What's Breaking In Clinical Trial Supply — And How To Fix It

By Ray Forslund, Ph.D., MBA, SVP, head of product development, Syner-G

Clinical trial supply rarely receives attention until it fails but is a critical piece of the puzzle. If a shipment stalls at customs, a comparator drug cannot be sourced quick enough, a packaging error halts distribution, or a temperature excursion invalidates an entire batch in transit, then entire clinical program pauses while teams scramble to respond. These types of failures are not rare events but rather are structural outcomes of how many organizations plan clinical trials. Clinical supply is frequently treated as an operational function rather than a strategic discipline, and by the time supply experts are deeply involved, protocol design, enrollment assumptions, and global site strategies are already fixed, constraining these experts to reactions rather than releasing their expertise for proactive risk mitigation.

When those clinical team decisions collide with manufacturing, logistics, regulatory requirements, and real-world enrollment behavior, the system breaks down. Understanding what consistently causes these clinical supply failures provides a path to fixing them. The problems are well known: lack of collaboration, weak forecasting models, comparator sourcing risk, packaging complexity, cold chain vulnerability, poorly integrated IRT systems, global distribution friction, and regulatory misalignment.

It Starts With Partnership: Collaboration Is Key

Clinical supply failures are almost inevitable when collaboration breaks down, because supply sits right at the intersection of multiple functions (clinical, manufacturing, QA, regulatory, logistics). When these functions operate in silos, forecasting becomes inaccurate due to misaligned enrollment assumptions and poor communication of site activation timelines, leading to drug shortages or excess inventory. Production planning suffers from missed manufacturing slots and inadequate contingency strategies, while ineffective inventory management results in poor visibility across depots and delayed resupply. Labeling and packaging errors may occur when cross-functional reviews are lacking, and regulatory or import/export delays arise from misaligned documentation and release timing. Additionally, the absence of shared risk management and clear escalation pathways allows minor issues to escalate into major disruptions. Vendor misalignment, particularly with CROs and interactive response technology (IRT) systems, further compounds these challenges, and communication gaps during protocol changes can quickly render supply strategies obsolete. Ultimately, without integrated data, real-time communication, and cross-functional alignment, clinical supply management becomes reactive rather than proactive, increasing the risk of missed patient dosing, protocol deviations, higher costs, and potential impacts to trial integrity.

Forecasting Future Use: Where Supply Problems Can Begin

Forecasting future consumption or use of the clinical drug is the foundation of clinical supply planning. It is also where many supply failures originate, for a number of reasons: Enrollment timelines rarely behave as predicted; protocol amendments alter dosing schedules; dropout rates fluctuate. Each variable shifts the amount of drug required to run the trial overall and at each location. Because these inputs change constantly, forecasting use demand requires many assumptions and remains inherently uncertain.

Poor demand forecasting creates two predictable outcomes: shortages that delay studies or overproduction that generates waste. Both outcomes occur regularly across studies of all sizes and in all therapeutic targets. Demand planning failures are a recognized driver of supply disruptions because enrollment variability and protocol changes make accurate predictions difficult.¹ The scale of the waste is substantial. Studies suggest that as much as 50%–70% of drug product manufactured for clinical trials never reaches patients. The unused inventory, often called clinical finished goods waste, represents a major cost driver for development programs² and is a major issue for sustainability initiatives.

Forecasting problems persist because many organizations treat demand planning as a one‑time calculation. In reality, forecasts must evolve throughout the trial. The organizations that manage supply effectively treat forecasting as a dynamic model tied directly to enrollment data and randomization activity. Scenario planning is updated continuously, allowing supply teams to adjust manufacturing or distribution before shortages occur.

Comparator Sourcing: A Growing Operational Risk

Comparator sourcing is one of the least predictable components of clinical supply, as sponsors often assume commercial products can be easily procured once the protocol is finalized. In practice, comparator drugs are frequently unavailable in certain markets, distributed in incompatible packaging formats, or restricted from resale across borders, complicating procurement. Global trials amplify the challenge, as different countries require locally sourced comparators that adhere to various compendial monographs, and supply availability can change quickly when shortages occur in commercial markets. Recent industry analyses highlight increasing operational complexity around comparator procurement as clinical trials expand across more geographies.³

