Best Practices For Clinical Supply Chain Management In Rare Disease Trials

By Ana-Zeralda Canals Hamann, Debiopharm

Clinical supply chain management (CSCM) is the process of planning, coordinating, and executing the delivery of clinical trial materials to study sites and patients. CSCM is a critical component of clinical research, as it ensures the investigational products' quality, safety, and availability.

However, CSCM also poses many challenges, especially for rare disease trials with unique characteristics and requirements. Rare disease trials are often complex, innovative, and adaptive and involve a limited and dispersed patient population, a high unmet medical need, and a fast-changing regulatory landscape. In this article, we will discuss some of the main challenges of CSCM in rare disease trials and how to overcome them with innovative solutions and best practices.

Challenge 1: Limited Patient Population And Geographic Dispersion

One of the most common challenges of CSCM in rare disease trials is the limited and dispersed patient population. Rare diseases are defined as those that affect fewer than 200,000 people in the United States or fewer than one in 2,000 people in the European Union. According to the National Institutes of Health, there are more than 7,000 rare diseases, affecting about 25 million to 30 million Americans, and 30 million to 40 million Europeans. However, the patient population for each rare disease is often very small, ranging from a few to a few thousand.

Moreover, the patients are often geographically dispersed across multiple countries or continents. This makes it difficult to recruit and retain patients for rare disease trials and to deliver the clinical trial materials to them in a timely and cost-effective manner. Some of the implications and consequences of this challenge are:

• increased complexity and variability of the supply chain network, as the clinical trial materials need to be shipped and distributed to multiple locations and stakeholders, with different customs, regulations, and logistics;
• increased risk and uncertainty of the supply and demand planning, as the patient enrollment and retention rates, the dosing schedules, and the trial duration may be unpredictable and fluctuate over time; and
• increased cost and waste of the clinical trial materials, as the overproduction, overstock, and expiry of the investigational products may occur due to the low and variable consumption and the limited shelf life.

Solution 1: Patient-centric And Flexible CSCM Strategies

To overcome the challenge of a limited and dispersed patient population, CSCM in rare disease trials should adopt a patient-centric and flexible approach. This means that the CSCM should be designed and implemented with the patient's needs, preferences, and convenience in mind, and should be able to adapt to changing circumstances and demands. Some of the patient-centric and flexible CSCM strategies include:

• Use direct-to-patient (DTP) or direct-from-patient (DFP) models, which allow the delivery or collection of clinical trial materials directly to or from the patient's home, rather than the study site. This can reduce the burden and travel costs for the patients and increase their adherence and retention. DTP and DFP models also require less storage and distribution infrastructure if the product is stored at room temperature, but it also means more control at the patient’s home and can enable faster and more responsive CSCM.
• Use decentralized or hybrid trial models, which combine traditional site-based visits with remote or virtual visits, using digital technologies such as telemedicine, mobile apps, wearable devices, and electronic patient-reported outcomes (ePRO). This can increase patient access and convenience and allow real-world data collection and continuous monitoring. Decentralized or hybrid trial models also reduce the dependency on on-site availability and capacity and can enhance the efficiency and quality of CSCM.
• Use adaptive trial designs, which allow the modification of key trial parameters, such as sample size, randomization ratio, dosing regimen, or endpoints, based on interim data analysis and feedback. This can improve the trial's statistical power and ethical validity, and optimize the use of clinical trial materials. Adaptive trial designs also require less up-front planning and forecasting and can enable more agile and responsive CSCM.

Challenge 2: Complex And Variable Regulatory Requirements

Another common challenge of CSCM in rare disease trials is the complex and variable regulatory requirements. Rare diseases often have no or limited existing treatments and, therefore, the clinical trials for rare diseases may be eligible for expedited or special regulatory pathways, such as Orphan Drug designation, Fast Track, Breakthrough Therapy, Priority Review, or Conditional Approval. These regulatory pathways aim to accelerate the development and approval of new therapies for rare diseases and may offer incentives or benefits, such as tax credits, fee waivers, market exclusivity, or reduced data requirements.

However, these regulatory pathways also entail challenges and uncertainties for CSCM, as they may involve different or additional requirements or expectations for the clinical trial materials, such as labeling, packaging, storage, documentation, or reporting.

For example, some countries may require more stringent labeling, packaging, or storage conditions, while others may allow more flexibility or exemptions. Additionally, the regulatory requirements for CSCM may change over time as new regulations or guidelines are introduced or updated. This makes it challenging to comply with the regulatory requirements for CSCM and to ensure the quality, safety, and traceability of the clinical trial materials. Some of the implications and consequences of this challenge are:

• increased complexity and variability of the supply chain operations, as the clinical trial materials need to meet different or changing standards and specifications, across different countries or regions, and for different regulatory pathways;
• increased risk and uncertainty of the regulatory compliance and approval, as the regulatory requirements and expectations may be unclear, inconsistent, or evolving and may result in delays, deviations, or rejections; and
• increased cost and waste of the clinical trial materials, as the regulatory changes or discrepancies may require the relabeling, repackaging, or disposal of the investigational products or the duplication of the testing or documentation.

