“Moving from clinical trials supply into commercial supply is just doing more of the same.”  That’s a statement we often hear when talking to potential clients or when visiting cell and gene conferences.  In some ways, especially for cell-based therapies, the statement is correct.  It is true that there is a significant amount of overlap in the physical aspects of clinical and commercial supply operations.  This especially applies when compared to “traditional” biopharma products, where (for example) packaging, distribution channels, and product volumes may be vastly different.

However, the “more of the same” statement is an oversimplification.  A clinical phase company will likely design its supply and treatment process in cooperation with several key clinical sites. Much of this experience will also be applied during commercialization, but on a larger scale. There are however key differences that a company must consider.  Focusing on cell-based therapies, this short article explores where and how a commercial supply chain can differ from a clinical one.

More Patients = Less Predictable Demand

In the commercial phase, the patient numbers for cell and gene therapies will obviously increase, though the rise will be less steep than it is for traditional biopharma products. However, the influx of patients will be less controlled than in a clinical trial.  The increase in patient volume may create challenges in securing sufficient manufacturing capacity.  In addition, demand will be less predictable, and we have seen cases in which development / clinical and commercial volumes were competing for scarce manufacturing capacity within an organization.

More Treatment Centers = Greater Logistical Challenges

The number of treatment centers also increases during the commercial stage.  In the clinical trial phase, biopharma companies are very selective in the number of sites to ensure optimal coordination and the quality of the trial. In the commercial setting, however, more treatment centers are required to fulfill the treatment need.

Of course, selecting the right treatment centers depends on their capabilities.  However, it also depends on their locations. New, sometimes more remote locations may create logistical challenges, especially for products with tight “vein-to-vein” lead-times.  Those challenges can become more acute if the supply chain depends on one or a few manufacturing sites.  Expansion may require upgrades to logistical capabilities, potentially including additional contracting and qualification efforts, sometimes even including test runs before initial commercial shipments.

As treatment centers cannot be in every geographical location, many patients will not have a treatment center close by.  In a clinical trial setting, patients are typically willing to travel for a potential lifesaving treatment and the biopharma company is willing to pay for it.  However, in the commercial setting, logistical and financial solutions must be found for patients that do not have a treatment center nearby.

There are several potential ways to address the challenge.  A company can choose to not have the cells travel from center to lab (bound to time restrictions), but to have the patient travel to a treatment center close by the lab, further away from home (or even abroad). This brings logistical and financial challenges that requires close collaboration between payor, biopharma company, and patient organizations.  Some companies have chosen for a “hub and spoke” set-up. In this case, the hub (the central treatment center) has close collaboration with more local centers that can perform apheresis, so the patient does not have to travel for every step of the treatment. All the above needs to be considered when planning and selecting potential treatment centers in the commercial setting.

Additional treatment centers also mean expanding onboarding, qualification, and training efforts. Another aspect is that, while clinical trial centers often are quite willing to follow sponsor procedures, this may be different in the commercial setting.  Biopharma companies mostly develop their own onboarding, qualification, and training programs, and have specific preparation and treatment procedures.  Hospitals, on the other hand, will want to establish a standard process as much as possible and are likely to push back. 

Also, onboarding and training processes can be cumbersome and take up valuable time depending on the approach.  This may vary from digital training to on-site training to a biopharma company staff member being present to support each treatment. We see hospitals expressing the need for simplification and standardization as the experience and number of different treatments grows.

More Complex Patient Engagement and Consent Processes

Processes and procedures for patient engagement and consent, patient and product journey, and related data management flows are different in the clinical and commercial phases. This means that new processes and procedures need to be established.  An example of this is the set-up of Chain of Custody and Chain of Identity management procedures.

Whereas these processes the clinical trial setting can often be handled in a manual or semi-manual manner, in the commercial phase with higher patient and treatment center numbers, a more robust set-up is needed. This may trigger expanding the use of IT tools.  In addition to working with an IT solutions provider, this requires implementation, training, and operational support efforts with multiple stakeholders (internal, hospitals, contract manufacturers and packagers, logistics service providers). Again, hospitals may push back to use yet another therapy-specific solution.

More Complex Labeling Requirements

We already mentioned how larger and less predictable volumes can create challenges in manufacturing and logistics, as well as increasing lead times. Another attention point relates to the labeling requirements for commercial product, especially with regards to variable data elements (e.g., patient identifiers), which are more extensive than for traditional biopharma products.  They are also more extensive for commercial vs. clinical packs. This requires a robust data exchange with the packaging site and well-designed data management processes.

More Complex Order-to-Cash Processes

Finally, a main difference between clinical and commercial supply chains is the payment process, also referred to as the order-to-cash process. For traditional biopharma products the commercial set-up is relatively straightforward with an invoice that corresponds to the amount of product shipped. For cell therapy products, this may be more complicated due to variations in product amounts and the number of treatments, as well as the increasing focus on pay-for-performance and complicated confidential pricing agreements.  All this means that the invoice and payment often cannot be directly linked to order shipments. This gets even more complicated when cross-border treatments come into play.

Thinking Ahead

In conclusion, there are a number of attention points when preparing the commercial supply chain for a cell-based product. Some of the elements related to those points are determined when setting up the supply chain for a pivotal clinical trial.  Our recommendation is to start design work early, probably at the end of phase 1 clinical trials.  It’s essential to think through the various challenges that will be specific to your therapy when it reaches the commercial stage and formulate solutions proactively.

As 2024 progresses, AIM will be publishing more information and resources related to supply chains for cell and gene therapies, so be sure to follow AIM’s LinkedIn page to stay up to date.  To discuss the contents of this article, or to inquire about how AIM can help you design and develop the optimum supply chain for a cell-based therapy, contact Joop Wijdeven at joop.wijdeven@aimconnection.eu.