Sponsor-Investigator Responsibilities (IND/IDE Holder)

1. Purpose

This SOP describes the additional obligations that apply when an investigator at [SITE NAME] both initiates and conducts a clinical investigation as a sponsor-investigator, including the decision whether an IND or IDE is needed, the submission, the sponsor duties that follow, safety and progress reporting to FDA, and ClinicalTrials.gov registration and results reporting. It is a supplemental SOP. It is used only if the site conducts investigator-initiated trials (IITs) of FDA-regulated products.

2. Scope

This SOP applies when a PI at [SITE NAME] is, or proposes to be, the sponsor of a clinical investigation of a drug, biologic or device, whether or not the investigation needs an IND or IDE, and whether or not a company provides product or funding.

It does not apply to industry-sponsored studies, where the company is the sponsor, or to studies where another institution or a CRO holds the IND or IDE and the site participates only as an investigator site.

This SOP is high-level. Sponsor obligations are extensive and product-specific. The site's other SOPs continue to apply to the investigator side of the study. Where FDA, the IRB, a funder or a product supplier sets a stricter requirement, follow it.

3. Responsibilities

4. Definitions

5. Procedure

5.1 Before agreeing to sponsor

• protocol and consent development, statistical design and data management
• monitoring by a qualified person outside the study team (site practice; see 5.5.3)
• safety assessment and expedited reporting to FDA
• regulatory submissions and annual reporting
• product supply, labeling, storage and accountability
• insurance for sponsor liability, and participant injury coverage
• ClinicalTrials.gov registration and results reporting

5.2 Drug and biologic studies: does the study need an IND?

• it is not intended to be reported to FDA as a well-controlled study supporting a new indication or any other significant labeling change
• for a prescription drug, it is not intended to support a significant change in advertising
• it does not involve a route of administration, dose, patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks)
• it is conducted in compliance with IRB review (21 CFR 56) and informed consent (21 CFR 50) requirements
• it complies with 21 CFR 312.7 (no promotion or commercialization of the investigational drug)

5.3 Device studies: risk determination and IDE pathway

• device labeling under 21 CFR 812.5
• IRB approval after presenting the NSR rationale, maintained throughout
• informed consent under 21 CFR 50
• monitoring under 21 CFR 812.46
• sponsor records under 21 CFR 812.140(b)(4) and (5), and sponsor reports under 21 CFR 812.150(b)(1) to (3) and (5) to (10)
• investigator records under 21 CFR 812.140(a)(3)(i) and investigator reports under 21 CFR 812.150(a)(1), (2), (5) and (7)
• the prohibitions on promotion and other practices in 21 CFR 812.7

5.4 IND or IDE submission

5.5 Sponsor duties during the study

• selecting qualified investigators and obtaining a signed Form FDA 1572, CV and financial disclosure information from each (21 CFR 312.53). Investigators must commit to update financial information during the study and for 1 year after completion (21 CFR 312.53(c)(4)).
• informing investigators of new observations, particularly adverse effects and safe use (21 CFR 312.55)
• monitoring the progress of the investigation, securing compliance or ending an investigator's participation and notifying FDA if compliance cannot be secured (21 CFR 312.56)
• keeping sponsor records of drug receipt, shipment and disposition and of investigator financial interests (21 CFR 312.57)
• permitting FDA inspection of sponsor records (21 CFR 312.58)
• ensuring return or authorized disposition of unused drug (21 CFR 312.59)

5.6 Safety reporting by the sponsor-investigator

• serious and unexpected suspected adverse reactions
• findings from other studies, animal or in vitro testing that suggest a significant risk to humans
• a clinically important increase in the rate of serious suspected adverse reactions over that listed in the protocol or investigator's brochure

5.7 Amendments and annual reports (IND)

• New protocol: submit to FDA. The study may begin once the protocol has been submitted to FDA and approved by the IRB.
• Change in protocol: submit any change that significantly affects participant safety (Phase 1), or safety, scope or scientific quality (Phase 2 and 3), and implement only after submission to FDA and IRB approval, except a change to eliminate an apparent immediate hazard, which may be implemented at once with FDA and IRB notification afterward.
• New investigator: notify FDA within 30 days of the investigator being added.

5.8 ClinicalTrials.gov

• registers the trial no later than 21 calendar days after the first participant is enrolled (42 CFR 11.24)
• updates the record as required, at least once every 12 months, and within the shorter timeframes required for specific changes such as recruitment status (42 CFR 11.64)
• submits results no later than 1 year after the primary completion date, unless a delay is allowed (42 CFR 11.44)

5.9 Study completion and IND or IDE closure

• final reports to the IRB and, as required, FDA
• ClinicalTrials.gov results
• withdrawal of the IND (21 CFR 312.38) or request for inactive status (21 CFR 312.45) when no further studies are planned, or IDE final report and completion notice
• disposition of unused product

5.10 Sponsor quality system minimum

• monitoring: a written monitoring plan (5.5.3)
• data management: a data management plan covering data capture, review, query handling, database lock and computerized systems
• safety management: receipt, assessment and expedited reporting of safety information as sponsor (5.6)
• trial master file: what sponsor records are kept, where, and for how long (5.9.2)
• service provider oversight: selection, agreements and oversight of any CRO, monitor, laboratory or other provider the sponsor-investigator uses for sponsor activities (SOP-105 applied to sponsor functions)
• a sponsor SOP set or index that lists these procedures, with version control under SOP-100

6. Related Forms and SOPs

• F-200-01 Study Feasibility Assessment
• F-105-01 Service Provider Qualification and Oversight Record
• F-306-01 Note to File
• F-501-01 SAE Reporting Tracker
• Appendix B Central and Site Responsibility Matrix (Model N only)
• SOP-100 Writing, Approving and Controlling SOPs
• SOP-104 Conflict of Interest and Financial Disclosure
• SOP-105 Oversight of Service Providers and Vendors
• SOP-201 Confidentiality Agreements, Clinical Trial Agreements and Budgets
• SOP-202 Medicare Coverage Analysis and Research Billing Compliance
• SOP-203 IRB Submissions, Approval and Continuing Oversight
• SOP-304 Investigational Product Management
• SOP-500 Adverse Event Identification, Assessment and Recording
• SOP-501 Serious Adverse Event and Expedited Safety Reporting
• SOP-502 Unanticipated Problems and Reportable New Information
• SOP-601 Study Closeout
• SOP-402 Record Retention, Archiving and Destruction
• SOP-700 Internal Quality Control and Quality Assurance Audits
• SOP-702 FDA Inspections and Remote Regulatory Assessments
• SOP-903 Network Oversight of Member Sites (Metrics, Central QA, Escalation) (Model N only)

7. References