Solving Pharmacy And Clinical Supply Challenges In Decentralized Trials

By Sachit Verma, MD, MBA, FACHE, FAPCR

Transitioning from a traditional site-centric approach to a patient-centric last-mile delivery model presents logistical challenges in investigational pharmacy and clinical supply for decentralized clinical trials (DCTs). The management of investigational pharmacy and clinical trial supply has evolved from simply handling medications to overseeing patient-focused delivery networks, all within a dynamic global landscape characterized by high sensitivity and volatility. The industry now focuses on navigating specialized delivery requirements while ensuring operational resilience amidst geopolitical and regulatory complexities. DCTs offer the significant benefit of reducing patient burden, particularly for the 70% of participants residing more than 2 hours away from study centers,¹ but they also introduce a series of logistical hurdles for investigational pharmacies to overcome.

The focus of this article is on the notable difficulties arising in logistical, regulatory, and operational aspects as a result of this transformation. Clinical sites are significantly impacted by these challenges, highlighting the crucial importance for clinical leaders to stay updated  and make well-informed decisions about them.

Last-Mile Logistics With Temperature Regulation

When it comes to getting investigational products (IP) to patients, we know how important it is to keep them at the right temperature. To ensure the proper management of the cold chain, we may need to explore alternative routes to achieve this goal.

• Environmental Risks: The significance of the final last mile delivery from a local depot to a mailbox or porch should not be underestimated, as it represents a crucial juncture where packages face vulnerability to extreme weather conditions, be it scorching heat in summer or freezing temperatures in winter. It is essential for delivery services to strategize and implement measures to protect packages during this critical stage to ensure they reach their destination in optimal condition.
• Unproven Routes: Direct-to-patient (DTP) routes diverge from traditional pathways to medical facilities by venturing into uncharted territory, exposing patients to unforeseen environmental risks. These untested paths can pose unpredictable challenges, emphasizing the need for careful navigation.
• Risk of Degradation for High-Value Items: Many experimental biological products, such as personalized medicines or GLP-1 agonists, are highly susceptible to temperature fluctuations, which can compromise their effectiveness, result in loss of potency, unusable data loss, or generate harmful byproducts.
• The management of temperature sensitivity poses a significant challenge in DCTs, especially when IP, notably biologics, are dispatched directly to patient residences rather than controlled clinical settings. Maintaining stringent cold chain integrity (often within 2 degrees C to 8 degrees C) becomes paramount, as even minor deviations in temperature can lead to denaturation, loss of efficacy, or the development of aggregates, jeopardizing the integrity of trial data and necessitating costly resupplies. Unlike pharmacies, home environments lack validated storage conditions, leaving room for potential breaches induced by malfunctioning refrigeration units, power interruptions, or improper product handling (e.g., storing items in refrigerator doors). Many biologics, such as monoclonal antibodies and vaccines, are sensitive to freezing temperatures, rendering them susceptible to harm from both high and low temperature fluctuations. The transportation of these products to various unconventional sites heightens the likelihood of delays, courier mishaps, and insufficient or incorrect packaging, particularly for items requiring ultra-cold storage (minus 70 degrees C to minus 80 degrees C).²

To address last-mile risks in DCTs, it is necessary to use validated thermal packaging along with ongoing digital monitoring to maintain stability during transportation from the pharmacy to the patient. In addition, utilizing specialized courier services and following clear protocols are crucial to protect the integrity of the drug upon delivery. In practice, this often requires qualifying multiple packaging configurations by region and predefining escalation protocols for temperature excursions or failed deliveries so issues can be addressed in real time.

1. Complex DTP Logistics

Delivering investigational medicinal products (IMPs) directly to patients' homes requires using robust, temperature-controlled, and often specialized logistical systems. This heightens the possibility of product deterioration, shipping delays, and mistakes, requiring increased flexibility. Despite the significant advantages for patient engagement, the DTP approach poses challenges, particularly in executing the final stage of delivery, primarily due to participant unavailability, logistical issues, and inadequate secure storage facilities.

