Managing Complex Sample and IP Logistics in Support of Cell and Gene Therapies

Managing Complex Sample and IP Logistics in Support of Cell and Gene Therapies

PAO-06-24-CL-11

The emergence of cell and gene therapies (CGTs) represents a paradigm shift in modern medicine, offering unprecedented potential for treating previously incurable diseases. However, the advance of these groundbreaking therapies brings forth a myriad of logistical challenges, particularly in the management of complex samples. As the CGT landscape rapidly evolves, clinical research companies face the critical task of navigating intricate supply chain management and transportation processes while safeguarding proprietary information vital for innovation and competitiveness. The PPD clinical research business of Thermo Fisher Scientific enables drug developers to deploy strategies, technologies, and best practices to overcome this web of complexities surrounding sample and IP logistics in support of CGT trials.

Navigating the Complexities of CGT Clinical Trial Logistics

Proper logistics management for cellular therapies, particularly during clinical trials, is a highly intensified process requiring meticulous planning, execution, and oversight. These therapies are exceptionally time- and temperature-sensitive, requiring efficiency and precise maintenance of transport and storage conditions. Both the biological starting materials collected to manufacture cell therapies and the cell therapy products are biohazardous materials that require specific storage and handling conditions throughout the supply chain.

The urgency of delivery compounds the complexity, especially for autologous therapies, which are manufactured from a patient’s own starting cellular material. Not only must these therapies be transported efficiently, but the drug product must be returned, maintaining a chain of custody with no margin for error. It is imperative that the logistics framework is robust, responsive, and designed to surmount these obstacles. This ensures the delivery of these critical therapies to patients not only safely and intact but also timed perfectly to align with the protocol’s schedule of events and patient milestones.

Streamlining CGT Sample Procurement and Distribution

The journey of cell therapy products from study design to patient receipt involves precise and regulated steps, tailored to the type of therapy being produced. Allogeneic therapies can be derived from cells collected from universal donors and suitable for all recipients or collected from matched donors and specifically processed to suit individual patients. In either case, the cells undergo isolation and combination at a facility for larger-scale processing. While these therapies are typically stored under liquid nitrogen (LN₂), their release from the manufacturing site or depot also requires careful scheduling to ensure timely delivery. Each batch must be properly packaged, labeled, and shipped within a short delivery window, aligning with the recipient’s medical needs.

For autologous cell therapy production, patient-specific cells are gathered through cell-collection methods, such as apheresis, and processed individually. The logistics for autologous therapies are notably complex, involving an in-depth chain of custody to ensure that materials not only arrive in time for integration with the patient’s treatment plan, including lymphodepletion in advance of therapy administration, but also maintain traceability and integrity throughout the process.

Throughout these steps, strict adherence to regulatory guidelines is paramount, ensuring the integrity of the materials via appropriate temperature management and monitoring solutions and their coordinating documentation and shipment tracking, as well as the protection of private patient data. Coordination is key — the logistics framework must ensure seamless integration of these steps to deliver therapies safely and effectively.

The time allotted for sample and product shipment may also depend on the stage of development and the specific protocol. Cryopreservation requires the establishment of a robust formulation and cryopreservation strategy to reduce the risk of cryopreservation-induced stress and cell damage.¹ The supply chain design must account for numerous variables, including:

• when patients are admitted and material is picked up,

• the distance between the clinic and the manufacturing site, and

• scheduling of patient pretreatment to coincide with delivery of the cell therapy product.

The complexity of these logistical considerations increases exponentially when trials span multiple clinical sites and require agile and proactive solutions to avoid deviations and align with trial protocols.

Personalized Manufacturing Processes for CGT

CGT trials are designed to adapt to each patient’s genetic profile or medical condition. Gene therapies are designed to treat narrowly defined patient groups with disorders defined at the genetic level. Allogeneic cell therapies are matched to patients based on compatible cellular characteristics, and autologous therapies involve modifying and expanding a patient’s own cells before reinfusion.

For smaller trials at limited sites, scheduling might be handled manually. However, in more extensive trials — those targeting common diseases or later phases, with increased participant numbers — spanning multiple international sites, sophisticated digital systems are indispensable for managing the complexities of patient and sample data, particularly for patient-specific autologous therapies.

Efficient supply chain operation is crucial to prevent any disruption that could compromise the integrity of samples or the timely treatment of patients. This requires continuous, transparent communication among all parties involved in the trial, including clinical and manufacturing sites and logistics providers. Adherence to good manufacturing, clinical, and distribution practices throughout this chain is not only ideal but essential to preserve the quality of both patient samples and finished products.

Ensuring Integrity through Chain of Custody in CGT Trials

Maintaining chain of custody for patient samples is essential to ensure traceability, quality control, and regulatory compliance. Adherence to the strictest standards is the goal, but uniform application is complex due to the diverse procedures and systems employed by various clinical sites, manufacturers, and logistics providers. In addition, while some critical standards have been established (e.g., ISBT-128), they are constantly evolving owing to the nascent nature of the CGT sector.

Clear, open communication is key to synchronize the disparate systems, especially with each sponsor using its own cloud-based platform that requires integration with multiple couriers’ networks. The tendency for sponsors to tailor processes to the needs of individual clinical sites complicates this further. Clinical sites must navigate various systems with frequently changing access credentials, a process that is not sustainable at scale. A unified system that can adapt to the array of CGT products and the needs of different sponsors and clinical sites would significantly enhance chain of custody support.

