refua-preclinical 0.7.1

GLP tox/pharmacology planning, in vivo scheduling, bioanalytical pipelines, and CMC workflows for Refua.

refua-preclinical

refua-preclinical adds operational preclinical R&D workflows to Refua:

• GLP tox/pharmacology study planning
• In vivo execution scheduling
• Bioanalytical ETL/QC/group summaries/NCA-like metrics
• CMC workflows: formulation/process development, batch records, stability studies, release criteria evaluation

The package is designed for direct integration into refua-studio and refua-deploy.

What It Provides

• Typed study specs for repeat-dose tox/pharmacology programs.
• GLP readiness scoring/checklist (QA, protocol approval, CSV, chain-of-custody, archival).
• Calendar-ready in vivo schedules for dosing, observations, sampling, and necropsy.
• Bioanalytical pipeline:
  • row-level validation and QC flags
  • BLQ tracking vs LLOQ
  • grouped concentration summaries (mean/SD/CV)
  • AUC-last/Cmax/Tmax by arm/analyte
• CMC toolkit:
  • formulation and process development planning with QTPP/CQA/CMA/CPP mapping
  • control strategy and process validation lifecycle sections (stage 1/2/3)
  • lifecycle/change-management planning aligned to ICH Q12 concepts
  • electronic batch record templates
  • stability sample scheduling and trend analysis
  • release criteria assessment (pass/hold decisions)
• CLI + Python API.

Install

cd refua-preclinical
pip install -e .

CLI Quickstart

Write starter config:

refua-preclinical init-config --output examples/default_study.json

Build a study plan:

refua-preclinical plan \
  --config examples/default_study.json \
  --output artifacts/plan.json \
  --markdown artifacts/plan.md

Build the in vivo schedule:

refua-preclinical schedule \
  --config examples/default_study.json \
  --output artifacts/schedule.json

Run bioanalysis from sample rows (JSON/CSV):

refua-preclinical bioanalysis \
  --config examples/default_study.json \
  --samples artifacts/samples.json \
  --lloq 1.0 \
  --output artifacts/bioanalysis.json

Run full workup:

refua-preclinical workup \
  --config examples/default_study.json \
  --samples artifacts/samples.json \
  --output artifacts/workup.json

Build a CMC plan:

refua-preclinical cmc-plan \
  --output artifacts/cmc_plan.json

Generate a batch record:

refua-preclinical batch-record \
  --batch-id BATCH-001 \
  --output artifacts/batch_record.json

Build a stability schedule:

refua-preclinical stability-plan \
  --batch-id BATCH-001 \
  --output artifacts/stability_plan.json

Evaluate release criteria:

refua-preclinical release-eval \
  --batch-results artifacts/batch_results.json \
  --stability-results artifacts/stability_results.json \
  --output artifacts/release_eval.json

Python API

from refua_preclinical import (
    build_formulation_process_plan,
    build_in_vivo_schedule,
    build_stability_study_plan,
    build_study_plan,
    build_workup,
    default_study_spec,
    generate_batch_record,
)

study = default_study_spec()
plan = build_study_plan(study, seed=11)
schedule = build_in_vivo_schedule(study)
workup = build_workup(study)
cmc_plan = build_formulation_process_plan()
batch_record = generate_batch_record(batch_id="BATCH-001")
stability_plan = build_stability_study_plan(batch_ids=["BATCH-001"])

Research Basis (Current as of March 2026)

The defaults/checks are intentionally aligned with recent primary guidance and standards.

1. FDA (April 10, 2025): plan to phase out animal testing requirements for some programs and increase NAM/model use. https://www.fda.gov/news-events/press-announcements/fda-announces-plan-phase-out-animal-testing-requirement-monoclonal-antibodies-and-other-drugs
2. EMA/ICH M10 (effective in EU from Jan 2023): bioanalytical method validation framework. https://www.ema.europa.eu/en/m10-bioanalytical-method-validation-scientific-guideline
3. FDA Study Data Technical Conformance Guide (December 2025): submission-facing data format expectations. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/study-data-technical-conformance-guide-technical-specifications-document
4. OECD GLP Advisory Document No. 24 (Nov 2024): GLP and IT security. https://www.oecd.org/en/publications/advisory-document-of-the-working-group-on-good-laboratory-practice-on-position-paper-on-good-laboratory-practice-and-it-security_90f42001-en.html
5. ARRIVE resources update (Nov 2024): Essential 10 reporting and study design hygiene. https://arriveguidelines.org/resources/author-and-reviewer-resource-centre
6. EMA/ICH S5(R3) (2023): reproductive/developmental toxicity modernization. https://www.ema.europa.eu/en/ich-s5-r3-guideline-detection-toxicity-reproduction-human-medicinal-products-scientific-guideline
7. NIH statement (July 7, 2025): prioritization of human-based research technologies. https://www.nih.gov/about-nih/who-we-are/nih-director/statements/nih-prioritize-human-based-research-technologies
8. CDISC standards development page (accessed 2026): ongoing SEND evolution workstreams. https://www.cdisc.org/standards/develop

CMC Basis

1. ICH Q8(R2): pharmaceutical development and quality-by-design framing. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q8r2-pharmaceutical-development
2. ICH Q9(R1) (May 2023): quality risk management modernization. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q9r1-quality-risk-management
3. ICH Q10: pharmaceutical quality system lifecycle expectations. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q10-pharmaceutical-quality-system
4. ICH Q11: drug substance development/manufacturing guidance. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q11-development-and-manufacture-drug-substances-chemical-entities-and-biotechnologicalbiological
5. ICH Q12 (Aug 2020): product lifecycle management and established conditions. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q12-technical-and-regulatory-considerations-pharmaceutical-product-lifecycle-management
6. ICH Q13 (Mar 2023): continuous manufacturing guidance. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q13-continuous-manufacturing-drug-substances-and-drug-products
7. ICH Q2(R2) + Q14 (Mar 2024): analytical validation and development lifecycle. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q2r2-validation-analytical-procedures https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q14-analytical-procedure-development
8. ICH Q1A(R2): stability testing framework. https://www.ema.europa.eu/en/ich-q1a-r2-stability-testing-new-drug-substances-products-scientific-guideline
9. FDA Process Validation (Jan 2011): process design, PPQ, CPV lifecycle. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/process-validation-general-principles-and-practices

Notes

• This package supports planning/operations and data processing; it does not establish efficacy.
• Regulatory expectations are jurisdiction- and program-dependent.