A framework for scaling cell and gene therapies, from clinical trial to commercialization

Cell and gene therapies (C&GT) are a revolutionary scientific achievement, capable of delivering life-changing outcomes for the patients who need them. But scaling operations for these therapies, from the clinical trial stage to commercialization and beyond, remains a common obstacle for C&GT manufacturers.

Despite 11 product launches in roughly six years, the biopharma industry is still struggling to meet commercial expectations—and the well-known manufacturing bottlenecks aren’t entirely to blame. Treaters are as dissatisfied with manufacturers’ operational processes as they are with product availability. With more than 500 U.S. companies developing C&GT products at more than 500 clinical sites in the U.S., the demand for late- and commercial-scale operations are growing as manufacturers struggle to transition from clinical to commercial more effectively.

While the reasons for operational inefficiency vary across manufacturers, a common theme we’ve seen is a lack of commercial launch readiness prior to approval. We’ve found that organizations delay preparedness exercises until they’re closer to launch, which is a mistake. We believe that organizations need to assess and optimize their processes in the clinical trial setting to ultimately define and shape their processes for delivering it at commercial scale. 

Based on our experience developing, scaling and launching C&GT products inside biotech and pharmaceutical organizations, as well as within treatment centers, we’ve created a tool that can help manufacturers assess, test and optimize the commercial readiness of their organizations. ZS’s Cell and Gene Therapy Comprehensive Operational Readiness (CORE) system creates harmonization across teams by:

1. Mapping the current processes, roles and responsibilities across the end-to-end patient and product journey
2. Assessing functional launch readiness across each process step
3. Testing the systems and capabilities via internal and external dry runs 

ZS’s CORE tool has four key components:

1. Process mapping: Organizations should think about commercial design planning during clinical trials and create a realistic and seamless clinical-to-commercial transition blueprint at this stage. Ideally, organizations should start mapping processes during phase 2 to phase 3. During process mapping, organizations must define and map all current processes, roles and responsibilities across the end-to-end journey as well as the ideal future commercial design. They should capture the cross-functional internal and external ecosystem, including third-party vendor collaboration, while confirming process step ownership and evaluating how cross-functional processes are managed. Process mapping enables awareness and cross-functional alignment and serves as a comprehensive visualization of steps involved in a functional launch operating system. This will serve as the commercial roadmap and blueprint for the ideal commercial design of the cell therapy product delivery and operating system.

2. Readiness assessment framework: The structure of the readiness assessment framework identifies and prioritizes areas and functions needing additional focus. The methodology consists of assessments across every step and functional group involved in the current and expected commercial roadmap. This approach also includes an assessment of all functional stakeholders across the company to ensure cross-functional procedures and processes are established and aligned. We engage the entire organization responsible for developing, producing and delivering product from clinical operations, supply chain, manufacturing, patient operations, quality, finance and other functional areas. The key to scaling commercialization operations successfully is taking a holistic approach to identifying inefficiencies and bottlenecks while creating capacity and increasing harmonization of treatment delivery. 

The framework assesses launch readiness across each step of the process, including patient identification and product manufacturing and encompasses a range of metrics across five categories. This ensures a holistic evaluation of various C&GT processes across key organizational functions and third-party vendors. When paired with the accompanying scoring system, C&GT companies can use this framework to identify gaps in processes that may have otherwise gone undiscovered.

Our framework also helps organizations pressure test their state of readiness at the cross-functional level. Leaders can determine whether current processes can be successfully executed at scale or if they’re likely to have trouble with capacity during ramp ups. Ultimately, this readiness exercise can help companies reconsider their priorities ahead of launch, refine launch plans and identify action items.

When we conduct readiness assessments, we often find organizations have not accurately judged their capabilities or considered what certain elements look like realistically at scale. For example, we find things like:

• Insufficient resourcing: While 10 supply chain personnel may be adequate in the clinical trial setting, scaling up for launch means identifying, hiring and training a significant number of new employees where talent is lacking.
• Lack of equipment: Treatment centers need significantly more storage, which organizations can no longer provide in the commercial setting. They need a plan to guide treatment centers on how to adequately source and store commercial products.
• Site support: Clinical treatment centers require a new level of support and resources when transitioning to the commercial setting. It’s easy to forget that entirely new teams are working on products in the approved setting and they need guidance on new ways of working.
  
• Workflows: What works in the clinical trial setting won’t necessarily work in the commercial setting. Organizations must roll out new processes and provide clear instruction on how patients will move through the process from registration to infusion, including support for bridging the gaps between departments within each treatment center.
  
• Scheduling: Organizations struggle with the “bottleneck syndrome,” which stems from capacity and demand planning. Treatment centers need flexible and dynamic scheduling systems and support to accommodate patient schedule changes, which is very common and increases dramatically at scale when more patients are treated.
  
• Organizational siloes: Organizations often realize how incredibly siloed departments are during internal assessments. The biggest gaps span manufacturing, supply chain and patient operations and pertain to roles, responsibilities and touchpoints, as well as who does what, when.

3. Internal dry runs: These allow teams to test processes, perform walk-throughs and give functional leads and team members an opportunity to react and respond to touchpoints. Functional representatives read scripts and have an opportunity to debrief their teams about steps and responsibilities and define clear action plans to close gaps. Internal dry runs allow organizations to optimize the ideal end-to-end path prior to launch. They bring together people, processes and technology for live multiday simulations to capture defects, enhancements and opportunities for improvement prior to or at launch.

4. External live end-to-end dry runs: These simulation events test end-to-end processes using imitation product and involve all stakeholders, including vendors, treatment sites, distributors and others. Simulations where stakeholders must “live” the end-to-end process can help stakeholders establish cross-functional procedures and processes for a successful launch. A simulated treatment experience is one of the most valuable ways for C&GT stakeholders to truly experience what is and isn’t working. 

C&GTs have changed how we treat diseases. But we must use lessons from previous launches to learn how to evolve and produce more sustainable and effective delivery models. Achieving commercial success with newly approved C&GT products requires tremendous effort, expertise and collaboration. C&GT companies must start planning earlier in the clinical development process. It’s unreasonable to expect them to perform their own commercial launch planning and assessment exercises without appropriate support and collaboration from commercial C&GT experts. Having an assessment strategy with the right tools and experts to guide C&GT companies from clinical to commercial alleviates the complexity, answers the unknown and creates a truly “best-in-class” treatment experience for patients, treatment centers and manufacturers alike.