Source ledger

Provenance for the version- and date-specific claims in this skill. Everything below was checked on 2026-07-27. Pharmacological and statistical methods that are stable textbook material are not listed; this covers the claims that go stale.

Verified by direct execution

Claim	How verified
Pharmpy 2.1.1 is the current release	`pip install pharmpy-core` into a clean environment; `pharmpy.__version__` returned `2.1.1`
Pharmpy exposes 19 `run_*` tools, including `run_pdsearch`, `run_modelrank`, `run_qa`, `run_vpc`	`dir(pharmpy.tools)` on the installed package
`modeling.add_placebo_model` no longer exists; `set_placebo_model` does	`hasattr` check on the installed `pharmpy.modeling`
`set_tmdd` accepts `full`, `ib`, `cr`, `crib`, `qss`, `wagner`, `mmapp`	`inspect.signature(pharmpy.modeling.set_tmdd)`
`add_indirect_effect` accepts `linear`, `emax`, `sigmoid` and a `prod` flag	`inspect.signature` on the installed package
Bioequivalence sample sizes (2×2, GMR 0.95, 80% power): 12/20/28/40/52/66 at CV 15/20/25/30/35/40%	`bioequivalence.py --power` reproduces the published PowerTOST table exactly
ABEL limits cap at 69.84–143.19% at CVwR = 50%	Computed from `exp(±0.760 · swR)` at the cap
NCA recovers λz, t½, CL/F and Vz/F from an analytical one-compartment oral profile	`nca.py` against a simulated noiseless profile with known parameters
The model library reproduces closed-form AUC = D/CL, Vss = ΣV, MRT = Vss/CL for 1-, 2- and 3-compartment models	Analytical checks in `tests/pkpd-modeling/test_scripts.py`

Package versions from PyPI

Retrieved from the PyPI JSON API on 2026-07-27.

Package	Version	Note
`pharmpy-core`	2.1.1 (2026-05-19)	2.1.0 on 2026-05-08; 2.0.0 on 2026-02-12; 1.12.0 on 2025-12-05
`numpy`	2.5.1
`scipy`	1.18.0	`requires_python >= 3.12`
`chi-drm`	1.0.3
`pints`	0.6.1
`lmfit`	1.3.4
`pkpy`	not on PyPI	Queried and returned no such project; PKPy is GitHub-only

Regulatory status

Claim	Source
ICH M12 Step 4 2024; FDA adopted 2 August 2024 with a Q&A; EU effective 30 November 2024; China 29 October 2024	FDA M12 final-guidance announcement and materials; EMA M12 scientific guideline page
ICH M13A Step 4 July 2024, effective 25 January 2025	ICH M13A Step 4 materials; EMA M13A scientific guideline page
ICH M13B endorsed 13 March 2025, Step 2b, consultation 9 April – 9 July 2025	EMA M13B scientific guideline page
ICH M13C covers highly variable drugs, NTI drugs and complex designs, and follows M13B	ICH M13 workplan as described in the M13A/M13B materials
ICH E11A Step 4 21 August 2024, effective 25 January 2025	ICH E11A Step 4 guideline; EMA E11A Step 5 document
FDA Population Pharmacokinetics guidance final February 2022; states model selection based on shrinkage is not necessary; lists VPC, pcVPC, NPC, NPDE	FDA guidance document and Federal Register notice of availability, 4 February 2022
FDA oncology dose-optimisation guidance (Project Optimus) finalised August 2024; PK sampling and analysis plan in each protocol sufficient for popPK and exposure-response	FDA final guidance and contemporaneous coverage
ICH E14/S7B 2022 Q&As introduced the double-negative nonclinical assessment	E14/S7B Q&A document; FDA review-experience analysis published 2025
FDA 2005 maximum-safe-starting-dose guidance supplies the Km body-surface-area conversion table	FDA guidance, Table 1

Software versions from vendor and project sources

Claim	Source
NONMEM 7.6 exists; adds ADVAN16 (RADAR5 stiff DDE), ADVAN17 (stiff delay DAE), NUTS Bayesian, SAEM sample storage	ICON NONMEM 7.6 workshop description and NONMEM 7.6.0 user guides dated November 2025
nlmixr2 requires rxode2 ≥ 5.0.0; CRAN package updated 30 November 2025, manual dated 9 May 2026	CRAN nlmixr2 package page and reference manual
`babelmixr2` and `monolix2rx` interchange models between nlmixr2, NONMEM and Monolix	nlmixr2 project documentation and a February 2026 methods paper
Open Systems Pharmacology Suite v12 (with Update 2) is current; `ospsuite` R package needs R 4.x and .NET 8	OSP Suite GitHub releases and v12 documentation
PKPy is a 2025 Python popPK framework	PeerJ 2025 paper and its GitHub repository
PKNCA and aNCA are the R NCA packages; aNCA is a Roche/Appsilon/Human Predictions pharmaverse project	Package documentation sites

Method sources

Standard methods used in the scripts, cited so the implementation can be checked:

Lambda_z by best adjusted r-squared, extend-backwards with a 0.0001 improvement threshold — the convention implemented in Phoenix WinNonlin and PKNCA.
Linear-up/log-down trapezoid and the corresponding AUMC formula — standard NCA texts; the AUMC log-down form is re-derived in the nca.py source comment.
Hyslop's linearised upper bound for the FDA reference-scaled criterion, with theta = ln(1.25)/0.25 — the method in FDA's progesterone product-specific guidance.
ABEL widening exp(±0.760·swR) capped at CVwR 50% — EMA bioequivalence guideline.
Beal's M1–M7 methods for BLQ data — Beal, J Pharmacokinet Pharmacodyn 2001.
Dayneka & Jusko indirect response models I–IV.
Sheiner effect-compartment link model.
Mager & Jusko TMDD; Gibiansky QSS approximation.
Anderson & Holford sigmoidal maturation on post-menstrual age (TM50 54.2 weeks, Hill 3.92 as generic clearance values).
Mahmood & Balian rule of exponents for interspecies scaling.
Savic transit-compartment absorption model.
2020 ASHP/IDSA/PIDS/SIDP consensus for vancomycin AUC₂₄/MIC 400–600.

Known gaps and deliberate omissions

USP and ISO documents are copyrighted and paywalled; where relevant they are cited by designation only, never transcribed.
Product-specific guidances change frequently and are not enumerated here.
The vancomycin population parameters in tdm_bayes.py are a conventional illustrative parameterisation, labelled as such in the code and output, not a validated published model.
PK/PD index targets for antimicrobials vary by organism, endpoint and study; the values given are commonly cited ranges, not regulation.