Reference
How a single protocol amendment travels through the platform — from a sponsor’s request, through staging and agent processing, across the Part 11 e-signature gate, to live promotion, audit trail, and inspector view. Read left to right.
Step 1 · Sponsor
Sponsor Portal (L5)
Sponsor submits a protocol amendment request via the sponsor portal. The request includes the rationale, the affected sections, and target studies. No regulated record is written yet — only an intent row.
Evidence trail
Step 2 · System
Staging tables (L1)
The orchestrator writes a structured staging_record bound to the sponsor request. All downstream agent work targets this staging row — never live tables. This satisfies the architectural invariant that agents write only to staging.
Evidence trail
Step 3 · Agent
Knowledge RAG Agent (L3)
The Knowledge RAG agent classifies the amendment (substantial vs. non-substantial, ICH E6(R3) categories) and tags the affected sections. All claims are citation-grounded against ICH/FDA guidance.
Evidence trail
Step 4 · Agent
Evaluation Agent (L3)
The Evaluation agent cross-checks the classification against the protocol, prior amendments, and applicable LCD/NCD coverage. It produces a risk score and a list of unresolved questions for human review.
Evidence trail
Step 5 · Human
E-Signature Service (L4)
A signed human reviewer re-authenticates, states intent, and signs. The signature row is immutable and binds the staging_record to a signer identity. This is the only path through which staging becomes live.
Evidence trail
Step 6 · System
Orchestrator (L2)
On valid signature, the orchestrator promotes staging→live atomically. Live writes carry the signature_id so any inspector can trace the live row back to the human who signed.
Evidence trail
Step 7 · System
Audit Trail Agent + provenance_event (L1)
Every step above has already written provenance_event rows. The audit trail agent compiles them into a chronological ALCOA+ narrative, ready for export. Nothing is reconstructed — only assembled.
Evidence trail
Step 8 · Human
Inspector Console (L5)
An FDA/EMA inspector (or internal QA) opens the inspection package. They see the full chain: sponsor request, staging, agent rationale + citations, signature, live row, audit narrative. Read-only, single-pane-of-glass.
Evidence trail