# Investigator Agreement - Regulatory Reference

Use this reference to confirm mandatory citations, timelines, and document controls for FDA-regulated studies.

## Governing Framework by Study Type

| Study type | Primary FDA framework | Core investigator duties |
|---|---|---|
| Drug/Biologic | 21 CFR Part 312 | Protocol compliance, subject safety, informed consent, records/reports |
| Device | 21 CFR Part 812 | Protocol compliance, investigational device control, records/reports |
| Both | 21 CFR Part 50, 21 CFR Part 56, ICH E6(R2) | Consent, IRB oversight, GCP documentation and data integrity |

## Core Citation Set

| Citation | Use in agreement |
|---|---|
| 21 CFR 312.60 | PI responsibility to ensure investigation follows protocol and regulations |
| 21 CFR 812.110 | Device-investigator responsibilities parallel to Part 312 duties |
| 21 CFR 312.62 / 812.140 | Investigator recordkeeping and investigational product/device accountability |
| 21 CFR Part 50 | Informed consent requirements |
| 21 CFR Part 56 | IRB composition, function, review requirements |
| 21 CFR Part 54 | Financial disclosure by clinical investigators |
| ICH E6(R2) Sections 4 and 8 | Delegation, PI oversight, essential documents, data quality controls |
| 45 CFR 164 | HIPAA privacy/security obligations for PHI in covered settings |
| 45 CFR 46 Subparts B/C/D | Additional protections for vulnerable populations (if applicable) |

## Timeline Baselines

These are drafting defaults. Verify protocol, sponsor SOP, IRB policy, and local law before final text.

| Event | Baseline timeline | Recipient |
|---|---|---|
| SAE awareness | Within 24 hours | Sponsor |
| FDA or authority inspection notice received | Within 24 hours | Sponsor |
| Protocol deviation for immediate hazard | Immediate implementation allowed; report promptly per IRB/sponsor policy | Sponsor and IRB |
| Copy of FDA 483/EIR/warning letter | Within 5 business days | Sponsor |
| IRB correspondence after submission/decision | Within 5 business days | Sponsor |

## Essential Document Checklist

- FDA Form 1572 (or device-study equivalent documentation package)
- Current protocol and all amendments
- IRB approvals, continuing review notices, and correspondence
- Signed and dated informed consent forms
- Delegation of authority log and training evidence
- Investigator brochure/instructions for use (as applicable)
- Investigational product/device accountability logs
- Source data and CRF/EDC audit trail records
- Financial disclosure records and updates
- Monitoring letters and CAPA documentation

## Records Retention Rule

Draft the retention clause as the longest applicable period among:

1. FDA baseline retention under the applicable part (for example, 2 years after marketing application approval or discontinuation notice).
2. Institutional retention policy.
3. State-law retention requirements.
4. Contractual retention requirements in the study documents.

Include sponsor notice before destruction.

## Financial and Compliance Guardrails

- Compensation terms should state FMV basis and anti-kickback compliance.
- Include financial disclosure update duties during the study.
- Add anti-corruption/export controls/sanctions compliance reps where required by sponsor policy.
- For public institutions that cannot indemnify, use insurance-backed risk allocation terms instead of prohibited indemnity language.

## Device-Study Substitution Map

When adapting a drug-focused template for device studies:

- Replace Part 312 citations with Part 812 equivalents where required.
- Replace product references with device/investigational device terminology.
- Confirm consent and IRB language still aligns with Parts 50 and 56.
- Confirm accountability and return/disposition language matches device handling practice.

## Citation Verification Pass

Before finalizing:

- Verify every CFR citation and section number against current text.
- Confirm sponsor SOP timelines do not conflict with agreement timelines.
- Confirm IRB policy references match the reviewing IRB's current SOPs.
- Mark unresolved legal/jurisdictional uncertainty as `[VERIFY]`.