The industry is progressing toward regulatory harmonization, with coordinated efforts at conferences and the establishment of the Standards Coordinating Body to bridge the gaps.² This collective endeavor indicates a strong commitment to developing comprehensive solutions that will streamline communication across all parties involved in CGT supply chains.

Critical Considerations for CGT Storage and Stability

Cell and gene therapies require stringent storage and stability protocols to preserve their biological integrity. Ensuring their viability and efficacy requires precise temperature regulation, robust packaging, and continuous monitoring to avert degradation during storage and transit.

Starting cellular material must be as viable as possible to enable manufacture of effective drug products. Those materials may be cryopreserved or kept as “fresh” material. Both must be maintained at the appropriate temperature throughout transport. Monitoring and control are necessary to ensure that no temperature excursion occurs that could impact the viability of materials being shipped to manufacturing sites or from manufacturing sites to clinics for infusion into patients. For cryopreserved products, the transition from storage to transport containers is a critical phase where maintaining the required temperature conditions is essential to prevent any alteration in the product’s state that could compromise its viability.

Complicating the situation is the fact that different countries have different levels of cold-chain capabilities. In addition, most clinical sites, including those in more mature markets, have limited low-temperature capabilities and capacities. Such variability, alongside the imperative for rigorous monitoring and control of patient and product milestones, underlines the pivotal role of logistics in CGT clinical management and the imperative of engaging with a strong partner like the PPD clinical research business that possesses a comprehensive global footprint of LN₂ capabilities and expert staff at all depots to assure robust temperature control, regardless of location.

The stakes are high — any deviation from the prescribed temperature can render a CGT starting material or product unusable, as it falls outside the established protocol, making its behavior unpredictable and potentially unusable. In a 2022 survey of 100 professionals involved in CGT trials, 26% identified complex transportation requirements (cryopreservation and cold-chain logistics) as the most challenging storage and logistics issue, followed by lack of storage partners with adequate licenses and qualifications (22%) and stringent storage requirements for cell therapies (21%).³

Collaboration with a logistics partner equipped with the right infrastructure, expertise, and materials — and ready with contingency plans — is indispensable. Such partnerships are crucial to ensure that CGT materials are consistently kept within the required temperature range, regardless of transit delays.

Coordinating CGT Clinical Logistics on a Global Stage

Conducting cell and gene therapy trials on an international scale involves a sophisticated orchestration of logistics. The task spans multiple sites and countries, each with its own set of import/export laws, customs protocols, shipping regulations, and local distribution networks. Effective global coordination is necessary to manage these diverse requirements and maintain the integrity of the cellular starting material and drug product.

The viability of CGTs can be jeopardized by delays inherent in the standard customs procedures, which often operate on a first-come, first-served basis. Differing levels of regulatory scrutiny — from straightforward document reviews to complex approval processes — further underscore the need for expert courier partnerships that specialize in swift and secure customs navigation to ensure that starting materials get to the manufacturing site and products get to patients as quickly as possible.

Moreover, CGT logistics demand a more robust contingency planning framework than what is typical for traditional pharmaceuticals like oral medications. A comprehensive, global network of depots is crucial, equipped for immediate recharging or replacement of temperature-controlled shipping containers. Such preparedness, combined with vigilant oversight, enables the preemptive identification and management of potential disruptions, such as weather, mechanical failures, or geopolitical events.

Our Strategic Approach to CGT Logistics and IP Management

Cell and gene therapies often provide the last hope for many patients. While the focus to date has been on rare diseases and specific cancers, a growing number of candidates are targeting more prevalent diseases, inevitably broadening the impact of advanced therapies in the future.

Success in this arena demands not just enhanced manufacturing processes but also a more stringent logistics framework. The complexity scales up with larger trials across multiple international locations, necessitating unprecedented levels of communication, collaboration, and logistical precision.

We are at the forefront of addressing the intricate logistics inherent in CGT trials. With a track record of supporting more than 130 trials in the sector (more than 75 gene and more than 55 cell therapy programs), we have an unwavering commitment to advancing these transformative treatments. Our expansive infrastructure, including a dedicated support group, regulatory and trade compliance expertise, a global depot network, and a wealth of cold-chain management knowledge, fortifies our capacity to handle the escalating demands and scalability of CGT trials.

Each trial benefits from the dedicated attention of a clinical logistics monitor. This point person coordinates the intricate choreography of materials and information among clinical sites, sponsors, and couriers, including monitoring of shipments to timing of raw material collection and product delivery to align with patient milestones. Proactive measures are ingrained in our approach, allowing us to anticipate and mitigate potential issues swiftly.

Our team’s expertise extends to navigating the regulatory maze, offering sponsors bespoke logistical strategies and assistance with any customs-related inquiries. The integration of our logistical, clinical trial management, and other supportive services facilitates a cohesive operation that enhances both efficiency and cost-effectiveness.

Our commitment to continuous improvement and learning — both internally and for the industry as a whole — ensures ongoing innovation in all aspects of CGT development and manufacturing, including advances in logistics solutions. The PPD Cell and Gene Therapy Institute exemplifies this dedication, spearheading developments that are shaping the future of CGT clinical trials.  

References

1.     Pike, Nirupama, Carl Dargitz, and Michael Weist.Freeze it and forget it: the value of having a robust formulation and cryopreservation strategy for cell therapy manufacturing.” Thermo Fisher Scientific. 2020. 

2.     Cell Therapy Clinical Trials Report. PPD. 2021

3.     “The Standards Coordinating Body for Regenerative Medicine.” Accessed 8 May 2024.

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