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获取原文件references/regulatory-guidance.md
Reviewed 2026-10-01. ICH adoption and regional implementation are distinct; an EU effective date is not a worldwide effective date. Product-specific guidance and intended use can change the analysis. Check the applicable authority before submission.
| Document | Current verified boundary | Primary source |
|---|---|---|
| ICH M12 | Step 4 2024; EU effective 30 November 2024; enzyme/transporter DDI framework | EMA |
| ICH M13A | Immediate-release solid oral BE; EU effective 25 January 2025; transition leaves regional replicate/NTI provisions | EMA |
| ICH M13B | EMA Step 5 adopted 17 September 2026, effective 17 March 2027; additional-strength biowaivers | Final PDF |
| ICH M13C | Under development; do not describe as adopted harmonized HVD/NTI rules | ICH workplan |
| ICH M15 | General model-informed development; EU effective 23 July 2026; FDA final June 2026 | EMA PDF, FDA |
| ICH E11A | Pediatric extrapolation framework; exposure criteria justified for context | FDA |
| FDA statistical BE | Final May 2026; replaces 2001; Appendix G includes HVD replicate statistics | FDA |
| FDA population PK | Final February 2022; intended-use model development/evaluation | FDA |
| E14/S7B Q&A | 2022 integrated QT/proarrhythmia assessment; clinical/nonclinical evidence requirements | FDA |
| FDA starting dose | 2005 healthy-adult MRSD framework; not a universal MABEL calculator | FDA |
Apply the relevant question
- NCA/BE: identify formulation, fasting/fed state, metric, sampling and jurisdiction; M13A is not a substitute for every special-design or product-specific requirement.
- Population PK/ER: predefine the decision, data provenance, model assumptions, uncertainty and evaluation relevant to that use. Synthetic fit recovery is software evidence, not clinical evidence.
- DDI: distinguish screening trigger from AUCR prediction and clinical action. Input uncertainty, metabolites and pathways outside the simplified model remain material.
- Pediatrics/FIH: integrate biology, exposure-response, species/population relevance and safety; a numerical exposure match or conservative calculator output alone is insufficient.
No licensed estimation engine, prospective study, patient outcome or regulatory submission was validated by this skill refresh. The helper outputs do not certify compliance.