• Around 6% of DTP shipments experience failures, often attributed to instances such as participants not being available at home, temperature variations, or errors made by the courier.³
• Timely deliveries are crucial and should align with scheduled home nursing visits. Even a slight delay of 2 to 3 hours can lead to disqualifications or major disruptions to the study timetable.
• Many households lack secure drop-off areas or the necessary refrigeration equipment to ensure stability post-courier delivery.

To optimize complex DTP logistics, sponsors must establish a centralized pharmacy model and employ state-of-the-art real-time tracking technology integrated with environmental sensors. This will ensure the integrity of the chain of custody and precise temperature regulation during the transportation of pharmaceuticals. Collaborating with a seasoned logistics provider equipped with regional distribution centers and extensive knowledge of local regulations is key to reducing customs delays and ensuring a dependable supply chain. Leading sponsors align delivery windows with patient availability and home health visits in advance to reduce failed delivery attempts and rescheduling days.

2. Inventory Management & Visibility

In DCTs, the challenge of managing the last mile to a patient’s home poses significant risks, as the lack of real-time tracking can create a data black hole. Without centralized visibility, pharmacies encounter difficulties in monitoring crucial factors like stock levels, expiration dates, and storage conditions, leading to costly overstocking or dangerous dosing interruptions. This issue often results in a substantial 50%-70% product waste due to inaccurate forecasting.⁴  

Adopting a centralized cloud-based inventory management platform is recommended. This platform should incorporate real-time tracking, automated expiry alerts, and blockchain technology for chain of custody verification. Many organizations integrate inventory data directly with IRT systems to enable more accurate forecasting and reduce the risk of overstocking or stockouts at the patient level.

3. Confidentiality And Integrity 

Ensuring the confidentiality of participants' personal information (including name, address, and medication) during DTP delivery via courier services is crucial. Compliance with privacy standards is essential for local staff, non-clinical personnel, and pharmacy staff. Finding the right balance between respecting data privacy laws like GDPR and HIPAA while still being able to collect and share data through decentralized channels can be challenging. It usually means having detailed and sometimes complicated data sharing agreements in place.

The use of mobile technology, such as BYOD (bring your own device), in DCTs introduces the possibility of data leaks if not adequately secured. Remote drug delivery methods (such as DTP, local pickups, and remote infusion centers) must consider three key factors: patient privacy, IP tracking and confidentiality, and compliance with regulations.⁵ Data collected from numerous real-world sources increases the potential for accidental disclosure or re-identification of anonymized data.

To safeguard sensitive patient data, organizations/clinical sites should prioritize the implementation of robust security measures. This includes using end-to-end encryption and tokenization to secure data, implementing role-based access controls with multifactor authentication to restrict data access to authorized personnel only, and maintaining real-time digital accountability logs along with blockchain-based tracking. These measures will not only enhance data protection but also ensure a tamper-proof audit trail for distributing and handling clinical supplies. Experience shows that performing regular access audits and simulating data breaches helps teams identify vulnerabilities before they impact trial integrity.

4. Supply Disruptions & Adaptive Trials

Managing investigational pharmacy and clinical supply in DCTs necessitates a high level of agility due to mid-study protocol changes and unexpected supply shortages, compounded by DTP requirements. These factors can lead to significant delays, requiring prompt repackaging and re-shipment. The challenges are further exacerbated in adaptive trials, which permit real-time adjustments based on interim data, necessitating flexible supply chains that can swiftly adapt to evolving trial needs. Protocol modifications during the trial can set off a chain reaction, demanding immediate adjustments in drug packaging, labeling, and distribution. Unlike traditional trials, DCTs mandate direct shipping to patient residences, adding complexity to last-mile logistics, chain of custody management, and temperature-controlled storage. The pressure on the supply chain is heightened by adaptive designs, which aim to enhance efficiency through modifications to trial parameters based on interim outcomes.

Implementing proactive AI-driven demand planning, regionalized inventory management, and flexible DTP logistics integrated with real-time IRT systems can enhance agility and compliance in DCTs supply chains and adaptive trials. Cross-functional coordination between clinical, supply chain, and data teams is critical to translate protocol changes into supply adjustments without disrupting patient dosing schedules.

