etmf

Electronic Trial Master File

Day 847 of your pivotal trial.

TMF documents file themselves by reference model. AI-drafted gap analysis and inspection packages. Unified with CTMS, EDC, and QMS.

Electronic Trial Master File

Day 847 of your pivotal trial

The FDA inspector opens her laptop. "Show me the informed consent for Subject 2847."

Your clinical operations lead searches. The consent should be in Zone 3, Section 3.1.3. It's not there. She tries the subject number. Nothing. She tries a date range. Hundreds of results, none matching.

Fifteen minutes pass. The inspector makes a note.

The consent exists. It was scanned at the site, emailed to the CRO, uploaded to their SharePoint, then exported to your TMF during the quarterly sync. But during the transfer, the metadata got stripped. It's filed as "scan_20240315_001.pdf" somewhere in the system.

The inspection continues. More documents take too long to find. By the end of day one, the inspector has enough observations for a Warning Letter.

Your pivotal trial—847 days in. Is now at risk.

TMF Reference Model Zones
Fig. 1 — TMF Reference Model Zones
§1

The 483s that write themselves

FDA 483 observations for TMF issues follow a pattern:

  • "Informed consent forms for multiple subjects could not be located."
  • "Monitoring visit reports missing for visits conducted between [dates]."
  • "Investigational product accountability records incomplete."

These aren't obscure requirements. The TMF exists to prove the trial was conducted properly. When documents are missing or unfindable, inspectors can't verify conduct. When they can't verify conduct, they question the data.

The question isn't whether you have the documents. It's whether you can produce them in seconds.

§2

Three zones. One truth.

The DIA TMF Reference Model is the universal language of trial documentation:

  • Zone 1: Central trial documents. Protocol, IB, regulatory submissions.
  • Zone 2: Global oversight. DMC charters, SAE reconciliation, coding dictionaries.
  • Zone 3: Site-level documents. Consents, delegation logs, monitoring reports.

Every inspector knows this structure. 01.01.01 is the final protocol. 03.01.03 is the signed consent. 05.01.01 is the monitoring visit report.

In Seal, the TMF Reference Model is built in. Documents classify automatically by zone, section, and artifact. Metadata captures study, site, country, subject. The structure enforces itself.

§3

Know what's missing before they ask

"What's your TMF completeness percentage?"

Inspectors ask because the answer reveals everything. A company tracking completeness knows what's there and what's missing. A company not tracking has no idea what the inspector might find.

Seal calculates completeness in real time:

  • Expected artifacts based on milestones. First subject enrolled? You need screening logs, consents, eligibility checklists.
  • Present artifacts matched against expectations.
  • Missing artifacts with aging. Not just "missing" but "missing for 47 days."
  • Overdue QC on documents filed but not reviewed.

The monitoring report from Site 107's March visit has been missing for 23 days. Someone follows up. It arrives. Problem solved. Before the inspector ever asks.

Completeness Metrics
Fig. 2 — Completeness Metrics
§4

Every document's complete journey

The inspector asks: "When was this consent received?"

In Seal, every document has a provenance chain:

  1. Origin. Site upload, CRO transfer, email, EDC export
  2. Receipt. System timestamp, not file metadata
  3. Classification. Auto-classified or manually filed
  4. QC Review. Who checked it, when, what they found
  5. Changes. Reclassifications, annotations, redactions

When inspectors ask about provenance, you show them the audit trail. Not memory. Not guesses. The immutable record.

Document QC Flow
Fig. 3 — Document QC Flow
§5

Sites and sponsors, one system

Investigator Site Files mirror the sponsor TMF with site-specific documentation. Protocol copies, delegation logs, screening logs, regulatory correspondence.

Seal manages both. Sites upload through a simple portal. Select document type, confirm subject, upload. Three clicks. They see what's missing for their patients. They confirm receipt.

The sponsor sees site-level completeness alongside their own. No surprises about what's at the site versus what's in the central TMF.

§6

Archive today, find it in 2045

The TMF must remain accessible for 15 to 25 years. Your current platform may not exist. Your organization may not exist in its current form. But the documents must remain findable.

Seal's archival:

  • Format preservation. Original files plus rendered PDFs
  • Full searchability. Archived studies are searchable, not just retrievable
  • Same structure. An archived TMF looks exactly like an active one

When FDA has questions about your approved drug in 2045, you need answers in minutes.

Capabilities

01TMF Reference Model
DIA TMF Reference Model structure built in. Zones, sections, artifacts. Documents classify automatically. Inspectors see the structure they expect.
02Real-Time Completeness
Know exactly what's missing before the inspector asks. Completeness metrics by study, site, country, milestone. Gap reports update automatically.
03Multi-Source Collection
Documents from sites, CROs, labs, internal teams, EDC exports. All flow into one TMF. Automatic classification based on content and metadata.
04Quality Control
Every document reviewed for legibility, completeness, and classification accuracy. Issues flagged, routed for correction, tracked to resolution.
05Investigator Site Files
Manage site-level documentation alongside sponsor TMF. Sites access their files through the same system. Bidirectional document flow.
06Complete Audit Trail
Every document's journey: arrival, classification, reviews, annotations. When inspectors ask about provenance, you have the complete answer.
07Study Close-Out
Archive TMF with full organization preserved. 15-25 year retention with maintained searchability. Ready for future regulatory queries.
08CTMS Integration
Connect to your Clinical Trial Management System. Study milestones drive expected documents. Site status reflects TMF completeness.
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TMF Reference Model
TMF Reference Model

Entities

Entity
Description
Kind
TMF Document
Essential documents for trial reconstruction. Classified by zone, section, artifact type.
type
Zone
TMF Reference Model zones: Trial Management, Central Trial Documents, Site-Level Documents.
type
Section
Sections within zones: Regulatory, IRB/Ethics, Investigational Product, Safety, etc.
type
Artifact Type
Specific document types: Informed Consent, Protocol Amendment, Monitoring Visit Report, etc.
type
Protocol
The trial protocol and amendments. Foundation of the entire TMF.
instance
Informed Consent
Patient consent forms. The document that matters most to inspectors.
instance
Monitoring Visit Report
Records of site monitoring. Evidence that oversight happened.
instance
Study
Clinical trial. The organizing unit for all TMF documentation.
type
Site
Investigator site. Has its own Investigator Site File mirroring sponsor TMF.
type
Completeness Metric
Real-time calculation of expected vs. present documents by study, site, milestone.
type
QC Review
Quality check on filed documents. Legibility, completeness, classification accuracy.
type

FAQ

Documents are analyzed for content, filename patterns, and metadata. A monitoring visit report from Site 101 for Study ABC is automatically classified to the correct zone, section, and artifact type, with study and site associations. You can review and correct classifications, but most documents file themselves correctly.
Yes. We support migration from Veeva Vault, Montrium, Florence, and file-based TMFs. The TMF Reference Model structure maps across systems. Most migrations preserve classification and metadata.
Sites get role-based access to their Investigator Site File. They can upload documents, view filed materials, and track their own completeness. Site access is logged and auditable. Sponsors see everything; sites see only their portion.
CROs can have delegated access based on their contracted responsibilities. They see the studies and sites they manage. Document flow from CRO to sponsor TMF can be automated or require sponsor approval, depending on your preference.
Seal connects to EDC systems to pull trial data that becomes TMF documentation. Subject enrollment records, SAE reports, protocol deviation logs. These flow into the appropriate TMF sections automatically.
You grant inspector access to specific studies. They see the TMF structure, can search and filter documents, and review audit trails. You track exactly what they accessed. When they request specific documents, you retrieve them in seconds.

Go live in 48 hours.