The Hidden Cost Of Convenience: Single-Use Supply Chain Vulnerabilities And Clinical Trial Continuity

By Lisa Cozza and Bill Connell, Tunnell Consulting

Single-use technologies have become the default manufacturing platform for clinical-stage biologics programs. Disposable bags, bioreactors, tubing assemblies, and filtration systems offer the flexibility and rapid changeovers that investigational product manufacturing demands, enabling CDMOs to run multiple programs through shared facilities and allowing sponsors to scale production in response to trial design without major capital investment. For clinical supply operations, the advantages are real and well understood.

But the COVID-19 pandemic exposed a structural fragility that the clinical supply community cannot afford to overlook. When global supply chains fractured, sponsors and CMOs discovered that their dependence on single-source disposable components placed investigational product supply (and, by extension, trial continuity) at serious risk. The regulatory frameworks that govern manufacturing changes compounded the problem. The lessons from that period have not been fully absorbed, and the vulnerabilities remain. The U.S. government's use of DX and DO priority designations to allocate scarce materials compounded the inequity further: on-market lifesaving products received top-priority access, while clinical trial programs, without the purchasing power or supplier relationships of commercial operations, found themselves deprioritized precisely when they could least afford it.

What The Pandemic Revealed About Investigational Supply Risk

The component shortages of 2020 and 2021 were not primarily a logistics failure; they were a strategic failure years in the making, and clinical programs felt the impact acutely. Sponsors and CDMOs had concentrated their single-use sourcing around single suppliers, drawn by pricing leverage and the operational simplicity of fewer vendor relationships. Procurement decisions driven by pricing incentives from top leadership often overruled SME recommendations for supplier diversification, compounding the concentration risk. When those suppliers hit capacity constraints, there were no qualified and/or approved alternatives to pivot to. Clinical trial timelines, which depend on reliable investigational product supply, had no buffer. Enrollment schedules slipped. Some programs were put on hold.

The regulatory dimension compounded the problem in ways that are directly relevant to clinical supply planning. In IND and early BLA submissions, many sponsors had described single-use components in granular detail, specifying not just materials of construction and performance parameters, but particular manufacturers and catalog configurations. That level of specificity, intended to demonstrate manufacturing control, became a constraint when components were unavailable. Substituting a functionally equivalent component required a regulatory amendment, and in some cases the timeline for approval of that amendment exceeded the window in which the trial could tolerate a supply disruption. The consequence was not just operational inconvenience; it was a direct threat to trial continuity.

One of us served on an industry materials task force during the pandemic and experienced this firsthand. The inability to maneuver was not an abstract regulatory inconvenience; it translated directly into manufacturing gaps that delayed dose preparation and threatened the integrity of active trials. Clinical supply chains have less slack than commercial ones: patient enrollment windows are narrow, investigational product has a finite shelf life, and a missed supply cycle can trigger a protocol deviation or require a trial hold. The cost of that lesson was steep, and its implications for clinical supply planning have not yet been fully internalized.

Second-Sourcing Is Not Optional, Even In Clinical

The fundamental corrective action is straightforward in principle, if not always in execution: when your clinical manufacturing operations depend on critical single-use components, you must have a qualified second source or a viable alternative manufacturing approach. During the pandemic, sponsors whose INDs were drafted broadly enough to permit production using traditional stainless-steel equipment were often able to pivot when single-use components became unavailable; those locked into overspecified submissions were not. Keeping IND language broad, supported by performance data rather than specific vendor designations, is the most effective supply chain insurance a clinical team can build at the filing stage. The assumption that second-sourcing is a commercial-stage concern, something to address after approval, when volumes justify the qualification investment, is a significant planning error. A supply disruption during Phase 2 or Phase 3 can have consequences just as severe as one at commercial scale: stalled enrollment, protocol violations, or a forced trial hold can cost as much time and money as a post-approval shortage and, in some cases, more. Supply chain resilience planning must begin when clinical manufacturing begins.

