Collecting, Filing and Staying Inspection-Ready
Part of Clinical Research Associate (CRA) Training: Regulatory Documents and the Site File.
About 6 minutes. Free, in your language, no account needed.
Why this matters
Collecting documents is the first big task of start-up and it never stops. A site file is not built once; it decays continuously as staff change, approvals expire and versions are superseded.
The CRA is the person who notices the decay.
The CRA's role in collection
A start-up specialist or project manager often leads document collection. The CRA makes sure it actually happens:
- The site knows exactly what is required.
- Deadlines are communicated clearly.
- Documents are collected promptly and are complete and accurate.
- Filed documents match approved versions.
- The site file is organized and inspection-ready at all times.
You are the bridge between operational readiness and regulatory compliance, which in practice means you are the person who asks the same question four times until it is answered.
The tools
- A regulatory document tracking log with columns for the required document, its version, its status, its expiry date, and any corrections needed.
- The trial master file, the sponsor's official repository. Ensure that what the site holds matches what has been uploaded.
- A start-up checklist establishing what must exist before the initiation visit.
- A site file table of contents, which makes gaps visible.
- The sponsor's electronic systems, where documents are uploaded and where you may be responsible for confirming upload.
Use the sponsor's tools rather than your own. Your personal spreadsheet is not a record anyone else can find.
Keeping the file current
Documents are not static. Four maintenance obligations recur.
When staff change. New coordinators need a CV, training records and a delegation entry. Leavers need an end date on the delegation log. A change of principal investigator requires an updated Form FDA 1572 where applicable, ethics and sponsor notification, and a new CV, license and training record. Verify that new staff complete all required training before performing tasks.
Version control. Protocol, consent form, Investigator's Brochure, laboratory and pharmacy manuals, safety updates, recruitment materials, and site SOPs where filed. Confirm current versions are in use and superseded versions properly archived, and help the site build habits that prevent version confusion.
Expiry dates. Investigator and sub-investigator licenses, GCP certificates, ethics approvals, and laboratory accreditation. Track them in the regulatory log, notify the site proactively, and follow up until the renewal is filed.
Inspection readiness. Documents filed in the correct sections; clean, complete and legible; ordered; free of loose pages and missing signatures; and accessible on demand.
E6(R3) Appendix C requires essential records to remain complete, readable and readily available, and directly accessible on request by regulatory authorities, monitors and auditors, with any alteration traceable. It also requires a record of where essential records are located, including source records.
Retention
ICH E6(R3) states no retention period in years. Section 3.16.3(b) requires the sponsor to inform the investigator, institution and, where appropriate, service providers in writing of the retention requirements, and to notify them in writing when records are no longer needed. Section 2.12.12 requires the site to retain essential records for the period required by applicable regulation, or until the sponsor says they are no longer needed, whichever is longest.
Section 2.12.13 requires the site to keep the sponsor informed of who is responsible for maintaining the essential records during the retention period.
What you check: the sponsor's written retention instruction is in the site file, and a named person is responsible for the archive. If a site cannot produce either, it does not know how long to keep anything.
Common issues and what to do
| Issue | CRA action |
|---|---|
| Missing signature or date | Request a corrected version immediately; confirm correct dating; never date on someone's behalf |
| Outdated protocol or consent form still in use | Ensure the current version is implemented and old copies removed the same day; verify training |
| Ethics continuing review lapsed | Escalate urgently; study procedures must stop until resolved |
| Staff performing tasks not on the delegation log | Flag as non-compliance; update the log going forward; assess affected data |
| Poorly organized site file | Work with the site's regulatory contact to reorganize; supply a table of contents |
| Missing safety letter or investigator review signature | Confirm receipt and review; file properly |
| Temperature log gaps | Investigate; ensure excursions are assessed; document corrective action |
In practice
Leah reviews a site file six months into VT-301 and finds the ethics committee's continuing review approval expired eleven days ago.
She does not finish the visit and mention it in the report. She tells the investigator and the coordinator immediately, and confirms that study procedures stop until approval is restored. She notifies her project manager the same day.
The site had submitted the renewal on time. The committee had requested a clarification, and the email went to a shared inbox nobody monitored.
Two participants had visits during the lapsed period. Those are documented as deviations and reported. Approval is restored within a week.
The corrective action is not "be more careful". The site moves ethics correspondence to a named person's inbox, and puts the continuing review date in a shared calendar with a reminder 90 days ahead. Leah adds the expiry date to her own pre-visit checklist for every site.
Expiry dates are the most predictable findings in clinical research, which makes them the least excusable.
Key takeaways
- The site file decays continuously as staff change, approvals expire and versions are superseded, and the CRA is the person who notices.
- Use the sponsor's tracking tools and trial master file, and confirm that what the site holds matches what has been uploaded.
- Appendix C requires essential records to be complete, readable, readily available and directly accessible on request, with a maintained record of where they are located.
- E6(R3) states no retention period in years; check that the sponsor's written retention instruction is in the site file and that a named person is responsible for the archive.
- A lapsed ethics continuing review stops study activity immediately, and expiry dates belong on both the site's calendar and the CRA's pre-visit checklist.