The Firefighting Era Of Clinical Supply Chain Is Over. Here's What Replaces It

By Nirav Shah, RPh., director, clinical supply chains, SK Life Science, Inc.

In 2025, pharmaceutical clinical supply chains reached an inflection point. Strategies that proved effective during the pandemic - such as buffer stock expansion and reactive mitigation - are becoming increasingly misaligned with emerging regulatory, economic, and sustainability constraints.

Three forces converged in 2025-2026 to accelerate this shift: regulatory acceleration (EU CTR finalized January 31, 2025 ¹; UK SI 2025/538 goes live April 28, 2026 ²), therapeutic complexity (radiopharmaceuticals exploded to a projected $42 billion market by 2033 ³), and a reckoning with carbon footprint that has moved from "nice to have" to "investor mandate."

But here's what most conferences aren't discussing yet: the solutions aren't just optimized versions of what we've been doing. They're fundamentally different paradigms.

Digital Twins: Simulating Before Executing

In 2025, digital twin technology migrated from manufacturing floors into clinical supply chain planning. Unlike traditional forecasting models that predict outcomes, digital twins create virtual replicas of the entire supply chain - manufacturing, packaging, depots, sites, patient enrollment - that update in real-time and allow sponsors to run thousands of "what-if" scenarios before committing resources.

BSH Home Appliances Group demonstrated the power in late 2025, using digital twins across 188 warehouses globally to simulate logistics scenarios before making structural decisions.⁴ Pharmaceutical applications are just emerging, but the implications are staggering.

Consider a Phase 3 oncology trial. Traditional planning: build a forecast, add 30-40% overage, manufacture, ship, hope. Digital twin planning: create a virtual replica of the trial, simulate 10,000 enrollment patterns using Monte Carlo techniques, test shelf-life scenarios (what if we extend from 10 to 12 months?), model country-specific lead time impacts, identify the exact overage needed for 95% confidence - then manufacture precisely that amount.

Early adopters report 20-30% waste reduction not from better forecasting, but from understanding the system's behavior before physical execution.⁵  The difference? Traditional forecasting asks, "how much will we need?" Digital twins ask, "how does this system respond to uncertainty?"

The Direct-To-Patient Paradox: When Patient-Centricity Conflicts With Sustainability

Decentralized clinical trials (DCTs) grew from $9.87 billion in 2025 to a projected $15.45 billion by 2032.⁶  The FDA finalized guidance in 2024.⁷  The regulatory barriers fell. And then sponsors discovered the sustainability paradox.

DCTs eliminate patient travel to centralized sites - a clear carbon win. But they replace it with hundreds or thousands of individual home shipments, each requiring specialized packaging, cold chain logistics, and courier services. A January 2026 analysis showed that while DCTs reduce site-level emissions, the total carbon footprint often increases 40-60% compared to traditional site-based models.⁸

The Sustainable Healthcare Coalition launched the Industry Low-Carbon Clinical Trials (iLCCT) consortium in 2025 with a carbon calculator specifically for clinical trials.⁹ Early data revealed uncomfortable realities: a representative Phase 3 trial generates 1,400-2,500 tonnes CO2e.¹⁰  Direct-to-patient models, despite reducing patient travel emissions, often increase total trial footprint through logistics intensification.

The leading-edge response isn't abandoning DCTs - it's redesigning them. Hybrid models with regional "micro-hubs" (patients travel 15 minutes instead of 2 hours, drug ships in consolidated batches instead of individual parcels). Pharmacy-led distribution networks that leverage existing last-mile infrastructure rather than building parallel courier systems. On-demand packaging that eliminates pre-manufactured buffer stock.

Speaking of which...

On-Demand Packaging: The Death Of "Pre-Kit and Pray"

Here's a statistic that warrants attention: 25-50% of all packaged and labeled clinical supplies are never used.¹¹  Even with sophisticated IRT systems and dynamic forecasting, we're still manufacturing units that expire at sites or in depots.

The breakthrough in late 2025 wasn't better forecasting - it was eliminating the forecast entirely for certain trial elements. On-demand packaging and labeling (sometimes called "just-in-time P&L") waits until the patient randomizes, then manufactures the specific kit configuration needed within 48-72 hours.

This isn't theoretical. Multiple CMOs now offer this as standard service. The economics work because eliminated waste (20-60% reduction in total manufacturing) offsets the premium for rapid turnaround.¹²  The sustainability impact is measurable: no pre-manufactured inventory means no expired units, no destruction costs, no transport of materials that will never reach patients.

The constraint? Product shelf life must exceed the P&L lead time plus shipment window. For stable small molecules, it's viable. For radiopharmaceuticals with 6-day shelf lives, it's mandatory (and already operational). For everything in between, sponsors are recalculating the "pre-make vs. on-demand" threshold.

