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| # Vertical Governance Policy: Pharmaceutical — 21 CFR Part 11 / FDA AI/ML Action Plan | |
| # Doctrine v6 | R3 Adversarial Receipts | |
| # Last revised: 2025-07 | |
| schema_version: "1.0.0" | |
| vertical: pharmaceutical | |
| regime: 21-CFR-Part-11/FDA-AI-ML | |
| effective_date: "2025-07-01" | |
| jurisdiction: US-FDA | |
| meta: | |
| title: "Pharmaceutical AI Governance Policy — 21 CFR Part 11 / FDA AI/ML Alignment" | |
| description: > | |
| Maps FDA 21 CFR Part 11 Electronic Records/Signatures, FDA AI/ML-Based SaMD | |
| Action Plan, and ICH E6(R3) GCP to Doctrine v6 Λ-axes for AI systems used | |
| in drug discovery, clinical trials, and regulatory submissions. | |
| authority: "21 CFR Part 11; 21 CFR Part 820 (QSR); FDA AI/ML Action Plan (Jan 2021); ICH E6(R3) (2023); ICH Q10" | |
| receipt_chain_required: true | |
| merkle_root_algorithm: SHA3-256 | |
| gxp_category: GCP/GMP/GLP | |
| regulatory_clauses: | |
| - clause_id: CFR11-11.10a | |
| title: "Closed Systems — Validation" | |
| citation: "21 CFR § 11.10(a)" | |
| full_ref: "21 C.F.R. § 11.10(a) — Validation of systems to ensure accuracy, reliability, consistent intended performance" | |
| lambda_axes: | |
| - axis: Λ8 | |
| label: Robustness | |
| weight: 1.0 | |
| enforcement: mandatory | |
| rationale: > | |
| AI/ML systems used in GxP contexts must be validated per ISPE GAMP 5 | |
| Category 5; validation protocol and results hashed into receipt chain. | |
| - axis: Λ7 | |
| label: Auditability | |
| weight: 0.95 | |
| enforcement: mandatory | |
| - clause_id: CFR11-11.10e | |
| title: "Audit Trails — Sequence of Events" | |
| citation: "21 CFR § 11.10(e)" | |
| full_ref: "21 C.F.R. § 11.10(e) — Use of secure, computer-generated, time-stamped audit trails" | |
| lambda_axes: | |
| - axis: Λ7 | |
| label: Auditability | |
| weight: 1.0 | |
| enforcement: mandatory | |
| rationale: > | |
| Tamper-evident audit trail for all AI-generated records; Merkle DAG | |
| satisfies "secure, time-stamped" requirement with TAI64N timestamps. | |
| - axis: Λ6 | |
| label: Security | |
| weight: 0.90 | |
| enforcement: mandatory | |
| - clause_id: CFR11-11.50 | |
| title: "Signature Manifestations" | |
| citation: "21 CFR § 11.50" | |
| full_ref: "21 C.F.R. § 11.50 — Signed electronic records must contain the printed name, date/time, meaning of signature" | |
| lambda_axes: | |
| - axis: Λ2 | |
| label: Accountability | |
| weight: 1.0 | |
| enforcement: mandatory | |
| rationale: > | |
| AI-generated regulatory submissions must carry qualified electronic | |
| signatures (QES per eIDAS or 21 CFR Part 11); signature metadata | |
| embedded in receipt chain leaf node. | |
| - axis: Λ1 | |
| label: Transparency | |
| weight: 0.88 | |
| enforcement: mandatory | |
| - clause_id: FDA-AIML-SAMD-PREDETERMINED | |
| title: "Predetermined Change Control Plan for AI/ML SaMD" | |
| citation: "FDA Draft Guidance — Predetermined Change Control Plan for AI/ML-Based SaMD (Apr 2023)" | |
| full_ref: "FDA Draft Guidance: Marketing Submission Recommendations for AI/ML-Based SaMD (2023 Apr)" | |
| lambda_axes: | |
| - axis: Λ8 | |
| label: Robustness | |
| weight: 0.92 | |
| enforcement: mandatory | |
| rationale: > | |
