Expert Q&A: Going Deeper on Early Supply Chain Strategy for CGT Programs 

Advanced therapy developers rarely have the luxury of perfect timing. Programs are often moving toward the next milestone with limited resources, data that’s evolving in real time, and pressure to make decisions before every variable is fully understood. 

That reality was at the center of the recent webinar, “Prevent Advanced Therapy Program Delays with Early Supply Chain Strategy,” where panelists discussed how early decisions around logistics, cryopreservation, packaging, site readiness, documentation, and cross-functional alignment can influence everything downstream. But recognizing that supply chain strategy should start earlier is only the first step. The harder question is what teams should actually do with that realization, especially when they’re balancing speed, budget, and the uncertainty that comes with early development. 

Following the webinar, we continued the conversation with Gwendolyn Erskine, Senior Director of Consulting Services at Cryoport Systems; Dominic Clarke, Associate Chief Scientific Officer of Cryoport Systems and Vice President of IntegriCell® Technical Operations; and Lorraine Hicks, an industry expert with extensive experience supporting cell and gene therapy programs across global regulatory pathways.  

The discussion moved beyond whether teams should start earlier and focused in on how to make better decisions when the program is still evolving.  

If a CGT team accepts that supply chain planning needs to start earlier, what should they do first?  

Gwen: The first step is not to jump straight into a full qualification plan. It’s to map the decisions that are already being made, even if the team doesn’t think of them as supply chain decisions yet. 

Site selection, collection schedules, material handling, packaging assumptions, courier models, customs expectations, temperature requirements, storage strategy… those are all decisions that can create downstream constraints. I would start by asking, “Which of these decisions could become difficult or expensive to change later?” 

From there, teams can prioritize. Not everything needs the same level of rigor in Phase I. But if a decision could affect product quality, regulatory expectations, commercial scalability, or patient access, it deserves attention early. 

Lorraine: I would begin with documentation. That may sound basic, but it is often where the biggest gaps start. Early teams are making decisions quickly, and the logic behind those decisions can live in meetings, emails, or individual memories. 

If you want to build regulatory readiness, you need to capture the rationale as the program evolves. Why was a site selected? Why was a fresh-material model considered acceptable? Why was a packaging configuration chosen? What assumptions were made, and what would cause the team to revisit them? 

Those details become part of the development story. If the story is not captured as it happens, it becomes harder to defend later. 

Dominic: From my perspective, the first step is to identify which decisions could affect the biology of the product or starting material. Cryopreservation is a good example. It may be discussed as a logistics solution, but it can also affect the characteristics of the material. 

If there is any reasonable chance the program may require cryopreservation in the future, teams should recognize that early. While implementation does not need to occur immediately, they should understand not only what data will ultimately be required to support a fresh or cryopreserved starting-material strategy, but also what data may need to be proactively generated before patients enter the clinic to preserve both options.

How should teams decide what needs attention now versus what can wait?

Gwen: I like to think about it in terms of reversibility. Some decisions are relatively easy to change. Others become embedded in the clinical model, the data package, the site network, or the regulatory strategy. 

If a decision is easy to reverse and does not affect quality, patient scheduling, product handling, or future qualification, it may not need a lot of early investment. But if changing that decision later would require new studies, site retraining, regulatory justification, or a different commercial model, then it needs to be discussed early. 

That’s where teams can avoid over-engineering. The question is not, “Can we make everything final now?” The question is, “Which decisions need enough evidence behind them that we are not boxed in later?” 

Dominic: For cryopreservation, I would ask: if we remain fresh now, what would have to be true for that model to work at the next stage? And what would make it fail? 

If the answer is, “It works as long as we have a small number of sites, predictable scheduling, short transport windows, and no major delays,” then the team needs to be honest about whether that reflects the future program. 

You don’t want to wait until the fresh model breaks before you understand the alternative. That is where programs lose time. 

Lorraine: I would also look at what regulators may eventually expect the team to explain. If a decision affects comparability, chain of custody, chain of condition, product quality, or process control, it should not be treated as informal. 

Phase-appropriate does not mean undocumented. Even if the level of evidence changes over time, the rationale should be clear from the beginning. 