Radiopharmaceuticals: Not A Niche, A Blueprint

The radiopharmaceutical sector hit an inflection point in 2025. Thirteen new actinium-225 trials posted in nine months - matching the previous three years combined.¹³  Novartis generated $2 billion from LUTATHERA® and PLUVICTO®.¹⁴  The market is no longer emerging; it's arrived.

But here's what matters for everyone else: radiopharmaceuticals can't use traditional supply chain strategies. No buffer stock (product decays). No depot inventory (shelf life measured in days). No second chances (one manufacturing batch = one patient dose). They require precision that traditional supply chains treat as optional.

The revelation? When companies are forced to operate with radiopharmaceutical-level precision for those programs, they start asking: why are we tolerating 60% waste in our stable small molecule trials?

The operational discipline radiopharmaceuticals demand - real-time manufacturing synchronization with patient scheduling, zero-inventory models, cold chain integrity with minute-level monitoring, backup supplier qualification - is becoming the standard ambitious sponsors apply everywhere.

The Carbon Accounting Mandate: From Disclosure To Design

AstraZeneca committed to net-zero for Scope 1 and 2 emissions by 2025 and supply chain (Scope 3) by 2030.¹⁵  Seven global pharma companies (AstraZeneca, GSK, Merck KGaA, Novo Nordisk, Roche, Samsung Biologics, Sanofi) jointly committed to emission reduction in Phase 2 and 3 trials.¹⁶

This isn't greenwashing. It's investor driven. ESG reporting now includes clinical trial carbon footprints. The iLCCT calculator provides standardized methodology. But measurement is only step one.

The shift in late 2025 was from carbon accounting to carbon-informed design. Protocol teams now receive carbon impact projections during feasibility. Supply chain presents scenarios: "Option A: traditional depot model, 2,400 tonnes CO2e. Option B: regional micro-hubs with on-demand packaging, 1,600 tonnes CO2e, 22% cost reduction."

When sustainability aligns with economics, adoption accelerates. AstraZeneca's Phase 3 trials analysis showed that the primary carbon drivers aren't mysterious - they're wasteful: overproduction of unused kits, inefficient shipping patterns, protocol amendments that obsolete inventory.¹⁷  The same factors that cost money generate emissions.

Circular Economy Models: Reverse Logistics As Competitive Advantage

The biopharmaceutical industry generates an estimated 94,000-200,000 metric tons of plastic waste annually - less than 1% of global plastic waste but representing significant volume given the industry's reliance on single-use materials for sterility and safety.¹⁸ Approximately half of this waste is single-use packaging. In 2025-2026, reverse logistics transitioned from "compliance burden" to "margin opportunity."

Leading CMOs now offer packaging asset return programs: temperature-controlled shippers, validated containers, specialized insulation - all tracked, returned, reconditioned, and redeployed. The savings compound: reduced material procurement, eliminated disposal costs, lowered carbon footprint, and in some cases, packaging becomes a revenue stream rather than a cost center.

Latin American medtech companies pioneered "micro-circular" models in 2025: hospitals recycle medical plastic waste (HDPE bottle caps, PVC IV bags) into 3D printing filament for anatomical models and device prototypes.¹⁹  This creates self-sustaining local manufacturing ecosystems that reduce both import dependence and carbon footprint.

The message for clinical supply? Asset recovery isn't just environmental stewardship - it's operational resilience.

The Uncomfortable Truth About Decentralization

DCTs promised democratized access and reduced burden. The reality is more complex. A 2025 study across respiratory and rare diseases found significant implementation gaps: investigators lacking full medical records, inability to perform physical exams remotely, difficulty ensuring patient comprehension of digital instructions, and low engagement without in-person touchpoints.²⁰

The mature perspective emerging in 2026: DCTs aren't replacements for traditional trials - they're additional tools requiring different supply chain architectures. Home nursing visits need different logistics than depot-to-site. Electronic consent needs different tracking than paper. Wearable devices need different distribution than investigational drugs.

The winners will be organizations that build modular supply chain capabilities - deployable in site-based, home-based, or hybrid configurations - rather than forcing every trial into one operational model.

The Path Forward

The supply chains succeeding in 2026 aren't just optimized - they're reimagined. They simulate before executing. They manufacture on-demand rather than forecast-and-hope. They design for carbon impact from protocol inception. They recover and redeploy assets rather than dispose and repurchase.

Most importantly, they recognize that the principles forcing precision in radiopharmaceuticals - zero waste tolerance, real-time synchronization, backup planning as standard practice - apply universally. The question is whether organizations are willing to implement them proactively rather than reactively.

Right drug, right patient, right time - but now, also right carbon footprint, right waste profile, and right resilience model. The era of heroic firefighting has given way to precision, simulation, and intentional design.

The organizations still running 2019 playbooks face mounting pressure from regulators, investors, and competitive forces driving the industry toward more sustainable and efficient operations.

