Decentralized trials call for supply chain flexibility: Marken

Coordinating the delivery of clinical trial drugs and other crucial supplies requires specialized expertise. Add in the complexities associated with decentralized and hybrid studies, as well as the limitations created by the COVID-19 pandemic, and the challenges increase.

Outsourcing-Pharma spoke with a number of clinical trial supply chain experts at Marken:

• Nina Vas, vice president of clinical distribution for cell and gene therapy supply chain
• Gaurang Majmudar, senior director of global patient-centric service.

These professionals addressed the ways in which decentralized studies challenge supply chain professionals (compared to traditional, onsite trials), and how flexibility and adaptability are a must.

OSP: ​Could you please talk about how the decentralized/hybrid trial supply chain has evolved in the months since COVID-19 started impacting research?​

NV: In many ways, the COVID-19 pandemic has accelerated much of the interest and actual implementation of decentralized clinical trials (DCT), and I believe they're here to stay. The patient burden removed in many cases by choosing a decentralized clinical trial design is of great benefit to our industry.

It is important to remember, though, that traditional versus decentralized is not a binary decision. Many trials may be hybrids with some clinical trial activities taking place at the investigator site and some at the patient’s home.

With all the discussion surrounding ePRO, eCOA, eConsent, and so on, one aspect of these trials that is often overlooked is supply chain. How are we getting drugs and supplies to our patients in their homes, retrieving samples and supplies from patients, and moving them to the appropriate destination? Are we providing supplies to home healthcare workers and nursing staff who can visit patients and perform many of the activities that would have traditionally been done at sites?

These considerations are critical to the success of putting a comprehensive, decentralized clinical trial paradigm into place. We’ve seen the life science industry face disruption on a global scale as many clinical supply chain providers were unprepared to meet the growing challenges.

With this exposure of supply chain vulnerabilities, it has become clear that an experienced, single-source partner may be best positioned to provide the control and transparency clients rely on to transport shipments in a secure, closed-loop environment that meets all GDP/GMP/GCP standards. In uncertain times, the resilience and agility to rapidly make and implement decisions without disrupting subsequent legs of the supply chain is key.

OSP: You mention the agility required to manage decentralized trial supply chains (SC) — could you please explain how management differs between decentralized clinical trials (DCT) and hybrid, versus traditional onsite studies? What unique challenges and concerns are involved—and, by contrast, are any aspects of SC easier to handle?​

GM: Compared with traditional clinical trials, decentralized and hybrid trial models require more agile supply chains to manage their many changing demands. Maintaining consistency and quality while meeting the needs of sites, patients and sponsors seamlessly and transparently is never easy. Having to address the increased variables of decentralized trials makes excellent performance even harder.

There are many moving parts when you decentralize a study — a whole continuum of flexible logistics that come into play, depending on the activities carried out within the patient’s home. These may range from the 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.

There are both the pre- and post-visit requirements that have to be managed seamlessly around a home visit, including identifying, training, and coordinating the nurse visit. 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 resilient DCTs relies on the integration of operations, systems, and data. Synergy among people, technology, process, and data knitted together in a single solution, enables a company to pivot quickly to fulfill the needs of the product, the patient, and the environment. State-of-the-art, GMP-compliant global central, regional and in-country depot networks with logistics hubs in key regions are also crucial.

OSP: Specifically, what sorts of solutions are put in place to ensure the security and effectiveness of a supply chain where the end product is handed directly to patients​ (civilians) rather than site staff?​

GM: Safeguarding the well-being of trial participants is paramount. To set the standard in the clinical supply chain for DTP/DFP services, supply chain partners must deliver, distribute and retrieve clinical trial supplies and sensitive biological materials directly to and from the patient’s location, effectively extending the reach of the trial, globally.

At Marken, our Global Home Healthcare team manages the whole process, providing fully integrated services that allow more patients to participate in clinical trials from the comfort and convenience of their own homes. From home pickup and delivery of biospecimens to the return of unused or expired trial materials, a range of solutions help improve patient retention rates and protocol compliance. Quality is guaranteed through full temperature sample monitoring and transparent electronic reporting in real-time in more than 57 countries.

