TGA adopts ICH M15 guideline: PBPK modelling now accepted for drug interaction and special population submissions

On 21 October 2026 the Therapeutic Goods Administration (TGA) ↗ confirmed adoption of the ICH M15 guideline on physiologically based pharmacokinetic (PBPK) modelling and simulation ↗ for use in regulatory submissions. PBPK models can now serve as primary evidence for drug-drug interaction (DDI) characterisation and dose recommendations in special populations — including paediatrics, pregnancy, renal impairment, and hepatic impairment — when clinical studies are not feasible.

Physiologically based pharmacokinetic modelling integrates drug-specific parameters (e.g. lipophilicity, protein binding, clearance pathways) with human physiological parameters (organ blood flows, tissue volumes, enzyme expression) to predict concentration-time profiles across tissues. Unlike classical compartmental PK, PBPK models mechanistically simulate absorption, distribution, metabolism, and excretion (ADME) — see our bioavailability glossary entry and drug metabolism guide for foundational concepts. A primer is available at NIH/NCBI (PubMed Central) ↗.

Under the adopted guideline, sponsors may use verified PBPK models to: (1) predict DDI risk for victim and perpetrator drugs; (2) extrapolate adult PK to paediatric populations when juvenile animal toxicology is available; (3) inform dose adjustments in renal or hepatic impairment without a dedicated clinical study; (4) support labelling claims for QT prolongation risk in the context of hERG inhibition + clinical exposure modelling. The TGA expects model verification packages to follow the ICH M15 qualification framework, including sensitivity analyses and prediction uncertainty ranges. The EMA and FDA simultaneously updated their PBPK guidance documents — creating a harmonised global standard for the first time.

For sponsors, ICH M15 adoption accelerates regulatory timelines for special-population dose recommendations — historically a bottleneck requiring sequential clinical trials. For prescribers, TGA-accepted PBPK modelling means product information (PI) documents will increasingly carry model-supported dose-adjustment tables for CKD, hepatic impairment, and high-risk DDI pairs. The TGA guidance repository ↗ contains the full adopted guideline text and implementation timeline. The EMA's ICH M15 page ↗ includes worked examples for DDI and paediatric applications. See our PBS drug listing guide for how regulatory evidence feeds into Australian PBS submissions.