An eTMF quality check that runs every day, scoring each site on what is due today
An inspection-ready trial master file every day, each site scored on what is due today.
See one case, screen by screen ↓A Phase 3 trial of 46 sites builds a trial master file of tens of thousands of documents from sites, CROs and vendors. Inspectors ask the same three questions of it every time: is it complete, was it filed on time, is it right? Many TMF teams answer with a quarterly, sampled QC review, a filing backlog worked by hand and an expected-document list kept in a spreadsheet.
That list goes stale the day a site changes staff. A new sub-investigator is recorded in a monitoring visit report, nobody updates the spreadsheet, and the site still looks green while its delegation log, CV, GCP certificate and financial disclosure are missing — the classic inspection finding. Late filings stay invisible too: a Form FDA 1572 that reaches the file 94 days after signing is found only when someone looks, and a pile of documents filed just before an inspection is itself a red flag.
Estimated split of the 38-day median to file seen by hand on the sample study, and of the 1.6-day target with the solution.
Four specialist agents file, extract, score and chase every document; the TMF lead confirms and signs.
VLT-302 is a Phase 3, randomised, double-blind study of Veltrimab in moderate-to-severe plaque psoriasis — 46 sites in 12 countries, run under a US IND. Here is what Lena Ortiz, its TMF lead, sees and does, screen by screen, in the working solution.
TMF Reference Model zones run down the side, sites across. The completeness checker scored every cell at 06:00: the study is 94.2% complete, 33 of 46 sites are ready in every zone and 37 gaps are open. Trial-level zones show a dash — they are filed once for the study — and late filings carry a red dot. The side panel lists the five weakest cells, Site 114 first.
“Each cell counts only the documents a site should have by today.”
Site 144 in Phoenix was activated on 29 Sep. Its Zone 06 cell is hatched, not red: the first IP shipment is planned for 14 Oct, so nothing in IP and Trial Supplies is due yet. Local lab documents become due at first patient, planned for 27 Oct, and visit reports after the first monitoring visit on 3 Nov.
“The cell turns on when that milestone is reached — until then a blank is not a gap.”
Harbourview Research Centre in Rotterdam has 12 of the 18 Site Management documents expected by today. The milestone strip shows why 18 are expected — selected 9 Mar, activated 30 Jun, first patient 14 Jul, a sub-investigator added 15 Sep, Visit 3 on 22 Sep — and 7 more are not expected yet. Five are missing, and three were filed late, the worst Dr. Elena Varga's Form FDA 1572: signed 12 Jun, filed 14 Sep, 94 days.
No spreadsheet knew Dr. Pieter Janssen had joined. The checker read it on page 3 of the Visit 3 monitoring report: he joined as Sub-Investigator on 15 Sep and performed PASI and IGA assessments for two subjects. It set that against delegation log v1, which has no entry for him, and section 6.3 of the VLT-302 TMF Plan v2.1, then opened gap G-1052 with each passage one click away.
Visit 3 report: “The Site Signature and Delegation Log has not yet been updated to include Dr. Janssen.”
The Zone 05 owner rule suggests Omar Haddad, the CRA for Sites 114 and 116. Lena assigns the delegation log v2 with the three gaps that go with it — Dr. Janssen's CV, GCP certificate and financial disclosure — due 13 Oct 2026, with a note on what to collect. For the late 1572, the gap follow-up agent drafts a request to Dr. Varga for a note to file.
“Nothing is sent until you press Send.”
The four Site 114 gaps now sit with Omar, assigned and requested. The register shows the 14 most urgent of the 37 open: Site 107's local lab normal ranges and lab certificate, 28 days open and overdue since 2 Oct, chased by Dana Okafor; Site 119's August temperature log with Ewa Nowak; a missing return record for expired IP kits at Site 129.
The expected-document list is rules from TMF Plan v2.1 and SOP TMF-104: when a site is activated, a staff member is added, an investigator signs a 1572, an amendment is approved, IP kits expire, a visit is held, a month of enrolment closes, IP ships or a site closes out, these documents are due by then. Re-deriving for 46 sites reads the milestones, applies the 9 rules and compares the result with the filed TMF.