Solutions to meet the logistical demands of global direct-to-patient drug delivery include:

• Consolidated clinical storage, distribution, and logistics
• Ability to pivot quickly to serve the needs of the product, patient, and environment
• A flexible clinical supply distribution strategy, including a DTP solution in combination with a global GMP depot network
• Global SOPs for uniform processes
• Understanding of local country regulations to ensure service compliance in data management and home care services
• Multiskilled project management team (GMP, GDP, logistics, and DTP experience)
• Track record of identifying and mitigating risks throughout the global supply chain

Examples of coordinated agility adapted to patient needs might be delivering medication to the patient at a pre-agreed time or reconstituting and delivering an injection in the correct time frame and shipping it at the correct temperature for planned administration by an appropriately qualified and trained nurse — with all necessary supplies included.

OSP: Are there any regulatory considerations SC professionals executing DCTs should know about? Please feel free to talk about national regulations, regional, anything you feel appropriate.​

GM: Distribution of clinical trial materials is more than simple logistics. In global trials, ensuring that the quality of service delivered in every country is as identical as it can be while complying with regional regulations, is always a major focus.

Experts focused on delivering shipments safely and securely, from setup through execution, must also have a clear understanding of the clinical trial process from the 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.

There's an entire continuum of flexible logistics that come into play, depending on the activities that are carried out within the patient's home. It may start with cutting-edge management platforms and the latest GPS technology for drug shipments, with 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.

This level of care must extend to handling data. Patient data must flow between nurse source documents and sites via secure channels, for example. The requirements for how data is managed and what data can be communicated may vary from country to country. Similarly, home healthcare activities, such as blood draws and ECGs, are usually allowed, but not always. A good provider will know and advise you.

To make sure services are as consistent as possible across countries and regulations, robust SOPs are vital. How are drivers managing the packaging? How are they handling confidentiality? How is medication being delivered, are the nurses trained similarly and how are logistics and nursing activities to be coordinated?

This necessitates secure systems, encrypted data flows and the flexibility of the same system to manage the requirements of differing local privacy rules, for instance even within two EU countries, such as the Netherlands and France.

And finally, if decentralized study home nursing is part of the protocol, it's crucial to have a partner with a wide network of qualified nursing partners with proper data security processes, training, and licensing.

It’s also worth noting that regulatory authorities such as the FDA are now looking more closely at patient demographics in every study and expect patients to be representative of the population being studied. From this standpoint, DCTs are advantageous as they enable a greater variety of people to participate.

OSP: Please explain the “central depot” logistics model—how does it work, what special considerations does it entail and how does it help mitigate border-crossing considerations (and other complexities)?​

NV: When patients and clinical trials depend on the delivery of therapies around the world, delays are unacceptable. For this reason, it’s paramount to store the drugs closer to patients across a network of strategically located depots capable of getting products to patients, faster.

Strategizing for the distribution of clinical trial products, equipment, preconditioned packaging solutions in relation to remote patients and difficult-to-reach labs allows for the best implementation of decentralized trials in combination with local, regional, and central depots.

While it is still key to monitor shipments and establish contingency actions throughout the clinical trial ecosystem, a central depot strategy decreases the risk of last-minute delays caused by any kind of transportation or customs issues because the materials, when summoned, have already cleared these hurdles. It enables teams to shift strategies mid-trial, and, when combined with a regional or in-country depot or affiliate, can mitigate the complexity of crossing borders in global trials.

This includes reducing transit times, serving difficult destinations, fulfilling import and export requirements, and ensuring the total supply chain has more than one option. Flexible supply chains can secure the timely delivery of clinical trial products and therapies to sites and directly to patients.

OSP: Could you please share tips and tricks on how to design an effective, efficient, and safe DCT/hybrid trial supply chain?​

NV: It is important to set up a clinical supply chain solution that offers flexibility, can handle the complexities of decentralized distribution, and also utilizes a central depot model to reduce the risk of delayed deliveries. A consolidated supply chain that integrates transport, management, data gathering, and home healthcare services is most likely to be able to adapt to interruptions in the supply chain.

Another key tip is to ensure that it is clear in the protocol that a decentralized model could be used as an option, to support parts of the study, for example, IMP delivery to patients in their home, or even administration. This way, the approval of this by the regulators is considered part of the initial process, saving time and further discussion at a later stage.