Flow of bioanalytical trials.
The bioanalytical workflow is sequential and gated. Each phase has a deliverable, a review point, and a regulatory artefact. Weak gate control is a frequent source of later validation questions.
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. Weak gate control is a frequent source of later validation questions because study-sample analysis depends on records created much earlier in the method lifecycle.
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 or cross-validation is assessed against the transfer context and ICH M10 expectations. Output: a controlled transfer record that explains equivalence, limits, and any changes.
Sample receipt & chain-of-custody.
Biospecimens arrive from clinical site. Temperature monitoring, integrity check, accession, and storage create the first study-sample evidence layer. Where electronic records or signatures are used, Part 11 controls may also become relevant.
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).
ISR is the post-validation reality check: selected study samples are reanalysed to test reproducibility in real matrix and real study conditions. The acceptance logic should be prespecified, justified, and traceable to the applicable method type and guidance.
In-study reanalysis & reasons.
Reanalysis should follow predefined criteria such as failed run, documented analytical issue, or values outside the validated range. Post-hoc or uncontrolled reasons are difficult to defend because they weaken the audit trail around generated concentration data.
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 reports support the relevant clinical, pharmacokinetic, bioequivalence, or submission package as applicable. Inspection readiness means SOPs, validation records, study-sample analysis records, deviations, audit trails, and raw data can be retrieved and explained.
Source anchors: ICH M10 Step 4 guideline · FDA ICH M10 guidance page · FDA 2018 BMV guidance page.
Source register.
official anchors · interpretation kept separateThis bioanalytical page uses official guidance as the source layer and separates iFeed interpretation from regulator text. Jurisdiction-specific details should be checked against the current regulator page before use in submissions, audits, or public checklists.
ICH M10 EU page.
EMA ICH M10 scientific guideline. Earlier EMA BMV guidance should be marked as historical where used for comparison.