The qualification burden is real and should be explicitly scoped into clinical development timelines and budgets. Testing for extractables and leachables is not a simple matter of substituting one plastic bag for another and, for investigational products where the patient population may be small and the therapeutic window less well characterized, the stakes of an inadequate leachables assessment are particularly high. Formal extractables and leachables studies are not required until a final process is established at Phase 3, but early-stage clinical teams should conduct high-level extractables screening on drug substance contact materials to identify gross concerns before they are compounded by a supplier switch under pressure. The polymer sourcing, manufacturing geography, and specific processing aids used by a given supplier can all affect the extractable profile of a component, and qualifying a replacement requires thoughtful experimental design and analytical work that clinical teams should scope explicitly, not as an afterthought.

Global sourcing introduces additional complexity that clinical supply planners must account for. Component manufacturing that appears standardized on paper may vary in practice across a supplier's facilities in North America, Europe, and Asia. For clinical programs with global trial sites, the risk of site-to-site variation in component performance is not theoretical; it can affect product consistency in ways that complicate regulatory submissions and create questions about comparability across trial cohorts. Qualification testing must confirm genuine equivalence, not just nominal membership in the same product family. Larger organizations typically have material review boards that evaluate supplier-provided equivalence data; smaller innovator companies at the Phase 1 and IND stage often lack those systems and may accept a supplier's equivalence claim without independent verification, an oversight that can surface as a comparability problem in later-phase submissions.

Smarter IND Filing Strategies For Clinical Supply Flexibility

A critical lesson from the pandemic is that IND filing strategy must be designed with supply chain contingency in mind from the start. For clinical supply teams, this means actively reconsidering the default toward overspecifying manufacturing components in regulatory submissions, a practice that can inadvertently lock trials into configurations that cannot be easily modified when supply disruptions occur.

The appropriate level of description for a single-use component in an IND or IMPD is typically the materials of construction, the intended function, and the general design characteristics, not the specific manufacturer, size, or catalog number. Where a particular material is genuinely critical to product quality or patient safety, it may be appropriate to identify the manufacturer; in those cases, the filing should name two qualified sources, not one. Critically, IND filing strategy and clinical supply chain strategy must be developed in parallel. A filing team making component specification decisions without input from supply chain and sourcing should be a red flag in any program review.

This approach requires an informed discipline with a deliberate resistance to the pull of overspecification. FDA reviewers evaluating IND amendments do not expect, and sophisticated clinical reviewers do not want, submissions that lock clinical manufacturing into configurations that were appropriate at the time of filing but cannot adapt as the trial progresses. Describing function and performance parameters rather than specific vendors preserves the operational flexibility that clinical supply demands across the arc of a multiyear trial, while giving regulators the assurance they need about product quality and patient safety.

Technology Selection: Rethinking The Clinical Default

Single-use technologies are not the right answer for every clinical manufacturing scenario, and their dominance as the default platform for investigational biologics deserves scrutiny. Clinical supply planners tend to select single-use systems early in development because they minimize capital commitment and simplify changeover between programs, both valid considerations. But that selection is not always revisited as programs advance. This calculus is also informed by the realities of clinical attrition: roughly 90% of Phase 1 programs never reach commercial approval, which means the decision to invest heavily in a permanent single-use infrastructure at the outset is often premature. Preserving flexibility, including the flexibility to switch technology platforms as a program advances, is itself a form of supply chain resilience. For late-stage trials running multiple batches per year at scales approaching commercial volumes, the economics of continued single-use dependence, compounded by supply chain fragility, warrant an honest reassessment. The technology choice made at Phase 1 is not necessarily the right technology choice for a Phase 3 trial supplying thousands of patients across global sites.

There are also operational handling dimensions that are easy to underestimate, particularly as clinical programs scale up. Single-use assemblies that are manageable at small clinical volumes become physically unwieldy at late-phase scales. Connections that work reliably at 200 liters become operationally challenging at 2,000 liters. Early scale-up implementations have frequently encountered failures at fold lines when bags were unpacked; these failures are caused not by process design errors but by the physical realities of handling large plastic assemblies in a manufacturing environment. Disposal of used materials and the costs of large-scale setups can also weigh significantly on COGS, an underappreciated offset to single-use's perceived economic advantages. These human factors must be designed into the manufacturing process and training program before they cause a batch failure that delays critical trial supply.

