SOP-03
IRB Oversight, Essential Records and Study Activation
- Number
- SOP-03
- Category
- Core
- Edition
- Lean Edition 2.0
- Approx. pages
- 7
[YELLOW] the site fills in. [DEFAULT: green] a value the site may keep or change.
On this page
1. Purpose
This SOP describes how [SITE NAME] obtains and keeps IRB approval, uses only IRB-approved materials, sets up and maintains the Investigator Site File (ISF), and confirms through the Study Activation Checklist (F-205-01) that every start-up requirement is met before the first study procedure.
2. Scope
This SOP applies to every study at [SITE NAME] from the first IRB submission through IRB closure and ISF archiving, and to activation of a new location or new PI on an active study. A central (commercial) IRB is the default; local IRBs and reliance arrangements are covered where a sponsor, funder or institution requires them. Each IRB's written policies are part of the requirements the site follows.
Reportable events are assessed under SOP-09 and SOP-08; this SOP covers how submissions are made and recorded. Contracts, budgets and coverage analysis are in SOP-M2, if adopted; the research billing confirmation every study needs before activation is in 5.10.5. Archiving is in SOP-12; close-out in SOP-15.
3. Responsibilities
| Role | Responsibilities |
|---|---|
| Principal Investigator (PI) | Responsible for IRB approval and compliance and for the site's essential records. Approves each site submission personally. Approves activation on F-205-01. |
| Regulatory Coordinator | Prepares and submits site submissions, tracks approval dates, distributes approved documents and withdraws superseded ones. Sets up and maintains the ISF, F-204-01 and F-205-01. |
| Lead CRC / CRC | Uses only current approved materials. Coordinates qualification and initiation visits, source plan, supplies and system access. Hands study records to the Regulatory Coordinator. |
| Research Pharmacist or IP Manager | Prepares IP storage, receives the first shipment, keeps IP records for the ISF. |
| Finance / Contracts Lead | Confirms the clinical trial agreement (CTA) and budget are executed and records them on F-205-01. Records the research billing confirmation and the no-claim checks on F-205-01 (5.10.5). |
| Site Director | Confirms the IRB of record, approves any non-default IRB or reliance agreement, confirms staffing and facilities, and co-approves activation. |
| Quality Lead | Checks IRB status, document versions and ISF completeness in QC (SOP-14). Approves any eISF system under SOP-12. |
4. Definitions
| Term | Definition |
|---|---|
| Institutional Review Board (IRB) | A board formally designated to review, approve the initiation of and periodically review research involving human subjects (21 CFR 56.102(g)). |
| IRB of record | The IRB responsible for review and oversight of the study at [SITE NAME]. |
| Reliance agreement | A written agreement under which an organization relies on another organization's IRB. |
| Continuing review | Periodic re-review of approved research; at least annually for FDA-regulated research (21 CFR 56.109(f)). |
| Lapse in approval | The period after approval expires and before it is renewed. |
| Essential records | Records that individually and collectively permit evaluation of the conduct of a trial and the quality of its data (ICH E6(R3) Appendix C). |
| Investigator Site File (ISF) | The investigator's repository of the site's essential records, paper or electronic (eISF). |
| Record location map | The part of F-204-01 listing where each essential record held outside the ISF is kept, who controls it and how the site keeps access. |
| Note to file (NTF) | A dated, signed explanation of a discrepancy, absence or decision, recorded on F-306-01. |
| Study activation | The point at which F-205-01 is approved and the sponsor has given written notice that the site may enroll. |
| Study-specific procedure | Any activity done only because of the study, including research-only tests, eligibility assessments beyond standard care and IP administration. |
5. Procedure
5.1 IRB of record and IRB requirements
5.1.1
The Regulatory Coordinator confirms the IRB of record with the sponsor and records it on F-205-01. The default is the central IRB the sponsor chooses; the Site Director approves any other.
