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a6a5d8e | 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 | # 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
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