5. Drug Accountability

Drug accountability is a growing challenge for investigational pharmacy and clinical supply teams as the focus shifts from centralized site control to remote patient-centered logistics. This shift places the responsibility of managing and securing IMPs onto the participant's home, posing risks such as storage issues, compliance monitoring, and maintaining the chain of custody. Returning unused medication from a participant's home to a central location for accountability can be complex, which may lead to data loss and errors. Moreover, ensuring that participants handle and administer the IMP correctly without direct in-person supervision remains a significant hurdle for teams involved in clinical trials.

Consider implementing digital logs and ePROs for patient-led reporting, along with using barcode scanning at each interaction point — from pharmacy to home delivery — to ensure a strict, automated chain of custody. Combining these tools with patient training and periodic compliance checks helps reduce reporting gaps and ensures more reliable accountability data.

6. Regulatory & Licensing Hurdles

 One of the main challenges in pharmacy regulations is the state-specific nature of these laws. Pharmacies engaged in DTP shipping are required to obtain licenses in every state where the patients reside. This can create complex compliance obstacles for shipping study drugs, as local laws may impose restrictions, especially when state regulations mandate the involvement of an in-state investigator or pharmacist. While FDA guidance, particularly under 21 CFR 312, offers a framework for shipping, it may not always override strict state laws governing pharmacy practice and dispensing authority. Third-party pharmacies must ensure they are licensed in each state where they ship medications and must conduct dispensing activities under the supervision of their own licensed pharmacist.⁶ State laws frequently mandate that pharmacists be responsible for dispensing IMPs, requiring strict adherence to local regulations and, in some instances, necessitating specific pharmacist counseling for patients. Some states, such as Tennessee, have particularly stringent protocols for dispensing IMPs, while others may provide certain exemptions, such as Missouri.⁷

Partnering with local regulatory professionals and healthcare providers familiar with site-specific pharmacy laws is key for navigating regulations. Collaborating with community pharmacies can improve dispensing processes and ensure compliance. Building relationships with FDA or EMA is helpful to streamline regulatory approvals. Early feasibility studies help identify regulatory opportunities and tackle challenges in the chosen therapeutic area, smoothing the pathway for pharmaceutical products. Mapping licensing requirements early in study start-up and maintaining a state-by-state compliance tracker can help prevent delays in DTP implementation.

7. Investigator Oversight

Principal investigators (PIs) are responsible for providing adequate supervision when delegating tasks to third-party staff such as home health nurses (HHNs). One challenge that arises is that HHNs are often not directly employed or controlled by the PI, leading to a scenario of remote supervision that can make it difficult to ensure consistent protocol compliance.

Another challenge is ensuring that third-party staff are properly trained on the protocol and the specific IPs. PIs may struggle to verify the competence of external staff that they have not personally trained. Additionally, patients who are not properly trained to self-administer, especially with complex devices or self-injection without direct in-person support from a research nurse, pose a safety risk. The FDA requires investigators to create and implement a safety monitoring plan for all DCTs to safeguard the well-being of trial participants. ⁸

To establish effective investigator oversight, implement a strong framework with digital transparency, clear delegation, and structured monitoring. Create a formal delegation of authority (DoA) defining roles/responsibilities of local pharmacy partners and healthcare providers. Use electronic source (eSource) and electronic case report form (eCRF) systems for PIs to review pharmacy documents and home visit reports remotely. Conduct mock inspections with remote staff to evaluate virtual oversight process and document retrieval workflow. Prioritize patient safety by requiring investigators to confirm patient identity at each visit and ensure proper administration of the IP. Regular check-ins between PIs and third-party providers help reinforce accountability and ensure consistent protocol adherence across decentralized teams.

The Road Ahead

The confluence of logistical, regulatory, and operational obstacles in pharmacy and supply chain management is driving a wave of innovation within the industry.

The trend toward a hybrid standard model in healthcare is transforming patient care by integrating on-site procedures with decentralized strategies for routine monitoring and medication distribution.

Technology plays a critical role in this transformation, with digital tracking and automated systems such as interactive response technology (IRT) and AI-driven forecasting tools ensuring smooth operations and uninterrupted supply chains in DTP settings.