5.1.2
A local IRB, institutional acknowledgment or reliance agreement is needed when federally funded cooperative research requires a single IRB (45 CFR 46.114; a Federalwide Assurance may be needed), when a hospital location requires its own review, or when state law or the sponsor requires it. The Site Director signs any reliance agreement; the Regulatory Coordinator files it and records on F-205-01 the local requirements the site must still meet.
5.1.3
The IRB's reportable-event categories, windows and submission route are recorded once, on the F-502-01 IRB page (SOP-09, 5.1.2); F-205-01 confirms that page is complete for the study. The Regulatory Coordinator records on F-205-01 what the IRB requires for personnel changes, location changes, deviations, continuing review and closure. Every "as the IRB requires" in this library is answered from these two records. F-205-01 also records the site's IRB portal accounts and who may submit for each investigator.
5.2 Submissions and approval
5.2.1
For central IRB studies, the Regulatory Coordinator confirms with the sponsor who submits what; usually the sponsor submits the protocol, Investigator's Brochure (IB) and master consent form, and the site its site-specific application.
5.2.2
The site submission contains what the IRB requires, including a site consent form and HIPAA authorization whose costs and injury language match the CTA, COI disclosures (SOP-02) and Appendix A state law entries.
5.2.3
The PI reviews and approves each site submission before it is sent. Where the portal needs the PI's electronic signature, the PI signs personally; staff never use the PI's credentials. The Regulatory Coordinator saves the confirmation and logs the submission in [IRB TRACKER].
5.2.4
The Regulatory Coordinator answers IRB requests for modification within the IRB's deadline, or [DEFAULT: 5 business days] if none is set.
5.2.5
On approval, the Regulatory Coordinator checks protocol version, PI and every location, consent versions and languages, recruitment materials, dates and conditions, and returns errors to the IRB before use. The Regulatory Coordinator files the approval in the ISF, sends copies to the sponsor as required, records it on F-205-01 and enters the next review date in [IRB TRACKER].
5.2.6
The Regulatory Coordinator distributes approved consent and participant materials, records version and release date on F-301-02, and removes superseded versions from clinic folders, shared drives, eConsent platforms and printed stock the same day (5.7.2). Staff do not alter approved documents, including formatting or contact details.
5.3 Amendments and changes
5.3.1
Changes to the protocol, consent, participant or recruitment materials, PI, locations or other items the IRB lists are approved by the IRB before use. The sponsor usually submits protocol amendments and master consent revisions; the Regulatory Coordinator submits site-specific changes.
5.3.2
A change may be made before IRB approval only to eliminate an apparent immediate hazard to participants; notice to the sponsor and IRB and the record follow SOP-08, 5.2.
5.3.3
Administrative changes the IRB does not require to be submitted (for example a new monitor) are recorded on F-306-01.
5.3.4
Before an approved amendment is implemented, the Regulatory Coordinator completes 5.2.5 and 5.2.6, the Lead CRC confirms staff training on the change (SOP-01) and re-consent where required (SOP-04), and any budget or billing updates under SOP-M2 (if adopted) are made.
5.3.5
IND safety reports go to the IRB, or the sponsor's submission on the investigator's behalf is confirmed and filed, under SOP-09, 5.7.3. Where the IRB states in writing that it will not accept them, the Regulatory Coordinator files that instruction. Every safety report received is filed in the ISF.
5.4 Continuing review and lapse
5.4.1
The Regulatory Coordinator tracks each study's continuing review or check-in date and sets reminders [DEFAULT: 60 and 30 days] before the IRB's deadline. FDA-regulated studies have continuing review at least yearly, including in follow-up, until IRB closure. Common Rule-only studies follow the IRB.
5.4.2
The Regulatory Coordinator prepares the submission with enrollment, safety, deviation and new-information data from the Lead CRC, the PI approves it, and it is submitted in time for review before expiry.
5.4.3
If approval lapses, the Regulatory Coordinator tells the PI, Lead CRC, Site Director and sponsor the same day. All research activity stops, including screening and consent; enrolled participants continue interventions only where the IRB, asked immediately by the PI, finds it in their best interests. The Regulatory Coordinator submits for renewal at once, the lapse is recorded as a deviation with CAPA (SOP-08), and activity resumes only after renewed approval is filed.