What does a practical “minimum viable” supply chain evidence package look like in early development? 

Lorraine: In early development, the evidence package does not need to look like a commercial filing package. But it should show that the team is thinking intentionally. 

At a minimum, I would want to see the decision rationale, the known risks, the assumptions being made, and the triggers that would cause the team to reassess. For example, if the team is using fresh material, what assumptions support that decision? Is it based on distance, timing, product stability, site capability, or manufacturing schedule? What happens if the program expands to additional sites or moves internationally? 

The evidence package should show that the team understands the current state and has a plan to mature it. 

Gwen: For logistics and packaging, early evidence might include a shipping risk assessment, a clear view of the proposed lanes, an understanding of site capabilities, and a plan for when lane studies or formal qualifications will be needed. 

It doesn’t have to be overbuilt, but it should be organized. Teams should know what has been evaluated, what has not been evaluated yet, and when those gaps will need to close. 

Dominic: On the cryopreservation side, an early evidence package might include development data showing how the material responds to freezing and thawing, what attributes are being monitored, and how the cryopreserved material compares to fresh material. 

Even if the program continues with fresh material, that information can be valuable. It gives the team a fallback strategy, and it reduces the risk of having to start from zero if the operating model changes. 

What are the warning signs that “phase appropriate” has become “underbuilt”? 

Gwen: One warning sign is when teams cannot explain the timeline required for the next level of work. If a team says, “We’ll qualify that later,” but no one knows how long protocol development, approvals, execution, reporting, or quality review will take, that is a problem. 

Another warning sign is when the team is relying on a single successful shipment or a mock shipment as evidence that the model is ready. A shipment arriving successfully is not the same as having a qualified, repeatable, documented process. 

Lorraine: I would add that it becomes underbuilt when decisions are being made without clear ownership. If no one owns the rationale, no one owns the documentation, and no one owns the evidence package, gaps will appear. 

In early development, informality can feel efficient. But as the program advances, that informality can become a liability. 

Dominic: Another warning sign is when the team assumes that because freezing is technically possible, it can be added later without much impact. 

The question is not simply whether cells can be cryopreserved. The question is what freezing does to the material, how that process is controlled, and what data are needed to support the change. If those questions have not been discussed, the strategy may be underbuilt. 

How should teams pressure-test a fresh-material strategy without committing to cryopreservation too early? 

Dominic: The team should start by defining the operating limits of the fresh model. What is the maximum acceptable time from collection to processing or administration? How much variability can the material tolerate? What happens if a flight is delayed, a courier misses a connection, or a manufacturing slot changes? 

Then the team should model what happens as the program expands. Add more sites. Add longer distances. Add weekends, holidays, weather events, borders, customs, and patient scheduling variability. If the model still works, that is useful information. If it breaks, it is better to learn that early. 

Pressure-testing fresh does not mean the team has to move to cryopreservation immediately. It means the team understands the risk and can make an informed decision. 

Gwen: From the logistics side, I would want to see the actual lanes and handoffs assessed. A route may look feasible on paper, but the real-world execution may depend on carrier availability, airport restrictions, dry ice or liquid nitrogen limitations, customs processes, or site operating hours. Any number of factors can influence real-world results that don’t always show up until real product is moving through real circumstances. 

That is why shipping risk assessments are valuable early. They help teams identify where the model is strong and where it may be fragile. 

Lorraine: I agree and would add that the key is to document the analysis. If the team decides to continue with fresh material, the rationale should be clear. If the team decides to develop a cryopreservation option in parallel, that rationale should also be clear. 

What matters is that the decision is intentional rather than assumed. 

What should site feasibility include beyond clinical capability? 

Gwen: Site feasibility should include a logistics-readiness view. Can the site receive the required shipping systems? Can it prepare outbound shipments? Does it have trained personnel available when shipments need to move? Can it handle dry ice or liquid nitrogen, if applicable? Are there restrictions related to storage, staging, or pickup times? 

Teams should also look beyond the site itself. What airports or carrier routes serve that location? What happens if the primary lane is unavailable? Are there border crossings or customs requirements? Are there local holidays or geographic factors that could affect timing? 

A clinically strong site may still create operational risk if these questions are not addressed. 

