The Hidden Risks in Your Supply Chain: How Regulatory Support Can Save Your CGT Program 

The temperature-controlled supply chain has become so much more than a straightforward logistics function, especially for advanced therapies. It has quickly evolved into a critical extension of your manufacturing process, your clinical trials, and your path to commercialization. Every step, from sourcing raw materials to delivering the final drug product to patients, must operate within strict regulatory and quality parameters where even the smallest oversight can cascade into regulatory delays, product loss, or even compromised patient safety.  

Still, even seasoned professionals can miss risks that are hidden in plain sight. Four of the most common risks that lead to downstream impact include:  

• Unvalidated shipping lanes that leave transport performance unproven 
• Poorly documented packaging qualifications that fall short during inspections 
• Regulatory inconsistencies that can create gaps between operational practices and submission requirements 
• A lack of pre-qualified backup shipping systems to mitigate shipper inventory shortages or unforeseen events like urgent order requirements  

Understanding these risks and putting the right controls in place can mean the difference between a smooth regulatory review and an unexpected program derailment.  

Addressing the Risk of Unvalidated Shipping Lanes 

Every shipping lane is unique. Factors like transit times, carrier performance, and environmental conditions can vary significantly between locations and seasons. Without validation, you’re trusting your sensitive (and often irreplaceable) materials to unproven assumptions that they will arrive intact, within the required temperature range, and on time.  

Unvalidated lanes leave room for hidden issues like temperature excursions that compromise product integrity, customs delays that extend transit times beyond acceptable hold time limits, and handoffs that increase the risk of misrouting or mishandling.  

The good news is that these risks are easily mitigated through proactive shipping lane qualifications. These types of studies simulate real-world transport conditions to ensure the lane performs within your critical limits. These studies capture data on transit duration, environmental conditions, and handling points, providing documented evidence for your regulatory filings and allowing you to move forward with the confidence that comes from proven conditions rather than assumptions.  

Addressing the Risk of Incomplete Packaging Qualification Documentation 

Temperature-controlled packaging systems, especially those used to transport extremely sensitive materials like cell and gene therapies (CGTs), are only as reliable as their qualification process. Many organizations complete basic qualification tests but fail to document results in a way that aligns with regulatory expectations.  

Common pitfalls include situations like missing calibration certificates for data loggers, insufficient evidence of repeatability across multiple shipments, and a lack of stress testing under worst-case conditions.  

A robust packaging qualification program includes performance testing under normal and extreme conditions, repeatability studies, and comprehensive documentation that can be used alongside your regulatory filings. This proactive approach not only satisfies regulators but also supports internal quality audits and client and/or vendor oversight.  

Addressing the Risk of Regulatory Inconsistencies 

CGT programs often move quickly from early-phase clinical trials to late-stage development, scaling up supply chain operations as needed along the way. In that transition, gaps can emerge between operational practices and regulatory commitments.  

For example, the shipping process may evolve, but regulatory submissions aren’t updated to reflect new procedures. Or perhaps validation protocols differ between collection sites, leading to inconsistent documentation. Maybe international programs fall out of alignment due to varying country-specific regulations and requirements. These inconsistencies can lead to questions during audits or inspections, or even delay approvals when regulators request additional data.  

Ongoing regulatory review of your supply chain documentation ensures alignment between practice and submission. Planning for future-state and commercialization infrastructure from the very start can also help to proactively mitigate risks and build a supply chain strategy that is designed to scale through clinical trials and into commercial distribution, fully compliant and aligned with regulatory expectations at every stage.  

Addressing the Risk of Not Pre-Qualifying Backup Shipping Systems 

Even the best supply chain plans can be derailed by unexpected disruptions like shipper inventory shortages, manufacturing delays from your packaging supplier, or the need for a rush order to maintain your clinical schedule. If your regulatory filings only include a single primary shipper, switching to an alternative on the fly can require new validations, potentially delaying shipments or creating compliance risks.  

By building redundancy into your program by pre-qualifying backup shippers (and including them in your regulatory filings from the start), you ensure that if your primary shipper becomes unavailable, or if a tight timeline demands a fast turnaround and a secondary solution, you have a compliant and validated solution ready to go.  

At Cryoport Systems, we maintain the industry’s largest wholly owned fleet of shipping systems, giving us the flexibility to provide a qualified replacement quickly (often within 24 hours or less) without compromising compliance or product integrity. In addition, Cryoport Systems is the only provider to decontaminate and fully requalify every shipping system before every use to ensure quality and compliance for even the most challenging shipping lanes.  

Strengthening Compliance and Reducing Risk 

Addressing these hidden risks requires a proactive, data-driven approach. Managing these activities fully in-house can stretch resources, especially when teams are already managing day-to-day demands. Partnering with a provider experienced in CGT logistics and regulatory compliance offers significant advantages. You are able to leverage specialized expertise for turnkey qualification services, from protocol design to execution and reporting, to support your regulatory filings with robust, compliance-ready documentation.  

At Cryoport Systems, our consulting and advisory services are designed to mitigate risks before they impact your program. We provide: 

• Shipping lane qualification tailored to your specific routes, carriers, and environmental conditions 
• Shipping risk assessments that map vulnerabilities and recommend mitigation strategies 
• Shipping system and packaging validation backed by comprehensive, audit-ready documentation 
• Backup shipper qualification so you’re prepared for any unanticipated disruptions, without losing regulatory compliance 

Whether you’re preparing your first clinical shipment or scaling toward commercialization, these services strengthen your regulatory position and safeguard the integrity of your supply chain.  

For advanced therapies, the supply chain is a regulated process and not a background operation. Unvalidated shipping lanes, incomplete documentation, regulatory inconsistencies, and a lack of pre-qualified contingency plans may feel like small considerations when you’re just starting your clinical program, but they can escalate into major issues if not proactively addressed. By applying robust risk assessment tools, conducting thorough qualifications and validations, and engaging expert consulting and advisory support from the earliest stages, you can build a resilient supply chain that meets the highest standards of compliance and performance. Because when the success of your program depends on the safe delivery of every shipment, there is no room for hidden risks.