Addressing the increasing operational complexity of comparator procurement in clinical trials requires a proactive, integrated strategy built on early planning, strong cross-functional alignment, and supply chain flexibility. This begins with engaging clinical,

regulatory, supply chain, and quality stakeholders early in study design to define a clear comparator sourcing strategy that accounts for country-specific requirements, labeling, and import/export constraints. Establishing strategic partnerships with global and regional suppliers helps mitigate availability risks and provides alternative sourcing options when market shortages or allocation issues arise. Implementing robust demand forecasting and scenario planning while incorporating enrollment variability, country activation timelines, and buffer strategies ensures more reliable supply continuity. Standardizing processes for packaging, labeling, and blinding, where feasible, can reduce complexity, while leveraging a centralized IRT system improves visibility across depots and enables timely resupply decisions. Additionally, maintaining strict quality oversight, including verification of product authenticity and chain of custody, is critical. Finally, defining clear governance, communication pathways, and escalation processes allows teams to identify and mitigate risks early. This ensures comparator supply remains aligned with study needs therefore minimizing delays, cost overruns, and risks to trial integrity.

Packaging: Where Operational Complexity Multiplies

Packaging is one of the most operationally complex elements of clinical trial supply. Each participating country introduces new label requirements, translation rules, regulatory text, and blinding constraints. Protocol amendments frequently require relabeling or repackaging campaigns mid‑study, and even minor errors in labeling or kit configuration can halt distribution across multiple depots. Packaging challenges often arise because packaging design begins late in trial planning, sometimes with modifications to geographical language requirements. Clinical teams finalize protocols and country lists before supply teams assess packaging feasibility. Integrating packaging strategy into early development planning reduces this risk. Kit design, labeling strategies, and country-specific regulatory requirements should be evaluated during trial design rather than after manufacturing begins.

Cold Chain: The Margin For Error Is Shrinking

The growth of biologics, cell therapies, and temperature‑sensitive medicines has increased reliance on cold chain logistics. Cold chain distribution now represents a dominant segment of the clinical trial logistics market, accounting for more than 60% of temperature‑controlled shipments in some analyses.⁵

Maintaining temperature stability across global shipping routes requires validated containers, real‑time monitoring, and carefully controlled handling procedures, adding to the complexity of shipping. Even small temperature excursions can compromise product stability and result in wasted product, effort, and attention. Global trials multiply the risk because shipments cross multiple climate zones, customs checkpoints, and logistics providers, each with their own risk for delay or impact on temperature maintenance.

Cold chain failures typically occur not because of a single mistake but because of weak visibility across the supply network. Unexpected delays at customs or as shipments reroute due to weather or geopolitical events can slow delivery of time-sensitive shipments. Sometimes the shipment enters the chaos of a fragile transportation network recovering from a large weather event coinciding with customs disputes between the originating country and the receiving country, resulting in shipment durations outside of the validation temperature control of the shipment box. Organizations that manage cold chain risk successfully implement real‑time monitoring and predictive alerts, instead of discovering excursions after shipment delivery. With new packaging options for real-time tracking, teams can detect risks during transit and intervene before product integrity is compromised.

IRT Systems: The Digital Backbone Of Clinical Supply

IRT systems, a broad term that often includes RTSM/IXRS systems, are custom-built programs that coordinate patient randomization and data collection, as well as drug allocation and randomization (dose level, active or placebo, comparator). As a consequence, these programs control how investigational product moves through the supply network and help track and monitor inventory at both depots and sites, becoming a crucial tool for forecasting supply levels. When configured correctly, IRT systems automate resupply triggers, manage depot balancing, and reduce the need for manual forecasting adjustments.

An additional, often overlooked aspect of IRT use in investigational studies is the timeline and cost to build it. Depending on vendor and study complexity and size, build times can take up to 12 weeks. As with all products, timelines can be shortened for a higher cost, with systems costing upward of $400,000 to bring online; this represents large teams of experts who validate and verify the program for proper drug dispensation and tracking. Sponsors often neglect the build duration when outlining initial supply plans, but the IRT serves as a fully auditable repository of transit records (and in the case of cold chain products, the temperature log) that is invaluable when completing the trial master file at study completion. And due to its integration with EDC and patient data, it can assist with data cuts and interim analyses.

Despite this central role, IRT systems are often implemented after supply strategies are already defined. When forecasting models and supply plans are built outside the IRT framework, the result is a misalignment between drug allocation algorithms and physical inventory movement. Late implementation of an IRT, or a switch mid-study, often results in excess investigational drug at sites and leads to significant waste. Supply strategies need to

account for 20%-30% additional investigational drug because of this mismatch, to prevent trial stoppage due to no inventory (stockout). Best practices and industry guidance emphasize the need to align forecasting and supply algorithms directly with IRT logic to prevent stockouts and excess inventory,⁶ but this is often not achieved until well into the study.