| Each model update under a PCCP must be documented with performance | |
| comparator receipts (pre/post-update metrics, distribution shift scores). | |
| - axis: Λ9 | |
| label: Explainability | |
| weight: 0.85 | |
| enforcement: mandatory | |
| - clause_id: ICH-E6R3-5.5 | |
| title: "GCP — Sponsor's Responsibilities: Trial Management" | |
| citation: "ICH E6(R3) § 5.5 (2023)" | |
| full_ref: "ICH E6(R3) Integrated Addendum § 5.5 — Sponsor responsibilities for trial management systems" | |
| lambda_axes: | |
| - axis: Λ2 | |
| label: Accountability | |
| weight: 0.88 | |
| enforcement: mandatory | |
| rationale: > | |
| Sponsor is accountable for AI-assisted randomization, EDC, and | |
| statistical analysis; each algorithm run hashed into trial receipt chain. | |
| - axis: Λ4 | |
| label: Fairness | |
| weight: 0.80 | |
| enforcement: mandatory | |
| rationale: > | |
| Clinical trial AI must not introduce bias in patient stratification; | |
| demographic parity receipts required for adaptive trial designs. | |
| - clause_id: CFR820-QSR-820.30 | |
| title: "Design Controls" | |
| citation: "21 CFR § 820.30" | |
| full_ref: "21 C.F.R. § 820.30 — Design and development controls for device software including AI/ML" | |
| lambda_axes: | |
| - axis: Λ5 | |
| label: Safety | |
| weight: 0.92 | |
| enforcement: mandatory | |
| - axis: Λ1 | |
| label: Transparency | |
| weight: 0.80 | |
| enforcement: mandatory | |
| rationale: > | |
| Design history file (DHF) must include AI model architecture, | |
| training data specifications, and risk management per ISO 14971. | |
| - clause_id: ICH-Q10-APQR | |
| title: "Annual Product Quality Review — AI-Assisted Manufacturing" | |
| citation: "ICH Q10 § 2.3; 21 CFR § 211.180(e)" | |
| full_ref: "ICH Q10 § 2.3 — Annual product quality review; 21 C.F.R. § 211.180(e)" | |
| lambda_axes: | |
| - axis: Λ3 | |
| label: Privacy | |
| weight: 0.72 | |
| enforcement: recommended | |
| rationale: > | |
| Patient-level data used in AI-assisted batch release must be | |
| pseudonymised; access receipts log data subject category. | |
| - axis: Λ7 | |
| label: Auditability | |
| weight: 0.90 | |
| enforcement: mandatory | |
| - clause_id: EU-AI-ACT-CLASS3 | |
| title: "EU AI Act — High-Risk Classification: Medical Devices" | |
| citation: "EU AI Act Art. 6(2); Annex III § 5(a) (2024/1689)" | |
| full_ref: "Regulation (EU) 2024/1689 Art. 6(2) — High-risk AI system classification; Annex III § 5(a) medical devices" | |
| lambda_axes: | |
| - axis: Λ1 | |
| label: Transparency | |
| weight: 0.90 | |
| enforcement: mandatory | |
| rationale: > | |
| High-risk AI systems must register in EU AI Act database; receipt | |
| chain provides registration evidence with EU notified body signature. | |
| - axis: Λ10 | |
| label: Sovereignty | |
| weight: 0.82 | |
| enforcement: mandatory | |
| compliance_thresholds: | |
| minimum_lambda_coverage: 7 | |
| mandatory_axes: [Λ2, Λ7, Λ8] | |
| receipt_retention_days: 5475 # 15 years GCP/GMP | |
| max_samd_inference_latency_ms: 300 | |
| gxp_validation_cycle_days: 365 | |
| receipt_chain: | |
| algorithm: SHA3-256 | |
| chaining: merkle_dag | |
| quorum: 2-of-3 | |
| nodes: [primary, gxp-backup, regulatory-archive] | |
| qualified_electronic_signature: true | |