Solution 2: Proactive And Collaborative CSCM Planning And Execution

To overcome the challenge of complex and variable regulatory requirements, CSCM in rare disease trials should adopt a proactive and collaborative approach. This means that the CSCM should be planned and executed with the anticipation and mitigation of potential regulatory risks and issues and with the involvement and communication of all the relevant stakeholders. Some of the proactive and collaborative CSCM planning and execution strategies include:

• Conduct a thorough and early regulatory assessment that identifies and analyzes the regulatory requirements and expectations for CSCM across different countries or regions and for different regulatory pathways. This can help to avoid regulatory delays or deviations and to ensure the compliance and quality of CSCM.
• Establish a cross-functional and multidisciplinary CSCM team that includes representatives from the sponsor, the contract research organization (CRO), the contract manufacturing organization (CMO), the logistics provider, the study sites, and the regulatory authorities. This can facilitate the coordination and communication of the CSCM activities and responsibilities, and the resolution of any regulatory challenges or conflicts.
• Implement a robust and integrated CSCM system, which enables the tracking and reporting of the clinical trial materials, from the manufacturing to the disposal, and across different locations and stakeholders. This can ensure the traceability and accountability of the CSCM and the availability and accuracy of the CSCM data.

Challenge 3: High Cost And Uncertainty Of CSCM

A third common challenge of CSCM in rare disease trials is the high cost and uncertainty of CSCM. CSCM is often a significant and variable component of the clinical trial budget, as it involves various activities and resources, such as manufacturing, packaging, labeling, testing, storage, distribution, and disposal of the clinical trial materials. Moreover, the CSCM in rare disease trials is often subject to high uncertainty and variability due to the limited and dispersed patient population, the complex and variable regulatory requirements, and the adaptive trial designs. This makes it difficult to estimate and control the cost and demand of the clinical trial materials, and to optimize the CSCM budget and resources. Some of the implications and consequences of this challenge are:

• increased complexity and variability of the supply chain optimization, as the CSCM needs to balance the trade-offs and constraints among various factors, such as quality, safety, availability, timeliness, and cost-effectiveness;
• increased risk and uncertainty of the supply chain performance and outcomes, as the CSCM may face unexpected or unforeseen events or changes, such as supply shortages, demand spikes, quality issues, or regulatory updates; and
• increased cost and waste of the clinical trial materials, as the CSCM may incur unnecessary or avoidable expenses or losses, such as overproduction, overstock, expiry, or disposal of the investigational products.

Solution 3: Data-driven And Value-based CSCM Optimization

To overcome the high cost and uncertainty of CSCM, CSCM in rare disease trials should adopt a data-driven and value-based approach. This means that the CSCM should be optimized and evaluated based on the collection and analysis of relevant and reliable data and the alignment and prioritization of the value drivers and outcomes. Some of the data-driven and value-based CSCM optimization strategies include:

• Using data analytics and simulation tools can help forecast and optimize the demand and supply of clinical trial materials based on various scenarios and assumptions. This can reduce waste and overstock and improve the CSCM's efficiency and effectiveness.
• Using risk management and mitigation techniques can help identify and assess the potential risks and issues of the CSCM and implement the appropriate actions and contingency plans. This can reduce the impact and likelihood of CSCM failures and disruptions and enhance CSCM reliability and resilience.
• Using value-based metrics and indicators can help measure and monitor the CSCM's performance and outcomes and compare and benchmark them with best practices and standards. This can improve the CSCM's quality and transparency and demonstrate its value and return on investment.

Conclusion

CSCM in rare disease trials is a challenging but vital process, which can make a difference in the lives of millions of patients who suffer from rare diseases. By adopting patient-centric and flexible, proactive, collaborative, and data-driven and value-based approaches, CSCM in rare disease trials can overcome the challenges of limited and dispersed patient population, complex and variable regulatory requirements, and high cost and uncertainty and deliver the clinical trial materials in a timely, cost-effective, and compliant manner.

About The Author:

Ana-Zeralda Canals Hamann is an associate director of clinical trial supplies at Debiopharm. She has more than a decade in sponsor-side pharmaceutical clinical operations, CMC, supply chain management, regulatory, IP, project management, and preclinical services. She earned her M.Sc. in clinical research administration and a Ph.D. in molecular medicine from the University of Oxford.