CSM Feasibility Begins With Research Strategy And Study Design

By Kaitlyn Enright, BSc, MSc, ACRP-CPI, Ph.D.

Clinical trial supply teams often spend significant time addressing issues that arose earlier in the study design process but only became apparent once clinical supply management (CSM) was engaged. Consider the following example: In a planning session for an active controlled drug trial, someone on the study team adds an additional country to accelerate enrollment, but no one verifies that the comparator is marketed there. Months later, someone has to explain a shipment stuck in customs. CSM is now managing a problem it had limited opportunity to identify or prevent. Earlier CSM involvement could have identified the comparator access issue before adding the extra country. However, once the shipment is delayed, the problem can appear to originate within clinical supply.

Typically, CSM reviews a protocol only after it's finalized, when key study design decisions have already been made and opportunities to address supply implications are limited. These decisions can range from the number of treatment arms and geographic scope to dosing schedules, visit requirements, and enrollment assumptions, each of which can affect sourcing, packaging, labeling, distribution, and regulatory considerations.^1,2

Geographical Expansion Creates Hidden Requirements

The same pattern of problems appears across study types. Consider a significant-risk medical device study in which U.S. sites are added after the device has been authorized for investigational testing in Canada.³ The study team assumes the device can ship to U.S. sites while maintaining the existing study timeline, but when CSM attempts to export the study devices, it is learned that a U.S. FDA approved investigational device exemption (IDE) is required. Although the IDE determination remains with the study sponsor and regulatory affairs, CSM is the first group to face the practical consequences of an unresolved requirement, since they execute the logistics.

Country-specific labeling requirements can create a similar downstream challenge. If Canada is added after packaging plans are set, CSM may need to revise the investigational statements on device labels to meet bilingual language requirements in both English and French.³ Each example (i.e., comparator sourcing, country-specific regulatory authorization, labeling) reflects the same core issue: study design decisions can create supply requirements that remain hidden until CSM reviews the finalized protocol or begins executing logistics.

Address Potential Supply Consequences During Protocol Development

This creates an opportunity to bring supply expertise into study planning, when it has the greatest value. The synopsis or draft protocol stage provides a practical opportunity to involve CSM before operational assumptions become fixed.^1,2 This stage can be used to resolve the supply-related questions most likely to affect study timelines and costs before protocol finalization and execution. Thus, earlier CSM involvement can prevent avoidable delays, protect study timelines and budgets, and keep supply teams focused on execution rather than remediation.

Titration Multiplies Kit Complexity

Titration schedules also help to illustrate this point. Four dose levels require manufacturing four different kit types because the drug quantity changes at each step. In a blinded study, matched placebo kits are also required at every dose level, doubling the total to eight kit types and increasing storage requirements at depots and sites.² A synopsis that briefly only states “double-blind, dose-titration design” may obscure this complexity. One site may recruit patients faster than expected and exhaust its second-level kits, while another site enrolls more slowly and has a surplus of the same kit types sitting unused and nearing expiry. No one intended a situation where some sites run out of the necessary supplies while others have a surplus and waste resources. It was a predictable outcome of design decisions made months before CSM became involved.

Late Changes Increase Cost And Study Burden

By bringing an operational assessment and supply implications into the synopsis review, study teams can reconsider design elements that add substantial time, cost, and complexity with limited scientific value before finalizing the protocol. Waiting until the study is underway makes the same adjustment far more expensive, time-consuming, and complicated. Kits already manufactured may be written off; a study amendment may be required, causing ethics re-approval across countries; sites trained on the earlier protocol version may need retraining; and participant re-consent increases site burden.²

The consequences differ by sponsor. A large device or pharmaceutical company may absorb a written-off kit run within its existing budget. A self-funded investigator-initiated study or other lean budget study may not withstand a similar process. Such considerations can determine whether the study completes successfully or fails.

Correcting this does not require expanding CSM’s role into protocol development. An early cross-functional review can give CSM an opportunity to identify operational concerns while authorship remains with the study team.

