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Official Source Ledger

skills/analytical-method-validation/references/source-ledger.md

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Official Source Ledger

Research date: 2026-07-27. Every framework claim in this skill traces to an entry below. Re-check each source before operational use — guidelines are revised, editions change, and regional implementation dates differ from adoption dates.

This ledger is a version baseline. It is not legal advice, an applicability determination, or a substitute for a controlled copy held under the laboratory's document control.

Documents read directly

These were downloaded and read as full text on the research date, so the requirements encoded in scripts/_catalog.py and summarised in references/ich-q2r2.md and references/ich-m10-bioanalytical.md come from the primary source rather than from secondary summaries.

ICH Q2(R2) Validation of Analytical Procedures

  • Source read: https://database.ich.org/sites/default/files/ICH_Q2%28R2%29_Guideline_2023_1130.pdf
  • Verified metadata: Final Version, adopted by the ICH Assembly Regulatory Members under Step 4 on 1 November 2023. Step 2 endorsement 24 March 2022. Supersedes Q2(R1) (November 2005).
  • Verified detail: an error correction dated 30 November 2023 covers Table 5 (dissolution with HPLC, reportable range linearity formulae, page 25) and Tables 6–11 (pages 26–32).
  • Content taken: section structure; Table 1 (tests by measured attribute); Table 2 (reportable range examples); recommended data for specificity, response, lower range limits, accuracy, precision, and robustness; sections 2.1–2.5; Annex 1 and Annex 2 table inventory; the relative response factor 0.8–1.2 rule from Annex 2 Table 3.
  • Licence: ICH permits use, reproduction, adaptation and distribution under a public licence provided ICH's copyright is acknowledged. Acknowledged here and in scripts/_catalog.py.
  • Limitation: adoption is not implementation. Confirm the date from which your regional regulator expects Q2(R2) with that regulator.

ICH M10 Bioanalytical Method Validation and Study Sample Analysis

  • Source read: https://database.ich.org/sites/default/files/M10_Guideline_Step4_2022_0524.pdf
  • Verified metadata: Step 4, dated 24 May 2022.
  • Content taken: chromatographic criteria (section 3) — calibration levels and tolerances, QC placement at four levels with the low/medium/high definitions, within-run and between-run accuracy and precision design and criteria, routine-run QC pass rules, carry-over, selectivity source count, dilution integrity, stability; ligand binding assay criteria (section 4) — calibration tolerances including anchor point exclusion, five QC levels, run and replicate structure, accuracy and precision criteria at LLOQ and ULOQ, and the total error criterion; incurred sample reanalysis (section 5) including the percent-difference basis and the pass fractions.
  • Verified distinction: the total error criterion (≤30%, ≤40% at LLOQ and ULOQ) appears for ligand binding assays. No equivalent criterion was found for chromatographic assays.
  • Licence: as for Q2(R2).
  • Limitation: regional implementation dates differ. Confirm with the regional regulator.

ICH Q14 Analytical Procedure Development

  • Source read: https://database.ich.org/sites/default/files/ICH_Q14_Guideline_2023_1116.pdf
  • Content taken: section structure; the minimal versus enhanced approaches (section 2.1); the analytical target profile (section 3) and that its formal documentation and submission is optional; robustness and parameter ranges (section 5); established conditions (section 6.1); lifecycle management and post-approval change (section 7); multivariate procedures (section 8).
  • Adopted alongside Q2(R2) by the ICH Assembly in the same session.
  • Licence: as for Q2(R2).

Documents identified but not read (paywalled)

Designation, title, and scope only. No requirement, threshold, or study design from any of these is reproduced anywhere in this skill. Where a numeric criterion is needed, read it from an authorised copy.

USP–NF general chapters

  • Official pages: <1220> https://doi.usp.org/USPNF/USPNF_M10975_02_01.html; <1225> https://doi.usp.org/USPNF/USPNF_M99945_40101_01.html; <1226> https://doi.usp.org/USPNF/USPNF_M870_03_01.html
  • Verified metadata for <1220>: incorporated into USP–NF 2022 Issue 1 on 1 November 2021, official 1 May 2022. It brings the concepts of <1224>, <1225> and <1226> into a single three-stage lifecycle. <1225> covers validation, particularly Stage 2 activities under <1220>; <1226> covers verification of compendial procedures.
  • Provenance limitation: this metadata came from secondary sources (publisher notices and trade press) rather than from the USP–NF text, which is behind subscription. Marked [confirm in USP–NF]. Confirm the current official text, revision, and any subsequent change.
  • Chapters referenced by designation only, not read: <1224>, <1010>, <621>, <711>, <1092>.

CLSI EP series

  • Publisher: https://clsi.org/standards/products/method-evaluation/
  • Designations and subjects recorded in references/compendial-and-clsi.md: EP05, EP06, EP07, EP09, EP15, EP17, EP25, EP28 (formerly C28), plus the EP17IG and EP28IG implementation guides.
  • Provenance limitation: designations, titles and edition numbers were taken from clsi.org product listings and secondary sources on the research date, not read from the documents. Every edition number carries [confirm edition] in the reference file. Editions change; verify on clsi.org before designing a study.

ISO standards

  • ISO/IEC 17025:2017 — https://www.iso.org/standard/66912.html. Edition 3; supersedes the 2005 edition. Relevant clauses: 7.2 (selection, verification and validation of methods), 7.6 (measurement uncertainty). Not read; identified by catalogue metadata.
  • ISO 15189, ISO 21748, ISO 5725 series — referenced by designation and scope only.
  • Provenance limitation: ISO catalogue pages have historically refused automated access. Confirm edition and status on iso.org or with a national member body. [confirm on iso.org]
  • See this repository's iso-standards-readiness skill and its own source ledger for the accreditation-level treatment of these standards.

Statistical methods

The statistical procedures in references/statistics.md and scripts/_common.py are standard published methods, not requirements of any framework:

  • Incomplete beta and gamma function implementations follow the standard continued-fraction and series algorithms; the t, chi-square and F distributions are derived from them.
  • Lack-of-fit F test against pure error: standard regression ANOVA.
  • Wald–Wolfowitz runs test: standard non-parametric test of randomness in a sequence of signs.
  • One-way random-effects variance components with the standard unbalanced expected-mean-square coefficient; Satterthwaite approximation for effective degrees of freedom of the total.
  • Deming regression with jackknife standard errors; Passing–Bablok with the rank-based slope interval.
  • Bland–Altman bias and limits of agreement.
  • Two one-sided tests (TOST) for equivalence.

Implementations are verified against published quantiles and hand-checkable cases in tests/analytical-method-validation/test_scripts.py. Where a framework prescribes a specific statistical treatment, the framework governs — these are the general-purpose tools.

What is deliberately absent

  • No numeric acceptance criteria are supplied for ICH Q2(R2) work. The guideline does not set them and neither does this skill; they come from the specification, the analytical target profile, or development data.
  • No text, table, threshold, or study design from any USP, CLSI, or ISO document.
  • No claim that a procedure is validated, a run acceptable, or an investigation closed.