References:

1. European Medicines Agency. Clinical Trials Information System (CTIS). Transition period ended 31 January 2025. https://www.ema.europa.eu/en/human-regulatory-overview/research-development/clinical-trials-human-medicines
2. U.K. Medicines and Healthcare products Regulatory Agency. The Human Medicines (Amendment) Regulations 2025 (SI 2025/538). Coming into force 28 April 2026. https://www.legislation.gov.uk/uksi/2025/538
3. DelveInsight. Radiopharmaceuticals Market Forecast to reach $42 billion by 2033. https://www.delveinsight.com/blog/radiopharmaceuticals-market
4. Siemens Digital Industries Software. Designing Resilient Supply Chains with a Digital Twin: Insights from BSH Home Appliances Group. January 2026. https://blogs.sw.siemens.com/digital-logistics/2026/01/27/designing-resilient-supply-chains-with-a-digital-twin-insights-from-bsh-home-appliances-group/
5. PSC Software. Digital Twin Technology: Unlocking Pharma & Biopharma Potential. September 2025. https://pscsoftware.com/digital-twin-technology-pharma-biopharma/
6. Transpire Insight. Decentralized Clinical Trials Market Size & Share by 2033. https://www.transpireinsight.com/press-details/decentralized-clinical-trials-market
7. U.S. Food and Drug Administration. Conducting Clinical Trials With Decentralized Elements. Final Guidance. December 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/conducting-clinical-trials-decentralized-elements
8. Applied Clinical Trials. Introducing Sustainability into the Clinical Trial Supply Chain. January 2026. https://www.appliedclinicaltrialsonline.com/view/introducing-sustainability-into-the-clinical-trial-supply-chain
9. Drug Information Association Global Forum. Sustainable Clinical Trials: Reducing Greenhouse Gas Emissions. March 2025. https://globalforum.diaglobal.org/issue/march-2025/sustainable-clinical-trials-reducing-greenhouse-gas-emissions/
10. Carbon footprint of industry-sponsored late-stage clinical trials. BMJ Open Quality 2023. https://bmjopenquality.bmj.com/content/12/3/e002274
11. Clinigen. Sustainability in Clinical Trial Supply Chains. 2023. https://www.clinigengroup.com/insight/insights/2023/sustainability-in-clinical-trial-supply-chains-the-shift-from-an-ideal-to-an-economic-imperative/
12. Clinigen. Sustainability in Clinical Trial Supply Chains: Risk-Based Optimization. 2023. https://www.clinigengroup.com/insight/insights/2023/sustainability-in-clinical-trial-supply-chains-the-shift-from-an-ideal-to-an-economic-imperative/
13. BioSpace. Radiopharmaceutical Supply Chain Analysis. 2025. https://www.biospace.com (search: actinium-225 clinical trials 2025)
14. Novartis Financial Reports. Lutathera and Pluvicto Revenue 2025. https://www.novartis.com/investors/financial-data
15. Top Trends in Pharmaceutical Sustainability for 2025. Bio-Focus. https://www.bio-focus.co.uk/sustainability/top-trends-in-pharmaceutical-sustainability-for-2025
16. Top Trends in Pharmaceutical Sustainability for 2025. Bio-Focus. https://www.bio-focus.co.uk/sustainability/top-trends-in-pharmaceutical-sustainability-for-2025
17. Carbon footprint of industry-sponsored late-stage clinical trials. BMJ Open Quality 2023. https://bmjopenquality.bmj.com/content/12/3/e002274
18. Pharmaceutical Commerce. Medicine for the Planet: Building a Sustainable Legacy in Pharma Supply Chains. February 2026. https://www.pharmaceuticalcommerce.com/view/medicine-for-the-planet-building-a-sustainable-legacy-in-pharma-supply-chains
19. 3DPrint.com. Sustainability Meets Speed: How Latin America's Medtech Industry is Reshaping Global Clinical Trials. December 2025. https://3dprint.com/322497/sustainability-meets-speed-how-latin-americas-medtech-industry-is-reshaping-global-clinical-trials/
20. Minetti M, Topole E, Rondinone I, et al. Opportunities in Development of Patient-Centric and Decentralized Clinical Trials: Insights from Patients and Healthcare Professionals in Respiratory and Rare Diseases. Therapeutic Innovation & Regulatory Science. 2025;59:1219-1237. https://link.springer.com/article/10.1007/s43441-025-00819-6

About The Author:

Nirav Shah, RPh, is director of clinical supply chain at SK Life Sciences, bringing over 20 years of experience designing end-to-end supply networks for global clinical trials across biotech and pharmaceutical companies. His portfolio spans oncology, gene therapies, and radiopharmaceuticals, where he has led supply chain transformations addressing complex logistics challenges including short shelf-life products and direct-to-patient distribution models. Previously at BioMarin, Regeneron, and Covance, Shah consistently achieved 99.5%+ on-time delivery rates across 200+ global sites while driving cost optimization and enterprise IRT implementations. A registered pharmacist, he specializes in translating therapeutic complexity into operational precision and sustainable supply chain design.