10 Questions For Early CSM Review

Clinical supply teams should consider these 10 questions while reviewing a study synopsis or draft protocol:

1. How many dose levels are required, including matched placebo kits for a blinded study?
2. Does the demand forecast account for randomization ratios, recruitment variability, titration, discontinuations, replacement kits (e.g., due to damaged kits, temperature excursions, shipment losses, expiry), and required overage?
3. Does an arm require a comparator or reference device from a third-party supplier, and is it available in every country?
4. Does an added country follow different device classification or labeling requirements?
5. Can the available shelf life support manufacturing, release, distribution, enrollment, treatment, and contingency time through the last participant’s final dose?²
6. Can depots and sites accommodate the required inventory volume, storage conditions, and resupply frequency throughout the study?²
7. Are manufacturing, testing, packaging, and batch release timelines compatible with planned country activation and first-patient-in dates?²
8. What happens if a supplier, packaging vendor, depot, or courier cannot meet the planned timeline?
9. How will delayed country or site activation affect inventory allocation, expiry risk, and resupply forecasts?
10. What kit, label, system, and inventory changes would be required if the dosing schedule, treatment duration, or visit structure changes?

Make Early Cross-Functional Review A Standard Checkpoint

These questions provide a practical framework for identifying supply risks while the study can still be shaped. They are not intended to transfer protocol ownership to CSM or allow operational preferences to override scientific objectives. Instead, they help the study team understand the logistical consequences of its decisions before committing to them. Making CSM review a standard checkpoint at the synopsis or draft protocol stage can reduce avoidable amendments, write-offs, activation delays, and supply disruptions. A short discussion early in development can prevent months of remediation later and give each study a more realistic path from protocol conception to study execution.^1,2

References:

1. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Harmonised Guideline: General Considerations for Clinical Studies E8(R1). Final version adopted October 6, 2021. Editorial correction February 4, 2022. Accessed September 2, 2026. https://database.ich.org/sites/default/files/E8-R1_Guideline_Step4_2022_0204%20(1).pdf
2. International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. ICH Harmonised Guideline: Guideline for Good Clinical Practice E6(R3). Final version adopted January 6, 2025. Accessed September 2, 2026. https://database.ich.org/sites/default/files/ICH_E6(R3)_Step4_FinalGuideline_2025_0106.pdf
3. Government of Canada. Medical Devices Regulations, SOR/98-282, Part 3, sections 79 to 88, particularly sections 80 to 83 and 86. Regulations current to June 21, 2026. Last amended June 17, 2026. Justice Laws Website. Accessed September 2, 2026. https://laws-lois.justice.gc.ca/eng/regulations/SOR-98-282/page-12.html
4. Investigational Device Exemptions, 21 CFR Part 812, particularly sections 812.2 and 812.20. Electronic Code of Federal Regulations. Current through August 31, 2026. Accessed September 2, 2026. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-H/part-812
5. U.S. Food and Drug Administration. IDE Approval Process. Updated November 25, 2020. Accessed September 2, 2026. https://www.fda.gov/medical-devices/investigational-device-exemption-ide/ide-approval-process

About The Author:

Kaitlyn Enright, BSc, MSc, ACRP-CPI, Ph.D., is a regulatory and clinical research strategist with more than 15 years of experience supporting academia, investigators, and life sciences companies across the research and development life cycle. She specializes in study design and regulatory strategy for programs reviewed by Health Canada, the U.S. FDA, and the European Medicines Agency, with a focus on dermatology, aesthetic medicine, plastic surgery, and dermatologic oncology. She serves on the scientific committees of the Global Symposium on Dermatology and Aesthetic Medicine and Nexus Conferences, contributing expertise in clinical innovation. She also advises the National Academy of Creative Arts on research governance and evidence-based learning, reviews for Q1/Q2 dermatology and aesthetic medicine journals, and mentors students and early-career investigators in research methodology and academic publishing. You can email her at info@klynical.com.