“38,655 documents expected across 46 sites today · 1,214 more will become due at future milestones.”
The batch arrived at 08:12 from the site upload portal (162), the vendor file drop (51) and CRA email (27): 612 pages. The classifier matched each document to a TMF Reference Model v3.3.1 artifact; the metadata extractor read site, document date, version, signatures and people named. 228 were filed at 90% confidence or more, 6 held for a QC reviewer and 6 set aside — 4 duplicates found by content and 2 that are not trial documents.
“Site 114 is still red in Zone 05 Site Management: the delegation log v2 was not in this batch.”
The Visit 3 follow-up letter came in titled “Site Visit Summary”, which visit reports often use, so 29% went to Monitoring Visit Report. But it is a letter to the PI with agreed action items, and it says the full visit report is held by the sponsor. The classifier puts it at 05.04.04 Monitoring Visit Follow-up Letter, highlights every passage it relied on, and holds it for Lena.
Lena files the letter to 05.04.04 with the meaning of her signature — “Reviewed — filing and details are correct”. Site 114 Zone 05 moves from 67% to 72%, 13 of 18 expected documents. The delegation log v2 is still with Omar, and the cell stays red until it arrives and passes QC.
“Your signature, the time and the reason are written to the audit trail and cannot be changed.”
The same trial master file, seen by the four people who keep it inspection-ready — what their week looked like, and what it looks like now.
Four specialist agents file, extract, score and chase every document; the TMF lead confirms and signs.
Reads each incoming document and matches it to a TMF Reference Model artifact — zone, section and artifact — with its top three candidates, a confidence and the reasons, each tied to a passage. Flags duplicates and documents that are not trial documents.
Pulls the study, site, document date, version, language, people named and every signature with its date, marks each value with its confidence and source passage, and checks that dates and signatures are present.
Works out each site's expected documents from its milestones and from events it reads in the documents — staff changes, expired IP kits, amendments — scores every zone at every site for completeness and timeliness, and opens gaps with the evidence passage, a suggested owner and a due date.
Drafts the request to the site and notes to file, sends reminders on the owner rules, and closes a gap when the document arrives and passes QC.
Confirms low-confidence filings and signs. The agents propose; a named person decides.
Ask in plain words about a site, a document or a gap — or say what to change. Every answer points to the passage it came from.
Why is Site 114 red in Zone 05?
Dr. Pieter Janssen joined Site 114 as Sub-Investigator on 15 Sep 2026 and has already done PASI and IGA assessments. The Visit 3 report says the delegation log was not updated; the TMF plan expects an update within 14 days of a staff change. That leaves 5 documents missing: delegation log v2, his CV, GCP certificate, financial disclosure — and the Aug–Sep screening log. Timeliness is red too: Dr. Varga's Form FDA 1572, signed 12 Jun, reached the file on 14 Sep — 94 days against a 30-day target.
Which sites are least ready for an inspection?
Two sites are below 80% in a zone: Site 114 (Rotterdam) at 67% in Zone 05 Site Management — a new Sub-Investigator is not on the delegation log — and Site 107 (Leeds) at 78% in Zone 08, where the local lab ranges effective 1 July are not filed yet. Next lowest: Site 119 at 84% in Zone 06 and Site 122 at 86% in Zone 05.
Why is the Site 114 follow-up letter only 64%?
Its title reads “Site Visit Summary”, which visit reports often use — so 29% went to Monitoring Visit Report. But it is a letter to the PI with agreed actions, and it says the full report is held by the sponsor. That makes it a follow-up letter (05.04.04). Confirming it lifts Site 114 Zone 05 from 67% to 72%.
How does auto-filing work?
The Classifier files a document on its own when it is 90% confident or more and the date and signature checks pass. Anything lower goes to a QC reviewer, and delegation logs, consent forms and ethics approvals always do. A 10% weekly sample of automatic filings is QC-checked too — 97.4% were kept as filed.
13 screens from the working solution, on its sample data. Pick one to see it large.
