What 21 CFR Part 11 Taught Us About Partial Compliance — and Why the Same Lessons Apply to ICH E6(R3) Today

When 21 CFR Part 11 was introduced, it promised to modernize how sponsors handle electronic records and signatures. But what followed was a period of confusion and overreach: sponsors and vendors alike rushed to claim compliance, often by focusing on narrow parts of the regulatory requirements without considering the integrity of the whole system. The FDA eventually clarified its enforcement priorities, making it clear that partial compliance is not enough. Owning one compliant tool in a disconnected ecosystem doesn’t make your entire system compliant.

Fast forward to today, and a similar pattern is emerging with ICH E6(R3).

ICH E6(R3): Raising the bar for biospecimen management

ICH E6(R3) is reshaping expectations for how clinical trials are conducted, with a sharper focus on risk-based quality, data governance, and sponsor oversight. One area that has flown under the radar for many sponsors? Biospecimen management.

While sponsors may assume their current paper-based processes, lab-specific e-requisitions, manual trackers, and other digital tools are "good enough," ICH E6(R3) raises the stakes. It emphasizes end-to-end oversight, traceability, and risk mitigation across the trial lifecycle — including the “collection, chain of custody, processing, analysis, and retention or destruction of biological samples.” That means sponsors must be able to demonstrate control, auditability, and consistency not just for specific processes, but across the entire biospecimen lifecycle.

A familiar compliance pitfall: Mistaking the part for the whole

This is where the parallel to 21 CFR Part 11 is so instructive. Back then, stakeholders mistook tool-specific validation for full compliance. Today, we see the same issue with lab-specific e-requisition tools. These solutions may help digitize a requisition form and transmit the information automatically to a lab. They might even mitigate some sample-related risks, including lab queries generated by a central lab. But they don’t manage the entire chain of custody. They don’t track the context in which samples were collected. They don’t mitigate risks in other critical sample management steps. They don’t integrate with the EDC. And they often don’t create a robust, sponsor-controlled audit trail across all trial sites and labs.

In short, these tools offer a slice of the data needed to demonstrate end-to-end compliance with ICH E6(R3). But in the absence of a system designed to orchestrate and connect biospecimen operations across the clinical trial ecosystem, that slice leaves sponsors exposed.

The risk of ICH E6(R3) noncompliance is real

ICH E6(R3) isn’t just about checking boxes. It’s about ensuring data integrity. Biospecimens are often tied to primary, secondary, and exploratory endpoints, which means any sample mishandling or data discrepancy could threaten the integrity of your trial operations.

Ask yourself:

• Can you demonstrate a full audit trail for every sample in your study?
• Are you confident that your requisition workflows aren’t introducing risk?
• Do your systems mitigate risk across the entire biospecimen lifecycle?

If the answer to any of these is no, your current approach may not align with the spirit — or the letter — of ICH E6(R3).

What sponsors need: A connected biospecimen management ecosystem

Partial solutions simply don’t cut it anymore. Sponsors need a centralized, end-to-end approach to biospecimen lifecycle management — one that captures complete chain of custody, supports collaboration across sites and labs, and gives sponsors the oversight they need to manage risk proactively.

Don’t wait for enforcement to catch up

Just as 21 CFR Part 11 enforcement took time to evolve, so too will ICH E6(R3). But by the time auditors come knocking, it could be a greater uphill battle to rebuild — or at the very least improve — your biospecimen workflows. Now is the time to assess your exposure and take steps to future-proof your biospecimen operations.

Learn more:

• Join our webinar on June 17: "The Future of Requisition Forms" — where we’ll explore how ICH E6(R3) compliance reshapes requisition workflows and more.
• Access our interactive guide: "Requisition Workflows, Reimagined" for a visual breakdown of how biospecimen workflows can evolve.
• Take our free ICH E6(R3) Risk Self-Assessment: Get a high-level scorecard of your biospecimen compliance readiness.