What Industry Data Is Telling Clinical Supply Teams

The structural vulnerability is now well documented, and the data carries direct implications for clinical supply planning. Cytiva's 2025 Global Biopharma Index (surveying 1,250 executives across 22 countries) found that more than 75% of biopharma leaders expect geopolitical volatility to significantly reshape their sourcing strategies. Nearly half reported difficulty finding high-quality CDMO and CRO partners capable of supporting their programs, a challenge that clinical supply teams trying to qualify backup manufacturers will recognize immediately. Manufacturing agility was among the lowest-scoring pillars in the survey, with one in four executives saying their organization would be slow or very slow to scale production of key modalities including cell and gene therapies and mRNA vaccines, precisely the modalities that account for a large share of current clinical-stage pipelines. The overall industry resilience score declined for the third consecutive survey period, falling to 5.96 out of 10 in 2025 from 6.60 in 2021.

The supply dependency picture is equally stark, and it extends well into clinical-stage operations. A February 2025 member survey by the Biotechnology Innovation Organization (BIO) found that 90% of U.S. biotech companies rely on imported components for a majority of their FDA-approved products, a figure that reflects sourcing patterns established during clinical development and carried forward. With 94% of respondents forecasting increased manufacturing costs from potential tariffs on EU imports alone, the exposure is embedded in the bill of materials for investigational programs as much as commercial ones. The Pharma and Biopharma Outsourcing Association (PBOA) has highlighted the clinical supply dimension directly: a surge demand scenario of the kind seen in 2020–2021, affecting single-use components and tubing, would hit clinical manufacturing capacity before commercial, because clinical programs have less purchasing power and fewer supplier relationships to draw on. The industry came very close to the edge. There is no guarantee the next disruption will offer more warning.

ISPE, which has operated a Drug Shortages Initiative since 2012 in collaboration with the Parenteral Drug Association, EFPIA, and other bodies, has consistently identified the same root causes across shortage events: lack of supply chain redundancy, single-source dependencies for critical materials, and quality system constraints that prevent rapid pivot to alternatives. The ISPE Drug Shortages Prevention Plan identifies second-sourcing of critical raw materials and components as a foundational element of resilient supply, not an advanced capability reserved for commercial operations but a baseline that should be established in clinical development. For clinical supply leaders, this framing matters: the planning decisions made during Phase 1 and Phase 2 either build that baseline or undermine it, and recovering from an entrenched single-source dependency under time pressure is far more costly than building redundancy from the outset.

Building Clinical Supply Chains That Can Withstand Disruption

Clinical supply chains will face further disruptions from geopolitical events, natural disasters, pandemics, or the more routine but equally disruptive realities of supplier consolidation and capacity constraints. The question for clinical supply leaders, trial sponsors, and their CDMO partners is whether those disruptions will find them prepared or scrambling. For clinical programs in particular, scrambling has a direct cost: a delayed trial is a delayed development timeline, with compounding consequences for regulatory milestones, competitive position, and patients waiting for access to investigational therapies.

Preparedness in clinical supply requires treating resilience as a design requirement built into the trial supply plan from the outset, not a contingency addressed after the primary supply chain is already in place. It means second-sourcing critical single-use components before you need them, qualifying alternatives while time and resources permit rather than under the pressure of an active trial. It means structuring IND submissions to preserve flexibility, not lock in configurations. It means building supplier relationships deep enough that when capacity is constrained, clinical programs are the customers that suppliers prioritize, not the ones they deprioritize because the volumes are smaller.

It also means being honest with development leadership about the cost and timeline implications of resilient clinical supply design. Qualification of a second component supplier during Phase 2 requires budget and analytical resources that may not be in the original clinical plan. Those investments are real. They compare significantly better, however, with the cost of a supply disruption that puts an active trial on hold, triggers a protocol amendment, or forces enrollment delays that push a key readout milestone into the next fiscal year.

The pandemic was an extreme case, but the vulnerabilities it exposed were structural, not anomalous, and they are as present in clinical supply chains as in commercial ones. Addressing them is ongoing work and, for clinical supply professionals, it begins with a clear-eyed acknowledgment: investigational product supply is not simply a manufacturing problem. It is a trial continuity problem. And the decisions that determine whether a trial can weather a supply disruption are made in development planning, not in a crisis.

About The Authors:

Lisa Cozza and Bill Connell are principals at Tunnell Consulting, specializing in outsourced manufacturing strategy, supply chain risk management, and CDMO relationship optimization for biopharmaceutical companies.