5.5 Reports to the IRB and closure
5.5.1
Through the Regulatory Coordinator, the PI reports to the IRB per its policy: unanticipated problems (SOP-09); immediate-hazard and other reportable deviations (SOP-08); changes significantly affecting conduct or increasing risk; new information that may adversely affect safety or conduct; sponsor suspension or termination, or PI termination without sponsor agreement, with reasons; and device reports (SOP-09, 5.8.2). Each report, confirmation and IRB response is filed in the ISF and logged in [IRB TRACKER].
5.5.2
If the IRB suspends or terminates approval, the PI tells the sponsor within [DEFAULT: 1 business day] (device studies: SOP-09, 5.8.2) and follows the IRB's instructions for enrolled participants.
5.5.3
IRB correspondence recording decisions is filed; calls affecting the study are recorded on F-306-01.
5.5.4
The Regulatory Coordinator submits the closure report after the last participant activity, completion of identifiable data collection and participant-contact queries, and sponsor confirmation, per IRB policy and SOP-15. Closure and acknowledgment are filed and recorded on F-601-01.
5.6 ISF set-up and content
5.6.1
Before the qualification visit or at the latest the initiation visit, the Regulatory Coordinator sets up the ISF on F-204-01, recording the format, and for a hybrid file which copy is the original. A sponsor index may be used if mapped to F-204-01. A sponsor eISF is accepted only with written confirmation of continuous access and a complete readable copy, or continued access, for the retention period.
5.6.2
F-204-01 names one controlling log for each study log (delegation, IP, deviations, screening): the sponsor's or the site's. The unused site form is marked "superseded by sponsor log".
5.6.3
Site-wide records (SOPs, staff and equipment files) may be held centrally with a pointer. Internal financial records and F-200-01 stay in [CONTRACTS FOLDER]; the executed CTA and budget are essential records. Signed consents, the participant identification code list and other identifying records are kept separately and securely with a pointer (SOP-12).
5.6.4
The Regulatory Coordinator completes the record location map at activation and updates it when a system or location is added: for each record held outside the ISF (EDC, IRT, eCOA, portals, EHR, eConsent, temperature system), the location, who controls it, how the site gets access and how it keeps a copy at close-out.
5.7 Filing, version control and notes to file
5.7.1
Staff give records to the Regulatory Coordinator, or file them if delegated, within [DEFAULT: 10 business days]; safety reports and IRB approvals within [DEFAULT: 5 business days]. Each record is legible and identifies protocol, title, version and date, with signatures where required.
5.7.2
One version of each controlled study document is current; superseded versions are kept, marked "superseded" with the date. Log pages are numbered in order. Emails recording decisions are filed as PDF.
5.7.3
Scanned wet-ink originals are kept unless the Quality Lead confirms a certified copy process under SOP-12 permits destruction.
5.7.4
A note to file (F-306-01) explains a missing record, discrepancy or undocumented decision: facts, reason, corrective action and any deviation or CAPA number, signed by the author (and the PI for investigator matters). It is written when the issue is found, gives the event and writing dates, and never replaces a required record, corrects source or substitutes for a deviation report.
5.8 Access and maintenance
5.8.1
The paper ISF is locked and limited to study staff; eISF access follows SOP-12. Monitors, auditors and inspectors get direct or read-only access on request (SOP-13). Records removed for copying are logged and returned the same day.
5.8.2
Before each monitoring visit, the Regulatory Coordinator checks the ISF against F-204-01 and records the date.
5.8.3
Originals stay at the site; the sponsor receives copies for its trial master file. Identifying records go to the sponsor only as consent and HIPAA authorization allow. Unblinding records are filed separately with restricted access (SOP-05).
5.9 Qualification visit, regulatory packet and initiation
5.9.1
For a qualification visit, the Lead CRC prepares aggregate population data (no PHI), staff, facility, IP storage, equipment and laboratory information, and the SOP index (F-100-03). Visitors are escorted and see no participant records or other sponsors' confidential materials. The PI answers oversight and population questions personally.