Lorraine: Exactly that. Also, for cross-border programs, the documentation requirements become especially important. Teams need to understand what is required not only by one agency or one country, but by every jurisdiction involved in the movement of the material. 

If a site is part of a future international strategy, those requirements should be discussed early. Otherwise, the team may select sites that are difficult to support later. 

Dominic: I would also consider whether the site is being asked to perform any critical handling steps, including cryopreservation or thawing. If multiple sites are performing those steps differently, variability can enter the process. That may be manageable early, but it becomes more difficult as the program matures. 

What governance model helps prevent supply chain decisions from becoming fragmented? 

Lorraine: There needs to be clear ownership of the end-to-end story. That does not mean one person makes every decision, but someone should be responsible for ensuring that the pieces connect. 

Regulatory, clinical, quality, logistics, manufacturing, and commercial teams may each own part of the process. The risk is that each function optimizes for its own milestone without seeing the downstream impact. Governance should create a forum where those tradeoffs are visible. 

Gwen: I would recommend a recurring cross-functional supply chain readiness review, especially as the program approaches major transitions. That review should look at site changes, lane changes, packaging decisions, qualification timelines, documentation status, and commercial-readiness implications. 

It does not need to be overly complicated. But it should force the right conversations before decisions become urgent. 

Dominic: I would add that for technical decisions like cryopreservation, governance should include the people who understand the biology, the process, the clinical model, and the logistics. If any of those perspectives are missing, the team may miss an important constraint. 

The goal is not to slow decisions down. It is to make sure decisions are made with enough context. 

What happens when a team realizes late that its supply chain strategy is fragile? 

Gwen: The first thing is to stop guessing and assess the actual gaps. Teams often lose more time trying to patch the issue quickly without understanding the root cause. 

Is the problem the lane? The packaging? The site’s handling capability? The documentation? The qualification strategy? The timeline? Once the team knows where the gap is, it can decide what needs to be addressed first. 

Lorraine: From a regulatory perspective, the team should identify what rationale exists and what is missing. If a decision was made earlier but not documented, can the team reconstruct the rationale with available evidence? If not, what additional work is needed? 

It is also important to prioritize based on risk. Not every gap has the same regulatory or operational impact. The team should focus first on issues that affect product quality, patient safety, comparability, or the ability to demonstrate control. 

Dominic: If the issue is related to cryopreservation or material handling, the team needs to understand whether it is dealing with an operational gap, a biological gap, or both. If a process change is needed, what data will support it? How will comparability be assessed? What controls need to be added? The sooner the team turns the problem into a structured plan, the better. 

What is one conversation CGT teams should have earlier than they usually do? 

Dominic: Teams should ask, “What happens if our early model works clinically but does not scale operationally?” 

That is a very common risk. Early clinical success can create momentum, but it can also expose the limits of the original operating model. If the team has not thought about scalability, success can actually create pressure. 

Gwen: I would ask, “What will our future selves wish we had documented, tested, or qualified earlier?” 

That question helps teams think beyond the current milestone without requiring them to solve everything immediately. 

Lorraine: My question would be, “Can we explain this decision clearly two years from now?” 

If the answer is no, then the team should document more, align more, or evaluate the decision more carefully. 

The bigger lesson: optionality is built before it is needed 

For CGT developers, early supply chain strategy is not about locking every decision before the program reaches the clinic. It is about understanding which decisions could limit the program later and building enough evidence to preserve flexibility. 

That includes pressure-testing fresh-material assumptions, evaluating cryopreservation before it becomes urgent, making logistics part of site feasibility, planning for shipping qualification timelines, documenting rationale, and creating governance that connects clinical, regulatory, quality, manufacturing, logistics, commercial, and external partners. 

The webinar made the case that regulatory readiness is built early. The deeper operational lesson is that optionality is built early, too. Teams that ask better questions sooner are better positioned to adapt as science, scale, sites, and regulatory expectations evolve. 

Our sincere thanks to Gwen, Dominic, and Lorraine for taking the time to share their thoughts and insights with us. You can catch the on-demand webinar, “Prevent Advanced Therapy Program Delays with Early Supply Chain Strategy,” to hear the original panel discussion that led to this follow-on conversation.