Decentralized and hybrid clinical trials require more agile supply chains than traditional, on-site models. Whether a trial is decentralized or traditional, different parts of a sponsor’s ecosystem, like CMOs, CROs and raw material providers, remain constant. In decentralized clinical trials (DCTs), the distribution structure becomes the unique engine that drives the model. Reliable, yet flexible storage, tracking and technology, among other variables, work in tandem to ensure the integrity of a DCT.

Challenges of Decentralized Trials
The complexities surrounding global distribution of time and temperature-sensitive clinical trial materials (CTMs) are nothing new. The constantly changing variables and myriad of regulatory considerations—all impacting potentially lifesaving treatments—have been a part of the pharmaceutical journey for years. But COVID-19 accelerated the adoption of decentralized clinical trials on a wider scale, and subsequent vaccine trials and their large-scale distribution shined a mainstream spotlight on temperature-controlled supply chain logistics and storage in a way that hadn’t occurred before.

The increased media focus for pharmaceutical supply chains has brought wider understanding to the fact that distribution of clinical trial materials requires more than simple logistics. In global trials, ensuring the same level of quality service in every country, while complying with local regulations is a major objective. Experts focused on delivering shipments safely and securely, from setup through execution, must have a clear understanding of the clinical trial process from both a global and regional perspective. Regulatory and trade compliance teams must apply their knowledge of key regional guidelines to determine the optimal import and export processes to follow as well as plan for ancillary procurement, storage and supplies. These and other factors must be considered and managed, all while continually providing near-constant real-time insight into the location and state of CTMs. As clinical researchers evolve to more patient-centric approaches, DCTs will continue to gain traction.

There are many moving parts in a DCT. An entire continuum of flexible logistics comes into play, depending on the activities carried out within the patient’s home due to Direct-to-Patient (DTP) delivery. These may range from procurement of ancillary supplies such as lab kits, medical devices and printed materials to storage and transportation with real-time access to chain of custody information and data for biological samples. Additionally, there are both the pre- and post-visit requirements that must be managed seamlessly around a home visit, including identifying, training and coordinating the nurse network.

For DCT models, the variables in all the areas mentioned previously are amplified. The illustration in Figure 1 provides insight to the various logistical demands for a patient-centric (e.g., decentralized or hybrid) trial compared to a traditional site-centric trial.

Supply Chain Solutions for DCTs
Executing a well-run DCT would not be possible without a supply chain partner that can orchestrate all the moving parts with both precision and agility. An effective supply chain partner must understand which of these parts have to move when and what the processes are behind them. A flexible distribution strategy for decentralized trials relies on many factors, but there are three critical components that form and fuel that engine and directly address the most obstinate challenges:

• An extensive GMP depot network and transport solutions: The breadth of global reach via commercial air capabilities and the depth of local/alternative, specialty transport solutions;
• Exceptional technology for logistics, packaging and tracking;
• An expert team that understands how to best strategize and execute around the unique foundation of supply chain logistics and technology.

The integration of operations, systems and data is what enables a flexible supply chain. Mastering some, but not all three of these areas produces an incomplete solution. If a partner has an extensive GMP depot network and transport solution but lacks the technology or specific expertise to coordinate it, the solution is lacking. If exceptional technology is in place, but there is not operational infrastructure to apply it to, then the technology is wasted. And if a team of experts is assembled, but the operational and technology components are inferior or disjointed, then that expertise is muted. Synergy between people, processes and technology—knitted together into a single solution—enables a company to provide a breadth and depth of services, and also pivot quickly to fulfill the requirements of the product, the patient and the protocol.

Infrastructure and Expertise: The Power Behind a Flexible Supply Chain
In conventional, linear supply chains, CTMs travel predictably from manufacturer to shipper to warehouse to transport to site of use. The flexible, patient-centric supply chain network that is needed for decentralized trials is more intricate, involving overlapping and redundant functionality. Shipping, supply and execution is both circular and multidirectional. Patient availability, location and requirements for safeguarding the drug products themselves drive decision-making, in addition to the requirements of the sponsor and manufacturer.

Placing the patient at the center of the supply chain strategy informs all the steps and processes contributing to a seamless transaction. As the total number of product destinations grows and as the shipping demands for each successive leg of the journey become more arduous, the more a specialized logistics team’s expertise is required—and exponentially more so when global routes are involved. With DTP/DFP, a global GMP depot network is ideal because storage facilities close to the patients are a primary driver of shorter delivery timelines, cost savings and proximity-driven agility options that can streamline the process. The DTP/DFP supply chain may also include home administration of therapies requiring an additional, non-transit-related layer of supply chain expertise.

A network of national, regional and local carriers—the spokes in the hub-and-spoke model—build out redundant capabilities, providing multiple avenues through which to fulfill supply chain requirements. The clinical trial protocol specifications (and those of the CTM in question) might suggest specific ways to optimize a patient-centric network and may involve multiple routes between the patient, sponsor, healthcare facility and/or research site. Localized CTM storage means the spokes can work independently or in concert with each other to best serve the patient.