5.9.2
After selection, the Regulatory Coordinator sends the regulatory packet the sponsor requests (for example 1572 or investigator agreement, CVs, licenses, financial disclosure and laboratory certificates), files a copy and records each item on F-205-01.
5.9.3
The PI and all staff who will be delegated attend the initiation visit or complete recorded make-up training before study tasks. Attendance and Q&A are filed, and training is recorded on F-103-01. Before first enrollment, the Lead CRC and PI record the source document plan (SOP-07).
5.9.4
The IP Manager prepares monitored storage and receives the first shipment under SOP-06. The Lead CRC confirms supplies, equipment calibration (SOP-11) and individual system access (F-401-01).
5.10 Study Activation Checklist and activation
5.10.1
The Regulatory Coordinator keeps F-205-01 through start-up. Each item is marked complete with date and record location, or not applicable with a reason. Minimum items:
- IRB approval of protocol, consent, recruitment and participant materials, and any local review or reliance agreement
- executed CTA and budget; research billing confirmation (5.10.5)
- signed 1572 or investigator agreement, financial disclosures, protocol signature page; covering investigator named and listed for the study (SOP-16, 5.6.2)
- CVs, licenses, GCP and debarment and exclusion screening for all delegated staff (SOP-01)
- F-302-01 signed by the PI; initiation and protocol training recorded
- IP received, stored and released with logs started (F-304-01, F-304-02, F-304-04); or, where the sponsor ships IP after first consent or randomization, the shipping trigger and lead time documented, with receipt and release required before first dose (SOP-06)
- DEA and state registrations for controlled-substance IP at each storage location (SOP-06)
- blinded studies: emergency unblinding procedure available, blinded and unblinded roles with backups, separated records and IP areas (SOP-05)
- supplies in date, laboratory certificates and normal ranges filed, equipment calibrated, system access for all delegated users
- source plan and worksheets ready (SOP-07); ISF and F-204-01 current
- AE, SAE and pregnancy trackers opened (F-500-01, F-501-01, F-503-01); the F-502-01 IRB page and IRB requirements (5.1.3)
- record retention period recorded (SOP-12)
- recruitment materials ready (SOP-M3, if adopted) and participant payment set up (SOP-10)
- study QC plan recorded on F-700-01 (SOP-14)
- written sponsor activation
5.10.2
The Lead CRC and Regulatory Coordinator review F-205-01. For the first study of a new PI, the Quality Lead checks it before approval (the Site Director checks it where the Quality Lead prepared it). The PI and Site Director sign it.
5.10.3
No one consents a participant, performs a study-specific procedure, randomizes or dispenses IP before F-205-01 is approved and sponsor activation is received. Pre-screening follows the single rule in SOP-05. Any procedure before activation is a deviation (SOP-08).
5.10.4
A new PI, location or laboratory (SOP-02, 5.4.4) needs IRB approval where required and sponsor confirmation before activity, recorded on a new F-205-01 limited to the changed items.
5.10.5
Research billing. Before activation, the Finance / Contracts Lead records one of the following on F-205-01:
- a no-billing attestation: no insurer or participant is billed for any protocol item, the budget covers every protocol item and the consent form implies no cost to the participant
- that the coverage analysis on F-202-01 is approved and matches the budget, CTA and consent form (SOP-M2, 5.9.5)
A site without SOP-M2 uses only the attestation. Where [SITE NAME] also bills clinical care, the Lead CRC flags each enrolled participant in [PRACTICE MANAGEMENT SYSTEM], and before each sponsor invoice and at closeout the Finance / Contracts Lead checks that no claim was created for a study item, recording the check on F-205-01. A claim found is a deviation with CAPA (SOP-08), corrected under SOP-M2, 5.9.11 or by the Site Director with [LEGAL COUNSEL].
