CTCAE v6.0 in Regulatory and Compliance Strategy

CTCAE v6.0 is more than a technical refresh; it is a new baseline for how regulators, sponsors, and pharmacovigilance teams talk about toxicity. Every term is now a MedDRA v28.0 lowest‑level term (LLT), tightening the connection between trial AE grading and global safety reporting.

Why CTCAE v6.0 Matters for Regulators

Regulators expect consistent, reproducible AE grading that integrates cleanly with MedDRA‑based safety systems. CTCAE v6.0 supports this by:

• Ensuring each CTCAE term is explicitly mapped to a MedDRA v28.0 LLT, reducing ambiguity in coding and signal detection.

• Providing updated, clinically realistic grading for modern oncology toxicities, especially labs and cytopenias, which directly affect benefit–risk narratives.

• Clarifying definitions and branching logic for abnormal baselines, which improves traceability in lab‑based grading.

For regulators, this translates into more interpretable AE tables, fewer unclassifiable terms, and clearer links between clinical trial data, E2B reports, and product labeling.

Documentation Expectations: Protocols, SAPs, and ISS

From a compliance perspective, CTCAE versioning must be explicit and traceable:

• Protocols should specify "CTCAE v6.0" and, where appropriate, link to NCI's official PDF/Excel resources.

• SAPs must state which CTCAE version applies to each dataset and how v5.0↔v6.0 mapping is handled for pooled analyses.

• Integrated summaries of safety (ISS) should describe any grade migration caused by v6.0 changes, especially in neutropenia and lab‑based AEs.

Regulatory reviewers will look for this level of transparency when assessing whether observed toxicity differences reflect biology or grading system artifacts.

MedDRA, E2B, and Risk Management

Because CTCAE v6.0 uses MedDRA v28.0 LLTs, downstream pharmacovigilance becomes more streamlined:

• E2B case safety reports can map CTCAE terms directly into MedDRA fields without custom dictionaries.

• DSURs, PSUR/PBRERs, and RMPs can cite aggregated AE patterns with confidence that terminology is harmonized across clinical and post‑marketing data.

Regulators in regions where MedDRA is mandated (for example, EMA, FDA, PMDA) have long encouraged this alignment, and CTCAE v6.0 fully operationalizes it.

Handling Mixed‑Version Portfolios

For several years, sponsors will have both v5.0 and v6.0 trials running. Regulatory‑grade handling requires:

• Using NCI's official v5.0→v6.0 mapping resources as a starting point, with documented sponsor‑level conventions where necessary.

• Flagging mapped vs native v6.0 records in analysis datasets, and performing sensitivity analyses to show robustness of safety conclusions.

• Explaining in clinical overviews when observed reductions or increases in Grade 3–4 events may be due in part to grading changes rather than improved safety.

This approach aligns with regulatory expectations for transparent methodology and mitigates the risk of misinterpreting cross‑trial comparisons.

Inspection Readiness and Quality Systems

CTCAE v6.0 reinforces the need for robust quality systems:

• Version‑controlled CTCAE libraries and MedDRA dictionaries in EDC and safety systems.

• SOPs describing version selection, mapping, and documentation in submissions.

• Training records showing investigators, monitors, and safety reviewers have been educated on key v6.0 changes.

During inspections, regulators will expect clear evidence that CTCAE v6.0 was implemented systematically, not ad hoc.

For regulatory and compliance teams, CTCAE v6.0 is an opportunity to modernize safety infrastructure and align even more tightly with MedDRA‑centric global expectations.