In Support of the Supply Chain

Stakeholders across the cell and gene therapy space are unanimously stressing the urgent need for establishing standards in response to the industry’s rapid growth. There is a particular need for improvement in chain of identity (COI) and chain of custody (COC) tools because these form the backbone of the complex supply chain process for advanced therapies. This need is especially true for autologous therapies where biological material must carefully be moved from a patient’s location to the site of production and back to the correct patient – without error and within tight timeframes.

Developers of advanced therapies may often feel that top-to-bottom, bespoke solutions are needed to fit their unique needs when it comes to supply chain management, but experience tells us this tends to be short-term thinking that ignores the challenges of scalability, interoperability, and long-term costs.

Here, I present five recommendations for supply chain orchestration and IT platform selection.

1. Digitize early
 

In the early days, cell and gene therapy developers started out with paper-based tracking workflows – and some early-stage projects still rely on this method. Unfortunately, processes that are workable in early development become unwieldy at scale-out. As the field has matured over the past decade, more and more companies are recognizing the limitations of a paper-based system and seeking out digital solutions.

Tracking the progress of a therapy on paper with multiple external partners is prone to human error – rendering it increasingly risky and onerous during scale-out. Well thought-out digital systems with development that meets the GAMP-5 standard can facilitate scale-out far more easily. These systems can also be validated within a quality system and against relevant regulations to ensure they are secure and compliant.

Despite the obvious advantages of digital orchestration, some companies still start with a paper-based system, with every intention of moving to a digital system when the time is right. But delaying implementation of a more robust digital system until later in drug development is likely to add unnecessary risk, as well as be a false economy. The earlier the switch to an appropriate digital solution, the better. 

2. Be cautious of custom approaches
 

Conventional wisdom has coalesced around digital approaches to COI and COC, but many developers understand that they require flexibility to match the unique workflow they are creating. A custom-built system may seem like an effective approach, but does not always provide the expected flexibility. 

Many first-wave cell therapy developers learned this the hard way after creating their own platforms in house to meet specific needs that were then unable to cope with scale up. I’ve seen developers begin with a custom-built orchestration solution before realizing that they need a complete rebuild. Many designers of the earliest commercial platforms had similar experiences: after launching with traditionally coded software solutions that had to be re-coded for each new deployment, the need for constant testing made them unscalable. The leading options have switched to configurable solutions built on cloud platforms, which enable quicker configuration, testing, validation, and deployment to support clinical trial and commercial therapy supply chains.

The upfront investment of time and effort to launch a custom solution can seem straightforward to estimate, whether it’s an outsourced or in-house build, but it means bearing the full task of ongoing testing and validation. Therapy developers often don’t realize the degree of future costs, particularly as longer-term maintenance and changes are generally not factored into the scope or roadmap. Furthermore, custom-built solutions tend to be based on a company’s experience to date – often just a small number of clinical-scale runs – which can be severely limiting.

Some developers have also found their bespoke systems are ill-prepared for the complexity of expanding into new geographies; language translations and regulatory/data privacy requirements vary from country to country, for example. It can be difficult to make sure your workflow is meeting all territory-specific requirements – and to adapt when rules, standards, or regulations change.

In short, custom builds can also be a false economy, with inflated costs over time. Though the largest pharmaceutical companies may have the resources to iteratively rebuild their orchestration platforms, many smaller companies and earlier-stage biotechs risk getting trapped in a situation that will be resource- and cash-intensive – conflicting with the core strategy of progressing the development of their therapy.

3. Harness the power of automation
 

Automation makes standard cases exceptionally easy to handle with minimal intervention. For CGTs, the reality is that a surprising amount of time is spent managing scenarios that don’t follow the ideal process. Technology can help by automatically identifying exceptions and managing escalations. Automation also accelerates development, which is crucial given that the patients enrolling in trials come with many potential variables. They are typically very unwell, often seeking third- or fourth-line treatment following the failure of standard-of-care approaches. This might mean that something as trivial as catching a cold can delay immune depletion, severely disrupting the tight schedule. And, of course, dealing with biological material also presents potential points of failure – from temperature deviations to limited cell yield. In short, your supply chain platform must be able to consider and address therapy-specific, patient-specific, and process-specific variables.

4. Consider long-term support and user training
 

As with any software, maintenance is an ongoing necessity and adoption and utilization are critical. User interfaces and other key components tend to get dated very quickly. For COI and COC, it can be advantageous to integrate solutions with partner systems, such as courier portals or software, to form a highly connected ecosystem from patient to therapy infusion and beyond. Any update to these systems or connectivity methodologies, such as application programming interfaces, must be accounted for. If the owner of a custom system can’t make rapid updates, there’s a risk the integration will fail – regardless of which party is responsible for the change. Given the health circumstances of most patients in CGT trials, the impact of delays due to system failures can be significant.

In general, IT system management must be forward-looking to anticipate changes and improvements in technology, particularly in an industry that is evolving as rapidly as the CGT space. For example, new technologies arise regularly in fast-developing fields, such as artificial intelligence. Assessing how these could be leveraged to improve a system is a mammoth task. This is before you have acted to incorporate the latest technological advances into a solution – a process that is never complete, if you are always keeping an eye on what’s coming next.

Commercial solution providers form their own partnerships with these vendors and have the resources to appropriately monitor and prepare for upcoming changes. Their solutions also have the advantage of bulk and can leverage their broad user base for better responsiveness, pushing external vendors to prioritize fixes. A mature provider with a large network of connected vendors can empower developers to adapt quickly if, for example, a courier of choice was unavailable and an alternative must be used.

5. Ease the pain for healthcare staff
 

As they move forward with clinical trials, cell therapy developers are no longer working in a vacuum. They need constant feedback from users at all points of the value chain to make sure their supply chain approach remains relevant. Through regular industry working groups and other outreach efforts, we understand that portal fatigue is a growing pain point at patient sites. For centers of excellence working with dozens of therapies, they may be grappling with a variety of shipping, manufacturing, and patient information portals for each therapy. Dealing with that complexity falls on the shoulders of healthcare practitioners, such as nurse navigators. These people don’t want different logins and workflows for each therapy. Integrated systems, with the ability to manage all of the therapies from a specific developer, can start to address this issue.

It takes a huge investment of time to manage the many integrations required for the suite of ecosystem partners, including logistics, enterprise resource planning solutions, manufacturing execution systems, benefits verification, and patient services. Throughout the rapidly evolving CGT space, everyone is coming to realize that – across all domains – the go-it-alone approach is untenable.