottle necks and mitigate risk of error.

Meeting process rule requirements

In autologous therapies, there is even greater complexity as there must be absolute certainty that cells collected from a patient are returned to that same patient. Because these cells must travel through multiple stakeholders and processes, and require specific handling throughout, they must be tracked and reported upon.

A chain of identity (CoI), the permanent, auditable record that tracks the cells from collection through manufacturing and subsequent infusion, ensures the patient receives the correct product. A chain of custody (CoC), which audits the possession of the cells throughout the process, provides oversight into the material conditions and that the product is safely maintained throughout the process.

Achieving CoI and CoC throughout the entire product process places an extreme administrative burden on the treatment center that cannot be overlooked. In addition to staffing and training needs, there are significant documentation and tracking conditions that must be met to satisfy both CoI and CoC process requirements. Treatment centers must have the labels and structure in place to support this level of documentation. There must be technology in place to capture and report on the process.

Determinations must be made in such key process categories as:

• Cell collection
• Shipping logistics
• Order management process
• Technology support

And then there are all the administrative and legal issues that must be addressed, including:

• Are there other order management systems in place to address different products throughout the process?
• Do these order management systems interface with existing treatment center systems or ERMs?
• What are the treatment center SOPs and do they need to be adjusted for your product?
• Can the treatment center manage the entire product process checklist?
• Will the center and manufacturer need to share processes to accommodate the therapy?

The list goes on. Ultimately, you want to reduce the complexity of the process so that the treatment center is willing and able to take on your product. The center needs to realize that it’s worthwhile for them to carry your product with its patient and management burden and time- consuming treatments in order to deliver the potential of the improved patient outcome your therapy offers.

Allogeneic therapies, although not dependent on cell collection from the patient as in autologous therapies, also face many similar process challenges in ordering and transporting the appropriate manufactured cells to the patient, especially when there is a constrained shelf life for the product.

How do you best minimize process burden?

Treatment centers often manage clinical trial and commercial patients across various products, sometimes managing both types of patients on the same product. The process burden for your product can become untenable.

To minimize the impact of product-unique requirements, you should start with your clinical trial design, keeping in mind the processes that will need to be consistent for the commercial state of the product. You will want to build your clinical trial processes so that the systematic parts can remain when you commercialize. It is helpful if you can minimize additional tests and/ or processes and align as much as possible with the treatment centers’ existing processes.

To facilitate this complex use process, you should initially address:

• Treatment management – Assess the impact of treatment at the center with its burden on specific roles and internal functions
• Order management – Build a process that embeds into treatment center processes and minimizes additional work.
• Logistics – Identify the platforms needed for tracking the material and its handoffs through cell collection, manufacturing, shipping, shipping containers, temperature conditions, specialty pharmacy /Hub, and final infusion.
• Patient support – Work to identify the entire treatment experience and the resources needed to deliver support from the patients’ diagnostic journey through their treatment center and therapy access, to the support trigger points within the treatment process itself.
• Scheduling changes and cancellation – Solidify at what point in the product process you will permit a site to cancel or change the parameters of an order. By doing this early, you can moderate potential issues later.

When changes are needed to the schedule there are a number of factors to consider such as: Is the product shelf stable for the delay? Will efficacy be reduced? Will the treatment center have capacity at the rescheduled times? Will logistic factors in shipping and packaging impact product availability?

If an order needs to be canceled the product might not be allogeneic for another patient and the product cost may become a loss to the manufacturer.

Establishing optimal systems

Undoubtedly, each manufacturer has a bespoke management platform(s) for its allogeneic and/or autologous product, and each is most likely different from the treatment center’s management and customer platforms. While addressing the technology, it is important to remember that mapping stakeholders to dedicated roles assigned to address specific issues, can help keep the process running smoothly and help define the best utilization of technology tools.

At the end of the day, you want to have a seamless manual process, or more ideally, a sophisticated integration of a broad array of systems that coordinate with the treatment center to manage and track the entire product process.

Thinking broadly across the entire process, It should:

• Incorporate the different stakeholders as well as the supply chain, patient activity, manufacturing operations, account management, and finance.
• Examine how field teams and other operations are involved in site certification and management.
• Take into account other key activities across the business such as patient support and general account management.
• Accommodate treatment center existing practices as much as possible to avoid site fatigue and ensure an optimal patient experience.
• Enable flawless coordination between internal team members, easy access to site relevant materials such as training, and visibility to certification/order status to designated team members.

Enabling success

In addition to establishing a product process and technological support amendable to the treatment center, there are other factors that are necessary to establish a successful partnership.

• Training/Education – Training of all internal and treatment center parties is essential before you can begin to address the product. This training should cover the product process as well as the resources available to the treatment center.It is important to understand the treatment center’s SOPs and ERM system and how your process might deviate so that the training covers this distinction. Keep in mind that the treatment center personnel could be entering information on their own systems, as well as yours and other manufacturers whose products they carry. This can become unnecessarily burdensome if not properly taken into account.You need to understand the adjustments that need to be made for what is unique to your product and train on the product and the order management system as well as the available resources. All personnel need to understand your process and the role they play within it. To make training more digestible, it is best to make it modular so it is more readily digested, and turnover at the treatment center doesn’t derail your processes with training.
• Process improvement-driven engagement – To keep the process running smoothly and to avoid costly errors, the manufacturer should assign an experienced problem solver(s) to the treatment center to identify potential pitfalls and work with the treatment center personnel to improve them. For example, in an autologous process, every third patient may not be getting enough cell counts. The problem solver would look to see why the apheresis process is not working as expected and suggest how to resolve the issue. Manufacturers should also offer a “batline,” a helpline for urgent questions.
• Connectivity to centers of excellence – A manufacturer can help to network the treatment centers it is working with, so that they can help and learn from each other.

The very success of allogeneic and autologous products depends on many to do their assigned process steps correctly, as well as interface with process systems that allow you to monitor and assess your product delivery. Partnering with the treatment center early and often to develop, train and support on systems and processes that are manageable for all is key.

Look for our next blog in this series, where we will address the challenges associated with financial concerns and reimbursement.

Want guidance with your upcoming CGT project?

Contact our team at Nuvera to leverage our deep treatment experience capabilities with allogenic and autologous therapies.

See our Case Example on CGT Therapy: Designing an End-to-End Therapy Order Management Process – Nuvera