5.11 Close-out and retention
5.11.1
At close-out, the Regulatory Coordinator reconciles the ISF against F-204-01 and the record location map, obtains the site's records from each external system (including EDC and eConsent audit trails) before access ends, and records gaps and receipt on F-601-01 (SOP-15).
5.11.2
The ISF is retained under SOP-12 for the longest of 21 CFR 312.62(c) or 812.140(d), the CTA, state law (Appendix A) and the sponsor's written release, and the sponsor is told who is responsible for the records.
6. Related Forms and SOPs
- F-100-03 SOP Master Index and Review Schedule
- F-103-01 Staff Training Log
- F-204-01 Investigator Site File Index
- F-205-01 Study Activation Checklist
- F-301-02 Consent Form Version Control Log
- F-302-01 Delegation of Authority Log
- F-304-01 Investigational Product Accountability Log
- F-304-02 Temperature Monitoring Log
- F-304-04 Participant IP Dispensing and Return Log
- F-306-01 Note to File
- F-200-01 Study Feasibility Assessment (SOP-M2, if adopted)
- F-202-01 Coverage Analysis Worksheet (SOP-M2, if adopted)
- F-401-01 Computerized System Inventory and Access Log
- F-500-01 Adverse Event Assessment Worksheet
- F-501-01 SAE Reporting Tracker
- F-502-01 Reportable New Information Assessment
- F-503-01 Pregnancy Report Tracker
- F-601-01 Study Closeout Checklist
- F-700-01 Internal QC Review Checklist
- Appendix A State Law Worksheet
- SOP-01 SOP Control, Training and Qualification
- SOP-02 Roles, PI Oversight, Delegation and Conflicts of Interest
- SOP-04 Informed Consent
- SOP-05 Pre-Screening, Screening, Eligibility, Randomization and Blinding
- SOP-06 Investigational Product Management
- SOP-07 Source Documentation and EDC
- SOP-08 Protocol Deviations and CAPA
- SOP-09 Safety Reporting (AEs, SAEs, IRB-Reportable Events, Pregnancy)
- SOP-10 Participant Retention, Withdrawal and Payments
- SOP-11 Specimens, Equipment and Laboratories
- SOP-12 Privacy, Electronic Systems and Record Retention
- SOP-13 Monitoring, Audits and Inspections
- SOP-14 Quality Control and Quality Review
- SOP-15 Study Closeout
- SOP-M2 Feasibility, Contracts, Budgets and Research Billing (if adopted)
- SOP-M3 Recruitment and Advertising (if adopted)
7. References
| Reference | Title |
|---|---|
| 21 CFR 56 | Institutional Review Boards (including 56.103, 56.108, 56.109) |
| 21 CFR 312.53, 312.62, 312.64, 312.66 | Form FDA 1572; records; investigator reports; assurance of IRB review |
| 21 CFR 812.43, 812.140, 812.150 | Device investigator agreements, records and reports |
| 21 CFR 11 | Electronic Records; Electronic Signatures |
| 45 CFR 46.103, 46.109, 46.114 | Common Rule: assurance, IRB review, cooperative research |
| ICH E6(R3) Annex 1, 1, 2.4 to 2.6, 2.12 and 2.13 | IRB/IEC; communication with IRB; protocol compliance; termination; records; reports |
| ICH E6(R3) Appendix C | Essential Records for the Conduct of a Clinical Trial |
| FDA Guidance (2012) | IRB Continuing Review after Clinical Investigation Approval |
| FDA Guidance (2006) | Using a Centralized IRB Review Process in Multicenter Clinical Trials |
| FDA Guidance (December 2025) | Investigator Responsibilities: Safety Reporting for Investigational Drugs and Devices |
| FDA Guidance (Oct 2024) | Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers |
| Reference Edition SOP-203, SOP-204 and SOP-205 | Background and full text |
Independent Site SOP Library. Licensed CC BY-NC 4.0 by the American Institute for Medical Research (AIMR), with added permission for any site's internal use (license terms). Not legal advice: each adopting site confirms state law, IRB and sponsor requirements with its own counsel and owns every step it approves.