What Do ICH E6(R3)’s Heightened Risk-Based Quality Standards Mean for Biospecimen Management?

The transition from ICH E6(R2) to ICH E6(R3) marks a pivotal shift in regulatory expectations for clinical trials, emphasizing a proactive, risk-based approach to quality management (also known as RBQM). While these principles apply broadly across trial operations, biospecimen management stands out as a critical area requiring heightened oversight. Sponsors who fail to integrate risk-based quality measures into their biospecimen workflows risk noncompliance and compromised data integrity.

What does ICH E6(R3) say about risk-based quality management?

ICH E6(R3) underscores that clinical trial quality should be built into study design and operations rather than assessed retrospectively. The guidelines mandate that sponsors establish systems to proactively identify, evaluate, and mitigate risks — especially in areas that can directly impact trial reliability and subject safety. This includes biospecimen collection, chain of custody, processing, storage, and data integrity.

Key sections of ICH E6(R3) that impact biospecimen management include:

• C.3.1.t: Essential records must document the collection, chain of custody, processing, analysis, and retention or destruction of biological samples. According to the guidelines, these records are to be used for sponsor oversight (including monitoring) of the trial, as well as during inspections by regulatory authorities to assess study conduct and the reliability of the trial results.
• 3.11.3: Risk-based quality control measures must be applied to all stages of data handling to ensure reliability and accuracy. Given that biospecimens are part of the essential record, biospecimens are considered data.
• C.2.4: Sponsors and investigators must maintain complete, searchable, and audit-ready records of essential study data — including biospecimen-related documentation.

These updates reinforce the regulatory expectation that biospecimens must be managed with the same level of rigor as other critical study activities. Without a structured, comprehensive risk-based approach that addresses the entire biospecimen lifecycle, sponsors leave their trials vulnerable to regulatory scrutiny and avoidable data integrity issues.

Dig into the updated ICH guidelines with leading regulatory experts. Sign up for our live webinar, “The Impact of ICH E6(R3) on Biospecimen Management.”

The high-stakes risks of noncompliance with RBQM requirements in ICH E6(R3)

Biospecimens are the backbone of clinical trials. However, their value, coupled with the complexity of today’s trials, also makes them a high-risk asset. 

Failure to implement a risk-based approach to your biospecimens can result in:

• Sample Mishandling: Errors in collection, labeling, or storage can lead to the loss of critical specimens.
• Lapses in Chain of Custody: Given the number of things that can go wrong with samples on a complex global trial, a lack of robust tracking heightens the risk of samples going missing, being mishandled, or not being collected at all — causing queries, delays, protocol deviations, and sample recollection events.
• Incomplete or Inaccessible Documentation: Without centralized, audit-ready records, sponsors may struggle to demonstrate compliance during inspections.
• Regulatory Penalties: As regulatory bodies begin enforcing ICH E6(R3), sponsors failing to implement proper risk-based controls could face audit findings.

How to align biospecimen management with updated requirements for RBQM

To stay ahead of the regulatory curve, sponsors must take proactive steps to integrate biospecimen workflows into their broader risk-based quality management systems. Key strategies include:

• Strengthening Sample Tracking Capabilities: Utilizing technology-driven solutions to ensure quicker visibility to samples and end-to-end chain-of-custody.
• Implementing Proactive Risk Mitigation: Identifying high-risk biospecimen activities and applying targeted controls to prevent errors and enhance oversight.
• Ensuring Audit-Ready Documentation: Centralizing records in a compliant, searchable system to facilitate regulatory inspections.
• Integrating Biospecimen Management with Data Governance: Treating biospecimens as critical study data and applying risk-based data handling practices.

Get expert insights and learn how to assess your compliance risk

Navigating these changes requires strategic planning and expert guidance. That’s why we’re bringing together industry leaders for a live webinar: “The Impact of ICH E6(R3) on Biospecimen Management.” Join Edye Edens (Life Sciences Legal and Regulatory Expert, Kulkarni Law Firm), Rust Felix (CEO, Slope), and Aman Khera (Regulatory Science and Innovation Advisor, President of TOPRA) as they discuss:

• Additional interpretation of the ICH E6(R3) language that directly impacts biospecimen operations, aside from risk-based quality. 
• How to align biospecimen management practices with the new regulatory framework. 
• Steps to assess compliance ahead of the EMA’s July implementation deadline.

Don’t miss this opportunity to future-proof your biospecimen management strategy. Sign up now to secure your spot!