Why Clinical Supply Risk Starts With Demand Signals

By Tom Walls, principal and founder, Axon Bridge Consulting

Clinical supply shortages are often attributed to manufacturing yield, capacity, or distribution execution. In reality, many of these issues originate much earlier — embedded in enrollment assumptions that go unchallenged. In Part 1 of a two-part series, we will focus on why demand signal quality is the true root of clinical supply risk and why supply teams must move beyond passive forecast receipt.

When a Phase 2 gene therapy trial faces a supply shortage three months before critical enrollment milestones, the post-mortem points to manufacturing yield issues or distribution delays. But the real failure happened six months earlier when clinical supply accepted an enrollment forecast of "30 patients by Q3" without asking the questions that would have revealed it was aspirational rather than achievable.

Clinical supply teams routinely manage the symptoms of demand signal failure while treating the symptoms as the disease. A site activation delayed by regulatory approval becomes a "last-minute demand surge." Screen failure rates that exceed assumptions become "unexpected enrollment challenges." Protocol amendments that alter dosing requirements become "scope changes." Each is framed as an external shock rather than a predictable risk that clinical supply should have surfaced and quantified.

The distinction matters because it determines where organizations invest their improvement efforts. For most clinical-stage ATMP programs, the binding constraint is not manufacturing capacity or yield. It is the quality of the demand signal that drives material commitments, manufacturing schedules, and inventory positioning decisions. Clinical supply teams that excel do not passively receive enrollment forecasts and translate them into material requirements. They actively pull better demand signals by exploring assumptions, stress-testing forecasts, and helping clinical operations surface risks that may not be fully visible.

Improperly communicated changes to enrollment can have disastrous effects on the regulatory timeline and filings. When enrollments are understated, a supply doesn’t meet the newly discovered demand – there is invariably a two-step process to mitigate the shortage. First, there is a meeting to see if another batch can be manufactured ASAP, which may or may not be possible (it will be expensive no matter what and, usually, too late). Second, even if another batch can be expedited, there will be a meeting to split up the rest of the material across other uses, including for critical analytical development demands, which may delay filings globally. Overstated or mistimed demands will lead to expired materials and a waste of supply chain materials.

Active Demand Pull Vs. Passive Receipt

Most clinical supply organizations position themselves as service functions. Clinical operations provides enrollment forecasts, and clinical supply fulfills material requirements. This model fails in clinical settings where demand signals reflect protocol-driven enrollment assumptions layered with site activation risk, screen failure uncertainty, and protocol amendment probability.

Supply chain planning functions, especially for clinical stage ATMP firms, are often an afterthought. There may not be a dedicated supply chain leader to properly manage supply and demand in totality. CMC teams often have these processes as part of their purview, without the proper understanding of supply chain planning and management to understand the risks and trade-offs across the entire supply chain for enrollment changes. It is critical that pre-commercial stage life sciences companies engage with supply chain professionals who understand the implications of enrollment changes.

Consider a typical scenario. Clinical operations forecasts 25 patients enrolled by Q2 based on six active sites enrolling at 1.4 patients per site per month. Clinical supply calculates material requirements and commits manufacturing slots. Three months later, actual enrollment is 12 patients. The gap is attributed to "enrollment challenges," but the real issue is that clinical supply never asked: "What's driving the 1.4 patients per site per month assumption? The last trial in a similar indication achieved 0.8. What's different this time?"

High-performing clinical supply teams operate differently. They bring supply chain perspective to enrollment planning by understanding site activation timelines, historical screen failure rates by indication, protocol complexity impacts, and regulatory milestone dependencies. When clinical operations presents a forecast, clinical supply helps stress test the assumptions by asking questions that surface hidden risks and constraints.

This active demand-pull approach requires clinical supply to develop new capabilities: understanding clinical trial design, interpreting protocol amendments, assessing site activation risk, and modeling enrollment scenarios. The organizational change is equally important. Clinical supply must be positioned as a planning partner, not a demand fulfillment function. In the S&OP framework described in my previous article, this means clinical supply participates actively in the demand review meeting, helping to refine enrollment assumptions rather than simply recording them.

Supply Chain As Demand Intelligence Function

Clinical supply organizations that excel at demand dialogue deliver measurable business value: reduced material write-offs, lower expedite costs, fewer patient dosing delays. More fundamentally, they change how the organization thinks about clinical supply risk. Instead of treating supply shortages as manufacturing failures, the organization recognizes that supply risk originates in demand signal quality. This shift requires investment. Clinical supply teams need training in clinical trial design and enrollment modeling. Organizations need to reposition clinical supply from service function to planning partner. S&OP processes need to explicitly include collaborative forecast refinement and risk assessment as core activities.

The practical starting point: identify one enrollment forecast from the last 12 months that was materially wrong. Work backward to determine what assumptions were embedded. Ask which questions clinical supply could have raised to surface the forecast risk and create shared understanding earlier.

That single exercise is your entry point for active demand pull. Once established, clinical supply becomes a partner in creating better demand signals rather than a passive recipient of forecasts that may not fully account for supply chain realities.

Risk from poor demand management will cause shocks throughout the entire organization. Completely capturing demand is the first step in comprehensive supply chain management. Leaders who recognize this and invest resources to capture demand completely will optimize speed to market and best serve their patients.

In the next article, we will focus on the specific information clinical supply teams need from clinical operations — and the structured questions and decision frameworks that enable supply leaders to translate uncertain enrollment forecasts into risk-informed material commitments.

About the Author

Tom Walls is principal and founder of Axon Bridge Consulting, specializing in advanced therapy medicinal products (ATMP) supply chain planning. With over 20 years of life sciences supply chain experience, he previously served as head of supply chain planning at Spark Therapeutics and has published in Cell & Gene Therapy Insights. He is the author of A Practical Guide to ATMP Supply Chain Planning and Orchestration Excellence and developed the R3M (Risk Measurement, Monitoring, and Mitigation) framework for ATMP supply chains. Contact: tom@axonbridgeconsulting.net.