The structure documents are filed to, the confidence that files on its own, the QC sample, the timeliness target and who approves what are settings — and the expected-document rules come from your own TMF plan.
| Setting | Default | Choose from |
|---|---|---|
| TMF structure | TMF Reference Model v3.3.1 | TMF Reference Model v3.3.1 · TMF Reference Model v3.2.0 · Company TMF index 2026 |
| File automatically at | 90% confidence | Step up or down; below it a QC reviewer confirms the filing |
| QC sample of automatic filings | 10% sample, checked every week | 10% sample · 5% sample · 20% sample · Every document |
| Always QC critical documents | On | Consent forms, delegation logs, ethics approvals, IP accountability logs |
| Timeliness target | 30 days from document date to filed | 30 days · 14 days · 60 days |
| QC sign-off | Lena Ortiz | Lena Ortiz · Dana Okafor · Any QC reviewer |
| Inspection export approver | Dr. Maya Chen | Dr. Maya Chen · Lena Ortiz |
| Who may mark a document “not required” | TMF lead | TMF lead · Clinical trial manager |
Every figure is labelled: a target the solution is built to, an estimate, a typical published result, or a proven one.
“demo” = seen in the working solution, on its sample study data · “target” = the design goal, measured in the live solution · “estimated” = our estimate · “typical” = published figures (Regulation (EU) 536/2014, Art. 57–58 — TMF content and archiving for at least 25 years). TMF Reference Model v3.3.1, ICH E6(R3) essential records and NIAID/DAIDS TMF oversight metrics (completeness, timeliness, quality) are named as context. People, sites, the sponsor and study VLT-302 named on this page are fictional — characters and sample data in the working solution.
A review of the electronic trial master file for the three things inspectors look at: completeness, timeliness and quality. eTMF Quality Check runs it every day instead of once a quarter — four agents file each document to the TMF Reference Model, work out what each site should have by today, and score every zone at every site on a heatmap, for the TMF lead to confirm and sign.
The completeness checker applies the expected-document rules from your TMF plan to each site's milestones — activation, first patient, visits, amendments, IP shipments and kit expiry — and to events it reads inside documents, such as a staff change recorded in a monitoring visit report. Documents not due yet show as hatched, not missing, so a red cell is a real gap.
Each filed document's days from document date to filed are compared with your timeliness target — 30 days by default, or 14 or 60. The heatmap switches between completeness and timeliness, and each late filing is listed with its days, like a Form FDA 1572 filed 94 days after signing on the sample study.
Only above the confidence you set — 90% by default — and only when the date and signature checks pass. Anything lower, and every consent form, delegation log, ethics approval and IP accountability log, goes to a QC reviewer who confirms with an electronic signature. A weekly sample of automatic filings, 10% by default, is QC-checked as well.
Yes. The agents file, score and draft; a QC reviewer confirms low-confidence filings and signs, only a person can mark a document “not required”, with a reason and approval, nothing is sent to a site until a person presses Send, and an inspection export needs the clinical trial manager's approval.
Yes. Documents can be filed to TMF Reference Model v3.3.1, v3.2.0 or your company TMF index, and the expected-document rules, deadlines, gap owners and reminders come from your TMF plan and SOPs. Gap owners and reminders are set by zone.
A read-only copy of the TMF for the study or a site, with the index, every document's metadata, QC record and audit trail, and the open gaps with their owners. It is sent to the clinical trial manager for approval first, and the inspector's access lasts 30 days.
The Agentic Solution Engine builds and deploys it from your requirements and documents — your TMF plan, TMF index, site milestones and a sample of trial documents — and it goes live once every quality gate has passed. We will walk you through it on your own documents first.
A checked first-draft protocol in days, in your approved language.
1-min demoClinical Study Report AuthoringResults drafted within days of database lock, linked to tables.
1-min demoProtocol Design OptimizationAvoidable amendments fixed before the committee meets, each flag tied to a past amendment.
1-min demoWe'll run eTMF Quality Check on a sample of your own trial documents, TMF plan and site milestones.