Global Distribution: Complexity Is Now Standard

Modern clinical trials operate across dozens of countries. Each location introduces regulatory requirements, customs documentation, depot logistics, and shipping constraints. The logistical burden continues to grow as decentralized trials expand. Direct‑to‑patient distribution models, regional depots, and hybrid site structures introduce additional coordination challenges. Global clinical trial supply networks are expanding rapidly. The clinical trial supply and logistics market was valued at roughly $4.3 billion in 2024 and continues to grow as trials become more global and operationally complex.⁷ Managing this complexity requires resilient distribution networks rather than centralized supply hubs. Regional depots, localized packaging strategies, and contingency shipping routes help prevent single‑point failures in global supply systems.

Regulatory Coordination: The Overlooked Constraint

Regulatory requirements also shape how clinical supplies move across borders. Each country maintains unique rules governing labeling, documentation, import permits, and product handling. If regulatory planning and supply planning occur independently, shipments often become stuck in customs or require last‑minute relabeling. The operational solution is simple but often ignored: regulatory and supply teams must plan together. Label design, comparator sourcing, and packaging configuration all depend on regulatory approval timelines. Aligning these activities early prevents delays once the trial begins.

Leadership Alignment: The Real Fix

Most clinical supply disruptions are not caused by technical limitations. They occur because supply expertise is introduced too late in the development process. Protocol design, site selection, and enrollment assumptions frequently occur without meaningful input from supply leaders. By the time supply teams evaluate the plan, operational risks are already embedded in the trial architecture. Effective organizations reverse this sequence. Supply strategy becomes part of early development planning rather than a downstream operational task. Clinical supply leaders participate in protocol feasibility discussions,

comparator planning, packaging strategy, and global distribution design. This early integration identifies operational risks before they disrupt timelines.

Conclusion

Clinical trial supply will always involve uncertainty. Enrollment rates fluctuate, logistics networks encounter disruptions, and regulatory requirements evolve. The objective is not to eliminate uncertainty but to design supply systems that can absorb it.

Organizations that treat clinical supply as a strategic discipline consistently outperform those that treat it as an operational afterthought. Dynamic forecasting models, early comparator planning, integrated packaging strategies, robust cold chain monitoring, aligned IRT systems, resilient distribution networks, and coordinated regulatory planning create supply systems capable of supporting complex global trials. When supply planning is integrated early and managed dynamically, trials run faster, waste decreases, and patients receive treatment without interruption. When it is not, the entire development program slows down.

References:

1. Medmarc. 2025 Supply Chain Challenges for the Life Sciences Industry. https://medmarc.com/life-sciences-news-and-resources/publications/2025-supply-chain-challenges-for-the-life-sciences-industry
2. Palm, G. Mapping Waste in a Clinical Supply Chain, Chalmers University. https://www.clinicaltrialsarena.com/features/sustainable-clinical-trial-supply-chains/
3. Clinical Trials Arena. Sustainable Clinical Trial Supply Chains.
4. Clinical Supply Leader. Trends Shaping Clinical Trial Supply (2025). https://www.clinicalsupplyleader.com/doc/the-trends-shaping-clinical-trial-supply-in-and-beyond-0001
5. Mordor Intelligence. Clinical Trial Logistics Market Analysis (2026).https://www.mordorintelligence.com/industry-reports/clinical-trial-logistics-market
6. Grand View Research. Clinical Trial Supply and Logistics Market Report (2024). https://www.grandviewresearch.com/industry-analysis/us-clinical-trials-supply-logistics-market-report
7. Applied Clinical Trials. Meeting the Clinical Supply Challenge with IRT. https://www.appliedclinicaltrialsonline.com/view/meeting-clinical-supply-challenge-irt\

About The Author:

Ray Forslund has over 15 years of experience in the industry working for both pharmaceutical and CRO/CMO companies. As a member of the Syner-G Executive Leadership team, he leads the CMC Development and Project Management business unit. His team is responsible for providing scientific solutions for drug development programs, including identifying and managing CRO/CMO/CDMOs for Syner-G’s clients to support drug substance, drug product, and analytical development activities in biologics, small molecules, and peptides.