A centralized model with multiple regional GMP depots enables trial sponsors to optimize inventory at each individual location. An advanced, real-time warehouse management system operating within a larger supply chain technological ecosystem allows drug developers to accurately track where and when their therapies are needed in localized patient communities. Inventory management technology enables each of these communities to have their needs addressed individually, lessening the need for high-volume inventory (which also increases the risk of expiration issues) while ensuring consistent supply.

What is clear is that each of the critical factors—GMP Depot Network and Transport Solutions, Technology and Expertise—are interrelated and inextricably connected. While an excellent GMP network and transport solutions may serve as a solid operational foundation, unifying technology is needed to enable efficient execution and agility. Applied expertise is then required to leverage these resources ensure cohesive, effective and flexible DCT supply chain solutions.

Single Source Brings It All Together
Maintaining consistency and quality while addressing the increased variables of decentralized trials means minimizing cold hand-offs between unrelated companies. Without an interconnected system offering direct insight into your CTM’s location, status and tracking at all times, there is an unavoidable reliance upon different—even competing—companies working together to connect their individual roles in supply chain execution. Through utilization of a single-source supply chain partner with comprehensive, end-to-end technology designed to ensure that quality standards remain intact, both in packaging and tracking, the needs of the patient and sponsors can be met seamlessly and more proactively. Providing real-time, track-and-trace capabilities including monitoring and reports for updates on location, temperature, motion, shock and more, to ensure your drug is handled with the highest level of care and precision.

A comprehensive GMP depot and transport solution, supported by unifying technology and orchestrated by a team of clinical trial supply chain experts enables the agility needed to execute decentralized and hybrid studies. The use of a single-source flexible supply chain partner instills cohesion and uniformity, while providing more holistic visibility, throughout the end-to-end solutions process.

Conclusion
From specific in-transit handling requirements to global regulatory considerations to expiration of sensitive medicines, a flexible supply chain is crucial to support global patients as they participate in a wide range of clinical trials from home. One reality of decentralized trials is that the general burdens of participation once borne by the patient, including making sure they are physically in the same place as the unexpired CTM and ready to have it professionally administered at a specific time, are now borne by the sponsor/CRO and its supply chain partner.

Successfully managing these demands means understanding that the specific solutions that may work in North America or Europe may not work as well in countries with less established national infrastructure. Your supply chain partner must have the expertise, capacity and ingenuity to solve individual fulfillment challenges as quickly as they arise. A comprehensive, integrated global network comprised of localized GMP depots working in concert with global commercial air capability all the way through alternative, specialty transport solutions is crucial to a flexible supply chain approach. It adds another layer of certainty in an unpredictable global transit environment.

The success of a decentralized clinical trial and the well-being of its enrolled patients both hinge on CTM distribution that is efficient and compliant with local regulations. To ensure flexibility, a supply chain provider must offer the storage of supplies and clinical drug products close to patients via a global GMP depot network and access to innovative packaging solutions and tracking technology. The functionality of which all depends upon expert global regulatory and trade compliance proficiency and the transport of shipments in a secure, end-to-end environment—all while meeting all GDP/GMP/GCP standards.

While individual factors are required and important, it is the combination and interoperability of them all that makes DCTs run. Sophisticated transportation networks, local depots and robust technology must operate together cohesively. Expertise across all of these areas enables flexibility that is inevitably needed. Having a single provider that can not only provide the services, but that can also apply the expertise, is the key to making this work for sponsors and patients.

Compared with traditional clinical trials, decentralized and hybrid models require more agile supply chains to manage their many changing demands. Flexible supply chain solutions enable drug developers to accommodate decentralized and hybrid clinical trial models, meeting the needs of sites, patients and sponsors seamlessly and transparently. Flexible supply chains are the engine that continue to move decentralized trials forward. 

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Gaurang Majmudar, senior director, global patient centric services at Marken, is responsible for overseeing the expansion of patient centric services in the EMEA and APAC regions and the development of new service offerings for Marken clients to further expand and streamline the clinical trial experience for patients and sponsors. Gaurang offers a wealth of experience from the pharmaceutical, distribution, and home healthcare industries. He has held senior marketing and commercial roles within pharmaceutical companies, where he was responsible for product development and launches within specialty medicines and orphan diseases sectors.

Nina Vas is Marken’s vice president, clinical distribution, cell & gene supply chain and leads Marken’s global GMP depot network as well as its fast-growing cell and gene division. She brings financial, operational, quality and PPI (Practical Process Improvement) experience managing the performance of the full supply chain which supported the execution of distribution for clinical trials to global destinations. Her background includes importing of drug product (from API to finished goods and ancillaries) with clinical research organizations, pharmaceutical importers, owned facilities and third-party depots.