Regulatory authorities such as the FDA and EMA are revising guidelines to support remote oversight and streamline DTP shipping processes.

This advancement is fueling significant market growth, with the clinical trial supply and logistics sector expected to double in size by 2032, reflecting substantial investment in advanced infrastructure.⁹

References:

1. Institute of Medicine (U.S.) Forum on Drug Discovery, Development, and Translation. Transforming clinical research in the United States: challenges and opportunities: workshop summary. Washington, DC: National Academies Press (US); 2010.
2. Yu, Y. B., Briggs, K. T., Taraban, M. B., Brinson, R. G., & Marino, J. P. (2021). Grand Challenges in Pharmaceutical Research Series: Ridding the Cold Chain for Biologics. Pharmaceutical research, 38(1), 3–7.
3. Heath, M., de Jong, A. J., Magorrian-Spence, S., Jin, C., van Weelij, D. R., Pagnier, L., van Rijswick, Y., Haufe, V., Lagerwaard, B., Zuidgeest, M. G. P., & Trials@Home consortium (2025). The Supply of Investigational Medicinal Product and Management of Study Materials for Decentralized Participants-Insights from the Trials@Home RADIAL Proof-of-Concept Trial. Clinical pharmacology and therapeutics, 118(5), 1079–1089.
4. Clinical supply innovation and sustainability. (2025). N-SIDE. https://www.n-side.com/en/insights/achieving-sustainability-through-clinical-supply-innovation/
5. Silva, D. J., Nelson, B. E., & Rodon, J. (2024). Decentralized Clinical Trials in Early Drug Development-A Framework Proposal. Journal of immunotherapy and precision oncology, 7(3), 190–200.
6. Navigating Legal and Regulatory Risks in Direct-to-Consumer Pharmacy Models | BakerHostetler. (2025, October 22). BakerHostetler. https://www.bakerlaw.com/insights/navigating-legal-and-regulatory-risks-in-direct-to-consumer-pharmacy-models/
7. Navigating US Regulations for Dispensing Investigational Drugs in Decentralized Clinical Trials. DIA Global Forum. https://globalforum.diaglobal.org/issue/february-2025/navigating-us-regulations-for-dispensing-investigational-drugs-in-decentralized-clinical-trials/
8. FDA Issues Draft Recommendations for Implementing Decentralized Clinical Trials. (2023, June 2). @Ebglaw. https://www.ebglaw.com/insights/publications/fda-issues-draft-recommendations-for-implementing-decentralized-clinical-trials.
9. Clinical Trial Supply & Logistics Market to Nearly Double in Size During 2025-2032: Adoption of Decentralized Clinical Trial Models Driving Demand for Localized Logistics Networks. (2025, December 24). https://www.businesswire.com/news/home/20251224490853/en/Clinical-Trial-Supply-Logistics-Market-to-Nearly-Double-in-Size-During-2025-2032-Adoption-of-Decentralized-Clinical-Trial-Models-Driving-Demand-for-Localized-Logistics-Networks---ResearchAndMarkets.com

About The Author:

Sachit Verma, MD, MBA, FACHE, FAPCR, is a board-certified healthcare leader with a diverse background in clinical research operations, administration, revenue cycle management, and compliance. Utilizing his expertise in clinical research, Dr. Verma has spearheaded systemwide initiatives to streamline trial delivery processes, uphold financial stewardship, and enhance operational efficiency by optimizing data analysis, budget management, and project life cycles. Dr. Verma has introduced and confirmed the validity of numerous important radiological signs and measurement methods on MRI, including the Angular Interface Sign, Myometrial Crack Sign, Dilated Cisterna Chyli Sign - a sign of uncompensated cirrhosis, Submucosal Interface-Dimension (I/D) Ratio, and Linear Liver Volumetry Metrics (MHP CC × MHP AP.). He possesses a diverse skill set in overseeing contracts, grants, feasibility assessments, study start-up initiatives, patient recruitment, enrollment and retention strategies, quality and performance improvement, and technology implementations. Additionally, he is a successful author, speaker, mentor, and board member who combines leadership, regulatory knowledge, and best practices to ensure the success of projects and clinical operations.