Flow of bioanalytical trials.
The bioanalytical workflow is sequential and gated. Each phase has a deliverable, a review point, and a regulatory artefact. Skipping a gate is the most common cause of late-stage validation failure.
Flow of bioanalytical trials.
From method development to submission · the operational pipelineThe bioanalytical workflow is sequential and gated. Each phase has a deliverable, a review point, and a regulatory artefact. Skipping a gate is the most common cause of late-stage validation failure.
Method development.
Reference standard sourcing, IS selection, extraction chemistry, chromatographic conditions, MS tuning. Output: candidate SOP. Typically 2-6 weeks for LC-MS/MS · 6-12 weeks for LBA.
Pre-study method validation.
Selectivity (6 / 10 lots), accuracy & precision (3-6 runs), calibration, carry-over, matrix effect (per-source), stability suite, dilution integrity. Output: validation report aligned to ICH M10. Typical duration 4-10 weeks.
Method transfer (if applicable).
Sponsor lab → CRO or CRO → CRO. Partial validation per ICH M10 §6 / PMDA 2024 framework. Output: transfer report demonstrating equivalence. Common stumble point in late-stage programmes.
Sample receipt & chain-of-custody.
Biospecimens arrive from clinical site. Temperature monitoring, integrity check, accession, storage. Documented under 21 CFR Part 11. The first inspection touchpoint for study sample analysis.
Study sample analysis.
Validated method runs against incoming samples. Run acceptance criteria: 75% of standards, 67% of QCs per concentration. Each run reviewed by analyst + reviewer. Authority for repeats documented.
Incurred sample reanalysis (ISR).
10% of samples reanalysed in pivotal studies. ≥67% within 20% (CC) / 30% (LBA). The post-validation reality check. ISR is the #1 inspection finding in 2025 (28% of 483s).
In-study reanalysis & reasons.
Reanalysis only on pre-defined criteria (above-ULOQ, IS variation, failed run · ANVISA stricter 3-reason closed list). Post-hoc justification rejected globally. Documented per study.
PK parameter derivation.
Concentration data → Cmax, Tmax, AUC, t½. Non-compartmental analysis (Phoenix WinNonlin, R PK) or population PK (NONMEM, Monolix). Bioanalytical outputs feed PK / PD / safety analyses.
Bioanalytical report assembly.
Method development summary, validation report, study sample analysis report, ISR results, deviations, conclusions. The CSR Module 5 component.
Submission + inspection readiness.
Bioanalytical report into eCTD Module 5.3.1. Inspection readiness: SOPs, method validation, raw data retrievable within audit window. Post-approval: change control, partial-validation triggers, ongoing ISR if commercial use.